Publication date: Sep 19, 2023

Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterised by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer and hypofibrinogenemia. To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT. Plasma from 18 suspected VITT cases was tested for anti-PF4 by ELISA and characterised as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII, plasmin-αantiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, factor XIII-A and plasminogen. VITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation (DIC) while 0/7 non-VITT patients met the criteria. VITT patients had significantly higher levels of inflammatory markers, IL-1β, IL-6, IL-8, TNFα and C-reactive protein. In VITT patients, both fibrinogen and factor XIII levels were significantly lower, while PAP and tPA-mediated plasmin generation were higher compared to non-VITT patients. Evidence of fibrinogenolysis was observed in 9/11 VITT patients but not in non-VITT patients or healthy controls. Fibrinogen degradation products were apparent, with obvious cleavage of the fibrinogen α-chain. PAP was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors. VITT patients show evidence of overt DIC and fibrinogenolysis, mediated by dysregulated plasmin generation, as evidenced by increased PAP and plasmin generation. These observations are consistent with the clinical presentation of both thrombosis and bleeding in VITT.

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