The Hematologist

January-February 2012, Volume 9, Issue 1

The Bloody Problem With VTE Prophylaxis

Margaret V. Ragni, MD, MPH

Published on: January 25, 2012

Dr. Ragni indicated no relevant conflicts of interest.

Qaseem A, Chou R, Humphrey LL, et al. Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2011;155:625-632.

Prophylaxis against VTE has become routine in the hospital setting. Yet the benefits and risks of this practice are nebulous. While bleeding that complicates prophylactic anticoagulation is generally mild, significant morbidity or even mortality can result when the central nervous system is involved. The American College of Physicians (ACP) Clinical Guidelines Committee recently reviewed VTE prophylaxis to develop practice guidelines.1 This committee systematically analyzed both randomized clinical trials and reviews of VTE prevention identified through MEDLINE and Cochrane Library searches published from 1950 to 2011.

Analyses of 10 trials comparing heparin prophylaxis to no VTE prophylaxis in 20,717 medical patients without stroke showed a reduction in pulmonary embolism, RR=0.69 [95% CI, 0.52-0.90] but no decrease either in the incidence of DVT or mortality, but significantly more bleeding in the heparin-treated patients compared with no prophylaxis, RR=1.34 [95% CI, 1.08-1.66]. In eight trials that involved a total of 15,405 patients with acute stroke, meta-analysis showed that compared with no VTE prophylaxis, heparin prophylaxis resulted in no statistically significant reduction in PE, DVT, or mortality, but a statistically significant increase in major bleeding was observed, RR=1.66 [95% CI, 1.20-2.28].

When LMWH prophylaxis was compared with unfractionated heparin (UFH) prophylaxis in nine trials of 11,650 subjects, there was no difference in mortality, pulmonary emboli, or major bleeding events. Among 2,785 acute stroke patients in five trials, compared with UFH, LMWH prophylaxis resulted in no statistically significant difference in mortality, PE, symptomatic DVT, or major bleeding.

Comparing the use of mechanical devices (i.e., compression stockings) in 2,518 subjects in one clinical trial and evidence from three reviews, there was no statistically significant difference in mortality, PE, or symptomatic DVT, as compared with no stockings. There was, however, a greater risk of skin damaged with stockings, RR=4.02 (CI, 2.34-6.91].

In a trial of 6,085 hospitalized medical patients classified as immobile, LMWH prophylaxis was given for 10 days and patients were randomized subsequently to stop prophylaxis or to continue heparin for an additional 28 days. Those randomized to continue LMWH had a significant reduction in symptomatic VTE and a significant increase in major bleeding, but not in mortality, as compared with those randomized to no additional heparin prophylaxis.

The Table compares the ACP VTE prophylaxis recommendations for hospitalized patients with those previously published by the American College of Chest Physicians (ACCP).1-3 Both place emphasis on individualized assessment of the risk of thrombosis versus the risk of bleeding; however, some differences are noted. For example, in contrast to the ACCP guidelines, the ACP guidelines suggest no reduction in the incidence of DVT for patients on prophylactic anticoagulation. Additionally, while bleeding risk is downplayed in the ACCP guidelines, it is a focal point of the ACP analysis. Stroke patients are grouped separately in the ACP analysis but not in the ACCP recommendations. The ACP focused on studies using compression stockings, while the ACCP recommendations featured a more general category of mechanical prophylaxis. Of note, recommendations related to mechanical prophylaxis are based on relatively sparse data from a small number of trials (Table), underscoring the need for prospective studies designed to establish benefit and risk of anticoagulant-independent DVT prophylaxis.

  1. Lederle FA, Zylla D, MacDonald R, et al. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: background review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2011;155:602-615.
  2. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:338S-400S.
  3. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:381S-453S.
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