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Previous Deep Vein Thrombosis Research: 2002-2006   
The Deep Vein Thrombosis File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Deep Vein Thrombosis, click HERE. 
   

Latest Research on
Deep Vein Thrombosis   
  
Blood. 2008 Jul 1;112(1):19-27.
Advances in understanding pathogenic mechanisms of thrombophilic disorders.
Dahlbäck B.
Department of Laboratory Medicine, Section of Clinical Chemistry, Lund University, University Hospital Malmö, Malmö, Sweden. bjorn.dahlback@med.lu.se

Venous thromboembolism is a major medical problem, annually affecting 1 in 1000 individuals. It is a typical multifactorial disease, involving both genetic and circumstantial risk factors that affect a delicate balance between procoagulant and anticoagulant forces. In the last 50 years, the molecular basis of blood coagulation and the anticoagulant systems that control it have been elucidated. This has laid the foundation for discoveries of both common and rare genetic traits that tip the natural balance in favor of coagulation, with a resulting lifelong increased risk of venous thrombosis. Multiple mutations in the genes for anticoagulant proteins such as antithrombin, protein C, and protein S have been identified and constitute important risk factors. Two single mutations in the genes for coagulation factor V (FV Leiden) and prothrombin (20210G>A), resulting from approximately 20,000-year-old mutations with subsequent founder effects, are common in the general population and constitute major genetic risk factors for thrombosis. In celebration of the 50-year anniversary of the American Society of Hematology, this invited review highlights discoveries that have contributed to our present understanding of the systems that control blood coagulation and the genetic factors that are involved in the pathogenesis of venous thrombosis.

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Ann Intern Med. 2008 Jul 15;149(2):73-82. Comment in: Ann Intern Med. 2008 Jul 15;149(2):137-9. Summary for patients in: Ann Intern Med. 2008 Jul 15;149(2):I40.
Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial.
Camporese G, Bernardi E, Prandoni P, Noventa F, Verlato F, Simioni P, Ntita K, Salmistraro G, Frangos C, Rossi F, Cordova R, Franz F, Zucchetta P, Kontothanassis D, Andreozzi GM; KANT (Knee Arthroscopy Nadroparin Thromboprophylaxis) Study Group. Unit of Angiology, University Hospital of Padua, Padua, Italy. giuseppe.camporese@sanita.padova.it

BACKGROUND: Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. OBJECTIVE: To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. DESIGN: Assessor-blind, randomized, controlled trial. SETTING: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. PATIENTS: 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. INTERVENTION: Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. MEASUREMENTS: Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. RESULTS: The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group. Limitations: The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies. CONCLUSION: In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings.

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Am Fam Physician. 2008 Jun 15;77(12):1709-16.
Venous thromboembolism during pregnancy.
Dresang LT, Fontaine P, Leeman L, King VJ.
Department of Family Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53713, USA. Lee.Dresang@fammed.wisc.edu

Venous thromboembolism is the leading cause of maternal death in the United States. Pregnancy is a risk factor for deep venous thrombosis, and risk is further increased with a personal or family history of thrombosis or thrombophilia. Screening for thrombophilia is not recommended for the general population; however, testing for inherited or acquired thrombophilic conditions is recommended when personal or family history suggests increased risk. Factor V Leiden and prothrombin G20210A mutation are the most common inherited thrombophilias, and antiphospholipid antibody syndrome is the most important acquired defect. Clinical symptoms of deep venous thrombosis may be subtle and difficult to distinguish from gestational edema. Venous compression (Doppler) ultrasonography is the diagnostic test of choice. Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. Multidetector-row (spiral) computed tomography is the test of choice for pulmonary embolism. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy.

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Plast Reconstr Surg. 2008 Jul;122(1):269-79.
Thromboembolic risk assessment and the efficacy of enoxaparin prophylaxis in excisional body contouring surgery.
Hatef DA, Kenkel JM, Nguyen MQ, Farkas JP, Abtahi F, Rohrich RJ, Brown SA.
Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA. dan.hatef@gmail.com

BACKGROUND: There is a paucity of evidence within the plastic surgery literature concerning risk stratification and management of patients with respect to thromboembolic disease. A retrospective chart review was conducted to examine whether the Davison-Caprini risk-assessment model could stratify patients undergoing excisional body contouring surgery, allowing prophylaxis to be managed in an evidence-based manner. METHODS: Three hundred sixty excisional body contouring patients at the University of Texas Southwestern Medical Center in Dallas, Texas, under the senior authors' (J.M.K. and R.J.R.) care were reviewed. Patients were stratified into groups according to the risk-assessment model and into groups based on procedure. Patient characteristics were investigated for their effects on thromboembolic risk. Complications of enoxaparin administration were analyzed. The data were analyzed using appropriate statistical procedures. RESULTS: The highest risk patients had a significantly increased rate of venous thromboembolism when compared with lower risk patients. Body mass index greater than 30 and hormone therapy use were associated with a significantly increased venous thromboembolism rate. Enoxaparin administration was associated with a statistically significant decrease in deep venous thrombosis in circumferential abdominoplasty patients. Enoxaparin administration was associated with higher bleeding rates. CONCLUSIONS: Low-molecular-weight heparin may affect the incidence of postoperative thrombotic complications in some surgical populations. In this study, patients who scored greater than four risk factors were at significant risk for venous thromboembolism. Enoxaparin significantly decreased deep venous thrombosis risk in patients undergoing circumferential abdominoplasty. This demonstrates the need for a multicenter, prospective, randomized study to examine various thromboembolic therapies and associated possible complications in these patients.

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Lancet. 2008 Jul 5;372(9632):31-9. Epub 2008 Jun 24. Comment in: Lancet. 2008 Jul 5;372(9632):6-8.
Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial.
Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, Soglian AG, Pap AF, Misselwitz F, Haas S; RECORD2 Investigators.

BACKGROUND: The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge. Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin. METHODS: 2509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to centre, with a computer-generated randomisation code, to receive oral rivaroxaban 10 mg once daily for 31-39 days (with placebo injection for 10-14 days; n=1252), or enoxaparin 40 mg once daily subcutaneously for 10-14 days (with placebo tablet for 31-39 days; n=1257). The primary efficacy outcome was the composite of deep-vein thrombosis (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal pulmonary embolism, and all-cause mortality up to day 30-42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. This study is registered at ClinicalTrials.gov, number NCT00332020. FINDINGS: The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2.0%) patients in the rivaroxaban group, compared with 81 (9.3%) in the enoxaparin group (absolute risk reduction 7.3%, 95% CI 5.2-9.4; p<0.0001). The incidence of any on-treatment bleeding was much the same in both groups (81 [6.6%] events in 1228 patients in the rivaroxaban safety population vs 68 [5.5%] of 1229 patients in the enoxaparin safety population; p=0.25). INTERPRETATION: Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism, including symptomatic events, in patients undergoing total hip arthroplasty.

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N Engl J Med. 2008 Jun 26;358(26):2776-86. Comment in: N Engl J Med. 2008 Jun 26;358(26):2827-9.
Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty.
Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F, Turpie AG; RECORD3 Investigators.

BACKGROUND: We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty. METHODS: In this randomized, double-blind trial, 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban, 10 mg once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary efficacy outcome was the composite of any deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. Secondary efficacy outcomes included major venous thromboembolism (i.e., proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death related to venous thromboembolism) and symptomatic venous thromboembolism. The primary safety outcome was major bleeding. RESULTS: The primary efficacy outcome occurred in 79 of 824 patients (9.6%) who received rivaroxaban and in 166 of 878 (18.9%) who received enoxaparin (absolute risk reduction, 9.2%; 95% confidence interval [CI], 5.9 to 12.4; P<0.001). Major venous thromboembolism occurred in 9 of 908 patients (1.0%) given rivaroxaban and 24 of 925 (2.6%) given enoxaparin (absolute risk reduction, 1.6%; 95% CI, 0.4 to 2.8; P=0.01). Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin (P=0.005). Major bleeding occurred in 0.6% of patients in the rivaroxaban group and 0.5% of patients in the enoxaparin group. The incidence of drug-related adverse events, mainly gastrointestinal, was 12.0% in the rivaroxaban group and 13.0% in the enoxaparin group. CONCLUSIONS: Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding. (ClinicalTrials.gov number, NCT00361894.) 2008 Massachusetts Medical Society

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Pol Arch Med Wewn. 2008 Apr;118(4):209-15.
Prophylaxis against venous thromboembolism in hospitalized medical patients: an evidence-based and practical approach.
Douketis JD, Moinuddin I.
Department of Medicine, McMaster University and St. Joseph's Healthcare, Hamilton, ON, Canada. jdouket@mcmaster.ca

To discuss the evidence regarding the efficacy and safety of anticoagulant prophylaxis against deep vein thrombosis (DVT) in hospitalized medical patients; to understand barriers to implementation of prophylaxis and how they can be overcome; and to have a practical approach as to which patients should and should not receive anticoagulant prophylaxis. The frequency of DVT in hospitalized medical patients, in the absence of prophylaxis varies from 10-15%. Autopsy studies have shown that pulmonary embolism (PE) is associated with 5-10% of deaths in hospitalized patients. With appropriate use of anticoagulant prophylaxis, there is a 57% reduction in the risk for symptomatic PE (relative risk [RR] 0.43, 95% CI 0.26-0.71), a 62% reduction in the risk for fatal PE (RR 0.38, 95% CI 0.21-0.69), and a 53% reduction in the risk for symptomatic DVT (RR 0.47, 95% CI 0.22-1.00). Anticoagulant prophylaxis is also associated with a non-significant increased risk for major bleeding (RR 1.32, 95% CI 0.73-2.37). Risk factors for DVT and bleeding in medical patients may help to identify patients in whom anticoagulant prophylaxis is indicated or contraindicated but validated risk stratifications schemes are lacking. Among hospitalized medical patients, randomized trials have established an acceptable therapeutic benefit-to-risk ratio of anticoagulant prophylaxis to reduce the incidence of clinically silent and symptomatic venous thromboembolism, including a reduction in the incidence of fatal PE. Additional research is needed to develop a validated risk stratification model for hospitalized medical patients that can help identify patients who would benefit most from anticoagulant prophylaxis.

