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Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands.
Meier, Romy T; Porcelijn, Leendert; Hofstede-van Egmond, Suzanne; Henskens, Yvonne M C; Coutinho, Jonathan M; Kruip, Marieke J H A; Stroobants, An K; Zwaginga, Jaap J; van der Bom, Johanna G; van der Schoot, C Ellen; de Haas, Masja; Kapur, Rick.
Afiliación
  • 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.
  • Kapur R; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Vox Sang ; 119(7): 728-736, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38597072
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombocitopenia / Trombosis / Factor Plaquetario 4 / Activación Plaquetaria / Receptores de IgG / Vacunas contra la COVID-19 Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Vox Sang Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trombocitopenia / Trombosis / Factor Plaquetario 4 / Activación Plaquetaria / Receptores de IgG / Vacunas contra la COVID-19 Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Vox Sang Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido