Blood Platelets Are Circulating Stores for Adhesive Proteins, Inflammatory Mediators, and Immunoglobulins – Role in Nonhemolytic Transfusion Reactions

Abstract

Objective: Blood platelets store within their α-granules a variety of substances that are involved in blood clotting, inflammation, and repair processes after a lesion of the vessel wall. Not all of these substances are synthesized within the megakaryocytes or platelets themselves, but some of them are taken up from the blood plasma by the circulating platelet. This article summarizes recent investigations on the internalization capabilities of platelets and the mechanism of endocytosis. Results: By means of immunoelectron microscopy and by incubations with gold-labeled peptides the uptake of fibrinogen, IgG, IgE, and the chemokine RANTES by the platelet can be demonstrated. Two different mechanisms of internalization are discerned: In resting platelets, the gold-labeled peptides are endocytosed and transferred to α-granules, whereas in platelets stimulated by ADP or thrombin the gold particles appear within the open canalicular system and not within granules. Conclusion: Platelets store and release not only proinflammatory mediators that are typical for the megakaryocyte-platelet lineage, but also blood-borne substances from other cellular sources. Due to activation and disintegration of platelets that are stored as concentrates for usage in transfusion medicine, these substances can accumulate in the platelet concentrate and might be responsible for transfusion-associated reactions. Further investigation in this field of platelet immunobiology is warranted.

Routine Automated Laboratory Methods Are Inadequate to Determine the Number of Platelets in Blood Salvaged and Processed for Autotransfusion

“…These showed a high expression of CD62 (P-selectin) and a high number of plateletderived microvesicles, indicating platelet activation. Showing platelet activation in the salvaged and processed blood, both studies indicate that the platelets contained may be detrimental rather than beneficial for the patient after transfusion since they may have a potential of inducing intravascular coagulation and systemic reactions to inflammatory mediators [1].…”

“…Various parameters are used to determine the quality of the product obtained: e.g. the content of platelets [1]. Great discrepancies between the platelet counts obtained by automated blood count devices and either microscopic or flow-cytometric methods were found in unwashed shed mediastinal blood [2,3].…”

An association of soluble CD40 ligand (CD154) with adverse reactions to platelet transfusions

“…The pathogenesis of reactions to PLT transfusion is incompletely understood 1‐3 12 . Traditional theory is that febrile reactions are due to donor white cells (WBCs) interacting with recipient antibody.…”

“…We hypothesized that PLT‐derived mediators cause some reactions seen in patients transfused with PLTs. PLTs are now known to be involved in inflammation and host defense, as well as their previously identified role in hemostasis 12,14 . Thus PLTs can be considered to possess functions similar to those of WBCs to some degree.…”

“…The pathogenesis of reactions to PLT transfusion is incompletely understood. [1][2][3]12 Traditional theory is that febrile reactions are due to donor white cells (WBCs) interacting with recipient antibody. Allergic reactions are thought to be caused by transfusion of donor allergens or soluble substances such as polymorphic plasma proteins to which the recipient is allosensitized.…”