Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies: A review.

INTRODUCTION: Despite high rates of venous thromboembolism (VTE) among patients with hematologic malignancies, few tools exist to assist providers in identifying those patients at highest risk for this potentially fatal complication. Laboratory biomarkers, such as d-dimer, have demonstrated utility in some clinical settings to distinguish patients at increased risk. MATERIALS AND METHODS: We performed a systematic review of the literature utilizing search terms including "biomarker", "venous thromboembolism", "hematologic malignancy", "lymphoma", "myeloma" and "leukemia" in the Medline database. A total of 25 studies investigating laboratory biomarkers of increased thrombotic risk in the setting of hematologic malignancy were identified and included in this review. RESULTS AND CONCLUSIONS: The most studied biomarkers, d-dimer and fibrinogen, demonstrated some degree of efficacy in identifying high-risk patients at levels >4.0 mg/L or <1.0 g/L respectively. Additional markers which demonstrated promise included thrombin generation, mean platelet volume, soluble VEGF, soluble P-selectin and extracellular vesicles. Other biomarkers reviewed, which did not consistently demonstrate significant associations with VTE included prothrombin fragments F1 + 2, factor VIII, protein C, protein S, von Willebrand antigen and activity, antithrombin, thrombin antithrombin complex, antiphospholopid antibody, plasminogen activator inhibitor, tissue factor pathway inhibitor and several variants associated with known hypercoagulable states (factor V Leiden, prothrombin gene variant, methylenetetrahydrofolate reductase variant). Data to support any of the biomarkers discussed here in routine clinical decision-making are currently lacking, but additional investigation in clinical studies, ideally in combination with clinical factors known to be associated with increased thrombotic risk, is warranted.

Patients treated for acute VTE during periods of treatment-related thrombocytopenia have high rates of recurrent thrombosis and transfusion-related adverse outcomes.

Venous thromboembolism (VTE) is a common complication of hematologic malignancies. Prolonged periods of thrombocytopenia are experienced universally by patients undergoing treatment for these diseases, yet data to guide management of anticoagulation in this setting are lacking. To obtain data on the management and outcomes of VTE in patients with thrombocytopenia related to the treatment of hematologic malignancies. This was an observational cohort study of patients experiencing VTE during periods of treatment-related thrombocytopenia over a 5-year period at the Fred Hutchinson Cancer Research Center. Medical records were reviewed for diagnostic, treatment and outcomes data, including bleeding events (categorized by WHO criteria) and progression or recurrence of VTE. Eighty-two patients meeting inclusion criteria were identified. Forty-eight percent were male and the median age was 55. Sixty-seven patients received anticoagulation, 88% of these were managed with transfusion support for a platelet goal of 50 × 109/L. Thirty-one patients experienced bleeding events, 22 of which were grade 2 and nine of which were grade 3/4. The median platelet count at the time of bleeding event was 54 × 109/L. Seven patients experienced progression of thrombosis and/or recurrence. Eleven patients experienced transfusion reactions and 30 experienced volume overload requiring diuretics or dialysis. While bleeding events were not uncommon, the majority of events were non-major/non-clinically relevant. Most bleeding events occurred while the platelet count was within the 'goal' range of ≥50 × 109/L, and many patients experienced transfusion related adverse events. Prospective studies are urgently needed to identify the optimal transfusion strategy for these patients.