Laboratory approach for vaccine‐induced thrombotic thrombocytopenia diagnosis in the Netherlands

Author:

Meier Romy T.1,Porcelijn Leendert2,Hofstede‐van Egmond Suzanne2,Henskens Yvonne M. C.3,Coutinho Jonathan M.4,Kruip Marieke J. H. A.5,Stroobants An K.6,Zwaginga Jaap J.7,van der Bom Johanna G.8,van der Schoot C. Ellen1ORCID,de Haas Masja27ORCID,Kapur Rick1ORCID

Affiliation:

1. Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam Amsterdam The Netherlands

2. Department of Immunohematology Diagnostics Sanquin Diagnostic Services Sanquin The Netherlands

3. Central Diagnostic Laboratory Maastricht University Medical Centre Maastricht The Netherlands

4. Department of Neurology Amsterdam UMC Amsterdam The Netherlands

5. Department of Haematology Erasmus University Medical Center Rotterdam The Netherlands

6. Department of Clinical Chemistry Radboud University Medical Center Nijmegen The Netherlands

7. Department of Hematology Leiden University Medical Center Leiden The Netherlands

8. Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands

Abstract

AbstractBackground and ObjectivesVaccine‐induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID‐19 vaccination. VITT pathophysiology is not fully unravelled but shows similarities to heparin‐induced thrombocytopenia (HIT). HIT is characterized by the presence of antibodies against platelet factor 4 (PF4)/heparin complex, which can activate platelets in an FcγRIIa‐dependent manner, whereas IgG‐antibodies directed against PF4 play an important role in VITT.Materials and MethodsWe characterized all clinically suspected VITT cases in the Netherlands from a diagnostic perspective and hypothesized that patients who developed both thrombocytopenia and thrombosis display underlying mechanisms similar to those in HIT. We conducted an anti‐PF4 ELISA and a functional PF4‐induced platelet activation assay (PIPAA) with and without blocking the platelet‐FcγRIIa and found positivity in both tests, suggesting VITT with mechanisms similar to those in VITT.ResultsWe identified 65 patients with both thrombocytopenia and thrombosis among 275 clinically suspected VITT cases. Of these 65 patients, 14 (22%) tested positive for anti‐PF4 and PF4‐dependent platelet activation. The essential role of platelet‐FcγRIIa in VITT with mechanisms similar to those in HIT was evident, as platelet activation was inhibited by an FcγRIIa‐blocking antibody in all 14 patients.ConclusionOur study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti‐PF4‐inducing, FcɣRIIa‐dependent platelet activation, suggesting an HIT‐like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (‘non‐HIT like’) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.

Publisher

Wiley

Reference41 articles.

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1. Ad26.COV2-S/Elasomeran/Tozinameran;Reactions Weekly;2024-09-07

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