Context.—

The blood bank is often consulted for transfusion support of patients with suspected platelet transfusion refractoriness (PTR). The workup is complex because testing includes specialized assays that are uncommonly ordered with limited availability. Add to this the variety of possible products—crossmatched platelets, human leukocyte antigen (HLA)–matched platelets, HLA antigen–negative platelets—and the approach to PTR can be overwhelming. Moreover, most literature on the subject is published in transfusion medicine journals aimed at transfusion medicine physicians and blood bank specialists in academic settings. Resources tailored to community hospital blood banks are lacking.

Objective.—

To provide pathologists who may not have subspecialized training in transfusion medicine and who direct blood banks algorithmic workflows based on clinical scenario and test availability to provide appropriate transfusion support for patients with PTR.

Data Sources.—

This review is a comprehensive overview of terminology, HLA testing procedures, interpretations, and practical recommendations for managing PTR in various scenarios based on expert opinion as well as relevant medical literature published from 2007 to 2022.

Conclusions.—

Consultation on PTR is complicated and encompasses many clinical and laboratory aspects. The lack of guidelines derived from high-quality prospective studies poses challenges in the workup and management of PTR. Hindering the process further are limited test availability, unfamiliarity with the technical assays, and the various specialized platelet products. The clinical evaluation algorithm presented herein along with the workflow pathways offer pathologists user-friendly and best-practice guidelines with different options based on the clinical scenario and the tests available.

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Author notes

Gammon serves on the Patient Blood Management Advisory Board at CSL Behring. The other authors have no relevant financial interest in the products or companies described in this article.