7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Prevention and treatment of venous thromboembolism in patients with acute stroke : Koto Ishida, MD : Scott E Kasner, MD : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Oct 04, 2021. INTRODUCTION Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism, which is potentially life-threatening. This topic will review the prevention and treatment of VTE in patients with acute ischemic and hemorrhagic stroke. Other aspects of acute stroke care are reviewed separately: Initial assessment and management of acute stroke Neuroimaging of acute stroke Approach to reperfusion therapy for acute ischemic stroke Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use Mechanical thrombectomy for acute ischemic stroke Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis Spontaneous intracerebral hemorrhage: Acute treatment and prognosis Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis Aneurysmal subarachnoid hemorrhage: Treatment and prognosis Complications of stroke: An overview RISK AND PREVALENCE https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 1/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate The risk of venous thromboembolism (VTE) is elevated in the first one to three months after stroke, due in part to stroke-related immobility [1,2]. Deep venous thrombosis Proximal deep vein thrombosis (DVT) is a serious problem because it may lead to life-threatening pulmonary embolism. The overall prevalence of clinically evident DVT after acute stroke is 1 to 10 percent [3-7]. The prevalence of asymptomatic DVT is even higher. In the largest observational report, which evaluated 5632 immobile patients with acute stroke using duplex ultrasound, DVT was detected within 10 days of enrollment in 11 percent, and within 30 days in 15 percent [6]. DVT development may occur as early as the second day after stroke onset and has a peak incidence between two to seven days [1]. Patients with hemiparesis are predisposed to DVT development, and the degree of paresis confers a graded risk of DVT [8]. In a report that included 542 patients with DVT and a weak leg, the DVT was ipsilateral to the weak leg in 73 percent, contralateral in 11 percent, and bilateral in 16 percent [6]. In addition, the presence of a DVT on the nonparetic side suggests the presence of DVT on the paretic side [8,9]. Additional important risk factors for DVT include advanced age, high stroke severity, and immobility [5,9]. Pulmonary embolism Pulmonary embolism, often unassociated with clinically recognized DVT, accounts for 13 to 25 percent of early deaths after stroke and is the most common cause of death at its peak occurrence about two to four weeks after stroke onset [1]. The incidence of pulmonary embolism in the first few months after stroke ranges from 1 to 3 percent [4,10-12]. The diagnosis of acute pulmonary embolism is reviewed elsewhere. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".) APPROACH TO VTE PREVENTION Indications Venous thromboembolism (VTE) prophylaxis is indicated for all patients with acute stroke and restricted mobility. The approach to VTE prevention differs according to the type of stroke. Approach in acute ischemic stroke Based upon the evidence presented below, we recommend VTE prophylaxis with thigh-length intermittent pneumatic compression (IPC), starting at admission, for patients within 72 hours of acute ischemic stroke onset who have restricted mobility. (See 'Intermittent pneumatic compression' below.) In addition to IPC, we suggest pharmacologic VTE prophylaxis for select patients within 48 hours of acute ischemic stroke onset who have restricted mobility. Exceptions include patients with https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 2/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate transient ischemic attack (TIA) or minor stroke who are being treated with dual antiplatelet therapy (DAPT) and patients receiving full-dose heparin or oral anticoagulation for another indication. Options for pharmacologic VTE prophylaxis include subcutaneous low molecular weight (LMW) heparin (eg, enoxaparin 40 mg daily, dalteparin 5000 units once daily, tinzaparin 4500 units once daily, or nadroparin 3800 units once daily if weight 70 kg, or 5700 units once daily if >70 kg), or subcutaneous low-dose unfractionated heparin (5000 units two to three times daily). This recommendation applies only to patients for whom the assessed benefit of anticoagulation is thought to outweigh the risk of bleeding. (See 'Low-dose heparin anticoagulation' below.) The approach to VTE prevention is modified according to individual circumstances; common situations include the following: After intravenous thrombolysis For patients who are treated with intravenous thrombolysis for acute ischemic stroke, IPC should be started on admission, while anticoagulation should be delayed until 24 hours after intravenous thrombolysis. