Platelet transfusions: impact on hemostasis, thrombosis, inflammation and clinical outcomes

Abstract

Platelet transfusion is one of the most crucial therapeutic approaches in Medicine. However, severe and fatal adverse reactions may develop. In addition to their important function in hemostasis, platelets' role in inflammation has become more evident. Recently, platelets are also recognized as the main source of circulating soluble CD40 ligand (sCD40L, (CD154)), which plays significant roles in hemostasis, platelet activation, clot stability, interactions with other cells, and upregulation of different mediators. In this review, we will briefly highlight the importance of platelet transfusion, its role in inflammatory and thrombotic transfusion reactions, and visit the most recent findings on sCD40L.

Figure 1

Panel A: The concentration of sCD40L in the storage supernatant of washed platelets prepared for transfusion is greatest at 3 or 4 days of storage. Soluble CD40L was measured by standard sandwich ELISA. Panels B and C: Human lung fibroblasts were stimulated with medium (unstimulated), PCS (platelet concentrate supernatant) or CD40L-depleted PCS. After 24 hours, the medium was analyzed for PGE₂ and IL-6 content. Unstimulated cells produced low levels of PGE₂ and IL-6, while PCS caused great amounts of these mediators to be produced by the fibroblasts. These high levels of production were reduced when CD40L was neutralized in the PCS via an anti-CD40L antibody. Mean +/− SEM, n = 9, * p < 0.001 PCS vs. Unstimulated, ** p < 0.001 PCS + anti-CD40L vs. PCS alone. (Reprint permission granted by Blumberg et al. and Springer Science + Business Media [43].)

Figure 2

Washed transfusions are associated with improved survival in leukemia patients. A Kaplan-Meier plot of survival of 118 consecutive adult patients (ages 18–80) treated with curative intent for acute leukemia is shown according to whether patients received washed versus unwashed transfusions during their entire course. Patients receiving washed transfusions had significantly better survival, even after adjusting for other prognostic factors by proportional hazards analysis. (Reprint permission granted by Blumberg et al. and Springer Science + Business Media [43].)

Figure 3

CD40L concentration in platelet concentrates is associated with transfusion-related acute lung injury (TRALI). Higher levels of CD40L in platelet transfusions implicated in cases of TRALI as opposed to non-implicated control platelet transfusions. (Reprint permission granted by Blumberg et al. and Springer Science + Business Media [43].)