Dose of prophylactic platelet transfusions and prevention of hemorrhage

Abstract

Background: We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia.

Methods: We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria).

Results: In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001).

Conclusions: Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.)

Figure 1. Days with Bleeding of Grade 2 or Higher in All three Treatment Groups, According to Morning Platelet-Count Categories

The percentage of days on which patients had bleeding of grade 2 or higher is shown, along with the associated 95% confidence intervals (dashed lines), according to the morning platelet-count category. Data are based on the 24,309 days during the study period on which patients had both a morning platelet count and information on bleeding of grade 2 or higher. Each patient-day was treated as a separate unit of analysis. Analyses were adjusted to take into account that for each patient, the results on various days may be correlated. The interaction between treatment group and morning platelet-count category was not significant, indicating that the effect of the morning platelet-count category did not differ significantly among the three treatment groups; therefore, the data from all three groups are combined.