Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands.

Autor: Meier RT; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Porcelijn L; Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Sanquin, The Netherlands., Hofstede-van Egmond S; Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Sanquin, The Netherlands., Henskens YMC; Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands., Coutinho JM; Department of Neurology, Amsterdam UMC, Amsterdam, The Netherlands., Kruip MJHA; Department of Haematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Stroobants AK; Department of Clinical Chemistry, Radboud University Medical Center, Nijmegen, The Netherlands., Zwaginga JJ; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., van der Bom JG; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., van der Schoot CE; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., de Haas M; Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Sanquin, The Netherlands.; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Kapur R; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Vox sanguinis [Vox Sang] 2024 Jul; Vol. 119 (7), pp. 728-736. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1111/vox.13633
Abstrakt: Background and Objectives: Vaccine-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 Methods: We 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.
Results: We 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.
Conclusion: Our 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.
(© 2024 International Society of Blood Transfusion.)
Databáze: MEDLINE
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