above): For patients treated with intravenous thrombolysis, IPC should be started on admission and pharmacologic VTE prophylaxis should be delayed until 24 hours after intravenous thrombolysis. It is reasonable to withhold pharmacologic VTE prophylaxis for patients with transient ischemic attack or minor stroke who are being treated with dual antiplatelet therapy (DAPT). Additional pharmacologic VTE prophylaxis is not needed for patients receiving full- dose heparin or oral anticoagulation for another indication. For patients with acute intracerebral hemorrhage, we suggest treatment, starting at admission, with thigh-length IPC alone rather than IPC combined with low-dose anticoagulation or low-dose anticoagulation alone (Grade 2C). Once intracranial bleeding has stopped, it may be reasonable to add low-dose LMW or unfractionated heparin after one to four days from intracerebral hemorrhage onset for selected patients with lack of mobility. (See 'Approach in intracerebral hemorrhage' above and 'Intermittent pneumatic compression' above.) For patients with acute subarachnoid hemorrhage and decreased mobility we suggest treatment, starting at admission, with thigh-length IPC alone rather than treatment with low-dose anticoagulation combined with IPC or low-dose anticoagulation alone (Grade 2C). Heparin (LMW or unfractionated) can be added once the aneurysm is secured for https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 12/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate patients who continue to have restricted mobility. (See 'Approach in subarachnoid hemorrhage' above.) We recommend not using graduated compression stockings for VTE prophylaxis in acute stroke of any type (Grade 1B). (See 'Ineffective or unproven treatments' above.) In most cases, we continue VTE prophylaxis for acute ischemic or hemorrhagic stroke for the duration of the acute and rehabilitation hospital stay, or until the patient becomes fully ambulatory. (See 'Duration of therapy' above.) Deep vein thrombosis should be suspected in patients who present with leg swelling, pain, warmth, and erythema. Pulmonary embolism has a wide variety of presenting features, ranging from no symptoms to shock or sudden death. The most common presenting symptom is dyspnea followed by chest pain and cough. However, many patients, including some with large pulmonary emboli, have mild or nonspecific symptoms or are asymptomatic. (See 'Suspicion for VTE' above and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".) The treatment of proximal deep vein thrombosis, symptomatic distal deep vein thrombosis, and/or pulmonary embolism in patients with acute stroke may require placement of an inferior vena cava filter. Full-dose anticoagulation may be appropriate for patients with acute ischemic stroke who have small to moderate sized infarcts, but is generally avoided for the first one to two weeks after stroke onset for patients with large infarcts, and is contraindicated for patients with acute intracerebral hemorrhage and patients with aneurysmal subarachnoid hemorrhage prior to aneurysm repair. For patients with severe acute pulmonary embolism who have contraindications to anticoagulation and thrombolysis, catheter or surgical embolectomy can be used if the necessary resources and expertise are available. (See 'Treatment for VTE' above and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kelly J, Rudd A, Lewis R, Hunt BJ. Venous thromboembolism after acute stroke. Stroke 2001; 32:262. https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 13/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate 2. Rinde LB, Sm brekke B, Mathiesen EB, et al. Ischemic Stroke and Risk of Venous Thromboembolism in the General Population: The Troms Study. J Am Heart Assoc 2016; 5. 3. Kamran SI, Downey D, Ruff RL. Pneumatic sequential compression reduces the risk of deep vein thrombosis in stroke patients. Neurology 1998; 50:1683. 4. 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. 5. Kelly J, Rudd A, Lewis RR, et al. Venous thromboembolism after acute ischemic stroke: a prospective study using magnetic resonance direct thrombus imaging. Stroke 2004; 35:2320. 6. Dennis M, Mordi N, Graham C, et al. The timing, extent, progression and regression of deep vein thrombosis in immobile stroke patients: observational data from the CLOTS multicenter randomized trials. J Thromb Haemost 2011; 9:2193. 7. Amin AN, Lin J, Thompson S, Wiederkehr D. Rate of deep-vein thrombosis and pulmonary embolism during the care continuum in patients with acute ischemic stroke in the United States. BMC Neurol 2013; 13:17. 8. Landi G, D'Angelo A, Boccardi E, et al. Venous thromboembolism in acute stroke. Prognostic importance of hypercoagulability. Arch Neurol 1992; 49:279. 9. Warlow C, Ogston D, Douglas AS. Deep venous thrombosis of the legs after strokes. Part I incidence and predisposing factors. Br Med J 1976; 1:1178. 