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Pol Arch Med Wewn. 2008 Apr;118(4):183-93.
Anticoagulation in patients with cancer: an overview of reviews.
Akl EA, Muti P, Schünemann HJ.
Department of Medicine, State University of New York at Buffalo, NY 14215, USA. elieakl@buffalo.edu

INTRODUCTION: Relative benefits and harms of anticoagulants are required for judgments regarding appropriate anticoagulation in patients with cancer. OBJECTIVES: To review the benefits and harms of anticoagulants for prophylactic, therapeutic, and survival improvement indications in patients with cancer. PATIENTS AND METHODS: Overview of 6 systematic reviews of anticoagulation in cancer following the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: Central venous catheters thromboprophylaxis with heparin or warfarin does not significantly reduce the incidence of symptomatic deep vein thrombosis (DVT) (relative risk [RR] 0.43, 95% CI 0.18-1.06 and RR 0.62, 95% CI 0.30-1.27 respectively). For perioperative thromboprophylaxis, low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have similar effects on mortality (RR 0.89, 95% CI 0.61-1.28) and morbidity outcomes. For the initial treatment of venous thromboembolism (VTE), LMWH compared with UFH reduces mortality at 3 months (RR 0.71, 95% CI 0.52-0.98). For the long-term treatment of VTE, LMWH compared with vitamin K antagonists reduces VTE recurrence (hazard ratio [HR] 0.47, 95% CI 0.32-0.71) but not mortality (HR 0.96, 95% CI 0.81-1.14). As interventions to improve survival, warfarin suggests a survival benefit at 6 months in the subgroup of small cell lung cancer (SCLC) (RR 0.69, 95% CI 0.50-0.96) while heparin suggests a survival benefit in patients with cancer in general (HR 0.77, 95% CI 0.65-0.91) and in those with limited SCLC in particular (HR 0.56, 95% CI 0.38-0.83). CONCLUSIONS: In patients with cancer, current evidence does not support routine use of thromboprophylaxis for central venous catheters or a specific anticoagulant for perioperative thromboprophylaxis. Anticoagulants may improve survival, but more data will be useful in deciding which subgroups benefit most.

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Arch Intern Med. 2008 Jun 23;168(12):1261-9.
Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta-analysis.
Akl EA, Terrenato I, Barba M, Sperati F, Sempos EV, Muti P, Cook DJ, Schünemann HJ.
Department of Medicine, State University of New York at Buffalo, Erie County Medical Center CC-142, 462 Grider St, Buffalo, NY 14215, USA. elieakl@buffalo.edu

BACKGROUND: The relative benefits and harms of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) are required for judgments regarding the appropriate perioperative thromboprophylaxis in patients with cancer. We systematically reviewed the literature to quantify these effects. METHODS: The comprehensive searches included (1) an electronic search of MEDLINE, EMBASE, ISI the Web of Science, and CENTRAL (The Cochrane Central Register of Controlled Trials); (2) a hand search of relevant conference proceedings; (3) a reference check of included trials; and (4) use of the PubMed "Related Articles" feature. Outcomes of interest included mortality, deep venous thrombosis, pulmonary embolism, bleeding complications, and thrombocytopenia. RESULTS: Of 3986 identified citations, we included 14 randomized clinical trials in the meta-analysis (all using preoperative prophylactic anticoagulation). The overall methodological quality was moderate. The meta-analysis showed no differences in mortality in patients receiving LMWH compared with UFH (relative risk [RR], 0.89; 95% confidence interval [CI], 0.61-1.28) or in clinically suspected deep venous thrombosis (RR, 0.73; 95% CI, 0.23-2.28). In a post hoc analysis including all studies assessing deep venous thrombosis, irrespective of the diagnostic strategy used, LMWH was superior to UFH (RR, 0.72; 95% CI, 0.55-0.94). There were no differences in rates of pulmonary embolism (RR, 0.60; 95% CI, 0.22-1.64), minor bleeding (RR, 0.88; 95% CI, 0.47-1.66), or major bleeding (RR, 0.95; 95% CI, 0.51-1.77). CONCLUSIONS: We found no differences in mortality in patients with cancer receiving perioperative thromboprophylaxis with LMWH vs UFH. Further trials are needed to more carefully evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population.

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Anesteziol Reanimatol. 2008 Mar-Apr;(2):82-5.
[Venous thromboses and pulmonary arterial thromboembolism in neurosurgical patients]
[Article in Russian]
Markina MS, Lubnin AIu, Madorskiĭ SV, Kirichkova OA.

The paper gives the results of a study conducted in 3 groups of neurosurgical patients in the analysis of autoptic material over 15 years in order to detect pulmonary arterial thromboembolism (PATE) as a cause of postoperative death in neurosurgical patients. In the latter, the incidence of PATE was ascertained to be 5.4%, as evidenced by autopsy and the distribution of the onset of a fatal outcome was biphasic. The informative value of determination of the blood level of fibrin D-dimer was analyzed in neurosurgical patients as a screening method for diagnosing prethrombosis. The method has shown to be of high informative value (about 90% sensitivity) and may be used in clinical practice. The effectiveness and safety of the combined procedure of preventing venous thromboembolic events (mechanical method with a subsequent switching over to pharmacological methods on days 3) were evaluated. The method has proven to be effective and safe.

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Thromb Haemost. 2008 Jun;99(6):1112-5.
Limited diagnostic workup for deep vein thrombosis after major joint surgery: findings from a prospective, multicentre, cohort study.
Monreal M, Peidro L, Resines C, Garcés C, Fernández JL, Garagorri E, González JC; NETCOT Investigators.
Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. mmonreal.germanstrias@gencat.net

While deep vein thrombosis (DVT) may be clinically suspected at several time points after major orthopedic surgery, clinical examination is often unreliable, and compression ultrasonography (CUS) screening at discharge is of limited value. A prospective cohort study was carried out in 1,033 consecutive patients who had undergone major hip or knee surgery, aimed to assess the accuracy of a strategy consisting of clinical investigation followed by CUS in the detection of proximal DVT before discharge. The circumferences of both legs were measured in all patients; those exhibiting >2 cm difference between them were considered to have suspected DVT, and underwent bilateral CUS. The same diagnostic workup was repeated on days 45 and 90 after surgery. Three patients developed pulmonary embolism (PE) during admission (one died). Five additional patients died before discharge. Routine clinical evaluation before discharge was done in 1,025 patients, and 105 (10%) had suspected DVT. CUS confirmed the diagnosis in 24 (2.3% of the overall series). After discharge, 59 patients had suspected DVT on day 45, 53 on day 90. DVT diagnosis was confirmed by CUS in 27 (26%). Three additional patients developed PE (1 fatal). This translates into a sensitivity of the routine examinations at discharge of 44%. A limited diagnostic workup for DVT before discharge has the capacity to identify 44% of those patients who will become symptomatic afterwards.

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J Comput Assist Tomogr. 2008 May-Jun;32(3):475-9.
New classes of anticoagulation and antiplatelet agents: preprocedure management and safety guidelines for imaging-guided intervention.
Ho LM, Hodulik KL, Suhocki PV, Hurwitz LM, Paulson EK.
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. lisaho@duke.edu

OBJECTIVE: New medications are available for prophylaxis of deep venous thrombosis, the treatment of venous thromboembolism, and also to reduce the risk of acute coronary syndrome and stroke. The purpose of this review is to provide the radiologist a practical and succinct summary of the new anticoagulation and antiplatelet medications and how to manage these medications in patients who are in need of a radiology intervention. CONCLUSION: This article provides recommendations for preprocedure management of new anticoagulants and antiplatelet agents in patients undergoing radiology intervention.

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Vasa. 2008 Feb;37(1):31-8.
Superficial vein thrombophlebitis—serious concern or much ado about little?
Blättler W, Schwarzenbach B, Largiadèr J.
Angio Bellaria--Centre for Vascular Diseases, Zürich, Switzerland. werner.blaettler@hin.ch

Superficial vein thrombophlebitis (SVTP) appears in two distinct forms: varicose vein thrombophlebitis (TP) represents the principal cause. It is characterized by a large thrombus in a varicose vein and a modest inflammatory process localized in the vessel surrounding but not in its wall. Rarely, SVTP affects a non-varicose vein. Abundant intima proliferation and media fibrosis with non-important thrombosis are the hallmark of this form which may be associated with a systemic disease. Although SVTP is perceived as trivial and benign coexistence of (mostly distal) deep venous thrombosis (DVT), propagation to popliteal or femoral DVT, and even pulmonary embolism (PE) have been reported. Data for prevalence vary greatly: 6-53% for coexistence, 2.6-15% for propagation, and 0-33% for (asymptomatic) PE. Risk factors for these complications are those known for DVT. SVTP is diagnosed in a clinical setting but ultrasonography is useful to check for concomitant DVT. Anticoagulant treatment is mandatory if DVT is present and thrombectomy should be considered in cases of thrombus propagation into the deep veins. Historical therapy of uncomplicated SVTP consists of compression with bandages or stockings and local or systemic anti-inflammatory agents. Low-molecular-weight heparin (LMWH) has been given in high-prophylactic doses and found equally effective when compared with anti-inflammatory agents and full-therapeutic dose LMWH. Prophylactic saphenous vein ligation alone was found less effective than conservative therapy. Ligation combined with stripping proved the potential of eliminating at once all problems associated with SVTP but was associated with a complication rate of 10% or higher. Careful patient selection and saphenous vein thrombectomy prior to stripping may be the clue for better results.

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Cancer. 2008 Apr 10 [Epub ahead of print]
Thromboprophylaxis for patients with cancer and central venous catheters: a systematic review and a meta-analysis.
Akl EA, Kamath G, Yosuico V, Kim SY, Barba M, Sperati F, Cook DJ, Schünemann HJ.
Department of Medicine, State University of New York at Buffalo, Buffalo, New York.

BACKGROUND.: Central venous catheter (CVC) placement increases the risk of thrombosis and subsequent death in patients with cancer. The objective of this systematic review was to determine the efficacy and safety of anticoagulation in reducing mortality and thromboembolic events in cancer patients with a CVC. METHODS.: The authors searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI the Web of Science databases. They included randomized controlled trials in patients with cancer comparing unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists, fondaparinux, or ximelagatran with no intervention, placebo, or each other. The standard methods of the Cochrane Collaboration were used for the analyses. RESULTS.: Of 3986 identified citations we included 9 randomized clinical trials, none of which evaluated fondaparinux or ximelagatran. Heparin therapy (UFH or LMWH) was associated with a trend toward a reduction in symptomatic deep venous thrombosis (DVT) (relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.18-1.06), but there was no statistically significant effect on mortality (RR, 0.74; 95% CI, 0.40-1.36), infection (RR, 0.91; 95% CI, 0.36-2.28), major bleeding (RR, 0.68; 95% CI, 0.10-4.78), or thrombocytopenia (RR, 0.85; 95% CI, 0.49-1.46). The effect of warfarin on symptomatic DVT also was not statistically significant (RR, 0.62; 95% CI, 0.30-1.27). CONCLUSIONS.: The balance of benefits and downsides of thromboprophylaxis in cancer patients with CVC are uncertain. Clinicians together with their patients must weigh these factors carefully when making decisions regarding thromboprophylaxis. Cancer 2008. (c) 2008 American Cancer Society.

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Pathol Biol (Paris). 2008 Apr 4 [Epub ahead of print]
[Venous thromboembolism associated with long-term use of central venous catheters in cancer patients.]
[Article in French]
Debourdeau P, Chahmi DK, Zammit C, Farge-Bancel D.
Service de médecine interne oncologique, hôpital Desgenettes, 108, boulevard Pinel, 69003 Lyon, France.

