Vaccine-induced immune thrombotic thrombocytopenia: current evidence, potential mechanisms, clinical implications, and future directions

Benjamin Marchandot; Anais Curtiaud; Antonin Trimaille; Laurent Sattler; Lelia Grunebaum; Olivier Morel

doi:10.1093/ehjopen/oeab014

Vaccine-induced immune thrombotic thrombocytopenia: current evidence, potential mechanisms, clinical implications, and future directions

Eur Heart J Open. 2021 Aug 2;1(2):oeab014. doi: 10.1093/ehjopen/oeab014. eCollection 2021 Sep.

Authors

Benjamin Marchandot¹, Anais Curtiaud¹, Antonin Trimaille^{1

2}, Laurent Sattler³, Lelia Grunebaum³, Olivier Morel^{1

2}

Affiliations

¹ Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, Strasbourg 67000, France.
² INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg 67000, France.
³ Haematology and Haemostasis Laboratory, Centre for Thrombosis and Haemostasis, Nouvel Hôpital Civil, Strasbourg University Hospital, 1 place de l'Hôpital, Strasbourg 67000, France.

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) (also termed thrombosis with thrombocytopenia syndrome or vaccine-induced thrombotic thrombocytopenia or vaccine-induced immune thrombocytopenia) is characterized by (i) venous or arterial thrombosis; (ii) mild-to-severe thrombocytopenia; (iii) positive antiplatelet factor 4 (PF4)-polyanion antibodies or anti-PF4-heparin antibodies detected by the HIT (heparin-induced thrombocytopenia) ELISA; (iv) occurring 5-30 days after ChAdOx1 nCoV-19 (AstraZeneca) or Ad26.COV2.S (Johnson & Johnson/Janssen) vaccination. VITT's incidence is 1 per 100 000 vaccinated people irrespective of age and up to 1 in 50 000 for people <50 years of age with the AstraZeneca COVID-19 vaccine. The exact mechanism by which adenovirus-vectored COVID-19 vaccines trigger this syndrome is still unclear, as for the increased risk for acute cerebral sinus venous thrombosis and splanchnic vein thrombosis as compared to other locations of venous thrombotic events. VITT is associated with the detection of anti-PF4 antibodies, unrelated to previous use of heparin therapy. PF4 antibodies are thought to activate platelets via the platelet FcγRIIA receptors leading to further platelet activation that causes thrombosis and thrombocytopenia.

Keywords: COVID-19; Cerebral sinus venous thrombosis; PF4; Thrombocytopenia vaccine-induced immune thrombotic thrombocytopenia; Thrombosis; Vaccine; Venous thromboembolism.