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Monitoring'.) No intravenous thrombolysis For patients who are not treated with intravenous thrombolysis, IPC should be started on admission, and low-dose heparin (LMW or unfractionated) can be added for patients who are not being treated with DAPT for minor stroke. On dual antiplatelet therapy For patients with a TIA or minor stroke (ie, a National Institutes of Health Stroke Scale [NIHSS] score 3) who are receiving short-term DAPT with aspirin plus clopidogrel, it is reasonable to use IPC alone and avoid anticoagulation for pharmacologic VTE prophylaxis. The indications for DAPT in acute ischemic stroke are discussed separately. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of DAPT'.) Already on anticoagulation For patients who are receiving oral anticoagulant therapy at the time of acute ischemic stroke, IPC is started on admission. Low-dose heparin (LMW or unfractionated) can be used for VTE prophylaxis (after 24 hours following intravenous thrombolysis) during the interval when full-dose oral anticoagulation is stopped, which is often done to reduce the risk of hemorrhagic transformation of the ischemic infarct during the acute phase stroke. There is no need for concomitant low-dose heparin for VTE prophylaxis if oral anticoagulation is continued, and no need for VTE prophylaxis once oral anticoagulation is restarted and has achieved a therapeutic level. (See "Early https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 3/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Limited role of early anticoagulation'.) Contraindication to anticoagulation For patients with a contraindication to any anticoagulation (eg, gastrointestinal or other major systemic bleeding, or symptomatic hemorrhagic transformation of ischemic infarction), IPC is used alone for VTE prophylaxis. Approach in intracerebral hemorrhage IPC is the mainstay for prevention of venous thromboembolism in patients with acute intracerebral hemorrhage (ICH) and should be started on admission [13-15]. (See 'Intermittent pneumatic compression' below.) Once intracranial bleeding has stopped, some experts add low-dose LMW or unfractionated heparin after one to four days from ICH onset for patients with lack of mobility [15]. The risk of hematoma expansion may be increased in certain settings (eg, contrast extravasation ["spot sign"] on initial CT angiography, poor control of hypertension, large hematoma volume), which may weigh against the use of anticoagulation. (See 'Low-dose heparin anticoagulation' below.) Approach in subarachnoid hemorrhage For patients with subarachnoid hemorrhage and decreased mobility, IPC is started on admission and prior to aneurysm treatment. Heparin (LMW or unfractionated) can be added once the aneurysm is secured for patients who continue to have restricted mobility. (See 'Intermittent pneumatic compression' below and 'Low-dose heparin anticoagulation' below.) Duration of therapy In most cases, we continue VTE prophylaxis for acute stroke (ischemic or hemorrhagic) for the duration of the acute and rehabilitation hospital stay, or until the patient becomes fully ambulatory [16,17]. Once patients become fully ambulatory, mechanical and pharmacologic interventions of VTE prevention are generally stopped. However, the definition of ambulatory is subjective; patients who have prolonged periods of immobility in between ambulatory periods should probably continue VTE prophylaxis. The optimal duration of VTE prophylaxis is uncertain, as the clinical trials have generally employed prophylaxis for two weeks, and longer periods of treatment are not well studied in patients with stroke. A subgroup analysis of one randomized trial suggested that longer-term prophylaxis (eg, up to six weeks) with enoxaparin reduced the risk of VTE and increased the risk of major bleeding [18]. INTERVENTIONS FOR VTE PREVENTION https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 4/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Effective options for the prevention of venous thromboembolism (VTE) in patients with acute stroke and limited mobility include intermittent pneumatic compression devices and low-dose anticoagulation with heparin or low molecular weight (LMW) heparin. For patients with acute stroke capable of walking, early and frequent ambulation may be encouraged in addition to mechanical and pharmacologic interventions, although there