The fear of catastrophic hemorrhage during severe hypoproliferative thrombocytopenia compels physicians to act preemptively with prophylactic platelet transfusions. Without additional risk factors, spontaneous bleeding increases significantly at platelet counts < 5 x 109/L. The current accepted prophylactic platelet transfusion trigger of ≤ 10 x 109/L derives from multiple randomized, prospective platelet transfusion trials and reflects the use of standardized platelet concentrate doses (3 x 1011 to 6 x 1011 platelets for adults).1 To meet the increasing demand for donor platelets in an era of dwindling supply, there is great interest in defining a minimum, safe prophylactic platelet dose that is also cost-effective. One recent study to determine whether low-dose products might provide equivalent safety as standard-dose products (the SToP trial) was prematurely closed after enrolling only 130 patients when > 5 percent absolute difference in WHO grade 4 bleeds occurred in the lower-dose arm.2
The platelet dose (PLADO) trial reported by Slichter et al. for the Transfusion Medicine/Hemostasis Clinical Trials Network prospectively evaluated 1,351 pediatric and adult patients (body weights 10-135 kg) with chemotherapy-induced hypoproliferative thrombocytopenia. Patients were randomized to receive low-, medium-, or high-dose products (1.1 x 1011, 2.2 x 1011, or 4.4 x 1011 platelets/M2 BSA, respectively) when their morning platelet count was ≤ 10 x 109/L. Among the 1,272 evaluable patients, the primary endpoint of WHO grade 2 or higher bleeding was not significantly different between the three groups (71 percent, 69 percent, and 70 percent, respectively), nor were there differences for the highest grade of bleeding. However, the total number of platelets transfused (9.25 x 1011, 11.25 x 1011, and 19.63 x 1011, respectively) and the median number of transfusion events (five in the low-dose group and three in the other two) were significantly different. The median post-transfusion platelet counts were 22 x 109/L, 34 x 109/L, and 50 x 109/L, respectively, while the median number of days until the next transfusion were 1.1, 1.9, and 2.9, respectively. Physician-initiated change to higher-dose product occurred more commonly in low-dose patients.
In Brief
What are the key findings of the PLADO trial, and should these results change transfusion practice? This large and carefully performed study refutes the safety concerns raised by the SToP trial and suggests that relatively few transfused platelets can maintain vascular hemostatic integrity and prevent clinically relevant bleeding. From a clinical and resource perspective, lower overall platelet requirements should translate into less donor exposures (when pooled products are used) and increased platelet inventories. However, cost-benefit analyses are eagerly awaited, since gains in product availability may be offset by greater administration and nursing costs, as suggested by an economic study of a smaller platelet dosing trial. Moreover, providing customized, body surface area-based platelet products will present technical challenges. Thus, implementation of a low-dose transfusion policy must be guided by further economic and logistical review of the PLADO data. Concurrent with these efforts, an ongoing, randomized controlled trial of prophylactic versus no-prophylactic platelet transfusions (the TOPPS trial) should yield valuable insights into whether therapeutic, rather than prophylactic, transfusions can be a safe and efficient practice for some patients.1
References
Competing Interests
Drs. Shenoi and Linenberger indicated no relevant conflicts of interest.
