Prothrombotic immune thrombocytopenia after COVID-19 vaccination

Abstract

We report five cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), arterial cerebral thromboembolism, and thrombotic microangiopathy (TMA). All patients had thrombocytopenia and markedly elevated D-Dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependant manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in three patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

COVID-19 vaccination and immune thrombocytopenia

“…2 ). The novel and distinctive clinical and serological features of this disorder, combined with preliminary studies implicating the virus in antigen formation 3 , support the proposal of a relationship between vaccination and the autoimmune response.…”

Atypical Hemolytic and Uremic Syndrome Triggered by Infection With SARS-CoV2

“…Cases of unexplained thrombocytopenia as well as aHUS-like syndromes have been reported after vaccination against SARS-CoV-2 6,7 . Vaccination against or infection with SARS-CoV-2 have been associated with new cases or relapses of certain nephropathies such as IgAnephropathy or minimal change disease, hinting towards a link with immune dysregulations 8,9 .…”

Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia

“…However, other serum factors could also contribute to platelet activation. Previous studies have demonstrated antibodies from VITT patients were able to activate platelets and cause platelet aggregation in the presence of adenoviral particles in a dose-dependent manner 1,23,24 . Thus, it is possible platelet activation caused by anti-PF4 antibodies in VITT patients may not be the only factor leading to the development of thrombotic events.…”