What is the best course of action for a patient with stage 4 melanoma, brain metastases, and recent ICH, on bisoprolol and dexamethasone, presenting with asymmetric leg swelling and no chest pain?

Immediate Workup for Deep Vein Thrombosis

This patient requires urgent Doppler ultrasound of the affected leg to rule out deep vein thrombosis (DVT), as asymmetric leg swelling in a patient with stage 4 melanoma and brain metastases represents a high-risk scenario for venous thromboembolism. 1

Clinical Context and Risk Assessment

• Patients with advanced malignancy, particularly melanoma with brain metastases, have an especially high risk of venous thromboembolism due to both the malignancy itself and mobility issues 1
• The combination of stage 4 melanoma, brain metastases, and recent intracranial hemorrhage creates a complex clinical scenario where anticoagulation decisions must carefully balance thrombosis prevention against bleeding risk 1
• Dexamethasone use (even at the tapered dose of 2mg daily) may contribute to edema, but unilateral presentation strongly suggests DVT rather than medication effect 2, 3

Diagnostic Approach

Immediate Steps

• Obtain compression Doppler ultrasound of the entire affected leg within 24 hours to evaluate for DVT 1
• Measure D-dimer if ultrasound is not immediately available, though this has limited utility given the patient's active malignancy 1
• Assess for clinical signs of pulmonary embolism including tachypnea, tachycardia, oxygen desaturation, or pleuritic chest pain (though patient currently denies chest pain) 1

Additional Considerations

• Review recent imaging of brain metastases to assess current hemorrhage status and size/number of lesions, as this impacts anticoagulation safety 1, 4
• Evaluate mobility status and recent immobilization, which increases VTE risk 1

Management if DVT is Confirmed

Anticoagulation Decision-Making

Despite the recent intracranial hemorrhage, anticoagulation should be strongly considered if DVT is confirmed, as the evidence suggests anticoagulation is relatively safe in melanoma patients with brain metastases. 4

Evidence Supporting Anticoagulation

• A retrospective study of 74 melanoma patients with brain metastases and VTE found that systemic anticoagulation did not significantly increase intracranial hemorrhage risk (4% in anticoagulated patients vs 0% in non-anticoagulated, p=1.00) 4
• Anticoagulated patients showed a trend toward longer overall survival (4.2 vs 1.2 months, p=0.06) 4
• Low-molecular weight heparin or direct oral anticoagulants constitute the mainstay of VTE management in cancer patients 1

Critical Caveat for This Patient

• However, a recent propensity-matched study demonstrated modestly increased intracranial hemorrhage risk with anticoagulation, particularly among melanoma patients with prior intracranial bleeds 1
• The indication for anticoagulation must be carefully weighed against ICH risk in this specific high-risk scenario 1

Recommended Anticoagulation Approach

• If DVT is confirmed and anticoagulation is deemed necessary, initiate low-molecular weight heparin (e.g., enoxaparin) rather than direct oral anticoagulants, as this allows for more rapid reversal if bleeding occurs 1
• Obtain repeat brain MRI within 1-2 weeks after starting anticoagulation to monitor for new or worsening hemorrhage 1
• Use anticoagulation cautiously given the combination of melanoma histology and prior intracranial hemorrhage 1

Alternative if Anticoagulation is Contraindicated

• Consider inferior vena cava (IVC) filter placement if anticoagulation is absolutely contraindicated due to recent ICH 1
• This decision should be made in consultation with neurosurgery, neuro-oncology, and interventional radiology 1

Steroid Management Consideration

• If significant peritumoral edema from brain metastases is contributing to symptoms, consider bevacizumab as a steroid-sparing agent to facilitate weaning dexamethasone, as corticosteroids may reduce immunotherapy efficacy 2
• Bevacizumab (5-7.5 mg/kg every 2-3 weeks) has been shown to reduce peritumoral edema and allow dexamethasone dose reduction by >50% in melanoma patients with brain metastases 2
• However, bevacizumab carries risks including intracranial hemorrhage, hypertension, and gastrointestinal bleeding, which must be weighed against benefits 2

Multidisciplinary Discussion Required

This patient's management must be discussed urgently in an interdisciplinary tumor board including medical oncology, neuro-oncology, neurosurgery, and potentially interventional radiology to determine the optimal balance between anticoagulation for VTE and hemorrhage risk from brain metastases. 1, 5