Shedding Light on the Possible Link between ADAMTS13 and Vaccine-Induced Thrombotic Thrombocytopenia.
Cells
; 10(10)2021 10 18.
Article
in English
| MEDLINE | ID: covidwho-1477931
ABSTRACT
Several recent reports have highlighted the onset of vaccine-induced thrombotic thrombocytopaenia (VITT) in some recipients (approximately 1 case out of 100k exposures) of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). Although the underlying events leading to this blood-clotting phenomenon has yet to be elucidated, several critical observations present a compelling potential mechanism. Thrombus formation requires the von Willebrand (VWF) protein to be in ultra-large multimeric state. The conservation of this state is controlled by the ADAMTS13 enzyme, whose proteolytic activity reduces the size of VWF multimers, keeping blood clotting at bay. However, ADAMTS13 cannot act on VWF that is bound to platelet factor 4 (PF4). As such, it is of particular interest to note that a common feature between subjects presenting with VITT is high titres of antibodies against PF4. This raises the possibility that these antibodies preserve the stability of ultra-large VWF complexes, leading to the formation of endothelium-anchored VWF strings, which are capable of recruiting circulating platelets and causing uncontrolled thrombosis in terminal capillaries. Here, we share our viewpoint about the current understanding of the VITT pathogenesis involving the prevention of ADAMTS13's activity on VWF by PF4 antibody-mediated stabilisation/ protection of the PF4-VWF complex.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Thrombocytopenia
/
ADAMTS13 Protein
/
COVID-19 Vaccines
/
COVID-19
Type of study:
Experimental Studies
/
Observational study
/
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Cells10102785
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