How should we anticoagulate and manage a 34‑year‑old male with ALK‑positive lung adenocarcinoma receiving cisplatin‑pemetrexed chemotherapy, platelet count 143 ×10⁹/L, normal renal function, and asymptomatic pulmonary artery filling defects suggestive of pulmonary embolism?

Anticoagulation Management for ALK+ Lung Adenocarcinoma with Pulmonary Embolism

Initiate therapeutic anticoagulation immediately with low-molecular-weight heparin (LMWH) at full dose without platelet transfusion support, as the platelet count of 143 ×10⁹/L is well above the safety threshold for cancer-associated thrombosis. 1

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Immediate Anticoagulation Strategy

Start LMWH (enoxaparin 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily) as the preferred agent for cancer-associated thrombosis. 1 LMWH is superior to unfractionated heparin in cancer patients, with demonstrated mortality benefit at 3 months and simpler dosing without laboratory monitoring requirements. 1

• Do not use direct oral anticoagulants (DOACs) as first-line therapy in this patient. 1 While edoxaban and rivaroxaban are acceptable alternatives to LMWH in cancer-associated thrombosis, they should be avoided in patients with gastrointestinal malignancies due to increased bleeding risk. 1 Although this patient has lung adenocarcinoma (not GI), the 2019 ESC guidelines recommend LMWH as the preferred initial therapy for the first 6 months in cancer patients. 1

• Unfractionated heparin is reserved only for hemodynamically unstable patients or those with severe renal dysfunction (CrCl <30 mL/min). 1 This patient is hemodynamically stable with normal renal function (Cr 0.7), making LMWH the optimal choice. 1

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Platelet Count Considerations

The current platelet count of 143 ×10⁹/L permits full therapeutic anticoagulation without dose reduction or platelet transfusion support. 1, 2

• Full-dose anticoagulation is safe at platelet counts ≥50 ×10⁹/L in cancer-associated thrombosis. 1, 2 This threshold is based on evidence showing comparable efficacy and acceptable bleeding risk above this level. 1, 2

• If platelets decline to 25–50 ×10⁹/L during treatment, reduce LMWH to 50% of therapeutic dose or switch to prophylactic dosing. 1, 2 Monitor platelet counts at least weekly during chemotherapy cycles. 1, 2

• If platelets fall below 25 ×10⁹/L, temporarily discontinue anticoagulation and resume full-dose LMWH when count rises above 50 ×10⁹/L without transfusion support. 1, 2

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Chemotherapy-Related Considerations

Cisplatin-based chemotherapy increases thrombotic risk but also causes myelosuppression, requiring vigilant platelet monitoring. 3 The current leukopenia (WBC 1.9, ANC 1.5) and anemia (Hgb 9.3) indicate bone marrow suppression from cisplatin/pemetrexed, though the platelet count remains adequate for anticoagulation. 3

• Monitor complete blood count with platelet count at least twice weekly during active chemotherapy cycles. 1, 2 Cisplatin and pemetrexed can cause progressive cytopenias, and rare cases of aplastic anemia have been reported with pemetrexed. 3

• Do not delay anticoagulation based on mild cytopenias. 1 The thrombotic risk from untreated PE in cancer patients far exceeds bleeding risk at this platelet level. 1

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Duration of Anticoagulation

Continue therapeutic anticoagulation indefinitely (or until cancer is cured) given the active malignancy and ongoing chemotherapy. 1

• LMWH monotherapy should be continued for at least 6 months as first-line therapy. 1 After 6 months, either continue LMWH or transition to edoxaban/rivaroxaban based on patient preference, bleeding risk, and cancer treatment response. 1

• The risk of VTE recurrence remains high (≥19% over 6 months) in lung cancer patients with active disease. 1 This patient has male sex (+1 point) and lung cancer (+1 point), placing him in the high-risk category for recurrence. 1

• Reassess anticoagulation duration after neoadjuvant chemotherapy completion and surgical resection. 1 If the patient achieves complete surgical resection and no evidence of disease, consider stopping anticoagulation after 3–6 months post-surgery, though data are limited. 1

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Monitoring and Follow-Up

Obtain baseline PT/INR, aPTT, and hemoglobin before starting LMWH. 1 No routine anti-Xa monitoring is required for standard-dose LMWH in patients with normal renal function. 1

• Monitor hemoglobin/hematocrit weekly to detect occult bleeding. 2 Cancer patients on anticoagulation have 2–3 times higher bleeding risk than non-cancer patients. 1

• Assess for bleeding symptoms at each clinical encounter: melena, hematuria, hemoptysis, or new/worsening anemia. 1, 2

• Repeat imaging (CT chest with PE protocol) is not routinely indicated unless clinical deterioration occurs. 1 The asymptomatic filling defects on non-PE-protocol CT should be treated as symptomatic PE given the cancer diagnosis. 1

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Critical Pitfalls to Avoid

Do not withhold anticoagulation based on "asymptomatic" PE in cancer patients. 1 Incidental PE in cancer should be managed identically to symptomatic PE when involving segmental or more proximal branches. 1

Do not use inferior vena cava filters as adjunct therapy. 1 Filters are indicated only when anticoagulation is absolutely contraindicated due to active hemorrhage, and should not delay anticoagulation initiation once bleeding resolves. 1

Do not administer thrombolytic therapy. 1, 4 Thrombolysis is reserved for high-risk PE with cardiogenic shock or persistent hypotension (systolic BP <90 mmHg for ≥15 minutes). 1, 4 This patient is hemodynamically stable (BP 128/80, HR 80, SpO₂ 99% on room air) without RV strain on imaging. 1, 4

Avoid concomitant antiplatelet agents (aspirin, NSAIDs) unless absolutely necessary for cardiovascular indications. 1, 2 These medications significantly increase bleeding risk even at higher platelet counts. 1, 2

Do not assume heparin-induced thrombocytopenia (HIT) without appropriate clinical context. 2 HIT typically presents 5–10 days after heparin initiation with platelet drop ≥50% or count <100 ×10⁹/L. 2 This patient's platelet count of 143 ×10⁹/L before heparin exposure makes HIT unlikely. 2

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Specific Dosing Recommendations

Enoxaparin 1 mg/kg subcutaneously every 12 hours (preferred for hospitalized patients) or 1.5 mg/kg subcutaneously once daily (acceptable for outpatient management). 1

• For a 70 kg patient: 70 mg subcutaneously every 12 hours or 105 mg (use 100 mg prefilled syringe) once daily. 1

• Dose adjustment is not required for mild renal impairment (CrCl >30 mL/min). 1 This patient's Cr 0.7 indicates normal renal function. 1

If transitioning to DOAC after 6 months, use edoxaban 60 mg once daily (after 5–10 days of LMWH) or rivaroxaban 15 mg twice daily for 21 days, then 20 mg once daily. 1 Avoid apixaban in lung cancer due to lack of specific data in this population. 1