Table 6.

Guideline recommendations for management of cancer‐associated VTE in special patient populations

Patient Population	American Society of Clinical Oncology 2020	International Initiative on Thrombosis and Cancer 2019	International Society of Thrombosis and Hemostasis 2018	National Comprehensive Cancer Network 2020	Spanish Society of Medical Oncology 2020
Extremes of weight	Treatment: LMWH: Use actual body weight. DOACs: Use caution with weight >120 kg, BMI >40 kg/m2. LMWH is preferred. If DOAC must be used, then check drug‐specific peak and trough levels.	No specific recommendations.	No specific recommendations.	Treatment: LMWH: Follow package insert for dosing; consider LMWH anti‐Xa levels. Fondaparinux: Use caution with weight <50 kg. DOACs: No specific recommendations. Prophylaxis: For BMI ≥40, use dalteparin 7,500 units s.c. daily, enoxaparin 40 mg s.c. twice daily, fondaparinux 5 mg s.c. daily, or UFH 7,500 units s.c. three times daily. Use aspirin 81–325 mg daily or VKA (INR 2–3) only for patients with myeloma. For weight <50 kg, consider checking LMWH anti‐Xa levels.	No specific recommendations.
Renal impairment	Treatment: LMWH: Anti‐Xa measurement is recommended in patients with moderate‐to‐severe renal impairment. If this is unavailable, UFH and VKA are safer options for initial and long‐term treatment, respectively. DOACs: Refer to package inserts for guidance.	Treatment: LMWH: Suggest use of UFH followed by VKA for CrCl <30 mL/min or LMWH adjusted to LMWH anti‐Xa levels (guidance). Prophylaxis: For CrCl <30 mL/min, mechanical prophylaxis can be used and UFH can be considered on case‐by‐case basis (guidance).	No specific recommendations.	Treatment: For CrCl 20–30 mL/min, use enoxaparin 1 mg/kg daily; consider LMWH anti‐Xa levels for dalteparin. For fondaparinux, use caution with CrCl 30–50 mL/min; avoid with CrCl <30 mL/min. DOACs: Avoid with CrCl <30 mL/min. For initial therapy, consider UFH and for chronic therapy, consider VKA. Prophylaxis: Consider UFH. For enoxaparin, reduce dose to 30 mg daily or use UFH or dalteparin. Avoid DOACs with CrCl <30 mL/min. No dose adjustment for aspirin or VKA.	No specific recommendations.
Hepatic dysfunction	Treatment: DOACs: Refer to package inserts for guidance.	No specific recommendations.	No specific recommendations.	DOACs: Avoid if clinically significant liver disease. Apixaban and edoxaban: Avoid if total bilirubin (not due to Gilbert's syndrome) >1.5 × ULN or transaminases >2 × ULN Dabigatran or rivaroxaban: Avoid if transaminases >3 × ULN.	No specific recommendations.
Proximal GI surgery	No specific recommendations.	No specific recommendations.	No specific recommendations.	No specific recommendations.	No specific recommendations.
Thrombocytopenia	No specific recommendations.	Treatment: Anticoagulation can be used with platelets >50,000/μL and no bleeding; if platelets <50,000/μL, decisions on dose and treatment should be made on case‐by‐case basis (guidance). Prophylaxis: Anticoagulation might be used if platelets >80,000/μL; if platelets <80,000/μL, anticoagulation should only be considered on case‐by‐case basis with utmost caution (guidance).	Treatment: For acute proximal DVT or PE or recurrent VTE (within 30 days) and platelets <50,000/μL, consider platelet transfusions to maintain platelets 40,000–50,000/μL, and continue therapy. For acute distal DVT or incidental subsegmental PE and platelets 25,000–50,000/μL, consider half‐dose (50%) or prophylactic‐dose LMWH. For platelets <25,000/μL, hold anticoagulation. For chronic VTE (beyond 30 days), consider half‐dose or prophylactic‐dose LMWH. For DOACs, hold if platelets <50,000/μL or transfuse platelets. Consider retrievable IVC filter on case‐by‐case basis if acute VTE with platelets <50,000/μL refractory to transfusional support. Prophylaxis: No specific recommendations.	Treatment: LMWH: If platelets >50,000/μL, use full‐dose therapy enoxaparin 1 mg/kg every 12 hours. If platelets 25,000–50,000/μL, suggest enoxaparin 0.5 mg/kg every 12 hours or transfuse platelets to maintain >50,000/μL or IVC filter. If platelets <25,000/μL, hold LMWH or consider platelet transfusion to continue therapy or IVC filter. DOAC: If platelets >50,000/μL, hold until platelet recovery or transfuse platelets or IVC filter. Prophylaxis: If platelets >50,000/μL, use standard doses. If platelets <30,000–50,000/μL, hold or use clinical judgment.	No specific recommendations.
Pregnancy	No specific recommendations.	Use standard doses of LMWH for treatment and prophylaxis (guidance).	No specific recommendations.	No specific recommendations.	No specific recommendations.
Primary or metastatic brain tumors	Treatment: Anticoagulation should be offered as it is for other patients with cancer, although uncertainty remains as to choice of agent and patients most likely to benefit. (Recommendation type: informal consensus; evidence quality: low; strength of recommendation: moderate.) Preliminary data suggest that DOACs may be associated with a lower risk of intracranial hemorrhage than LMWH in patients with metastatic brain tumors.	Prevention: Recommend use of LMWH or UFH postoperatively for VTE prevention in neurosurgery patients (grade 1A). Primary pharmacological prophylaxis of VTE is not recommended in patients with a brain tumor who are not undergoing neurosurgery (grade 1B). Treatment: LMWH or DOACs can be used for anticoagulation in patients with a brain tumor and VTE (grade 2B).	No specific recommendations.	No specific recommendations.	Treatment: In the absence of contraindications, patients with primary or metastatic brain tumors should be managed similarly to other solid tumors (grade 2B). For patients with brain metastases from melanoma or kidney cancer, a 25%–50% dose reduction in LMWH dose maybe considered (grade 2C). For patients with brainstem glioma, a 25%–50% dose reduction in LMWH dose is suggested (grade 2C).

Abbreviations: BMI, body mass index; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; GI, gastrointestinal; INR, international normalized ratio; IVC, inferior vena cava; LMWH, low‐molecular‐weight heparin; PE, pulmonary embolism; UFH, unfractionated heparin; ULN, upper limit of normal range; VTE, venous thromboembolism.