Clinical resemblance of heparin-induced thrombocytopenia in some cases after COVID-19 vaccination
A Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced Thrombocytopenia Following Coronavirus-19 Vaccination
Introduction and methods
In the battle against the COVID-19 pandemic, vaccines against SARS-CoV-2 have been developed as countermeasure. The European Medical Agency (EMA) approved 4 vaccines between December 2020 and March 2021: a nucleoside modified mRNA COVID-19 vaccine (Pfizer/BioNTech); an mRNA-based vaccine encapsulated in lipid nanoparticle (Moderna); a recombinant adenoviral (ChAdOx1) vector encoding the spike protein antigen of SARS-CoV-2, AZD1222 (AstraZeneca); and a recombinant adenovirus type 26 vector encoding SARS-CoV-2 spike glycoprotein COVID-19 Vaccine (Janssen).
In the EU, ~55 million doses of vaccines have been administered by March 2021. Some cases of thrombotic events combined with thrombocytopenia have been reported in patients after COVID-19 vaccination.
This study describes 9 patients presenting with prothrombotic thrombocytopenia beginning 4 to 16 days after COVID-19 vaccination with AZD1222 in Austria and Germany from February-March 2021. Because of resemblance to heparin-induced thrombocytopenia (a prothrombotic thrombocytopenic disorder triggered by heparin and other anions), sera was collected from 4 patients and analyzed for platelet-activating antibodies directed against platelet factor 4 (PF4)/heparin by enzyme-immunoassay (EIA).
- Thrombotic events were pulmonary embolism (n=2), cerebral vein thrombosis (n=7), splanchnic vein thrombosis (n=1), arterial thrombosis (n=1) (some patients had more than 1 event).
- 8 of 9 patients were female
- All patients presented with thrombocytopenia (median platelet count nadir was 29 per cubic millimeter, range 9-100).
- Two patients had pre-existing autoimmune disease and two underlying coagulation disorder.
- Strong reactivity in the PF4/heparin EIA was observed for sera of all 4 patients, which was inhibited by addition of 100 IU unfractionated heparin (which inhibits PF4 dependent reactions).
- Sera of four patients activated platelets from healthy volunteers, either in presence of PF4 or in the presence of AZD1222 vaccine. This reaction was blocked by Fcγ receptor-blocking antibodies, demonstrating that platelet activation was mediated through Fcγ-receptors.
- One serum showed platelet activation in the presence of heparin.
Moderate to severe thrombocytopenia combined with thrombotic complications at unusual sites starting ~one week after COVID-19 vaccination by AZD1222 observed in some cases suggest a disorder clinically resembling heparin-induced thrombocytopenia, but with a different serological profile.