Patient Safety Tip of the Week

April 19, 2011  

DVT Prophylaxis in Acute Stroke: Controversy Reappears



The controversy over DVT prophylaxis in stroke patients resurfaced last week in a series of letters in the Annals of Internal Medicine (Sprigg 2011; Kearon 2011). Though the debating letters were titled “Should Patients With Stroke Wear Compression Stockings?”, the controversy was really about pharmacological, not mechanical, VTE prophylaxis.


Patient with acute stroke, particularly those with significant lower extremity weakness, are at significant risk for DVT and pulmonary embolism. This applies to both acute ischemic infarcts and intracerebral hemorrhages. And in both types there is either significant risk of hemorrhagic transformation or worsening of hemorrhage when pharmacological prophylaxis is used.


So, for years, graduated compression stockings have been used as a strategy to prevent DVT in patients with stroke. Though in the US we have felt that the evidence for use of these (as opposed to pneumatic compression stockings) in stroke patients was scant, they have been used extensively in other countries. And, while we were skeptical about their effectiveness, most of us took an attitude that “it can’t hurt”.


Then the CLOTS trial 1 (see our What’s New in the Patient Safety World column for July 2009 “Unintended Consequences of a DVT Prevention Strategy”) showed that not only do thigh-high graduated stockings not prevent DVT in stroke patients, they actually cause harm. Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to graduated compression stockings than in those allocated to avoid their use.


Then the CLOTS Trial 2 (see our October 2010 What’s New in the Patient Safety World column “Graduated Compression Stockings: CLOTS Confuses Clinicians”) published its results and they absolutely confused the issue. Clots Trial 2 compared thigh-length graduated compression stockings to below-knee stockings and found fewer cases of VTE with the thigh-length stockings. The study populations and protocols for the two trials were the same, though the sites differed. The CLOTS Trial 2 was discontinued early because of the results of CLOTS Trial 1 but had already reached its predetermined enrollment goal. Proximal DVT, the primary study outcome, had an absolute risk reduction in the thigh-length group of 2.5% and the relative risk reduction was 31%. There were no differences in distal DVT, pulmonary emboli or deaths between the 2 groups. There were more cases with skin problems in the thigh-length group but these were relatively mild.


The authors consider several possible explanations for the seemingly contradictory results of the 2 trials. One is that below-knee stockings might actually increase the risk for DVT in stroke patients. The other is that the first CLOTS trial may have underestimated a positive effect of the thigh-length stockings.


In the accompanying editorial (Kearon 2010) it was noted there remain significant uncertainties as to how to best prevent DVT in stroke patients. Moreover, these studies highlight the need for randomized controlled trials of graduated compression stockings in other patient populations since they are so widely used in other patient populations. Even in surgical patients, where graduated compression stockings have been shown in multiple studies to reduce the occurrence of VTE, there has been no comparison of thigh-length vs. below-knee stockings. And while guidelines generally recommend use of thigh-length stockings, below-knee stockings are probably used more frequently in actual practice.



The new controversy is not about the mechanical DVT prophylaxis but about whether pharmacological prophylaxis is indicated in any patients with acute stroke. It was raised by Sprigg et al. who point out that data from 2 previous large trials (Bath 2001, IST 1997) suggest such pharmacoprophylaxis is as likely to cause symptomatic intracerebral hemorrhage as it is to prevent pulmonary embolism. Kearon et al., in their response (Kearon 2011), are quick to point out they did not advocate routine use of pharmacoprophylaxis.



Note that the most recently published consensus guidelines on DVT prophylaxis in acute stroke (Albers 2008) recommend: “For acute ischemic stroke patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low-molecular-weight heparins (Grade 1A).” They did review multiple studies, including the above mentioned ones, to arrive at that conclusion. A systematic review (André 2007) also suggested that prophylactic low-dose subcutaneous heparin or low-molecular-weight heparins are partially effective but that the findings are stronger for their preventing DVT than pulmonary emboli or death.


Suffice it to say that we still have much to learn about the best VTE prophylaxis in patients with acute stroke and significant weakness or immobility. Graduated compression stockings probably should not be used and, if they are used, careful attention to the underlying skin is a must. We will have to await the results of the CLOTS Trial-3, which is looking at both the efficacy and safety of pneumatic compression stockings in stroke patients. And the issue of pharmacoprophylaxis remains controversial. It may well turn out that use of low-dose unfractionated heparin or low-molecular-weight heparins may someday prove to have a desirable risk:benefit ratio, particularly after the period of maximum risk of hemorrhagic transformation, but that remains controversial. It’s clear that further study is necessary on both mechanical and pharmacological methods of VTE prophylaxis in acute stroke patients and it is the net benefit (risk of reducing the VTE risk vs. risk of intracerebral hemorrhage) that is most important.



In the interim, we’d probably advocate for use of pneumatic compression stockings. But don’t be surprised there if unintended consequences pop up! They also have a potential for skin complications, tend to further immobilize some patients, and are more expensive. Hopefully CLOTS-3 will provide us answers soon.





Sprigg N, Geeganage CM, Bath PMW. Should Patients With Stroke Wear Compression Stockings? Annals of Internal Medicine 2011; 154(7): 506



Kearon C, O'Donnell M. Should Patients With Stroke Wear Compression Stockings? Annals of Internal Medicine 2011; 154(7): 506-507



The CLOTS Trials Collaboration. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. The Lancet 2009; 373:1958 - 1965, 6 June 2009



The CLOTS (Clots in Legs Or sTockings after Stroke) Trial Collaboration. Thigh-Length Versus Below-Knee Stockings for Deep Venous Thrombosis Prophylaxis After Stroke

A Randomized Trial. Annals of Internal Medicine 2010. Published early on line September 21, 2010



Kearon C, O'Donnell M. Should Patients With Stroke Wear Compression Stockings to Prevent Venous Thromboembolism? (Editorial). Annals of Internal Medicine 2010; 153(9): 610-611



The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349: 1569-81



Bath PM, Lindenstrom E, Boysen G, De Deyn P, Friis P, Leys D, et al. Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial. Lancet. 2001; 358: 702-10



Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P; American College of Chest Physicians. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133: 630S-669S



André C, de Freitas GR, Fukujima MM. Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles. Eur J Neurol. 2007; 14:21-32









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