Optimal Platelet Dose Strategy for Management of Thrombocytopenia

BACKGROUND: It is important to identify the safest and most cost effective strategies for providing platelet support that will achieve effective disease management without depleting platelet supplies. Informative clinical data have been provided concerning the platelet transfusion trigger. In contrast, the optimal quantity of platelets to be used per transfusion remains a highly controversial subject. No prospective platelet transfusion studies have been performed in which patients are randomized to an assigned platelet dose throughout their period of thrombocytopenia. DESIGN NARRATIVE: After obtaining consent and verifying eligibility requirements, the patients will be randomized to one of three doses for prophylactic platelet transfusions (lower, medium, or higher dose). The dosage is based on the patient's body surface area (BSA). The dose targets are as follows: 1) the lower dose is 1.1 x 10\^11/m²; 2) the medium dose is 2.2 x 10\^11/m²; and 3) the higher dose is 4.4 x 10\^11/m². A dose within 25% of this value in either direction is considered to be in the target range. For many adult patients, the typical dose of one unit of apheresis platelets would fall in the target range for the medium dose. All prophylactic transfusions provided while the patient is in the study will be given according to the randomized target dose range. Only blood bank staff, not clinical staff, will have access to the target dose range for each patient. The patient's morning platelet count will be taken every day. If this value is less than or equal to 10,000, a prophylactic platelet transfusion will be given. Otherwise, no prophylactic platelet transfusion will be given that day. Platelet transfusions may be given at any time, and at any dose, to treat active bleeding or in association with an invasive procedure. A hemostatic assessment will be carried out every day to identify any bleeding the patient may experience. This assessment involves a patient interview, physical assessment, and a chart review. Data on all transfusions (e.g., platelets and red blood cells), all transfusion-related events, all serious adverse events, and protocol deviations will also be recorded. Patients will participate in the study either until 30 days after the initial platelet transfusion, until they have not received a platelet transfusion for 10 days after the most recent platelet transfusion, or until hospital discharge (whichever comes first). Each of the three pairwise dose comparisons is of interest. Therefore, the primary and secondary endpoints will be analyzed using three separate pairwise comparisons, each at the 0.017 significance level to adjust for multiple comparisons. This study has been approved by the National Heart, Lung, and Blood Institute (NHLBI)-appointed protocol review committee and data and safety monitoring board (DSMB), and each participating institution's institutional review board. An interim monitoring plan was developed by the protocol team and DSMB, and is described in the protocol. The study is being monitored in accordance with this plan.