is no direct evidence that this approach is effective for preventing VTE. Intermittent pneumatic compression We suggest VTE prophylaxis with thigh-length intermittent pneumatic compression (IPC), starting at admission, for most patients with acute ischemic or hemorrhagic stroke. (See 'Approach to VTE prevention' above.) IPC is effective for deep vein thrombosis (DVT) prevention in immobilized patients with acute stroke and has few clinically important side effects. Supporting evidence comes from the open- label multicenter CLOTS 3 trial, which randomly assigned over 2800 immobile patients within the first three days of admission for acute stroke (ischemic or hemorrhagic) to treatment with thigh- length IPC or no IPC [13]. Treatment was continued for at least 30 days or until the patient regained mobility, was discharged from the hospital, or could not tolerate continuation; the median duration was 9 days. At 30 days, there was a significant reduction in the rate of DVT in the femoral or popliteal veins (ie, proximal DVT) for the IPC compared with the no IPC group (8.5 versus 12.1 percent, absolute risk reduction 3.6 percent, 95% CI 1.4-5.8; adjusted odds ratio [OR] 0.65, 95% CI 0.51-0.84). In addition, the IPC group had significantly lower rates of symptomatic DVT (proximal or calf veins) and any DVT (symptomatic or asymptomatic, proximal or calf). In the subgroup of 322 patients with hemorrhagic stroke, IPC was associated with reduced risk of proximal DVT at 30 days (6.7 versus 17 percent; OR = 0.36, 95% CI 0.17-0.75). No major adverse events were associated with IPC treatment, but the IPC group had a significantly higher rate of skin breaks (3.1 versus 1.4 percent). Approximately one-third of patients in both groups received either anticoagulant prophylaxis or therapeutic anticoagulation. The effectiveness of IPC for VTE prevention in patients on anticoagulation is not firmly established, but a 2016 meta-analysis found moderate quality evidence that combining IPC and pharmacologic prophylaxis decreased the incidence of VTE in hospitalized patients when compared with IPC alone or pharmacologic prophylaxis alone [19]. In addition, a 2013 meta- analysis of randomized controlled trials evaluating hospitalized patients found that IPC plus pharmacologic prophylaxis provided an additive benefit for DVT prevention compared with IPC alone (relative risk reduction 0.54, 95% CI 0.32-0.91) [20]. The 2012 American College of Chest Physicians (ACCP) guidelines, which were published prior to the CLOTS 3 trial, had found only indirect evidence from other populations, mainly postoperative https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 5/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate patients, showing that IPC was associated with reduction in DVT of approximately 50 percent compared with no treatment [16,21]. Administration There are several types of intermittent pneumatic compression devices (eg, multichamber versus monochamber, pressure applied sequentially or uniformly, whole leg versus calf only). It is not known what type is optimal for VTE prevention in stroke patients. The CLOTS trial cited above used a multichamber device that applied sequential pressure to the entire leg [13]. Less than total compliance by patients and caregivers can limit the effectiveness of IPC, so strict adherence should be encouraged for patients with limited mobility. Contraindications IPC is contraindicated in those with overt evidence of leg ischemia caused by peripheral vascular disease, and in those with leg ulcerations, dermatitis, severe leg edema, or confirmed DVT. It should not be started in patients who have already been at bed rest or immobilized without VTE prophylaxis for more than 72 hours since stroke onset, since IPC may cause a newly formed clot to dislodge. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Intermittent pneumatic compression and venous foot pump'.) Low-dose heparin anticoagulation We suggest low-dose LMW heparin or unfractionated heparin for most patients with acute ischemic stroke onset who have restricted mobility. Exceptions include patients with transient ischemic attack (TIA) or minor stroke who are being treated with dual antiplatelet therapy (DAPT) and patients receiving full-dose heparin or oral anticoagulation for another indication. (See 'Approach in acute ischemic stroke' above.) The use of low-dose anticoagulation with LMH heparin or unfractionated heparin has a more restricted role for patients with acute intracerebral hemorrhage or subarachnoid hemorrhage. (See 'Approach in intracerebral hemorrhage' above and 'Approach in subarachnoid hemorrhage' above.) Efficacy Efficacy in ischemic