Increased incidence of cancers and the development of totally implanted venous access devices that contain their own port to deliver chemotherapy will lead to a greater than before numbers of central venous catheter-related thrombosis (CVCT). Medical consequences include catheter dysfunction and pulmonary embolism. Vessel injury caused by the procedure of CVC insertion is the most important risk factor for development of CVCT. This event could cause the formation of a fresh thrombus, which is reversible in the large majority of patients. In some cases, thrombus formation is not related to catheter insertion. The incidence of CVC-related DVT assessed by venography has been reported to vary from 30 to 60% but catheter-related DVT in adult patients is symptomatic in only 5% of cases. The majority of patients with CVC-related DVT is asymptomatic or has nonspecific symptoms: arm or neck swelling or pain, distal paresthesias, headache, congestion of subcutaneous collateral veins. In the case of clinical suspicion of CVC-related deep venous thrombosis (DVT), compressive ultrasonography (US), especially with doppler and color imaging, currently is first used to confirm the diagnosis. Consequently, contrast venography is reserved for clinical trials and difficult diagnostic situations. There is no consensus on the optimal management of patients with CVC-related DVT. Treatment of CVC-related VTE requires a five- to seven-day course of adjusted-dose unfractionated heparin or low molecular weight heparin (LMWH) followed by oral anticoagulants. Long-term LMWH that has been shown to be more effective than oral anticoagulant in cancer patients with lower limb DVT, could be used in these patients. The efficacy and safety of pharmacologic prophylaxis for CVC related thrombosis is not established and the last recommandations suggest that clinicians not routinely use prophylaxis to try to prevent thrombosis related to long-term indwelling CVCs in cancer patients. Additional studies performed in high risk populations with appropriate dosage and timing will help to define which patients could benefit from prophylaxis.

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Pathol Biol (Paris). 2008 Apr 2 [Epub ahead of print]
[Treatment of venous thromboembolic disease in cancer patients.]
[Article in French]
Farge-Bancel D, Florea L, Bosquet L, Debourdeau P.
Service de médecine interne et pathologie vasculaire, base moléculaires de l’homéostasie cutanée, Inserm U67, hôpital Saint-Louis, 10, avenue Claude-Vellefaux, 75010 Paris, France.

Venous thromboembolism (VTE) disease, as defined by the occurence of deep venous thrombosis or pulmonary embolism, occurs among 4 to 20% of patients with cancer and is a leading cause of death among these patients. Use of classical anticoagulation to treat VTE in a cancer patient is associated with a higher risk of major bleeding and of VTE recurrence as compared to noncancer patients. Updated comprehensive and systematic review of current data from the medical literature allows to reconsider the classical approach used for anticoagulant treatment in cancer patients and to implement adapted recommendations. In 2008, the use of daily subcutaneous low-molecular-weight heparin (LMWH) for at least three to six months is recommended as first line therapy to treat VTE disease in cancer patients. If LMWH are contra-indicated (renal insuffisiency), other therapeutic appraoches are warranted, such as use of unfractionated heparin (UFH) with early introduction of anti-vitamin K for at least three months or venous cava filter in case of absolute contra-indications to anticoagulation. VTE prophylaxis in cancer patients relies on the same therapeutic approaches as currently used for noncancer patients at high risk of VTE. The definition of more specific prophylactic approaches for patients with cancer considered at higher risks of VTE, will be the subject of many clinical trials in the forthcoming years.

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Curr Opin Crit Care. 2008 Apr;14(2):149-155.
Venous thromboembolism prophylaxis and treatment in patients with acute stroke and traumatic brain injury.
Vergouwen MD, Roos YB, Kamphuisen PW.
aDepartment of Neurology, The Netherlands bDepartment of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

PURPOSE OF REVIEW: Patients with acute stroke and traumatic brain injury are at risk to develop venous thromboembolism. This review analyzes the available literature to propose guidelines for the prevention and treatment of venous thromboembolism in these groups of patients. RECENT FINDINGS: In acute ischemic stroke, low-dose low-molecular-weight heparin has the best benefit-risk ratio to prevent venous thromboembolism. Patients with primary intracerebral hemorrhage and traumatic brain injury should receive intermittent pneumatic compression, followed by low-dose low-molecular-weight heparin or unfractioned heparin 3-4 days after stroke onset or 24 h after injury or surgery, respectively, and after cessation of bleeding. Concerning treatment, in patients with deep-vein thrombosis lower doses of heparin are indicated to prevent pulmonary embolism, and a vena cava filter should be considered. In patients with pulmonary embolism, treatment could be more aggressive, because of a high mortality risk. SUMMARY: Adequate prevention of venous thromboembolism with intermittent pneumatic compression or pharmacological prophylaxis is important. The best treatment of venous thromboembolism remains unclear. In case of pulmonary embolism, more aggressive treatment is warranted.

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J Vasc Interv Radiol. 2008 Apr;19(4):521-8.
Ultrasound-accelerated Thrombolysis for the Treatment of Deep Vein Thrombosis: Initial Clinical Experience.
Parikh S, Motarjeme A, McNamara T, Raabe R, Hagspiel K, Benenati JF, Sterling K, Comerota A.
Department of Interventional Radiology, Swedish Medical Center-Cherry Hill Campus, Seattle, Washington.

PURPOSE: To evaluate the success of lysis and clinical outcomes in patients treated with ultrasound (US)-accelerated thrombolysis for deep vein thrombosis (DVT). MATERIALS AND METHODS: Forty-seven patients with 53 cases of DVT were treated with US-accelerated thrombolysis at eight centers in the United States. Sixty percent of the occlusions were in the lower extremity, 36% were in the upper extremity, and 4% were hepatic. The clot was acute (</=14 days) in 47% of cases, subacute (15-28 d) in 8%, chronic (>28 d) in 17%, acute-on-chronic in 17%, and not specified in 11%. Patients were treated with urokinase (UK), tissue plasminogen activator (tPA), recombinant plasminogen activator (rPA), or tenecteplase. RESULTS: Complete lysis (>/=90%) was seen in 37 of 53 cases (70%) and overall lysis (complete plus partial) was seen in 48 (91%). No lysis occurred in five cases (9%), four of which were chronic. The median thrombolysis infusion time was 22.0 hours. Major complications (hematoma at site of earlier surgery) occurred in only two patients (3.8%), with no incidence of intracranial or retroperitoneal hemorrhage. US-accelerated thrombolysis exhibited comparable or better lysis with a lower average drug dose and shorter median treatment times than reported in the National Venous Registry and a more recently published study of standard catheter-directed thrombolysis. CONCLUSIONS: US-accelerated thrombolysis was shown to be a safe and efficacious treatment for DVT in this multicenter experience. The addition of US reduces total infusion time and provides a greater incidence of complete lysis with a reduction in bleeding rates.

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Perspect Vasc Surg Endovasc Ther. 2008 Mar;20(1):87-91. Epub 2008 Apr 2.
Endovascular management of deep venous thrombosis.
McLafferty RB.
School of Medicine, Southern Illinois University, Springfield, Illinois, rmclafferty@ siumed.edu.

The past decade has witnessed new developments for the treatment of deep venous thrombosis (DVT) as well as more information about the virulent nature of DVT over the long term. Symptoms of pain, edema, skin changes, and/or ulceration can affect upwards of 70% of individuals to some degree. Studies have determined that early intervention of thrombus removal may help prevent postthrombotic syndrome in a significant number of patients. Several devices now specifically combine mechanical or ultrasound energy with chemical thrombolysis. These devices include the Trellis-8, Angiojet Power Pulse System, and the Ekos Endowave. Other important aspects central to successful endovascular removal of DVT include using ultrasound guidance for access, understanding venous anatomy and physiology in relation to endovascular techniques, knowing when to perform venous interventions, and using intravascular ultrasound. Endovascular removal of DVT is increasingly becoming the standard of care, p
articularly that affecting the iliofemoral segments.

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Semin Thromb Hemost. 2008 Feb;34(1):58-73.
Survival of heparins, oral anticoagulants, and aspirin after the year 2010.
Fareed J, Hoppensteadt DA, Fareed D, Demir M, Wahi R, Clarke M, Adiguzel C, Bick R.
Hemostasis and Thrombosis Research Laboratories, Loyola University Medical Center, Maywood, Illinois.

The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the U.S. Food and Drug Administration did not approve the orally active antithrombin agent ximelagatran for several indications. The synthetic pentasaccharide (fondaparinux) has undergone an aggressive clinical development. Unexpectedly, fondaparinux also produced major bleeding problems at minimal dosages. Fondaparinux represents only one of the multiple pharmacologic effects of heparins. Thus, its therapeutic index will be proportionately narrower. The newer antiplatelet drugs have added a new dimension in the management of thrombotic disorders. The favorable clinical outcomes with aspirin and clopidogrel have validated cyclooxygenase (COX)-1 and P2Y (12) receptors as targets for new drug development. Prasugrel, a novel thienopyridine, cangrelor, and AZD 6140 represent newer P2Y (12) antagonists. Cangrelor and AZD 6140 are direct inhibitors, whereas prasugrel requires metabolic activation. Though clinically effective, recent results have prompted a closure of a large clinical trial with prasugrel due to bleeding. The newer anticoagulant and antiplatelet drugs are attractive for several reasons; however, none of these are expected to replace the conventional drugs in polytherapeutic approaches. Heparins, warfarin, and aspirin will continue to play a major role in the management of thrombotic and cardiovascular disorders beyond 2010.

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Vitam Horm. 2008;78:265-79.
Vitamin K and thrombosis.
Merli GJ, Fink J.
Professor of Medicine, Director Jefferson Center for Vascular Diseases, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.

Vitamin K was discovered in the 1930s during cholesterol metabolism experiments in chickens. It is a fat-soluble vitamin which occurs naturally in plants as phylloquinone (vitamin K1) and is produced by gram-negative bacteria in the human gastrointestinal tract as menaquinone (vitamin K2). This vitamin was found to be essential for normal functioning of hemostasis. In addition, a number of clinical conditions in which vitamin K deficiency was found to be the underlying pathophysiologic problem were discovered. These conditions include hemorrhagic disease of the newborn, obstructive jaundice, and malabsorption syndromes. The importance of this vitamin has become more apparent with the discovery of the anticoagulant warfarin which is a vitamin K antagonist. There are millions of patients on this therapy for a variety of thrombogenic conditions such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and prosthetic cardiac valves. The wide use of this narrow therapeutic index drug has resulted in significant risk for major bleeding. Vitamin K serves as one of the major reversing agent for patients over-anticoagulated with warfarin. In the past few years, research has focused on new areas of vitamin K metabolism, which include bone and endovascular metabolism; cell growth, regulation, migration, and proliferation; cell survival, apoptosis, phagocytosis, and adhesion. These new areas of research highlight the significance of vitamin K but raise new clinical questions for patients who must be maintained on long-term warfarin therapy.