10. Langhorne P, Stott DJ, Robertson L, et al. Medical complications after stroke: a multicenter study. Stroke 2000; 31:1223. 11. Johnston KC, Li JY, Lyden PD, et al. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke 1998; 29:447. 12. Pongmoragot J, Rabinstein AA, Nilanont Y, et al. Pulmonary embolism in ischemic stroke: clinical presentation, risk factors, and outcome. J Am Heart Assoc 2013; 2:e000372. 13. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration, Dennis M, Sandercock P, et al. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013; 382:516. 14. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e195S. https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 14/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate 15. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032. 16. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S. 17. Winstein CJ, Stein J, Arena R, et al. Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2016; 47:e98. 18. Turpie AG, Hull RD, Schellong SM, et al. Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: results from the EXCLAIM study. Stroke 2013; 44:249. 19. Kakkos SK, Caprini JA, Geroulakos G, et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database Syst Rev 2016; 9:CD005258. 20. Ho KM, Tan JA. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation 2013; 128:1003. 21. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e227S. 22. Kamphuisen PW, Agnelli G. What is the optimal pharmacological prophylaxis for the prevention of deep-vein thrombosis and pulmonary embolism in patients with acute ischemic stroke? Thromb Res 2007; 119:265. 23. Sandercock PA, Leong TS. Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke. Cochrane Database Syst Rev 2017; 4:CD000119. 24. Shorr AF, Jackson WL, Sherner JH, Moores LK. Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis. Chest 2008; 133:149. 25. Paciaroni M, Agnelli G, Venti M, et al. Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. J Thromb Haemost 2011; 9:893. https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 15/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate 26. Paciaroni M, Agnelli G, Alberti A, et al. PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis. Eur Neurol 2020; 83:566. 27. Hackett CT, Ramanathan RS, Malhotra K, et al. Safety of venous thromboembolism prophylaxis with fondaparinux in ischemic stroke. Thromb Res 2015; 135:249. 28. Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2011; 155:602. 29. CLOTS Trials Collaboration, Dennis M, Sandercock PA, et al. 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. Lancet 2009; 373:1958. Topic 121857 Version 7.0 https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 16/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate GRAPHICS Suggested dose adjustments of low molecular weight (LMW) heparins in adults with renal insufficiency VTE treatment VTE prophylaxis* CrCl 30 mL/min: No adjustment CrCl 30 mL/min: No adjustment Enoxaparin CrCl <30 mL/min: Reduce to 1 mg/kg once daily CrCl <30 mL/min: Reduce to 30 mg once daily (medical or surgical patients) CrCl 30 mL/min: No adjustment CrCl 30 mL/min: No adjustment Dalteparin CrCl <30 mL/min: Use an anticoagulant with less dependence on renal clearance CrCl 50 mL/min: No adjustment CrCl 50 mL/min: No adjustment Nadroparin (not available in the US) CrCl 30 to 50 mL/min: Reduce dose by 25 to 33% if clinically warranted CrCl 30 to 50 mL/min: Reduce dose by 25 to 33% if clinically warranted CrCl <30 mL/min: Contraindicated CrCl <30 mL/min: Reduce dose by 25 to 33% CrCl 30 mL/min: No adjustment CrCl 30 mL/min: No adjustment Tinzaparin (not available in CrCl <30 mL/min: Use with caution, CrCl <30 mL/min: Use with caution, the US) although evidence suggests no accumulation with CrCl as low as 20 mL/min although evidence suggests no accumulation with CrCl as low as 20 mL/min Suggested dose adjustment of LMW heparins for reduced renal function (subcutaneous dosing). Caution should be used in all patients with renal insufficiency, and all patients should be observed for signs of bleeding. Accumulation may occur with repeated doses. An alternative anticoagulant such as unfractionated heparin may be preferred, especially for individuals with CrCl <30 mL/min, with renal failure, or receiving dialysis. Examples of alternatives include: [1] Unfractionated heparin An LMW heparin with lower renal clearance A DOAC with low renal clearance (apixaban, renal clearance approximately 25%) Use of LMW heparin in patients with renal insufficiency has been associated with hyperkalemia. Refer to the UpToDate topics on the use of heparin and LMW heparin in specific clinical conditions, for infants and children, and for acute coronary syndromes and myocardial infarction (for which there are separate