1. Fibrinogenolysis and fibrinolysis in vaccine-induced immune thrombocytopenia and thrombosis.
- Author
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Simpson M, Narwal A, West E, Martin J, Bagot CN, Page AR, Watson HG, Whyte CS, and Mutch NJ
- Subjects
- Humans, Fibrinolysis, Fibrinolysin, COVID-19 Vaccines adverse effects, Fibrinogen, Purpura, Thrombocytopenic, Idiopathic, Disseminated Intravascular Coagulation chemically induced, Disseminated Intravascular Coagulation diagnosis, Thrombocytopenia chemically induced, Thrombocytopenia diagnosis, Thrombosis etiology, Vaccines
- Abstract
Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer, and hypofibrinogenemia., Objectives: To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT., Methods: Plasma samples from 18 suspected VITT cases were tested for anti-PF4 by ELISA and characterized as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII (FXIII), plasmin-α
2 antiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, FXIII-A, and plasminogen., Results: VITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation, 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 FXIII 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 complex was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors., Conclusion: VITT patients show evidence of overt disseminated intravascular coagulation 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., Competing Interests: Declaration of competing interests The authors have no relevant conflict of interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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