key: cord-0709996-d8icqhxk
authors: Melas, Nikolaos
title: “Portal vein thrombosis occurring after the first dose of mRNA SARS-CoV-2 vaccine in a patient with antiphospholipid syndrome”
date: 2021-09-03
journal: Thrombosis Update
DOI: 10.1016/j.tru.2021.100069
sha: 03f43344474d055a7a0eb2afd414ae700af32277
doc_id: 709996
cord_uid: d8icqhxk

nan

Medicines Agency (EMA) has approved four vaccines, two of which are based on mRNA technology (BNT162b2 and mRNA-1273) and two of which employ an adenovirus vector (ChAdOx1-S and Ad26.COV2) [1] . The EMA Pharmacovigilance Risk Assessment Committee (PRAC) has recently assessed the safety profile of ChAdOx1-S following many reports of blood clotting events emerging days to weeks after the vaccine's first or second injection [2] .

Following the report of six cases of thrombocytopenia and cerebral venous sinus thrombosis in female recipients aged 18 to 48 years, the Food and Drug Administration (FDA) suspended the use of the AD26.COV2 vaccine in the United States (US) in April 2021 [3] . This type of vaccine-induced immune thrombotic thrombocytopenia (VITT), also called thrombotic thrombocytopenia (TTS), implies an immunological reaction that mimics heparin-induced thrombocytopenia (HIT) [4] . SARS-CoV-2 infection is linked to an increase in venous thromboembolic (VTE) events, most likely because of a thrombotic state caused by inflammation and immune-mediated thrombosis [5] . More recently, some rare cases of classical VTE have been observed in citizens who received the mRNA-based vaccine (BNT162b2/Comirnaty/Pfizer/BioNTech) [6 -8] . However, the link between COVID-19 vaccinations and thrombotic events remains unknown, while an immune-mediated mechanism analogous to what occurs in antiphospholipid syndrome (APS) could be a possibility. Furthermore, the majority of those who developed severe coagulation disorders after being vaccinated were young women, who are also the APS target population [9, 10] . To my knowledge, this is the first reported case of manifestation of APS in the form of portal vein thrombosis after the first dose of mRNA vaccine (BNT162b2/Comirnaty/Pfizer/BioNTech). It is supposed that pre-existent antiphospholipid antibodies (aPLs) might predispose to this complication, acting as the first trigger, although this is not determined a priori. Given the clinical resemblance between thrombotic events following COVID-19 vaccination and APS, researchers from Italy provided a pathogenic theory for this rare adverse event that involves a pre-existent or a de novo aPL positivity.

While adenoviral vector-based vaccines may induce the synthesis of aPLs due to a molecular mimicry mechanism, the mRNA-based vaccines may instead trigger a more complex pathway, characterized by activation of Toll-like receptor (TLR), generation of a Type I Interferon (IFN) response, NETosis and the direct initiation of the coagulation cascade. Disruption of the physiological cross-talk occurring between platelets and endothelial cells drives these cells toward a pro-inflammatory and pro-coagulant phenotype [11] .

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