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J Intern Med. 2008 Jan;263(1):52-60.
Efficacy and safety of anticoagulant prophylaxis to prevent venous thromboembolism in acutely ill medical inpatients: a meta-analysis.
Själander A, Jansson JH, Bergqvist D, Eriksson H, Carlberg B, Svensson P.
Department of Internal Medicine, Sundsvall Hospital, Sundsvall, Sweden. anders.sjalander@lvn.se

OBJECTIVES: Venous thromboembolism (VTE) is a potentially serious complication of hospitalization and immobilization. The use of anticoagulant prophylaxis in acutely ill medical inpatients is still under debate. New data including a recent meta-analysis have recently been published. We aim at studying the efficacy and safety of anticoagulant prophylaxis in acutely ill medical inpatients, and demonstrate differences between meta-analyses due to different data extraction from the heterogeneous studies included. SUBJECTS: The Cochrane Library, MEDLINE and EMBASE were searched from 1980 to present. Manual searches were performed regarding abstracts from major meetings. Seven blinded randomized controlled clinical trials assessing the prophylactic effect of heparin in acutely ill medical patients were identified and included in the meta-analysis. RESULTS: Low-molecular weight heparin (LMWH) prophylaxis prevented 48% of symptomatic pulmonary embolism (PE), 48% of symptomatic deep vein thrombosis (DVT) (not significant) and 51% of asymptomatic DVT. A nonsignificant trend towards higher bleeding risk during LMWH prophylaxis was found. Death was not significantly affected. We compared our data with a recent meta-analysis with different study selection and data extraction and found similar results. CONCLUSIONS: As DVT and PE are manifestations of the same illness, VTE, one can argue that anticoagulant prophylaxis prevents approximately half of the expected events. Most medical inpatients have short hospital stays, and a low risk of VTE. The important task for the clinician is to identify patients with a sufficiently high risk of symptomatic VTE to warrant LMWH prophylaxis. Despite differences in study selection and data extraction, our study shows results similar to a recent meta-analysis.

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Drugs. 2008;68(1):105-22.
Parnaparin : a review of its use in the management of venous thromboembolism, chronic venous disease and other vascular disorders.
McKeage K, Keating GM.
Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA.

Parnaparin (Fluxum(trade mark)) is a low molecular weight heparin (LMWH) that is effective and generally well tolerated in the prevention of venous thrombosis, and in the treatment of chronic venous disease and venous and arterial thrombosis. Overall, the efficacy of parnaparin is at least as good as that of unfractionated heparin (UFH), but recent data indicate that parnaparin is more effective in preventing a triple composite endpoint of death, acute myocardial infarction (MI) and myocardial revascularisation in patients with unstable angina or acute ST-segment elevation myocardial infarction (STEMI). As with other LMWHs, parnaparin has a more convenient, once-daily, subcutaneous administration regimen and better local tolerability than UFH. Very little evidence comparing LMWHs is available but, because of similarities between these agents, very large studies would be needed to show significant differences. Meanwhile, data indicate that parnaparin is a useful option in the
range of available LMWHs.

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Minerva Cardioangiol. 2007 Dec;55(6):741-53.
Effectiveness of mesoglycan in patients with previous deep venous thrombosis and chronic venous insufficiency.
Andreozzi GM.
Angiology Care Unit, University Hospital of Padua, Padua, Italy gm.andreozzi@angio-pd.it.

AIM: Retrospective analysis of mesoglycan therapeutic activity in venous disorders. The clinical data have been selected from the outpatient database of the Chair of Angiology of the University of Catania (from 1988 to 1997) through a cross survey between the prescription commercial name of mesoglycan and the key words varicose veins, deep venous thrombosis (DVT), chronic venous insufficiency (CVI), post-thrombotic syndrome (PTS), venous thrombosis, venous ulcer. METHODS: Patients have been selected on the basis of definite data relative to principal diagnosis, clinical history, clinical and instrumental objective phlebological picture, posology and duration of treatment, follow-up visits in the first three years following the first observation. Group 1: 56 patients with first episode DVT; Group 2: 27 patients with recurrent DVT; Group 3: 182 patients with CVI (107 with primitive CVI and 75 with secondary CVI). The selected patients data have been included in new databases. DVT patients were evaluated for recurrence prevalence during the follow-up period (6, 12, 18, 24, 30 and 36 months). In Group 2 the recurrence prevalence in the normal follow-up period was evaluated and, in addition, the clinical chronology of the recurrence previous to observation was drawn, in order to find out the recurrence prevalence of the thrombotic episode preceding our observation. The two prevalence trends ( mesoglycan treatment and episode preceding our observation) have been compared with the Student t test. CVI patients (Group 3) were classified according to CEAP classification criteria. The effectiveness of treatment was assessed according to the changes in the scores of venous dysfunction of CEAP classification (disability score; pain; oedema; skin color change; cutaneous ulcer). The mean and standard deviation of the considered scores have been evaluated with the Student t test comparing each series with the immediately previous series and with the T0 series. The mean dose of mesoglycan was 50 mg twice per day. RESULTS: Group 1 (1(st) episode DVT): the recurrence prevalence was 3.5% at 6 months, 9% at 12 months, 12.5% at 18 months, 14.28% at 24, 30 and 36 months. At the end of the 3 follow-up years the PTS diagnosis could be performed in 10 patients (17.85%). Group 2 (recurrent DVT): the recurrence prevalence was 3.7% at 6 months, 11.11% at 12 months, 14.81% at 24 months, 18.51% at 36 months during mesoglycan treatment. In the preceding period the prevalence was 11.11% at 6 months from the preceding episode, 16.66% at 12 months, 33.33% at 24 months and 37.03% at 36 months. In the remaining 62.96% the recurrence occurred at 36 and 48 months. The comparison between the two series showed a significant difference with P < 0.0004. PTS prevalence at the end of the 3 follow-up years was 17.85% in patients with a first episode of DVT and 81.41% in patients with recurrent DVT. Group 3 (CVI): all the venous dysfunction scores showed a significant improvement during the follow-up period, both in comparison with the beginning of treatment and with the immediately preceding control visit. CONCLUSION: The results obtained in groups 1 and 2 show that mesoglycan is effective in preventing thrombotic recurrence in patients with previous DVT. The recurrence prevalence in patients with DVT at 1(st) episode was lower than the prevalence reported by the literature data (17.5% within 2 years and 24.6% within 5 years). The positive trend was also confirmed in the recurrent DVT group, although with a major prevalence (18.51%) due to a higher thrombotic risk. However, the prevalence in the treatment period is significantly lower than the previous thrombotic episode. Mesoglycan was also effective in CVI patients, with a progressive and significant improvement of disability, pain and edema, which are the pathophysiologic elements responsible for the impairment of quality of life. At the various follow-up points the mean score value significantly reduced compared to T0 and to the values of the preceding control. In conclusion mesoglycan is a useful and effective medication in the treatment of venous disorders, both in the subacute phase of DVT and in the long-term therapy for CVI, and is worth more extensive documentation, in accordance with the criteria of evidence-based medicine.

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Cardiovasc Intervent Radiol. 2007 Dec 14 [Epub ahead of print]
The Need for Anticoagulation Following Inferior Vena Cava Filter Placement: Systematic Review.
Ray CE Jr, Prochazka A.
Department of Radiology, University of Colorado Denver and Health Sciences Center, Denver, Colorado, USA.

PURPOSE: To perform a systemic review to determine the effect of anticoagulation on the rates of venous thromboembolism (pulmonary embolus, deep venous thrombosis, inferior vena cava (IVC) filter thrombosis) following placement of an IVC filter. METHODS: A comprehensive computerized literature search was performed to identify relevant articles. Data were abstracted by two reviewers. Studies were included if it could be determined whether or not subjects received anticoagulation following filter placement, and if follow-up data were presented. A meta-analysis of patients from all included studies was performed. A total of 14 articles were included in the final analysis, but the data from only nine articles could be used in the meta-analysis; five studies were excluded because they did not present raw data which could be analyzed in the meta-analysis. A total of 1,369 subjects were included in the final meta-analysis. RESULTS: The summary odds ratio for the effect of anticoagulation on venous thromboembolism rates following filter deployment was 0.639 (95% CI 0.351 to 1.159, p = 0.141). There was significant heterogeneity in the results from different studies [Q statistic of 15.95 (p = 0.043)]. Following the meta-analysis, there was a trend toward decreased venous thromboembolism rates in patients with post-filter anticoagulation (12.3% vs. 15.8%), but the result failed to reach statistical significance. CONCLUSION: Inferior vena cava filters can be placed in patients who cannot receive concomitant anticoagulation without placing them at significantly higher risk of development of venous thromboembolism.

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Thromb Res. 2007 Dec 11 [Epub ahead of print]
Physical activity in patients with deep venous thrombosis: A systematic review.
Kahn SR, Shrier I, Kearon C.
Center for Clinical Epidemiology & Community Studies, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

OBJECTIVES: We performed a systematic review to assess the benefits or risks of physical activity in patients with an acute or previous DVT of the leg. DATA SOURCES: PubMed, EMBASE and Science Citation Index were searched without language restrictions up to July 2007. Bibliographies of retrieved articles and personal files were also searched. REVIEW METHODS: Randomized trials and prospective cohort studies that included patients with acute or previous DVT, described an exercise intervention or exercise exposure, and described any related clinical outcome were selected. Data were independently extracted by 2 investigators. RESULTS: Seven randomized trials and two prospective observational studies were included. Early exercise, compared with bed rest, was associated with a similar short-term risk of pulmonary embolism in patients with acute DVT and led to more rapid resolution of limb pain. In patients with acute DVT, a 6 month daily walking program led to similar degrees of vein recanalization and improvement in quality of life as controls. In patients with previous DVT, 30 min of vigorous treadmill exercise did not worsen venous symptoms and improved calf muscle flexibility; a 6 month exercise training program improved calf muscle strength and pump function; and high levels of physical activity at one month tended to be associated with reduced severity of postthrombotic symptoms during the subsequent 3 months. CONCLUSIONS: Early walking exercise is safe in patients with acute DVT and may help to reduce acute symptoms. Exercise training does not increase leg symptoms acutely in patients with a previous DVT and may help to prevent or improve the postthrombotic syndrome.

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Semin Thromb Hemost. 2007 Nov;33(8):821-8.
Thrombolysis for pulmonary embolism and venous thrombosis: is it worthwhile?
Douma RA, Kamphuisen PW.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.

Venous thromboembolism is a frequently occurring and potentially fatal disease characterized by short-term and long-term sequelae. Conventional treatment consists of heparin and vitamin K antagonists, but there is an ongoing controversy if more aggressive therapy, such as thrombolytic drugs, should be used in selected patients to achieve faster clot lysis in pursuit of better clinical outcome. A review of the literature shows that thrombolytic therapy is not recommended in the treatment of venous thrombosis. Although in deep vein thrombosis systemically administered and catheter-directed thrombolysis both offer advantages in improving vein patency and reducing the postthrombotic syndrome (PTS), prevention of severe PTS remains unproved while the bleeding risk is high. In pulmonary embolism (PE), thrombolytic therapy is generally recommended for patients with massive PE and hemodynamic instability, despite scarce and inconclusive evidence. There is no evidence that thrombolysis has a benefit over standard anticoagulant treatment in normotensive patients with acute PE, but more research is needed to better identify the subgroup of patients with nonmassive PE in whom the risk-benefit ratio is most favorable. Until this group is defined and the benefit of thrombolytic therapy is demonstrated, thrombolytic therapy should only be considered in patients with signs of massive PE and hemodynamic shock.

