Table 1.

Potential causes of anticoagulant failure in cancer

FactorsDetailsManagement implications
Anticoagulation adherence • Noncompliance
• Drug interruptions 
• Counseling or alternative anticoagulant
• Bridging or IVC filter if additional interruptions needed 
Drug-drug interactions • CYP3A4 inducers (Table 2) • Alternative anticoagulant or increased doses of DOAC with Xa monitoring 
Extrinsic compression • Tumor compression
• May-Thurner syndrome
• Thoracic outlet obstruction 
• Consideration of intravascular stenting 
LMWH ineffectiveness • Heparin-induced thrombocytopenia
• Antithrombin deficiency (eg, asparaginase therapy)
• Appropriate weight-based dosing 
• Diagnosis of HIT mandates alternative anticoagulants such as direct thrombin inhibitors, DOAC, or fondaparinux
• In cases of asparaginase deficiency, strategies include confirmation of therapeutic factor Xa levels, antithrombin repletion, alternative anticoagulants 
DOAC ineffectiveness • Antiphospholipid antibody syndrome
• Reduced gastrointestinal absorption 
• Warfarin for antiphospholipid antibody syndrome
• LMWH if reduced absorption, rivaroxaban largely absorbed in the stomach 
Intravascular • Central venous catheter
• IVC filter 
• Consider removal of central venous catheter in setting of thrombosis 
Tumor thrombus • Renal cell carcinoma
• Hepatocellular carcinoma
• Thyroid cancer
• Metastatic disease 
• Tumor-directed therapy
• Benefit of anticoagulation uncertain 
Myeloproliferative neoplasms • Polycythemia vera
• Essential thrombocythemia 
• Consideration of cytoreductive therapy with hydroxyurea ± aspirin 
FactorsDetailsManagement implications
Anticoagulation adherence • Noncompliance
• Drug interruptions 
• Counseling or alternative anticoagulant
• Bridging or IVC filter if additional interruptions needed 
Drug-drug interactions • CYP3A4 inducers (Table 2) • Alternative anticoagulant or increased doses of DOAC with Xa monitoring 
Extrinsic compression • Tumor compression
• May-Thurner syndrome
• Thoracic outlet obstruction 
• Consideration of intravascular stenting 
LMWH ineffectiveness • Heparin-induced thrombocytopenia
• Antithrombin deficiency (eg, asparaginase therapy)
• Appropriate weight-based dosing 
• Diagnosis of HIT mandates alternative anticoagulants such as direct thrombin inhibitors, DOAC, or fondaparinux
• In cases of asparaginase deficiency, strategies include confirmation of therapeutic factor Xa levels, antithrombin repletion, alternative anticoagulants 
DOAC ineffectiveness • Antiphospholipid antibody syndrome
• Reduced gastrointestinal absorption 
• Warfarin for antiphospholipid antibody syndrome
• LMWH if reduced absorption, rivaroxaban largely absorbed in the stomach 
Intravascular • Central venous catheter
• IVC filter 
• Consider removal of central venous catheter in setting of thrombosis 
Tumor thrombus • Renal cell carcinoma
• Hepatocellular carcinoma
• Thyroid cancer
• Metastatic disease 
• Tumor-directed therapy
• Benefit of anticoagulation uncertain 
Myeloproliferative neoplasms • Polycythemia vera
• Essential thrombocythemia 
• Consideration of cytoreductive therapy with hydroxyurea ± aspirin 

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