Many patients with hematologic malignancies develop dangerously low platelet counts due to their disease, their treatment, or both. To mitigate the risk of bleeding, such patients have historically received prophylactic platelet transfusions. Recently, however, the value of this practice has been called into question. Does it really help to give platelets on a preventative basis? Or is it sufficient to provide therapeutic transfusions when bleeding occurs?
Stanworth et al.sought to answer this question by conducting a randomized controlled trial of 600 patients with hematologic malignancies who were thrombocytopenic (platelet count <50×109/L) or expected to become thrombocytopenic. Half were randomized to receive prophylactic platelet transfusions if the platelet count fell below a threshold of 10×109/L, while the other half received no prophylaxis. The primary outcome was the percentage of patients who developed World Health Organization (WHO) grade 2-4 bleeding within 30 days, where grade 2 is defined as moderate bleeding (transfusion not acutely needed), grade 3 is severe (transfusion required within 24 hours), and grade 4 is life-threatening.
Fewer transfusions per patient were performed in the no-prophylaxis arm as compared to the prophylaxis arm (1.7 versus3.0 transfusions [SD 3.2]). However, the study failed to show that a “no prophylaxis” strategy was non-inferior to the accepted practice of prophylactic transfusions. WHO grade 2-4 bleeding occurred in 50% of patients in the no-prophylaxis group, as compared to 43% of patients in the prophylaxis group. In other words, prophylactic transfusions reduced the proportion of patients with bleeding by 7%.
More patients in the no-prophylaxis group developed grade 3-4 bleeding, although this difference was not statistically significant. Patients in the no-prophylaxis group experienced longer bleeding durations and shorter times to the first bleed.
The investigators also performed a sub-group analysis for patients who had undergone autologous stem cell transplants (auto SCT) as treatment for their malignancy. In previous studies, auto SCT patients who were assigned to the no-prophylaxis group experienced higher rates of bleeding as compared to those who received prophylaxis. In this study, however, no significant difference was found in bleeding rate between the groups.
In an accompanying editorial, Sherrill J. Slichter, M.D., of the University of Washington School of Medicine writes: “[T]he reduction in the use of platelet transfusions does not justify subjecting patients to the increased bleeding risks associated with a therapeutic-only platelet-transfusion strategy in any category of patients with hypoproliferative thrombocytopenia.”
NEJM Deputy Editor Dan Longo, M.D., states: “Prophylactic platelet transfusions do not fulfill Benjamin Franklin’s famous aphorism that an ounce of prevention is worth a pound of cure, but they are sufficiently beneficial that their standard use seems warranted in patients with platelet counts of 10,000/microliter or less.”
This study offered the benefit of a clinically relevant primary outcome. Bleeding rates, more than units transfused, capture the impact of prophylaxis or lack of prophylaxis on health. Does prophylaxis actually benefit patients who face the risk of thrombocytopenia? At least based on these results, the answer is yes, and prophylactic transfusions should continue to be used.
How do you manage the risk of bleeding in patients with hematologic malignancy and thrombocytopenia? Does your approach differ for patients who pursue auto SCT versus other treatments for their malignancy?