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] . J o u r n a l P r e -p r o o f Treatments and vaccines for COVID-19: authorized medicines Signal Assessment Report on Embolic and Thrombotic Events (SMQ) with COVID-19 Vaccine Covid-19 Vaccine AstraZeneca (Other Viral Vaccines) Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination Coagulopathy in COVID-19 Deep vein thrombosis (DVT) occurring shortly after the second dose of mRNA SARS-CoV-2 vaccine Cerebral Venous Thrombosis after BNT162b2 mRNA SARS-CoV-2 vaccine A 59-Year-Old Woman with Extensive Deep Vein Thrombosis and Pulmonary Thromboembolism 7 Days Following a First Dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine COVID-19 Vaccine AstraZeneca: Benefits Still Outweigh the Risks Despite Possible Link to Rare Blood Clots With Low Blood Platelets Women's issues in antiphospholipid syndrome Antiphospholipid antibodies and risk of post-COVID-19 vaccination thrombophilia: The straw that breaks the camel's back? Cytokine Growth Factor Rev