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. 2024 Jul;119(7):728-736.
doi: 10.1111/vox.13633. Epub 2024 Apr 10.

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

Romy T Meier  1 , Leendert Porcelijn  2 , Suzanne Hofstede-van Egmond  2 , Yvonne M C Henskens  3 , Jonathan M Coutinho  4 , Marieke J H A Kruip  5 , An K Stroobants  6 , Jaap J Zwaginga  7 , Johanna G van der Bom  8 , C Ellen van der Schoot  1 , Masja de Haas  2   7 , Rick Kapur  1
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Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands

Romy T Meier et al. Vox Sang. 2024 Jul.

Abstract

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.

Keywords: COVID‐19; platelet factor 4; thrombocytopenia; thrombosis; vaccination.

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