stroke Prospective studies have established that both unfractionated heparin and LMW heparin are effective in reducing DVT and pulmonary embolism in patients with stroke [22,23]. In a 2007 systematic review of randomized controlled trials comparing early (typically within 48 hours) administration of either LMW heparin or unfractionated heparin with control (placebo or no treatment) for VTE prevention in patients with acute ischemic stroke, low-dose LMW heparin offered the best benefit-to-risk ratio for VTE prophylaxis [22]. Low- https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 6/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate dose LMW heparin reduced the risk of both DVT (OR 0.34, 95% CI 0.19-0.59) and pulmonary embolism (OR 0.36, 95% CI 0.15-0.87), with no increased risk of major intracranial or extracranial hemorrhage. The numbers needed to treat with low-dose LMW heparin to prevent DVT and pulmonary embolism were 7 and 38, respectively. Low-dose unfractionated heparin ( 15,000 units/day) decreased the risk of DVT but had no significant effect on the risk of pulmonary embolism and no significant effect on the risk of major intracranial or extracranial hemorrhage. In a meta-analysis of three randomized trials with over 2000 patients who had ischemic stroke, LMW heparins (enoxaparin in two trials and certoparin in one trial) were superior to unfractionated heparin for the prevention of any VTE (OR 0.54, 95% CI 0.41-0.70) [24]. In addition, LMW heparin use resulted in a reduction of pulmonary embolism (OR 0.26, 95% CI 0.07-0.95), though the number of events was small. There was no significant difference between groups for rates of intracerebral hemorrhage, overall bleeding, or mortality. Efficacy in hemorrhagic stroke There are limited data regarding the risks and benefits of anticoagulation for VTE prevention after acute intracerebral hemorrhage; data for subarachnoid hemorrhage are virtually nonexistent. A 2011 meta-analysis of four studies, two randomized, that compared anticoagulation therapy (unfractionated heparin, LMW heparin, heparinoids) with other treatments in patients with acute ICH found that anticoagulation therapy was associated with a significant reduction in pulmonary embolism (1.7 versus 2.9 percent); rates of DVT and mortality were nonsignificantly decreased, and rates of hematoma expansion were nonsignificantly increased [25]. A 2020 meta-analysis identified only two randomized controlled trials (with a total of 194 patients) evaluating anticoagulation for VTE prevention in the setting of acute ICH [26]. Compared with other treatments, low-dose enoxaparin (40 mg daily) was associated with a trend towards a lower rate of PE (OR 0.38, 95% CI 0.14 1.05) and similar rates of VTE (OR 0.77; 95% CI 0.38 1.57), hematoma enlargement (OR 0.63, 95% CI 0.03 12.51), and mortality OR 1.17, 95% CI 0.47 2.94). The trial designs in these meta-analyses varied in quality and few pulmonary emboli occurred. Therefore, these results should be interpreted cautiously. Comparison of LMW heparins with unfractionated heparin LMW heparins have a number of advantages over unfractionated heparin, including a longer duration of anticoagulant effect (permitting administration only once daily), better correlation between dose and anticoagulant response (permitting administration of a fixed dose without laboratory monitoring), and a lower risk of heparin-induced thrombocytopenia. (See "Clinical presentation and diagnosis of heparin- induced thrombocytopenia", section on 'Incidence and risk factors'.) https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 7/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate Potential disadvantages of LMW heparin compared with unfractionated heparin include the longer duration of action (making it more difficult to rapidly stop therapy), less effective reversal with protamine sulfate, and a prolonged half-life in patients with renal failure, especially with enoxaparin. These issues are discussed in greater detail separately. (See "Heparin and LMW heparin: Dosing and adverse effects".) Dosing of LMW heparin For VTE prevention with LMW heparin, the suggested doses for most patients with creatinine clearance >30 mL/minute and no extremes in body weight are the following: Enoxaparin 40 mg subcutaneously once daily Dalteparin 5000 units subcutaneously once daily Tinzaparin (not available in the United States) 4500 units subcutaneously once daily Nadroparin (not available in the United States) 3800 units subcutaneously once daily for patients 70 kg body weight, or 5700 units subcutaneously once daily for patients >70 kg body weight) A dose reduction of enoxaparin is needed for those