DAMPS and complement activation in platelet concentrates that induce adverse reactions in patients.

Abstract

Patients with severe thrombocytopenia due to bone marrow failure and after chemotherapy are still treated with platelet transfusions. Platelet concentrates (PC) are associated with a high incidence of adverse reactions (AR). Platelet-derived damage-associated molecular patterns (DAMPS) and complement were proposed to play a role in the pathology of AR. Single donor apheresis platelet concentrates (SDA PCs) were produced in a regional setting of the French Blood Establishment. After transfusion samples were collected from PC and possible AR in patients were recorded. Platelet activation markers, High mobility group box 1 (HMGB1) and complement activation products (CAP) were measured. The correlation between platelet activation, and HMGB1 and complement activation was analyzed. A total of 56 PC were included in the study. 30 PC induced no AR, and 26 induced AR (Febrile non-hemolytic transfusion reaction n= 16; Atypical Allergic Transfusion Reactions n= 11; hemodynamic instability n= 5) in the patients. The levels of P-selectin, sCD40L, HMGB1, C3b/c, and C4b/c were all significantly increased in PC that induced AR following transfusion in patients. Additionally, HMGB1, C3b/c, and C4b/c were positively correlated with P-selectin and sCD40L. In this study, we observed an association between HMGB1 and CAP and the incidence of AR. Furthermore, we demonstrated that both HMGB1 and complement activation were correlated to platelet activation.