Platelet transfusion for patients with platelet dysfunction: effectiveness, mechanisms, and unanswered questions

Abstract

Purpose of review In this review, we discuss current clinical guidelines and potential underlying mechanisms regarding platelet transfusion therapy in patients at risk of bleeding, comparing management of patients with thrombocytopenia versus those with qualitative platelet disorders. Recent findings Platelet transfusion therapy is highly effective in managing bleeding in patients with hypoproliferative thrombocytopenia. Clinical trials have demonstrated that platelet transfusion can be used at a lower trigger threshold and reduced platelet doses, and may be used therapeutically rather than prophylactically in some situations, although additional data are needed. In patients with inherited platelet disorders such as Glanzmann's Thrombasthenia or those with RASGRP2 mutations, platelet transfusion may be ineffective because of competition between transfused and endogenous platelets at the site of vascular injury. Successful management of these patients may require transfusion of additional platelet units, or mechanism-driven combination therapy with other pro-hemostatic agents. In patients on antiplatelet therapy, timing of transfusion and inhibitor mechanism-of-action are key in determining therapeutic success. Summary Expanding our understanding of the mechanisms by which transfused platelets exert their pro-hemostatic function in various bleeding disorders will improve the appropriate use of platelet transfusion.

Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia

“…AFs are usually contraindicated in the presence of hematuria [13,32]. rFVIIa, is a potent coagulation-enhancing treatment, that acts to amplify thrombin generation on the platelet surface, driving the formation of fibrin to improve platelet plug stability [29]. rFVIIa is approved for Glanzmann Thrombasthenia (GT) patients that have become alloimmunized and/or refractory to platelet transfusion.…”

“…Desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) is used for managing bleeding episodes in patients with platelet function disorders and mild bleeding symptoms [ 29 , 30 , 31 ]. Since not all patients respond, a test dose is recommended to identify those who may benefit from receiving this agent for future spontaneous bleeding episodes.…”

“…rFVIIa is approved for Glanzmann Thrombasthenia (GT) patients that have become alloimmunized and/or refractory to platelet transfusion. It has also been successfully used in BDPLT18 patients (GT-like or RASGRP2-RD) failing to respond to platelet transfusion [ 29 , 34 , 35 ]. Patients lacking the expression of specific GPs, such as GT or BSS are at higher risk of alloimmunization.…”

“…Platelet transfusion is a standard therapy to prevent or treat bleeding in thrombocytopenic patients, ( Figure 2 ) [ 29 ]. The goal of platelet transfusion is to increase the number of healthy circulating platelets.…”

UV light-emitting diode (UV-LED) at 265 nm as a potential light source for disinfecting human platelet concentrates

“…Platelets play a central role in stopping bleeding under either low or high flow rate conditions through surface molecules including glycoproteins, such as GPIb/IX/V (CD42) and GPIIb/IIIa (CD41/CD61), and released molecules in platelet granules, which activate the surrounding platelets. Platelet concentrates (PCs) are commonly transfused to stop bleeding in thrombocytopenia patients who have active bleeding and are also used prophylactically for patients receiving chemotherapy [1][2][3]. PCs are usually stored at room temperature (20-24˚C) with continuous agitation; however, this storage condition allows any contaminating bacteria to proliferate quickly.…”