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Clin Ther. 2007 Nov;29(11):2395-405.
Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients.
Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS.
Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, 19 Foster Street, Worcester, MA 01608, USA.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between anticoagulants exist in medically ill patients. OBJECTIVE: This meta-analysis was conducted to assess UFH and LMWH (including the selective factor Xa inhibitor fondaparinux) in the reduction of in-hospital VTE in unselected medically ill patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry databases from January 1981 through September 2007 (English language) for randomized controlled trials using the following terms: dalteparin, enoxaparin, fondaparinux, nadroparin, and heparin. References of included articles and key review papers for additional studies were also searched. Data from studies were included in the analysis if the studies included medically ill patients with risk factors for VTE who had been followed up for 7 to 21 days. RESULTS: A total of 12,391 patients (of whom 8357 were in placebo-controlled trials) from 9 studies were included. Mean age for the entire cohort was 72.8 years; mean (SD) body mass index, 25.6 kg/m2; and mean (SD) actual body weight, 68.2 kg. Deep vein thrombosis (DVT) was significantly reduced with the addition of an LMWH compared with placebo (odds ratio [OR], 0.60; 95% CI, 0.47-0.75; P < or = 0.001), but rates of DVT were similar when comparing LMWH with UFH (OR, 0.92; 95% CI, 0.56-1.52). No significant differences in pulmonary embolism (PE) or death were found among the UFH, LMWH, and placebo groups. LMWH was associated with a significant increased risk for minor bleeding compared with placebo (OR, 1.64; 95% CI, 1.18-2.29; P = 0.003). However, no significant difference was found between LMWH and UFH (OR, 0.68; 95% CI, 0.27-1.70). Major bleeding events were similar among all groups: LMWH/fondaparinux versus placebo, OR, 1.65 (95% CI, 0.8-3.4); LMWH/fondaparinux versus UFH, OR, 0.69 (95% CI, 0.29-1.68); LMWH/fondaparinux versus UFH or placebo, OR, 1.16 (95% CI, 0.66-2.04). CONCLUSIONS: This analysis suggests that VTE prophylaxis with an LMWH (including fondaparinux) or UFH is effective in reducing the rate of DVT, but this benefit did not extend to enhanced protection against PE. Additionally, LMWH and UFH had similar bleeding outcomes.

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J Thromb Haemost. 2007 Jul;5 Suppl 1:310-7.
Venous thrombosis in the elderly.
Rosendaal FR, VAN Hylckama Vlieg A, Doggen CJ.
Department of Clinical Epidemiology and Hematology, Leiden University Medical Center, Leiden, The Netherlands. f.r.rosendaal@lumc.nl

While the overall incidence of venous thrombosis is 1-2 per 1000 per year, it is close to 1% per year in the very old. The case-fatality rate of thrombosis is high in the elderly, particularly among those with cancer. The risk of major hemorrhage during anticoagulant treatment is also strongly age-dependent, contributing to the vulnerability of the old patient with thrombosis. From this perspective it is surprising that far fewer studies into the etiology and treatment of venous thrombosis have focused on the elderly than on young and middle-aged patients. In this review we discuss that, while environmental risk factors, such as immobilization and cancer, are important causes of thrombosis in the elderly, abnormalities of the coagulation system are equally, or even more, important than in young individuals. In addition to a review of the literature, new data are presented from the MEGA-study. Thrombosis in the elderly should be a focus of future studies.

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J Burn Care Res. 2007 Jul 19;Publish Ahead of Print [Epub ahead of print]
Practice Guidelines for Deep Venous Thrombosis Prophylaxis in Burns.
Faucher LD, Conlon KM.
From the University of Wisconsin.

Measures to prevent deep venous thrombosis (DVT), including low-dose subcutaneous heparin, low molecular weight heparin, or sequential compression devices, may be considered in high-risk patients, specifically those with a previous history of thromboembolic disease, and in patients with significant burns of the lower extremities. The purpose of this guideline is to review the principles of prophylaxis for DVT in burn patients and to present a reasonable approach for the treatment of patients during burn resuscitation. This guideline is designed to aid those physicians who are responsible for the triage and initial management of burn patients. DVT in the burn patient is a more common event than previously reported, with incidence ranging from 1% to 23% in the few available series. The suspected risk of bleeding using low-dose heparin has deterred most burn surgeons from using heparin routinely in all burn patients. Much remains unknown, however, regarding the real risks and benefits of this complication and its treatment. A Medline search of all English language citations from 1966 through 2006 was undertaken using the key words "deep vein thrombosis" and "deep venous thrombosis" with "burns." This produced 18 references. The addition of the key words "pulmonary embolism" with "burns" produced a total of 82 references, of which 7 were felt to be relevant to this topic based on evidentiary classification of the data. There are no prospective, randomized, controlled studies evaluating the effectiveness of any prophylactic preventive measures against DVT in burn patients. The apparently low incidence of this condition in burn patients would appear to preclude its evaluation in a single-center study, and no multicenter studies have been conducted.

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Arch Intern Med. 2007 Jul 23;167(14):1476-86.
Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials.
Wein L, Wein S, Haas SJ, Shaw J, Krum H.
National Health and Medical Research Council Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.

BACKGROUND: There is uncertainty regarding which pharmacological agents most effectively prevent venous thromboembolism in hospitalized medical patients. We therefore performed a meta-analysis to determine this. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1950, 1966, and 1800, respectively, through June 30, 2006, for randomized controlled trials that involved medical patients comparing unfractionated heparin (UFH) or low-molecular-weight heparin or heparinoid (LMWH) with a control, LMWH with UFH, or selective factor Xa inhibitors with a comparator. Study selection, validity assessment, and data abstraction were performed by 2 independent reviewers (L.W. and S.W.). Data synthesis was undertaken by 1 blinded investigator (S.J.H.). RESULTS: Thirty-six studies were included. Compared with the control, UFH was associated with a reduced risk of deep venous thrombosis (DVT) (risk ratio [RR], 0.33; 95% confidence interval [CI], 0.26-0.42) and pulmonary embolism (RR, 0.64; 95% CI, 0.50-0.82), as was LMWH (RR, 0.56; 95% CI, 0.45-0.70; and RR, 0.37; 95% CI, 0.21-0.64, respectively). A UFH dosage of 5000 U 3 times daily was more effective in preventing DVT than a UFH dosage of 5000 U twice daily when compared with the control (RR, 0.27; 95% CI, 0.20-0.36; vs RR, 0.52; 95% CI, 0.28-0.96). Neither UFH nor LMWH reduced mortality. When directly compared with UFH, LMWH was associated with a lower risk of DVT (RR, 0.68; 95% CI, 0.52-0.88) and injection site hematoma (RR, 0.47; 95% CI, 0.36-0.62), but no difference was seen between the 2 agents in the risk of bleeding or thrombocytopenia. CONCLUSIONS: Both UFH and LMWH reduce venous thromboembolic risk in hospitalized medical patients, but neither agent alters mortality. When directly compared, LMWH is more effective in preventing DVT.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003679.
WITHDRAWN: Anticoagulant and aspirin prophylaxis for preventing thromboembolism after major gynaecological surgery.
Oates-Whitehead R, D'Angelo A, Mol B.

BACKGROUND: The reported overall risk of deep venous thrombosis in gynaecological surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in nearly 1% of these women. Pharmaceutical interventions are one possible prophylactic measure for preventing emboli in women undergoing major gynaecological surgery. Agents include unfractionated heparin (low-dose and adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin. OBJECTIVES: The objective of this review was to evaluate the effectiveness of warfarin, heparin and aspirin in preventing thromboembolism after major gynaecological surgery. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 15 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL (1982 to April 2003). References from relevant articles were searched and authors contacted where necessary. In addition we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of heparins, warfarin or aspirin to prevent thromboembolism after major gynaecological surgery were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Thirty-three trials were identified in the initial search. On careful inspection only eight of these met the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using odds ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used. MAIN RESULTS: The meta-analysis of heparin versus placebo found a statistically significant decrease in the number of DVTs in both the all women group (including those with and without malignancy) (OR 0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR 0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22, 95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87). Meta-analyses of UH and LMWH showed no statistical difference in any comparison. No studies compared aspirin alone to placebo, heparin or warfarin. There was a statistically significant increase in injection site haematomas associated with heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89). AUTHORS' CONCLUSIONS: Women, undergoing major gynaecological surgery and without contraindications to anticoagulants should be offered thromboprophylaxis. Evidence suggests that UH and LMWH are equally as effective in preventing DVT and the one trial available suggests that warfarin is as effective as UH. There is no evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of PE.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003076.
Home versus in-patient treatment for deep vein thrombosis.
Othieno R, Abu Affan M, Okpo E
.
BACKGROUND: Deep vein thrombosis (DVT) occurs when a blood clot blocks blood flow through a vein. This can happen after surgery, trauma, or when a person has been immobile. Clots can dislodge and block blood flow to the lungs, causing death. Heparin is a blood-thinning drug used in the first 3-5 days of DVT treatment. Low molecular weight heparins (LMWH) allow people with DVT to receive their initial treatment at home instead of in hospital. OBJECTIVES: To collate randomised controlled trials (RCTs) comparing home (LMWH) versus hospital (LMWH or UH) treatment for DVT, and to compare the safety, efficacy, acceptability and cost implications of home versus hospital treatment. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group trials register (inception to May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched Issue 2, 2007) which includes searches of MEDLINE (January 1966 onwards) and EMBASE (January 1980 onwards). We also handsearched non-listed journals and contacted researchers in the field. SELECTION CRITERIA: RCTs of home versus hospital treatment for DVT in which DVT was clinically confirmed and treated with either LMWH or UH. DATA COLLECTION AND ANALYSIS: One reviewer selected the material for inclusion and another reviewed the literature and selection of trials. Two reviewers independently extracted data. Outcomes included PE, recurrent DVT, gangrene, heparin complications, and death. MAIN RESULTS: Six RCTs involving 1708 participants with comparable treatment arms were included. All six had fundamental problems including high exclusion rates, partial hospital treatment of many in the LMWH arms, and comparison of UH in hospital with LMWH at home. The trials showed that patients treated at home with LMWH are less likely to have recurrence of venous thromboembolism (VTE) compared to hospital treatment with UH or LMWH (fixed effect relative risk (FE RR) 0.61; 95% confidence interval (CI) 0.42 to 0.90). Home treated patients also had lower mortality (FE RR 0.72; 95% CI 0.45 to 1.15) and fewer major bleeding (FE RR 0.67; 95% CI 0.33 to 1.36), but were more likely to have minor bleeding than those in hospital (FE RR 1.29; 95% CI 0.94 to 1.78) though these were not statistically significant. AUTHORS' CONCLUSIONS: The limited evidence suggests that home management is cost effective and preferred by patients. Further large trials comparing these treatments are unlikely to occur. Therefore, home treatment is likely to become the norm; further research will be directed to resolving practical issues.

