A Therapeutic Platelet Transfusion Strategy without Routine Prophylactic Transfusion Is Feasible and Safe and Reduces Platelet Transfusion Numbers Significantly: Preliminary Analysis of a Randomized Study in Patients after High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation
Authors: Wandt Hannes , Wendelin Knut , Schaefer-Eckart Kerstin , Thalheimer Markus , Schubert Mario Stephan , Conradi Roland , Schwerdtfeger Rainer , Leimer Lothar , Kaufmann Martin , Dölken Gottfried , Klenner Anne Friederike , Schaich Markus , Ehninger Gerhard 
Published: April 2020

We performed a multicenter randomized trial comparing the traditional prophylactic platelet transfusion strategy -arm P- (trigger: morning platelet count ≤ 10/nL) with an experimental therapeutic transfusion strategy -arm T- where patients (pts) received platelet transfusions only if they experienced clinically relevant bleeding (more than petechias or minimal mucosal bleeding). The morning platelet count was no trigger in arm T for transfusion as well as fever per se. Fever was no additional risk factor for bleeding in thrombocytopenic pts treated with our therapeutic transfusion strategy as published recently. (Wandt, H et al. Bone Marrow Transplant2006; 37:387–392) For safety reasons prophylactic transfusion was recommended in arm T, however, for pts with invasive aspergillosis, sepsis syndrome and unexpected headache. Randomisation was stratified according to age (&lt;50 years), sex and center. Different diagnoses (multiple myeloma, non Hodgkin’s lymphoma, Hodgkin’s disease, acute leukemia) were well balanced between both arms. One hundred seventy one consecutive pts with a median of 56 years (19–68) who signed informed consent were included in the study. Primary objective was a reduction of platelet transfusions of 15–25%; secondary objectives were safety, duration of leuko- and thrombocytopenia, hospitalisation, and numbers of red blood cell transfusion. Red blood cells should be transfused when hemoglobin level dropped below 8 g/dL or as clinically indicated.

Results: Platelet transfusions could be reduced significantly by 27% in arm T compared with arm P (p0.004). In arm T 46% of pts did not need any platelet transfusion and this was more than the double compared to arm P (0.001). Between younger and older pts there was no difference in numbers of platelet transfusions needed. Overall, adherence to the protocol was good. Since clinically relevant bleeding (more than petechias and minimal mucosal bleeding) was the trigger for platelet transfusion in arm T consequently more such hemorrhages occured in arm T (28.7% vs 9.5%). No life threatening or fatal bleeding was registered. Hemorrhages were mainly (21.8%) epistaxis or mucosal, 6.9% were minor bleedings (e.g. vaginal, hematochezia, hemoptysis, hematuria). One pt with sudden headache had a minor cerebral hemorrhage (subarachnoid) documented by ct-scan without any clinical sequelae. Days with hemorrhage overall were rare but significantly increased in arm T (0.69 vs 0.17 days per pt). Age was no risk factor for bleeding. As already expected by our former experience we could show that fever and infection were no additional risk factor for bleeding in arm T compared with arm P despite the very stringent platelet transfusion strategy in the experimental transfusion arm. In pts with multiple myeloma bleeding events were very rare compared to other diagnoses (p &lt;0.0001). Numbers of red blood cell units were not significantly different between the two arms, as well as the duration of leukocytopenia and hospitalisation. In contrast duration of thrombocytopenia &lt;20/nL was significantly longer in arm T (median 5 vs 3 days; p 0.004) as expected.

We conclude that our therapeutic platelet transfusion strategy is cost effective and safe in pts after autologous stem cell transplantation. Despite more minor hemorrhages in the experimental arm compared with the traditional prophylactic strategy all bleeding events could be safely controlled by consecutive platelet transfusion. Development of major bleeding could be prevented by the therapeutic transfusion strategy according to our protocol.