tables). VTE: venous thromboembolism; CrCl: creatinine clearance as determined by Cockcroft-Gault equation (a calculator is available in UpToDate); US: United States; LMW heparin: low molecular weight heparin; DOAC: direct oral anticoagulant. https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 17/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Applies to short-term VTE prophylaxis (up to 10 days). For long-term use, periodic anti-factor Xa activity testing may be useful to rule out drug accumulation. [2-4] May consider checking anti-factor Xa activity, consistent with some authorities; ranges have not been established from clinical trials and no dose adjustment nomograms have been clinically validated. Other experts and a 2018 guideline from the American Society of Hematology recommend against checking anti-factor Xa activity and suggest dose adjustments based on information in the product labeling or switching to an alternative anticoagulant such as those listed above. If monitored, levels should be measured 4 to 6 hours after dosing, following at least the third however, or fourth dose. The following represent peak (4 hours after the dose) expected on-therapy values for therapeutic dosing (for VTE) for anti-factor Xa activity, although these have not been clinically validated: [1,2] [5] Enoxaparin twice daily: 0.6 to 1.0 anti-factor Xa units/mL (range, 0.5 to 1.5 Enoxaparin once daily: >1.0 anti-factor Xa units/mL Dalteparin once daily: 1.05 anti-factor Xa units/mL (range, 0.5 to 1.5 ) [6] ) [7] Nadroparin once daily: 1.3 anti-factor Xa units/mL Tinzaparin once daily: 0.85 anti-factor Xa units/mL [8] Data from: 1. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Advances 2018; 3257. 2. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S. 3. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: Available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009; 43:1064. 4. Lexicomp Online. Copyright 1978-2023 Lexicomp, Inc. 5. Enoxaparin sodium injection. US FDA approved prescribing information (revised October, 2013). Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020164s102lbl.pdf. 6. Dalteparin sodium injection. US FDA approved prescribing information (revised May, 2019). Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020287s072lbl.pdf. 7. Nadroparin calcium injection. Canada product monograph (revised January 2019). Available at: https://pdf.hres.ca/dpd_pm/00049107.PDF. 8. Tinzaparin sodium injection. Canada product monograph (May 26, 2017). Available at: https://pdf.hres.ca/dpd_pm/00040736.PDF. Graphic 90258 Version 15.0 https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 18/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Contraindications to fibrinolytic therapy for deep venous thrombosis or acute pulmonary embolism Absolute contraindications Prior intracranial hemorrhage Known structural cerebral vascular lesion Known malignant intracranial neoplasm Ischemic stroke within 3 months (excluding stroke within 3 hours*) Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Significant closed-head trauma or facial trauma within 3 months Relative contraindications History of chronic, severe, poorly controlled hypertension Severe uncontrolled hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg) History of ischemic stroke >3 months prior Traumatic or prolonged (>10 minutes) CPR or major surgery <3 weeks Recent (within 2 to 4 weeks) internal bleeding Noncompressible vascular punctures Recent invasive procedure For streptokinase/anistreplase Prior exposure (>5 days ago) or prior allergic reaction to these agents Pregnancy Active peptic ulcer Pericarditis or pericardial fluid Current use of anticoagulant (eg, warfarin sodium) that has produced an elevated INR >1.7 or PT >15 seconds Age >75 years Diabetic retinopathy SBP: systolic blood pressure; DBP: diastolic blood pressure; CPR: cardiopulmonary resuscitation; INR: international normalized ratio; PT: prothrombin time. The American College of Cardiology suggests that select patients with stroke may benefit from thrombolytic therapy within 4.5 hours of the onset of symptoms. Reproduced with permission from the American College of Chest Physicians. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e419S. Copyright 2012. Graphic 95035 Version 5.0 https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 19/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Contributor Disclosures Koto Ishida, MD No relevant financial relationship(s) with ineligible companies to disclose. Scott E Kasner, MD Grant/Research/Clinical Trial Support: Bayer [Stroke]; Bristol Meyers Squibb [Stroke]; Medtronic [Stroke]; WL Gore and Associates [Stroke]. Consultant/Advisory Boards: Abbvie [Stroke]; AstraZeneca [Stroke]; BMS [Stroke]; Diamedica [Stroke]; Medtronic [Stroke]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 20/20