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Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307.
Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis.
Koscielny J, Kiesewetter H, Jörg I, Harenberg J.
Institute for Transfusion Medicine, Charité Humboldt University, Campus Charité Mitte, Berlin, Germany.

The treatment of acute venous thromboembolism and prophylaxis of recurrent events with heparin/low molecular weight heparin followed by vitamin K antagonists is limited by several factors. Oral direct thrombin inhibitors (ODTIs) showed a better pharmacological activity and might be an alternative in the treatment of venous thromboembolism. The Thrombin Inhibition in Venous Thromboembolism (THRIVE) program performed some studies developing the ODTI ximelagatran for this indication, and it is presented in the overview. The aim of the THRIVE I study was the dose finding, and that of the THRIVE IV study the applicability in hemodynamic stabile pulmonary embolism. A prospective, randomized, double blind trial was performed to compare oral ximelagatran with enoxaparin/warfarin for a 6-month treatment of acute venous thrombosis (THRIVE II and V). A second double blind study compared ximelagatran with placebo over 18 months after a 6-month anticoagulant therapy of acute deep vein thr
ombosis. The efficacy and safety of treatment of patients with acute deep venous thrombosis who received 2 infinity 36 mg ximelagatran was not inferior to that of patients who received a conventional anticoagulant for prophylaxis of recurrent events over 6 months. Ximelagatran 2 infinity 24 mg significantly reduced recurrent thromboembolic events compared to placebo without increasing the risk for hemorrhage. A reversible symptomless increase of alanine aminotransferase occurs in 6% to 9.6% of patients between months 2 and 4. The results of the follow-up studies suggest that thromboembolic events may recur in patients with acute venous thromboembolism after termination of treatment with both vitamin K antagonists and ximelagatran.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD006212.
Vena caval filters for the prevention of pulmonary embolism.
Young T, Aukes J, Hughes R, Tang H.

BACKGROUND: Pulmonary emboli can have potentially fatal consequences. Inferior vena caval filters are metal alloy devices that mechanically trap fragmented thromboemboli from the deep leg veins en route to the pulmonary circulation. Filters in current clinical use are designed to be introduced (and in the case of retrievable filters, removed) percutaneously. Although their deployment seems of theoretical benefit, their clinical efficacy and adverse event profile is unclear. OBJECTIVES: To examine evidence for the effectiveness of vena caval filters in preventing pulmonary embolism (PE). Secondary outcomes were mortality, distal (to filter) thrombosis, and filter-related complications. SEARCH STRATEGY: Searches were conducted in the Cochrane Peripheral Vascular Diseases Group Specialised Register (last searched May 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), MEDLINE (1966 to May 2007), and EMBASE (1966 to May 2007). Filter manufacturers and clinicians interested in filters were contacted for information. SELECTION CRITERIA: Controlled clinical trials (CCTs) and randomised controlled trials (RCTs) that examined the efficacy of filters in preventing PE were selected. DATA COLLECTION AND ANALYSIS: Three authors extracted information independently. Incidence figures were extracted from survival tables. Dichotomous outcomes were analysed as hazard ratio estimates. MAIN RESULTS: One RCT met the inclusion criteria. The PREPIC trial was an open RCT of 400 participants with documented proximal deep vein thrombosis (DVT) or pulmonary embolism and who received concurrent anticoagulation.PREPIC demonstrated the efficacy of permanent caval filters in preventing PE at eight years (HR 0.37, 95% CI 0.17 to 0.79, in favour of the filter). No reduction in mortality was seen, but this reflected an older study population (mean age 73 years); the majority of deaths were due to cancer or cardiovascular causes. There was an increased incidence of DVT in the filter group (HR 1.52, 95% CI 1.02 to 2.27). No details were recorded of adverse events of filters. No CCTs suitable for inclusion were found. AUTHORS' CONCLUSIONS: Limited generalisability prevents any conclusions to be drawn from PREPIC. PREPIC employed permanent filters and lacked statistical power to detect a reduction in PE over shorter and more clinically significant time periods. However, PREPIC demonstrated that permanent caval filters are associated with an increased risk of long term lower limb DVT. There is a marked paucity of evidence regarding caval filter outcomes when used within their currently approved indications. There is also a lack of retrievable filter trials. Further trials are needed to assess vena caval filter safety and effectiveness.

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Chir Ital. 2007 May-Jun;59(3):331-5.
Prophylaxis of venous thromboembolism in bariatric surgery.
Cossu ML, Pilo L, Piseddu G, Tilocca PL, Cossu F, Noya G.
Chirurgia Generale e della Grande Obesità e Patologie Correlate, Policlinico Universitario, Università degli Studi di Sassari.

Patients with morbid obesity who undergo bariatric surgery are usually considered at high risk of developing venous thromboembolism. Considering that deep vein thrombosis is often asymptomatic, primary prevention is the key to reducing morbidity and mortality. Between 1995 and 2003, 151 patients underwent surgery for morbid obesity at the Obesity Surgery Centre-University of Sassari. At the beginning of our experience in this field, in the first 65 cases, prophylaxis of thromboembolism consisted in a single intravenous injection of heparin sodium at the time of induction of anaesthesia. The dose of heparin ranged from 2500 to 5000 IU according to weight and any diseases associated with obesity. In a later stage of our experience (86 cases) we modified the drug therapy and used low doses of calcic heparin: the dose was obtained by daily monitoring of Pt, TT and aPTT in order to obtain good anticoagulation. This treatment was usually begun 4-5 days before the operation and continued until the patient was discharged (8-9 days). In the first group of patients we had 2 cases (3%) of fatal acute pulmonary embolism. In the second group 1 (1.16%) case of non-fatal pulmonary embolism developed on postoperative day 20. No clear consensus emerges from the literature as to the best approach to reduce the risk of thromboembolism in bariatric surgery to a minimum. Our experience suggests that "personalized heparin prophylaxis" before, during and after bariatric surgery could be the key to reducing morbidity and mortality.

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Rev Prat. 2007 Apr 15;57(7):751-7.
[Initial treatment of venous thromboembolic events]
[Article in French]
Mismetti P, Decousus H, Moulin N.
Service de médecine interne et thérapeutique, unité de pharmacologie clinique, Groupe de recherche sur la thrombose EA 3065 CIE3, CHU de Saint-etienne, 42055 Saint-Etienne. patrick.mismetti@chu-st-etienne.fr

Initial treatment of venous thromboembolic events is currently based on antithrombotics. This treatment is validated and identical for deep vein thrombosis (DVT) and pulmonary embolism. For distal DVT, this treatment has still to be validated. This reference therapeutic strategy is firstly parenteral and based on low-molecular-weight heparins (LMWH) or fondaparinux, subcutaneously prescribed at fixed dosage based on body weight without any systematic dose adjustment on hemostasis tests. Unfractionated heparin is steel the reference treatment in case of severe renal insufficiency. This parenteral treatment has to be relieved by vitamin K antagonists (VKA). VKA has to be co-administrated for at least 3 days, without any loading dose and can be early initiated. VKA dose needs to be adjusted in order to maintain INR between 2 and 3. However, in case of cancer, LMWH have to be carried on for 6 months. A part this antithrombotic treatment, thrombolytics are recommended in case of m
assive PE and vena cava filter should be used in case of recurrence despite adequate antithrombotic treatment or in case of contraindication to antithrombotic.

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Acta Haematol. 2007 Apr 10;118(1):10-18 [Epub ahead of print]
Upper Limb Deep Vein Thrombosis: A Literature Review to Streamline the Protocol for Management.
Sajid MS, Ahmed N, Desai M, Baker D, Hamilton G.
Department of Vascular Surgery, Royal Free Hospital, Hampstead, London, UK.

Objective: The objective of this article is to provide up-to-date information about aetiology, pathogenesis, diagnostic modalities and treatment of upper limb deep vein thrombosis (ULDVT). Methods: Generic terms including ULDVT, axillary-subclavian DVT, and complications of central venous catheters were searched on electronic database. We analysed original studies, review articles and evaluation studies published over the last 25 years. Results: Forty-seven studies on ULDVT encompassing 2,557 patients were evaluated. The incidence of ULDVT was quoted 1-4% of the total DVT. Primary ULDVT (20% of the total) was due to activity-related venous trauma. Secondary ULDVT (80% of the total) was due to central venous catheters and malignancy. Duplex ultrasound (sensitivity 78-100% and specificity 82-100%), contrast venography (gold standard) and magnetic resonance venography were the diagnostic tools used. Pulmonary embolism (2-35%) and post-thrombotic syndrome (7-46%) were the main sequelae. Anticoagulation was the universal intervention, giving 79% symptom relief (13.2% rethrombosis rate). Thrombolysis and/or percutaneous thrombectomy were used in 38% of cases for the management of ULDVT, giving 83% symptom relief (90% recanalization rate and 9% rethrombosis rate). Surgical decompression, venous angioplasty and superior vena cava filters were the main adjunctive interventions. Conclusion: ULDVT, although rare, is associated with considerable morbidity and mortality (29-40%) due to potential risks of pulmonary embolism, post-thrombotic syndrome and loss of vascular access. Simple anticoagulation is suitable for the majority of patients. Thrombolysis/thrombectomy is often successful but less frequently used. Surgical decompression, venous angioplasty and superior vena cava filters have some role in recurrent cases. An optimal management protocol can be established using a multimodality approach. Copyright (c) 2007 S. Karger AG, Basel.

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J Thromb Haemost. 2007 Apr;5(4):746-53.
A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement.
Agnelli G, Haas S, Ginsberg JS, Krueger KA, Dmitrienko A, Brandt JT.
Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Background: LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development. Objectives: The aims of this proof-of-concept study in patients undergoing total knee replacement (TKR) or total hip replacement (THR) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism (VTE) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin. Methods: In a double-blind, parallel-arm, dose-ranging study, patients undergoing TKR or THR were randomly allocated to receive once-daily oral LY517717 (25, 50, 75, 100, 125 or 150 mg), started 6-8 h after wound closure, or s.c. enoxaparin, 40 mg, started in the evening before surgery. The primary efficacy endpoint was the composite of deep venous thrombosis (DVT), detected by mandatory bilateral venography performed at the end of the study treatment (between days 5 and 9), and objectively confirmed symptomatic DVT and/or pulmonary embolism (PE), occurring during the treatment period. The combination of major and minor bleeding was the primary safety endpoint. Results: Five hundred and seven patients received at least one dose of LY517717 or enoxaparin (safety population). Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and/or PE (primary efficacy population). LY517717 treatment resulted in a dose-dependent decrease in the incidence of thromboembolic events (P = 0.0001). The incidences of VTE with 100, 125, and 150 mg of LY517717 were 19%, 19% and 16%, respectively, compared to 21% with enoxaparin. The efficacies of 100-mg, 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria. Bleeding events were uncommon in both LY517717 and enoxaparin patients. Conclusions: Doses of 100, 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR, and are associated with similar low rates of bleeding.

