STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis

The current proposal is for the pilot trial to assess feasibility of a full-scale RCT. To determine feasibility, the pilot and the full-scale trials will use the same recruitment strategy, inclusion/exclusion criteria, interventions, follow up duration, and measurement/adjudication of clinical outcomes. If the pilot trial finds that the full-scale trial is feasible, and no changes to the study design are indicated, the data from the pilot trial will be included in the full-scale trial, which will be efficient and reduce the recruitment time and costs of the full-scale trial.

The START trial is a multi-centre RCT with prospective, open-label, blind-evaluator (PROBE) design. Adult patients with acute cancer-associated thrombosis (diagnosed within 14 days) and thrombocytopenia (platelet count < 50,000/µL) secondary to cancer therapy or cancer itself will be randomized 1:1 to modified dose LMWH or higher dose LMWH with platelet transfusion support, to evaluate the superiority of a modified dose LMWH strategy in reducing clinically relevant bleeding events compared to full dose LMWH with platelet transfusion. The PROBE design is an efficient use of research funds while maintaining the benefits of randomization and blinded evaluation of endpoints.

Inclusion criteria

• Adult patients (age ≥ 18) with active malignancy (malignancy diagnosed or treated within the previous 6 months, or progressive/relapsed);
• Objectively confirmed VTE within last 14 days for which therapeutic anticoagulation is planned;
• Thrombocytopenia with a platelet count < 50,000/uL from cancer therapy or malignancy itself;
• Able to provide written informed consent

Exclusion criteria

• Receipt of anticoagulant for index VTE with platelet count < 50,000/uL for > 72 hours;
• Superficial vein thrombosis only;
• Life expectancy < 1 month (as judged by the treating physicians);
• Creatinine clearance < 30 ml/min;
• Contraindication to LMWH such as a history of heparin induced thrombocytopenia;
• Thrombocytopenia from other causes, such as thrombotic microangiopathy, immune thrombocytopenia, disseminated intravascular coagulation;
• Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies;
• Refusal of blood products;
• Anticoagulation at any dose is deemed unsafe (i.e. active bleeding or bleeding disorders)