Some cases after COVID-19 vaccination show clinical resemblance of heparin-induced thrombocytopenia

A Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced Thrombocytopenia Following Coronavirus-19 Vaccination

Literature - Greinacher A, Thiele T, Warkentin TE et al. - Research Square 2021 (NOT PEER-REVIEWED), doi.org/10.21203/rs.3.rs-362354/v1

Introduction and methods

In the battle against the COVID-19 outbreak, 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 AZC1222 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).

Main results

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.

Conclusion

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.

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