How I treat recurrent venous thromboembolism in patients receiving anticoagulant therapy

Abstract

Oral anticoagulant therapy for venous thromboembolism is very effective. When oral anticoagulants are managed well, the risk of recurrence is approximately 2 per 100 patient-years. The main reasons for a breakthrough event are underlying disease and subtherapeutic drug levels. The most common underlying disease that results in recurrence on treatment is cancer. Subtherapeutic drug levels can be caused by poor adherence to the drug regimen, interactions with other drugs or food, or inappropriate dosing. It is important to investigate and understand the cause whenever such an event occurs and to improve management of anticoagulants thereby avoiding further recurrences. Here we present 4 illustrative cases together with a discussion of the underlying pathology. Whereas the mechanisms are usually quite well understood, the management of further anticoagulation after a breakthrough event is based on minimal or no clinical trial evidence.

Hypercoagulable States and Thrombophilias: Risks Relating to Recurrent Venous Thromboembolism

“…Therefore, these patients usually require systemic therapy with immunomodulators such as infliximab or colchicine to reduce this risk. 14 Myeloproliferative neoplasms are also considered an acquired thrombophilia. Patients with JAK2 V617F mutations are at particular risk of splanchnic vein thrombosis, most commonly hepatic vein thrombosis (Budd-Chiari syndrome) and portal vein thrombosis.…”

Massive Fatal Pulmonary Embolism While on Therapeutic Heparin Drip

“…32 The most common causes of the breakthrough PE are subtherapeutic anticoagulation (incorrect dose, drug interaction, or poor adherence) or underlying disease that can cause hypercoagulability such as active cancer, 37 vasculitis (Behcet disease), 38 myeloproliferative neoplasms, 39 heparin-induced thrombocytopenia, 40 vascular malformation, 41 antiphospholipid antibody syndrome, 42 and JAK2 V617F mutation. 31,43 In our patient, inadequate anticoagulation was less likely as his aPTT was 1.5 times the control all the time (Table 2), which should significantly decrease the risk of recurrent thrombosis and prevent extension. 20,21 Heparin resistance was also less likely as the patient did not require high doses of heparin to keep his aPTT at goal.…”

Asymptomatic “breakthrough” thrombosis and anticoagulant “failure”: Keep calm and carry on

“…We do not recommend serial imaging to monitor for further progression in the absence of symptoms; while this practice is advised for some cases of untreated superficial and distal lower extremity venous thrombosis, with initiation of anticoagulation if thrombus propagates closer to the proximal deep veins, evidence is lacking for the same strategy in cases of treated proximal DVT with asymptomatic progression . As data on outcomes of symptomatic DVT progression without changes in anticoagulant therapy are scarce, we feel that these cases cannot be dismissed and that switching to an alternative anticoagulant should be strongly considered, as recommended in a recent review by Schulman et al …”