Three Cases Highlighting Three Potential Pitfalls in the Platelet Refractory Workup

• Published in: American journal of clinical pathology 2022-11, Vol.158 (Supplement_1), p.S160-S160
• Main Authors: Attieh, M, Dent, E A, Then, C E, Barrette, E, Alter, D N, Duncan, A, Roback, J D, Sullivan, H C, Happney, L
• Format: Article
• Language: English
• Subjects: ABO system; Antibodies; Aplastic anemia; Histocompatibility antigen HLA; Histocompatibility testing; Laboratories; Patients; Platelets; Sensitivity analysis
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqac126.340

Abstract Introduction/Objective Platelet refractory (PR) patients do not achieve expected post-transfusion platelet counts. We investigate such patients with a post-transfusion platelet count, indirect Platelet Antibody Screen (ind-PAS), Class I HLA Antibody (HLA-Ab) testing, and platelet crossmatch (PXM). The following three cases highlight potential pitfalls of laboratory investigations for PR patients. Methods/Case Report Case #1 (57-year-old male with AML) revealed discrepant predicted and observed donor compatibility. Antibody testing demonstrated no platelet glycoprotein antibodies and HLA-ab to B13, corresponding to 4% calculated PRA (CPRA), indicating 96% predicted donor compatibility. However, PXM revealed that the patient was compatible with 11/14 (79%) screened donors. Communication with the reference laboratory revealed that two PXM incompatible units were ABO incompatible. Case #2 (27-year-old female with aplastic anemia) is a highly sensitized patient (99% CPRA). PXM revealed compatibility with 1/14 screened donors; however, she failed to respond to the compatible donor. To investigate this poor response, patient’s plasma was tested against HLA incompatible donors. Neat serum demonstrated compatibility with all donors, whereas 1:8 dilution resulted in positive crossmatches with half the donors. The false negative crossmatches are likely explained by prozone in the setting of high HLA-ab burden. Case #3 (79-year-old male with AML) demonstrated a discrepancy between the ind-PAS (PakPlus, Immucor), which was negative for HLA-ab, and HLA specificity testing (LABScreen, OneLambda), which revealed Class I antibodies, corresponding to 38% CPRA. Per the ind-PAS package insert, the sensitivity of the assay was 85%-91% compared to selected HLA-ab tests; other sources have demonstrated lower sensitivity of 68%. Results (if a Case Study enter NA) NA. Conclusion The three cases highlight the importance of investigating incongruent results. Cases #1 and #2 demonstrate pitfalls in the PXM: ABO incompatibility can result in positive PXM and false-negative PXM can occur in the setting of high HLA-ab burden. Case #3 reveals the importance of knowing a test’s limitation, especially sensitivity. Centers that only perform ind-PAS may miss HLA-ab detection.