There and back again: the once and current developments in donor-derived platelet products for hemostatic therapy

Abstract

More than 100 years ago, Duke transfused whole blood to a patient with thrombocytopenia to raise the platelet count and prevent bleeding. Since then, platelet transfusions have undergone numerous modifications from whole blood-derived platelet-rich plasma to apheresis-derived platelet concentrates. The storage time and temperature have also changed. The mandate to store platelets for a maximum of 5 to 7 days at room temperature has been challenged by recent clinical trial data, ongoing difficulties with transfusion-transmitted infections, and recurring periods of shortages that were further exacerbated by the COVID-19 pandemic. Alternative platelet storage approaches are as old as the first platelet transfusions. Cold-stored platelets may offer increased storage times (days) and improved hemostatic potential at the expense of reduced circulation time. Frozen (cryopreserved) platelets extend the storage time to years but require storage at -80°C and thawing before transfusion. Lyophilized platelets can be powder-stored for years at room temperature and reconstituted within minutes in sterile water but are probably the least explored alternative platelet product to date. Finally, whole blood offers the hemostatic spectrum of all blood components but has challenges such as ABO incompatibility. We know more than ever before about the in vitro properties of these products, and clinical trial data are accumulating. The purpose of this review is to summarize the findings of recent preclinical and clinical studies on alternative, donor-derived platelet products.

Graphical abstract

Figure 1.

Refrigeration-induced phenotypic and functional changes in platelets associated with clearance. (A) Platelets circulate at 37°C (body core temperature). (B) Exposure to RT results in low-level activation with intracellular calcium release and integrin activation. (C) Further decreasing the temperature to 1°C to 6°C leads to shape change, increase in calcium concentration, and specific clearance mechanisms via αMβ1 on liver macrophages and VWF. (D) Extended storage leads to aggregate formation, clearance by the hepatic Ashwell-Morell receptor (AMR), loss of GPVI and other glycoproteins, phosphatidylserine (PS) exposure, and α-degranulation. MP, microparticles. Figure 1 was created at BioRender.com.