Increased complement activation during platelet storage

It has been shown that platelet transfusion carries a higher incidence of transfusion-related adverse events than any other blood components, and prolonged platelet storage is associated with more transfusion reactions, most of which are considered to be inflammatory responses. However, the role of complement, which has very important proinflammatory activities, in the pathogenesis of platelet-related adverse events has not been fully understood.

Three units of platelets collected by apheresis were stored on a platelet rotator with the temperature controlled between 22 and 24°C. Plasma samples were obtained using a sterile technique on Days 2 through 7. Complement components were assayed to evaluate the activation of complement activation and included C4d (classical pathway), Factor Bb (alternative pathway), C3a (common pathway), C5a (terminal pathway), and C5b-9 (terminal pathway).

Both C4d and C3a were elevated on the first day of testing (Day 2) compared with the established normal ranges and continued to increase over time in storage. In contrast, Factor Bb levels remained stable and were within the normal range over time. Over a span of 7 days in storage, the terminal complement factors C5a and C5b-9 were also significantly increased, although the magnitude of increases was not as striking as those in C4d and C3a levels.

Our results demonstrate that substantial complement activation occurs in platelets under standard storage conditions, and this activation increases with the duration of storage. After transfusion, these activated complement components might result in accelerated complement activation in recipients, leading to transfusion-related adverse events.