Thrombocytopenia and bleeding in myelosuppressed transfusion-dependent patients: a simulation study exploring underlying mechanisms

BACKGROUND: Hematology–oncology patients often become severely thrombocytopenic and receive prophylactic platelet transfusions when their platelet count drops below 10×10(9) platelets/L. This so-called “platelet count trigger” of 10×10(9) platelets/L is recommended because currently available evidence suggests this is the critical concentration at which bleeding risk starts to increase. Yet, exposure time and lag time may have biased the results of studies on the association between platelet counts and bleeding risks. METHODS: We performed simulation studies to examine possible effects of exposure time and lag time on the findings of both randomized trials and observational data. RESULTS: Exposure time and lag time reduced or even reversed the association between the risk of clinically relevant bleeding and platelet counts. The frequency of platelet count measurements influenced the observed bleeding risk at a given platelet count trigger. A transfusion trigger of 10×10(9) platelets/L resulted in a severely distorted association, which closely resembled the association reported in the literature. At triggers of 0, 5, 10, and 20×10(9) platelets/L the observed percentages of patients experiencing bleeding were 18, 19, 19, and 18%. A trigger of 30×10(9) platelets/L showed an observed bleeding risk of 16% and triggers of 40 and 50×10(9) platelets/L both resulted in observed bleeding risks of 13%. CONCLUSION: The results from our simulation study show how minimal exposure times and lag times may have influenced the results from previous studies on platelet counts, transfusion strategies, and bleeding risk and caution against the generally recommended universal trigger of 10×10(9) platelets/L.