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J Thromb Haemost. 2007 Mar 31; [Epub ahead of print]
Effect of obesity on outcomes after fondaparinux, enoxaparin, or heparin treatment for acute venous thromboembolism in the Matisse Trials.
Davidson BL, Buller HR, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob GE, Segers AE, Lensing AW; for the MATISSE Investigators.
University of Washington School of Medicine, Seattle, WA, USA.

Background: Selecting initial anticoagulant dosage by patient weight for acute pulmonary embolism and deep-vein thrombosis has clinical credibility but uncertainty remains regarding how to dose obese patients with newer anticoagulants because outcome data are sparse. Objectives: Use the Matisse Trials' comparison of sq fondaparinux once daily with control heparin therapies (intravenous unfractionated heparin for pulmonary embolism, sq enoxaparin 1 mg/kg bid for deep-vein thrombosis) for initial treatment to compare primary outcomes (venous thromboembolism [VTE] recurrence and major bleeding) in obese patients. Patients/Methods: Primary outcomes were compared in subsets composed of patients weighing </= or > 100 kg and with body mass index (BMI) < 30 and >/= 30 kg/m(2). Medians and ranges for weight and BMI were compared for patients suffering either recurrence or major bleeding. Results: 2201 patients received fondaparinux, 2217 received enoxaparin or unfractionated heparin. 496 patients (11%) weighed > 100 kg; 1216 (28%) had BMI >/=30. Treatment groups had similar characteristics. The upper limit in subject weight for recurrence was 166 kg (BMI 58); for major bleeding, 120 kg (BMI 39). The incidence of recurrence and major bleeding was similar for each patient subset of weight and BMI for both fondaparinux and heparin treatment groups. Among patients with a primary outcome, median weights and BMIs were also similar. Conclusions: Current dosing recommendations for VTE treatment for fondaparinux and heparins appear to provide similar protection against recurrence and major bleeding to one another and to obese and non-obese patients.

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Catheter Cardiovasc Interv. 2007 Mar 21; [Epub ahead of print]
Catheter-directed thrombolysis (intrathrombus injection) in treatment of deep venous thrombosis: A systematic review.
Alesh I, Kayali F, Stein PD.
Department of Research, St. Joseph Mercy-Oakland Hospital, Pontiac, Michigan.

Methods of delivery of thrombolytic agents for massive or limb threatening deep venous thrombosis (DVT) include a systemic infusion, local-regional administration, and catheter-directed therapy (tip of catheter placed inside the thrombus). We evaluated the effectiveness of catheter-directed therapy and compared the results with randomized clinical trials of systemic and local-regional thrombolytic therapy. Many who used catheter-directed thrombolysis used balloon angioplasty, stents, or thrombectomy in addition. Pooled data showed higher rates of complete early opening of occluded veins with catheter-directed thrombolysis alone, 90%, or with catheter-directed thrombolysis often followed by adjunct therapy, 76%, than with a systemic infusion, 28%, or local-regional administration, 20%. The prevalence of postthrombotic syndrome was lower with catheter-directed combined with adjunct therapy, 26%, compared with 56% and 69%, respectively. Rates of any bleeding were higher with catheter-directed thrombolytic therapy, but bleeding was usually minor. In conclusion, the data suggest that catheter-directed thrombolytic therapy may be more beneficial than systemic or local regional administration. An advantage is that it lends itself to adjunct treatment following the administration of thrombolytic agents if the thrombolysis is inadequate. (c) 2007 Wiley-Liss, Inc.

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Blood. 2007 Mar 14; [Epub ahead of print]
A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of post-thrombotic syndrome in children.
Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ.
Mountain States Regional Hemophilia & Thrombosis Center, Aurora, CO, United States.

Important predictors of adverse outcomes of thrombosis in children, including the post-thrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thrombolytic regimen versus standard anticoagulation for acute, occlusive deep venous thrombosis (DVT) of the proximal lower extremities in children in whom plasma factor VIII activity and/or D-dimer concentration were elevated at diagnosis, from within a longitudinal pediatric cohort. Nine children who underwent the thrombolytic regimen and 13 who received standard anticoagulation alone were followed from time of diagnosis with serial clinical evaluation and standardized PTS outcome assessments conducted in uniform fashion. The thrombolytic regimen was associated with a markedly decreased odds of PTS at 18-24 months when compared to standard anticoagulation alone, which persisted after adjustment for significant covariates of age and lag time to therapy (OR=0.018, 95% CI=<0.001-0.483; P=0.02). Major bleeding developed in one child, judged clinically as not directly related to thrombolysis for DVT. These findings suggest that the use of a thrombolysis regimen may safely and substantially reduce the risk of PTS in children with occlusive lower-extremity acute DVT, providing the basis for a future clinical trial.

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J Bone Joint Surg Br. 2007 Mar;89(3):316-22.
Early mobilisation after conventional knee replacement may reduce the risk of postoperative venous thromboembolism.
Pearse EO, Caldwell BF, Lockwood RJ, Hollard J.
1North Sydney Orthopaedic & Sports Medicine Centre, 286, Pacific Highway, Crows Nest 2068, New South Wales, Australia.

We carried out an audit on the result of achieving early walking in total knee replacement after instituting a new rehabilitation protocol, and assessed its influence on the development of deep-vein thrombosis as determined by Doppler ultrasound scanning on the fifth post-operative day. Early mobilisation was defined as beginning to walk less than 24 hours after knee replacement. Between April 1997 and July 2002, 98 patients underwent a total of 125 total knee replacements. They began walking on the second post-operative day unless there was a medical contraindication. They formed a retrospective control group. A protocol which allowed patients to start walking at less than 24 hours after surgery was instituted in August 2002. Between August 2002 and November 2004, 97 patients underwent a total of 122 total knee replacements. They formed the early mobilisation group, in which data were prospectively gathered. The two groups were of similar age, gender and had similar medical comorbidities. The surgical technique and tourniquet times were similar and the same instrumentation was used in nearly all cases. All the patients received low-molecular-weight heparin thromboprophylaxis and wore compression stockings post-operatively. In the early mobilisation group 90 patients (92.8%) began walking successfully within 24 hours of their operation. The incidence of deep-vein thrombosis fell from 27.6% in the control group to 1.0% in the early mobilisation group (chi-squared test, p < 0.001). There was a difference in the incidence of risk factors for deep-vein thrombosis between the two groups. However, multiple logistic regression analysis showed that the institution of an early mobilisation protocol resulted in a 30-fold reduction in the risk of post-operative deep-vein thrombosis when we adjusted for other risk factors.

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Ann Pharmacother. 2007 Mar 13; [Epub ahead of print]
Systemic Anticoagulant Prophylaxis for Central Catheter-Associated Venous Thrombosis in Cancer Patients (April).
Chan A, Iannucci A, Dager WE.
Oncology Specialty Resident, Department of Pharmaceutical Services, University of California Davis Medical Center, Sacramento, CA.

OBJECTIVE: To review the literature regarding the incidence of thrombosis in cancer patients with central venous catheters (CVCs) and weigh the evidence supporting thromboprophylaxis in this patient population. DATA SOURCES: Clinical literature was identified by searching MEDLINE (1966-February 2007) using the key search terms malignancy, cancer, catheters, prophylaxis, thrombosis, and central venous catheters. STUDY SELECTION AND DATA EXTRACTION: An evaluation of retrospective and prospective clinical trials that studied the use of systemic anticoagulants (eg, warfarin, heparin, and low-molecular-weight heparin [LMWH]) to prevent thrombosis with CVCs was performed. Different patient populations, including those manifesting with solid tumor or hematologic malignancy and those undergoing hematopoietic stem cell transplant, were evaluated for this review. DATA SYNTHESIS: Thrombosis associated with CVCs is a common complication in cancer patients. Most CVC thrombosis will occur within 30 days after placement, with a majority within 8 days. The incidence may depend on the type of CVC and location of the catheter tip. Despite recommendations against the use of systemic anticoagulation for prophylaxis against CVC thrombosis, a potential role continues to be explored in selected settings. Several variables are noted between published clinical trials, making any comparisons difficult to determine whether any benefit exists. Generally, the use of mini-dose warfarin, LMWH, or low-dose unfractionated heparin did not consistently reach significance in reporting a reduction in CVC thrombosis. CONCLUSIONS: Available data do not support the routine use of anticoagulants for thromboprophylaxis to prevent CVC-related thrombosis. However, several inconsistencies can be found in the studies done to date. More studies are needed to identify subsets of cancer patients who are at higher risk of developing CVC thrombosis and may benefit from prophylactic systemic anticoagulation.

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J Gen Intern Med. 2007 Jan;22(1):107-14.
Air travel and venous thromboembolism: a systematic review.
Philbrick JT, Shumate R, Siadaty MS, Becker DM.
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. jtp9b@virginia.edu

CONTEXT: Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. OBJECTIVES: To review the methodologic strength of the literature, estimate the risk of travel-related VTE, evaluate the efficacy of preventive treatments, and develop evidence-based recommendations for practice. DATA SOURCES: Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. STUDY SELECTION: We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. DATA EXTRACTION AND ANALYSIS: Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. DATA SYNTHESIS: Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (<6 hours compared to 6-8 hours, OR 0.011), and clinical risk ("higher" risk travelers compared to "lower," OR 3.6) were significantly related to VTE rate. Clinical VTE after prolonged travel is rare [27 PE per million flights diagnosed through usual clinical care, 0.05% symptomatic deep venous thrombosis (DVT) diagnosed through screening ultrasounds], but asymptomatic thrombi of uncertain clinical significance are more common. Graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies), aspirin did not, and low-molecular-weight heparin (LMWH) showed a trend toward efficacy in one study. CONCLUSIONS: All travelers, regardless of VTE risk, should avoid dehydration and frequently exercise leg muscles. Travelers on a flight of less than 6 hours and those with no known risk factors for VTE, regardless of the duration of the flight, do not need DVT prophylaxis. Travelers with 1 or more risk factors for VTE should consider graduated compression stockings and/or LMWH for flights longer than 6 hours.

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J Thromb Haemost. 2007 Jan 9; [Epub ahead of print]
The quality of oral anticoagulant therapy and recurrent venous thrombotic events in the Leiden Thrombophilia Study (LETS).
Gadisseur AP, Christiansen SC, van der Meer FJ, Rosendaal FR.
Department of Haematology/Haemostasis Unit, Antwerp University Hospital (UZA), Edegem, Belgium.