with severe renal insufficiency ( table 1). For those who develop severe renal insufficiency during hospitalization, it is prudent that selected LMW heparins be discontinued and replaced with unfractionated heparin. (See "Heparin and LMW heparin: Dosing and adverse effects".) Dosing of unfractionated heparin For VTE prevention with unfractionated heparin, the suggested dose is 5000 units subcutaneously two to three times daily. There is no consensus regarding the optimal frequency of dosing (two versus three times daily), as discussed separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Low-dose unfractionated heparin'.) The dose of unfractionated heparin does not need to be adjusted for patients with renal failure. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Low-dose unfractionated heparin' and "Heparin and LMW heparin: Dosing and adverse effects".) Adverse effects Immune-mediated heparin-induced thrombocytopenia (HIT) is a potentially life-threatening complication that occurs in a small percentage of patients exposed to unfractionated heparin or LMW heparin, regardless of the dose, schedule, or route of administration. Thrombosis occurs in up to 50 percent of patients who develop HIT, with venous being more common than arterial thrombi. Thrombosis can lead to skin necrosis, limb https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 8/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate gangrene, and organ infarction. The risk of HIT is somewhat greater with unfractionated heparin compared with LMW heparin. Individuals with a presumptive diagnosis of HIT should have immediate discontinuation of all heparin exposure. The evaluation and treatment of suspected HIT is discussed in detail elsewhere. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".) Non-immune thrombocytopenia, often of no clinical importance, occurs in a minority of patients treated with heparin or LMH heparin. It is characterized by a mild, transient drop in platelet count that typically occurs within the first two days of heparin exposure. The platelet count usually returns to normal with continued heparin administration. The mechanism appears to be a direct effect of heparin on platelets, causing non-immune platelet aggregation. The typical platelet count nadir is approximately 100,000/microL. Ineffective or unproven treatments Fondaparinux Fondaparinux has not been well-studied for VTE prevention in patients with acute stroke. One retrospective study found no difference in symptomatic VTE or hemorrhagic complications for patients with acute stroke who were treated with fondaparinux or unfractionated heparin, but the study design does not permit definitive conclusions [27]. Fondaparinux is superior to placebo and likely as effective as LMW heparin for VTE prevention among patients who are not critically ill. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Fondaparinux'.) Graduated compression stockings We recommend not using graduated compression stockings for VTE prophylaxis in acute stroke of any type. Graduated compression stockings are not beneficial and may be harmful in the setting of acute stroke [28]. In the randomized controlled CLOTS 1 trial that evaluated 2158 patients within one week of acute stroke, thigh-length graduated compression stockings did not reduce occurrence of symptomatic or asymptomatic proximal DVT (the primary outcome) or VTE [29]. However, skin lesions (breaks, ulcers, blisters and necrosis) were more common in patients assigned to graduated compression stockings. Direct oral anticoagulants Most direct oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban) have not been evaluated for VTE prophylaxis in patients hospitalized with acute stroke, and further study is needed to determine their utility for VTE prophylaxis in this setting. Aspirin As a separate indication, early aspirin therapy is recommended for most patients with acute ischemic stroke or transient ischemic attack (TIA) who are not receiving oral https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 9/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate anticoagulants because it reduces the risk of early recurrent stroke or death. This is discussed in detail elsewhere. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of aspirin'.) However, aspirin alone is not considered effective for VTE prevention in hospitalized medical patients. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults", section on 'Aspirin'.) APPROACH TO VTE Suspicion for VTE Deep vein thrombosis (DVT) should be suspected in patients who present with leg swelling, pain, warmth, and erythema. Symptoms are usually unilateral but can be bilateral. Symptoms are confined to the calf in patients with isolated distal DVT, while patients with proximal DVT may have calf or whole leg symptoms. The clinical presentation and evaluation for DVT is reviewed in detail separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".) 