Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

Abstract

Advanced SARS-CoV-2 infections not uncommonly associate with the occurrence of silent or manifest thrombotic events which may be found as focal or systemic disease. Given the potential complexity of COVID-19 illnesses, a multifactorial causation is likely, but several studies have focused on infection-induced coagulopathy. Procoagulant states are commonly found in association with the finding of antiphospholipid antibodies. The correlation of the latter with thrombosis and/or clinical severity remains controversial. Although measures of antiphospholipid antibodies most commonly include assessments for lupus anticoagulant, anticardiolipin, and anti-ß2-glycoprotein-I antibodies, lesser common antibodies have been detected, and there remains speculation that other yet undiscovered autoimmune thrombotic events may yet be found. The recent discovery of post-vaccination thromboses associated with platelet factor 4 antibody has created another level of concern. The pathogenesis of antiphospholipid antibodies and their role in COVID-19-related thrombosis deserves further attention. The multifactorial nature of thrombosis associated with both infection and vaccination should continue to be studied as new events unfold. Even if a cause-and-effect relationship is variable at best, such dedicated research is likely to generate other valuable insights that are applicable to medicine generally.

Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review

“…However, ideally, the administered IVIG should be the ones collected before the pandemic. The plausible explanation being vaccine response deterioration due to COVID-19 antibodies present in the donated IGs [ 43 ].…”

Maternal COVID-19 Vaccination and Its Potential Impact on Fetal and Neonatal Development

“…Martirosyan et al reviewed cases of paediatric Henoch-Schonlein purpura and lupus associated with influenza vaccines and suggested that long-term effects such as thrombosis could be expected, since antiphospholipid antibodies remained elevated in some lupus patients for at least 6 months post-vaccination [119]. In the case of COVID-19 and COVID-19 vaccine-related AVRs, the role of antiphospholipid antibodies remains controversial, and more data are needed to establish potential cause-effect relationships [120].…”

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

“…Common findings in the cases described were the presence of elevated levels of D-dimer and antibodies against PF4 (identified by ELISA-based assays) and protein S, combined with thrombocytopenia but also hypofibrinogenemia, factor XIII deficiency, MTHFR C677T heterozygosis, and folate deficiency with increased levels of homocysteine and/or antiphospholipid antibodies [68,[70][71][72]186,[203][204][205][206].…”

“…Although most of the reports on VITT have focused on the role of platelets, it is likely that VITT pathogenic antibodies bind and activate other cells that express FcγRIIa, notably, leucocytes and endothelial cells. The association between thrombocytopenia and often multiple thrombotic complications with a rapidly worsening clinical course is known to occur in other syndromes on autoimmune basis, such as antiphospholipid syndrome, already demonstrated in COVID-19 [196,206], or thrombotic thrombocytopenic purpura.…”