Background: The INR target range is a relatively narrow range in which the efficacy of oral anticoagulant treatment, i.e. prevention of extension and recurrence of thrombosis, is balanced with the risk of haemorrhagic complications. Over the years different INR target ranges have been implemented for individual indications depending on their thrombotic potential. In most of the studies defining these INR targets the treatment of the patients was aimed at a certain INR range, but in the analysis no account was taken of the time the patients spent within this range in reality. Methods: The Leiden Thrombophilia Study (LETS) is a population-based case-control study on risk factors for venous thrombosis, in which many genetic and acquired factors have been investigated. Our aim was to investigate the effect of the quality of the oral anticoagulant therapy for the initial venous thrombosis and its relationship with recurrence of thrombosis. Quality of anticoagulation was defined as the time spent at various INR levels during treatment, and we focused on the effect of sustained intensities above a certain INR in preventing recurrences later on. Results: 266 patients with a total follow up of 2495 patient-years were studied. Mean duration of the initial anticoagulant therapy van 194.5 days (range 48 - 4671). During follow up 58 recurrences were diagnosed (cumulative recurrence rate of 21.8% over 9 years). Mean INR during initial therapy was 2.90, with 90.3% (CI(95) 88.4 - 92.3%) of the time spent above an INR of 2.0, and 39.1% (CI(95) 35.5 - 42.7%) above an INR of 3.0. Patients who spent more time below the target range or who had shorter duration of anticoagulation, did not experience a higher risk of recurrence after the initial period of anticoagulation had passed. Conclusions: Provided oral anticoagulant treatment is adequately managed, according to international guidelines, recurrent thrombosis can not be ascribed to variation in the primary treatment. Further progress in reducing the risk of recurrence should therefore be aimed at identifying other explanatory factors and subsequently fine-tuning the target ranges.

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Ugeskr Laeger. 2007 Jan 8;169(2):109-11.
[Deep venous thrombosis—epidemiology, diagnosis and treatment]
[Article in Danish]
Sejersen HM, Nielsen HK, Thyssen JP, Husted SE.
Sygehus Vendsyssel, Medicinsk Afdeling, Braedstrup Sygehus.

The pathogenesis of deep vein thrombosis (DVT) involves vascular changes or injury, stasis and alterations in the blood composition. The risk increases with age; however, important risk factors are cancer, surgery, immobilisation and hormone therapy. DVT most often appears in the crural veins. The diagnosis is based on ultrasound, d-dimer and clinical examination. Correct treatment requires gradient compression hosiery, low-molecular heparins and anticoagulant therapy. Duration of treatment depends on the individual risk of recurrence.

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Eur J Neurol. 2007 Jan;14(1):21-32.
Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles.
Andre C, de Freitas GR, Fukujima MM.
Neurology Service, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. andrecmd@unisys.com.br

We performed a systematic review of the literature on venous thromboembolism (VTE) prophylaxis following cerebral infarct (CI) and haemorrhagic stroke. MEDLINE, Cochrane, LILACS and SciELO databases were scanned, and the Abstracts from Brazilian, American and European Neurology and Stroke Congresses were scrutinized for clinical trials. Moreover, the reference lists of articles and reviews were searched. A pooled analysis of two large studies with aspirin was made. Both unfractionated heparin and low molecular weight heparins/heparinoids (LMWH) are partially effective for VTE prophylaxis after CI, and should be routinely used in patients with motor deficit and reduced mobility and no contraindications. Reduction of deep venous thrombosis is better established than the effect over pulmonary embolism or mortality. Some evidence points to a greater efficacy of LMWH. The available evidence does not support the use of mechanical methods or dextran. Aspirin may have a mild protective effect. Low-dose Warfarin might be useful in the rehabilitation setting. Strict recommendations cannot be made in patients with haemorrhagic stroke but intermittent pneumatic compression merits further study. There are important limitations of current VTE preventive strategies following stroke. Additional studies on the combination of methods after CI and of low doses of anticoagulants following cerebral haemorrhage are urgently needed.

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J Orthop Trauma. 2007 Jan;21(1):52-57.
Prolonged Thromboprophylaxis With Dalteparin After Surgical Treatment of Achilles Tendon Rupture: A Randomized, Placebo-Controlled Study.
Lapidus LJ, Rosfors S, Ponzer S, Levander C, Elvin A, Larfars G, de Bri E.
>From the *Department of Orthopaedics; daggerDepartment of Clinical Physiology; double daggerDepartment of Internal Medicine, Department of Clinical Science and Education, Karolinska Institutet at Sodersjukhuset Hospital, Stockholm, Sweden; and section signAleris, Department of Radiology, Taby Hospital, Stockholm, Sweden.

OBJECTIVES:: Prophylaxis against thromboembolic complications has become routine after major orthopedic surgery. In contrast, it remains an issue for debate whether prophylaxis after minor surgery and immobilization is necessary, even though these treatments are well-known risk factors for deep-vein thrombosis (DVT). The objective of this study was to evaluate the efficacy of dalteparin during lower-limb immobilization after surgical treatment of Achilles tendon rupture. DESIGN SETTING, AND PATIENTS:: Randomized, placebo-controlled, double-blind study of 105 consecutive patients surgically treated for Achilles tendon rupture in a trauma hospital. DVT screening with color duplex sonography was conducted 3 weeks and 6 weeks after surgery. All DVTs were confirmed with phlebography. Intervention was placebo or dalteparin (5000 U) given subcutaneously once daily for 6 weeks postoperatively. MAIN OUTCOME MEASURE:: DVT incidence. RESULTS:: Primary endpoint analysis was available for 91 patients. DVT was diagnosed in 16 of 47 patients (34%) in the dalteparin group and in 16 of 44 patients (36%) in the placebo group. These figures are not significantly different (P = 0.8). Proximal DVT was diagnosed in 1 patient (2%) in the dalteparin group and in 3 patients (6%) in the placebo group (P = 0.6). No pulmonary emboli or major bleeding occurred in either of the groups. CONCLUSIONS:: DVT is common after surgical treatment of Achilles tendon rupture, and therefore effective thromboprophylaxis is desirable. In our study, thromboprophylaxis with dalteparin, however, does not affect the incidence of DVT during immobilization after Achilles tendon rupture surgery. Long-term effects of immobilization, such as the risk for postthrombotic syndrome, need to be investigated further.

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Am J Med. 2007 Jan;120(1):72-82.
Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.
Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, Wong T, Cook R, Solymoss S, Poon MC, Raskob G; LITE Trial Investigators.
University of Calgary, Calgary, AB, Canada. Jeanne.Sheldon@calgaryhealthregion.ca

PURPOSE: A substantial clinical need exists for an alternate to vitamin K antagonists for treating deep vein thrombosis in many patients. Long-term low-molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis. METHODS: We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months. RESULTS: Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH. CONCLUSION: Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.

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World J Surg. 2007 Jan;31(1):98-104.
Utility of once-daily dose of low-molecular-weight heparin to prevent venous thromboembolism in multisystem trauma patients.
Cothren CC, Smith WR, Moore EE, Morgan SJ.
Department of General Surgery, Trauma Service, Denver Health Medical Center, University of Colorado Health Sciences Center, 777 Bannock Street, MC 0206, Denver, Colorado 80204, USA. clay.cothren@dhha.org

INTRODUCTION: Venous thromboembolism is a preventable cause of death in the severely injured patient. Low-molecular-weight heparins (LMWHs) have been recommended as effective, safe prophylactic agents. However, LMWH use remains controversial in patients at risk for bleeding, those with traumatic brain injury, and those undergoing multiple invasive or operative procedures. We hypothesized that a protocol utilizing once-daily LMWH prophylaxis in high-risk trauma patients, regardless of the need for invasive procedures, is feasible, safe, and effective. METHODS: From August 1998 to August 2000, all patients admitted to our American College of Surgeons-verified Level I trauma facility following injury were evaluated for deep venous thrombosis (DVT) risk and prospectively followed. Patients at high risk for DVT, including those with stable intracranial injuries, were placed on our institutional protocol and prospectively followed. Patients on the protocol received daily injections of the LMWH, dalteparin; DVT screening was performed with duplex ultrasonography within 48 hours of admission and after 7 to 10 days after injury. Regimen compliance, bleeding complications, DVT rates, and pulmonary embolus (PE) rates were analyzed. RESULTS: During the 2-year study period, 6247 trauma patients were admitted; 743 were considered at high risk for DVT. Most of the patients were men (72%), with a mean age of 38.7 years (range 15-89 years) and a mean injury severity score (ISS) of 19.5. Compliance with the daily regimen was maintained in 74% of patients. DVT was detected in 3.9% and PE in 0.8%. The wound complications rate was 2.7%, and the need for unexplained transfusions was 3%. There were no exacerbations of head injury following dalteparin initiation due to bleeding. There were 16 patient deaths; none was caused by PE or late hemorrhage. CONCLUSIONS: Once-daily dosing of prophylactic LMWH dalteparin is feasible, safe, and effective in high-risk trauma patients. Our protocol allows one to "operate through" systemic prophylaxis and ensures timely prophylaxis for brain-injured and multisystem trauma patients.

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J Thromb Thrombolysis. 2006 Dec 22; [Epub ahead of print]
Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study.
Isma N, Johanssson E, Bjork A, Bjorgell O, Robertson F, Mattiasson I, Gottsater A, Lindblad B.
Department of Vascular Diseases, University Hospital MAS, Malmo, Sweden, nazim.isma@spray.se.

OBJECTIVES: The aim of the present study was to evaluate weather early supervised exercise improves recanalization of acute deep vein thrombosis (DVT) and reduces symptoms. PATIENTS AND METHODS: From September 2001 to March 2004, of 381 patients, 72 eligible patients were included and with a mean age 54 +/- 14 years, 39 (52%) men with deep vein thrombosis (DVT) proven with phlebography were randomized to: an exercise group (n = 36) receiving routine anticoagulation, class II compression stockings and additionally supervised exercise and a control group (n = 36) receiving the same therapy but no exercise. Patients were followed-up during six months. Phlebography was scored initially and at six-months. RESULTS: There were at inclusion no differences between the two groups regarding age, body weight, body mass index (BMI), calf circumference of the affected leg, and overall quality of life estimated by visual analog scale (VAS)-scale. In both groups there were significant reductions regarding calf circumference in the affected leg compared to the inclusion time, both at one-month (P = 0.0012) and six month (P = 0.0002) follow-up. The degree of recanalization of the affected venous segments was high and did not differ between groups. There were no recurrent DVT or pulmonary emboli or other treatment complications in any individual during the six-month follow-up period. CONCLUSIONS: Early exercise did not acutely exacerbate the risk of complications in patients with DVT. No benefits of early exercise were seen regarding the degree of recanalization of the thrombi, or faster resolution of pain or swelling. Nevertheless, our study shows that early exercise/ambulation is safe in combination with anticoagulation and compression stockings for the majority of patients with DVT.
  
Previous Deep Vein Thrombosis Research: 2002-2006   
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