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. The clinical presentation and evaluation of suspected pulmonary embolism is discussed in detail elsewhere. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".) Treatment for VTE When acute pulmonary embolism is suspected, initial care should focus on stabilizing the patient. This may require respiratory and hemodynamic support in the intensive care unit. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Initial approach and resuscitation'.) In other settings, venous thromboembolism (VTE) is often treated with full-dose anticoagulation. However, anticoagulation increases the risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke, and increases the risk of hematoma expansion and rebleeding in patients with intracranial hemorrhage. Full-dose anticoagulation may be appropriate for select 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 ischemic infarctions, which are associated with an increased risk of hemorrhagic transformation. Full-dose anticoagulation is generally contraindicated for patients with acute intracerebral hemorrhage and patients with aneurysmal subarachnoid hemorrhage prior to https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 10/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate aneurysm repair. In all patients, the decision to use anticoagulation for VTE treatment should be individualized and the benefits weighed against the risk of bleeding. (See "Venous thromboembolism: Initiation of anticoagulation".) For patients with acute proximal DVT, symptomatic distal DVT, or hemodynamically stable patients with pulmonary embolism, an inferior vena cava filter should be placed promptly if the bleeding risk associated with full-dose anticoagulant therapy is excessive. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Inferior vena cava filter' and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Anticoagulant therapy'.) For patients with severe acute pulmonary embolism who have contraindications to anticoagulation and thrombolysis, catheter or surgical thrombectomy (embolectomy) can be used if the necessary resources and expertise are available. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy'.) Systemic thrombolytic therapy is seldom if ever appropriate for pulmonary embolism when treating patients with acute ischemic stroke (beyond 4.5 hours from stroke onset) or hemorrhagic stroke ( table 2). (See "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration", section on 'Assessing risk of bleeding and contraindications'.) Definitive pulmonary embolism treatment is discussed in detail separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Definitive therapy'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anticoagulation" and "Society guideline links: Stroke in adults" and "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".) SUMMARY AND RECOMMENDATIONS Proximal deep venous thrombosis is a serious complication of stroke because it may lead to life-threatening pulmonary embolism. Patients with hemiparesis, immobility, severe https://www.uptodate.com/contents/prevention-and-treatment-of-venous-thromboembolism-in-patients-with-acute-stroke/print 11/20 7/5/23, 12:07 PM Prevention and treatment of venous thromboembolism in patients with acute stroke - UpToDate stroke, and advanced age are predisposed to the development of deep vein thrombosis. (See 'Risk and prevalence' above.) Venous thromboembolism (VTE) prophylaxis is indicated for all patients with acute stroke and restricted mobility. The approach to VTE prevention differs according to the type of stroke. (See 'Indications' above.) For most patients with acute ischemic stroke who have restricted mobility and no contraindications, we suggest combined treatment, starting at admission, with thigh- length intermittent pneumatic compression (IPC) plus low molecular weight (LMW) heparin (Grade 2C). Low-dose unfractionated heparin is an alternative to LMW heparin. We prefer LMW heparin in this setting because of ease of use and lower risk of heparin- associated thrombocytopenia compared with unfractionated heparin. (See 'Approach in acute ischemic stroke' above and 'Low-dose heparin anticoagulation' above.): Certain modifications and exceptions apply (see 'Approach in acute ischemic stroke' 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. 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