Thromboprophylaxis in Cancer Patients

Introduction to Thromboprophylaxis

The International Clinical Practice Guidelines recommend VTE primary pharmacological prophylaxis in patients with myeloma treated with immunomodulatory drugs combined with steroids or other systemic anticancer therapies (grade 1A) 1

Multiple myeloma patients have an increased risk of VTE, especially when receiving immunomodulatory drugs, and the decision to use apixaban should be based on treatment regimen factors and patient-specific risk factors such as history of previous thromboembolism, immobilization, advanced age, obesity, central venous catheter, and comorbidities 1
The Khorana score can be used to identify high-risk patients, with points assigned for very high-risk cancer types, high-risk cancer types, prechemotherapy platelet count, hemoglobin, prechemotherapy leukocyte count, and BMI, with a high risk defined as a score of 3 points or more, as recommended by the American Society of Clinical Oncology 2

For multiple myeloma patients receiving IMiDs, low molecular weight heparin (LMWH) at prophylactic doses, low-dose aspirin, and apixaban at prophylactic doses have shown similar efficacy 3
LMWH should be preferred for patients with additional risk factors such as prior history of thromboembolism 3
Apixaban represents an effective oral option for thromboprophylaxis in multiple myeloma patients receiving immunomodulatory therapy, with clinical evidence supporting its safety and efficacy in this population 1
The recommended dose of apixaban for VTE prophylaxis in cancer patients is 2.5 mg twice daily, as recommended by the Journal of Clinical Oncology and Journal of Thrombosis and Haemostasis 2, 4

The AVERT trial demonstrated that apixaban 2.5 mg twice daily significantly reduced VTE risk in cancer patients receiving chemotherapy, with a VTE rate of 4.2% compared to 10.2% with placebo (HR 0.41; 95% CI, 0.26-0.65) 2
Major bleeding occurred in 3.5% of apixaban patients vs. 1.8% in placebo group (HR 2.00; 95% CI, 1.01-3.95), with higher bleeding risk in patients with GI or mucosal tumors, concurrent antiplatelet therapy, history of bleeding, or renal or hepatic impairment 2

Apixaban should be avoided in patients with severe renal impairment (CrCl <15 mL/min) 5
Apixaban should be avoided in patients with significant hepatic disease (transaminases >2x ULN or total bilirubin >1.5x ULN) 5
Alternative thromboprophylaxis should be considered in patients with active bleeding, high bleeding risk, or platelet count <50,000/μL 6
Combining apixaban with antiplatelet agents significantly increases bleeding risk without providing additional protection against thromboembolism 7

Regular assessment of renal function, particularly in elderly patients, and monitoring for signs of bleeding are recommended 2, 7
Monitor for signs of bleeding, including unexpected bleeding or bruising, red/pink/brown urine, red or black stools, coughing up blood, or vomiting blood 7
Abrupt discontinuation increases thrombotic risk, and coverage with another anticoagulant may be needed if apixaban must be temporarily interrupted 8
Andexanet alfa has been approved for reversal of apixaban-associated life-threatening bleeding 9
Particular caution is needed regarding drug interactions between apixaban and anticancer treatments, with potent inhibitors or inducers of P-glycoprotein and cytochrome P450 3A4 able to interact with apixaban 2

The American College of Cardiology recommends reducing the dose to 2.5mg twice daily when combining apixaban with strong CYP3A4 and P-glycoprotein inhibitors 9
Patients already on the 2.5mg twice daily dose should avoid concomitant use of these inhibitors 9
Apixaban can be used in patients with moderate renal impairment (CrCl 30-50 mL/min) without dose adjustment unless other dose reduction criteria are met 9, 8
The National Comprehensive Cancer Network recommends avoiding apixaban in patients with severe renal impairment (CrCl <15 mL/min) 5
Patients with CrCl 15-30 mL/min should be monitored closely if apixaban is used 5
Apixaban should be avoided in patients with hepatic impairment (transaminases >2 times the upper limit of normal or total bilirubin >1.5 times the upper limit of normal) 5
No routine coagulation monitoring is required for patients on apixaban 8, 7
Regular assessment of renal function is recommended, particularly in elderly patients 7