In a patient with active malignancy, how should venous thromboembolism be risk‑assessed, prophylaxed, and treated, including choice of anticoagulant, dosing, renal function adjustments, and management of contraindications?

Management of Venous Thromboembolism in Patients with Active Malignancy

For patients with active malignancy, use the Khorana score to risk-stratify ambulatory patients, provide pharmacologic thromboprophylaxis to all hospitalized patients with acute illness or reduced mobility, and treat established VTE with low-molecular-weight heparin (LMWH) for both initial therapy (5-10 days) and long-term secondary prophylaxis (at least 6 months), with direct oral anticoagulants (apixaban or rivaroxaban) now acceptable as alternatives in select high-risk ambulatory patients. 1

Risk Assessment

Ambulatory Patients:

• Calculate the Khorana score before starting new systemic chemotherapy to identify high-risk patients (score ≥2) who may benefit from prophylaxis 1
• Assess bleeding risk factors including thrombocytopenia, renal dysfunction, and drug interactions before initiating prophylaxis 1
• Periodically reassess VTE risk throughout the cancer treatment course 1

High-Risk Features to Identify:

• Cancer types: pancreas, brain, lung, gynecologic, renal, gastric, bladder, and hematologic malignancies carry particularly elevated risk 1
• Metastatic disease presence significantly increases VTE risk 1
• Recent hospitalization, immobilization, infection, or neutropenia 1
• Prechemotherapy platelet count ≥350,000/μL 1

Prophylaxis Strategies

Hospitalized Patients

Pharmacologic prophylaxis should be offered to:

• All hospitalized patients with active malignancy who have acute medical illness or reduced mobility, unless bleeding or contraindications exist 1
• Hospitalized patients with active malignancy even without additional risk factors may receive prophylaxis if no contraindications 1

Do NOT provide routine prophylaxis to:

• Patients admitted solely for minor procedures or brief chemotherapy infusions 1
• Patients undergoing stem-cell or bone marrow transplantation 1

Ambulatory Patients

The 2020 ASCO guidelines represent a significant shift from earlier recommendations:

High-risk ambulatory patients (Khorana score ≥2) may receive:

• Apixaban, rivaroxaban, or LMWH for thromboprophylaxis, provided no significant bleeding risk factors or drug interactions exist 1
• This recommendation requires shared decision-making discussion about benefits, harms, cost, and duration 1

Important caveat: Earlier guidelines (2013-2015) stated that novel oral anticoagulants were NOT recommended for cancer patients with VTE 1. The 2020 update reversed this position based on newer trial data, now endorsing apixaban and rivaroxaban as options 1.

Do NOT provide routine prophylaxis to:

• All ambulatory cancer patients without risk stratification 1

Special Population - Multiple Myeloma:

• Patients receiving thalidomide or lenalidomide with chemotherapy and/or dexamethasone require prophylaxis 1
• Lower-risk patients: aspirin or LMWH 1
• Higher-risk patients: LMWH preferred 1

Perioperative Patients

All patients with malignancy undergoing major surgery should receive:

• Pharmacologic thromboprophylaxis with unfractionated heparin (UFH) or LMWH unless active bleeding or high bleeding risk 1
• Prophylaxis commenced preoperatively 1
• Continuation for at least 7-10 days postoperatively 1

Extended prophylaxis (up to 4 weeks) should be considered for:

• Major abdominal or pelvic cancer surgery with high-risk features 1
• Patients with impaired mobility after major operations 2

Mechanical methods:

• May be added to pharmacologic prophylaxis but should NOT be used as monotherapy unless pharmacologic methods are contraindicated 1

Treatment of Established VTE

Initial Therapy (First 5-10 Days)

LMWH is the preferred agent for initial treatment of DVT and PE in cancer patients 1, 3

Key advantages of LMWH over UFH:

• More effective than warfarin for secondary prevention without increased bleeding 3
• Does not require the same intensive monitoring as UFH 3

Long-Term Secondary Prophylaxis

LMWH should be continued for at least 6 months for long-term secondary prophylaxis after acute VTE 1, 3

Critical distinction from earlier guidelines:

• 2013-2015 guidelines explicitly stated that novel oral anticoagulants were NOT recommended for cancer patients with established VTE 1
• The 2020 update now permits apixaban and rivaroxaban as alternatives for prophylaxis in high-risk ambulatory patients, though the primary treatment recommendation for established VTE remains LMWH 1

Renal Function Adjustments

For patients with severe renal failure or ESRD:

• UFH is preferred over LMWH due to the significant prothrombotic state in dialysis patients 4
• Initial UFH dosing: 5000 IU bolus, then approximately 30,000 IU over 24 hours 4
• Target aPTT of 1.5-2.5 times baseline 4
• Monitor aPTT every 6 hours initially until stable, then daily 4
• Transition to warfarin with INR goal of 2-3 after at least 5-7 days of therapeutic anticoagulation 4

Management of Contraindications

Absolute contraindications requiring holding or modifying anticoagulation:

• Active bleeding 1, 4
• Platelet count <50 × 10⁹/L (though full-dose appropriate if platelet count adequate, e.g., 159) 4
• Recent intracerebral hemorrhage 4

Relative contraindications requiring careful assessment:

• High bleeding risk based on tumor location (e.g., brain metastases, GI malignancies with mucosal involvement) 1
• Significant drug interactions with direct oral anticoagulants 1
• Severe thrombocytopenia (platelets 50-100 × 10⁹/L) may require dose reduction or alternative strategies 4

Monitoring During Anticoagulation

For UFH therapy:

• aPTT every 6 hours until stable, then daily 4
• Hemoglobin monitoring if recent anemia or transfusion history 4

For warfarin therapy:

• INR daily once started until therapeutic for 2 consecutive days 4
• Then INR 2-3 times weekly (frequency may vary based on stability) 4

For LMWH therapy:

• Routine anti-Xa monitoring generally not required except in renal insufficiency, extremes of body weight, or pregnancy 3

Patient Education

Oncology professionals must educate patients about:

• Signs and symptoms of DVT: unilateral calf, leg, or thigh swelling or pain 1
• Signs and symptoms of PE: shortness of breath, tachypnea, pleuritic chest pain, hemoptysis, tachycardia, syncope 1
• Importance of reporting symptoms promptly for evaluation 1

Common Pitfalls to Avoid

Do not use anticoagulation solely to extend survival in cancer patients without other indications for VTE treatment or prophylaxis 1

Avoid inappropriate phlebotomy in patients with cancer-related erythrocytosis, as this can cause iron deficiency and microcytosis, which paradoxically increases thrombotic risk 5

Do not assume all cancer patients need prophylaxis - risk stratification is essential to avoid unnecessary bleeding risk in low-risk ambulatory patients 1, 6, 7

Recognize that VTE risk persists beyond hospital discharge after major cancer surgery, warranting extended prophylaxis consideration 1, 2