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.

American College of Physicians (ACP) (2011)1American College of Chest Physicians (ACCP) (2008)3
  1. Assess bleeding and clotting risk before initiating VTE prophylaxis.
  2. Initiate prophylaxis for VTE in medical patients, unless bleeding outweighs risks.*
  1. Thromboprophylaxis (LMWH, low-dose unfractionated heparin, or fondaparinux) is recommended for acutely ill medical patients admitted to hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors including active cancer, previous VTE, sepsis, acute neurologic disease, or inflammatory bowel disease (Grade 1A).✝
Mechanical Propylaxis
  1. Avoid mechanical prophylaxis (compression stockings) for VTE prevention.§
Mechanical Prophylaxis
  1. Optimal use of mechanical prophylaxis is recommended for medical patients with risk factors for VTE and for whom there is a contraindication to anticoagulant thromboprophylaxis. (Grade 1A).¶
  2. Mechanical methods of thromboprophylaxis are recommended primarily in patients at high risk of bleeding (Grade 1A), or possibly as an adjunct to anticoagulant-based thromboprophylaxis (Grade 2A).

*In hospitalized medical patients, heparin prophylaxis decreases PE but not mortality or DVT and increases bleeding risk.

✝Randomized trials conducted over the past 30 years provide evidence that thromboprophylaxis prevents DVT and PE and reduces hospital cost. Data from meta-analysis and blinded, randomized clinical trials demonstrate little or no increase in rates of clinically important bleeding with thromboprophylaxis.

§Mechanical compression does not improve clinical outcomes but damages lower extremity skin.

¶Mechanical thromboprophylaxis has not been studied in a large enough sample size to determine reduction in risk of death or PE. Potential advantages include reduction in leg swelling and lack of increase in risk of bleeding. Potential limitations include lack of clinical trials of mechanical devices; lack of established standards for size, pressure, and physiologic features; lack of blinding in most mechanical thromboprophylaxis trials; poor compliance by patients and staff; and unknown effects on PE and death.

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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