Principal Investigator: James George, MD

Abstract:

As platelet use continues to increase at a rate disproportionately higher than that of red cells, it is important to identify the most cost-effective strategies for providing platelet support.  Identification and implementation of the most safe and cost effective strategies for providing platelet support is crucial for effective disease management without depleting platelet supplies.

The two most important factors within the control of the ordering physician that will significantly influence the total amount of platelets transfused are:

1) the prophylactic platelet transfusion trigger selected for transfusion; and

2) the number of platelets given per transfusion. 

Informative clinical data have been provided in the last fifteen years concerning the platelet transfusion trigger. The optimal quantity of platelets to be used per transfusion remains a highly controversial subject. To date, no prospective platelet transfusion trials have been performed in which patients are randomized to an assigned platelet dose throughout their period of thrombocytopenia to evaluate the effects of different doses on transfusion outcomes.  There may be safety issues associated with different dosing strategies for platelet therapy.

Maintaining a higher platelet count for a greater percentage of the time with higher dose platelet transfusion therapy might provide better hemostasis than lower dose therapy. On the other hand, trigger study data suggest that there may be no hemostatistically-related safety issues based on the dose of platelets transfused as long as a baseline level of > 5,000 platelets is maintained.  This study will investigate the safety of three different dosing strategies for inpatients with thrombocytopenia related to stem cell transplants or chemotherapy. The primary endpoint is the percentage of patients in each treatment arm who have at least one day with Grade 2 or higher bleeding. The most important secondary endpoints, capturing key data on costs and safety, are the total number of platelets dispensed, the total number of transfusion events, the highest grade of bleeding, and the bleeding severity score (if such a score has been validated and published by the end of the Platelet Dose trial, and the necessary information to calculate the score was collected). The results of this trial could have a major effect on standard medical practice.  The Platelet Dose Trial is a multi-site trial that will enroll 1350 patients in the United States.  Patients will be randomized with equal allocation to three platelet transfusion therapy groups based on body surface area (BSA):

Lower dose: 1.1 x 1011/m2 (half of the medium dose)

Medium dose: 2.2 x 1011/m2

Higher dose: 4.4 x 1011/m2 (twice the medium dose)

An acceptable dose will be a dose that is within a range of 25% either above or below the target dose. Patients will be prophylactically transfused at their assigned dose for morning platelet counts of <10,000/ul. If the post-transfusion platelet count is not <10,000/ul the physician will be allowed to order another platelet transfusion but is not required to do so. The protocol allows for additional platelets in the case of invasive procedures or active bleeding.  Assessment of bleeding by study personnel will be performed daily by means of physical assessment of the patient, patient interview and review of patient chart and laboratory data. The actual assignment of the bleeding grades will occur at the Data Coordinating Center by a computerized algorithm programmed to evaluate the data from the case report forms, plus adjudication of death due to bleeding.

Participant Inclusion Criteria:

1. Patients with, or expected to have, hypoproliferative thrombocytopenia who are expected to have a platelet count of < 10,000 ul for > 5 days, and be in the hospital for > 5 days.

2. Weight between 10 and 135 kilograms.

3. Patients whose PT/INR, PTT and fibrinogen assays, measured within 72 hours before study entry, are as follows:

a) PT < 1.3 X upper limit of normal for the laboratory

b) PTT < 1.3 X upper limit of normal for the laboratory

c) Fibrinogen > 100mg/dL

4. Patients with any diagnosis undergoing or with completed hematopoietic stem cell transplantation, and patients with a diagnosis of acute or chronic leukemia, non-Hodgkins and Hodgkins lymphoma, myeloma, myelodysplasia, or non-hematologic malignancy undergoing or with completed chemotherapy.

5. During this hospitalization, the patient has not yet received any platelet transfusions related to the current or planned course of therapy. Individual platelet transfusions given prior to the study and unrelated to thrombocytopenia will not exclude the patient.

Participant Compensation:

No

Contact Information:

Dee Terrell (405) 271-4222 Ext 48386 or E-mail dee-terrell@ouhsc.edu