Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia

Tubingen, 1 August 2021, Althaus et al, Haematologica

Summary

We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (five females, three males) with a median age of 41.5 years (range, 24-53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccination. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5×109/L (range, 8-92). Three had a fatal outcome and five were successfully treated. Autopsies showed arterial and venous thromboses in various organs and the occlusion of glomerular capillaries by hyaline thrombi. Sera from VITT patients contain high-titer antibodies against platelet factor 4 (PF4) (optical density [OD] 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (Pselectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.

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Imaging example of three illustrative cases. Imaging examples of case #1 (A to C), case #8 (D to F) and case #4 (G and H). In case #1, non-enhanced computed tomography imaging (A) showed a parenchymal and subdural hemorrhage (arrows in A), causing a midline shift (arrowheads in A). Digital subtraction angiography was performed (B) showing thrombosis of the right sigmoid and transverse sinus, superior sagittal sinus (arrows in B), and straight sinus. Angiography after mechanical recanalization (C) shows the recanalized cerebral sinuses (superior sagittal sinus marked with arrows). In case #8, cerebral imaging 7 days after vaccination was unremarkable (curved reconstruction of the left transverse and sigmoid sinus shown in the right upper corner of D and F). She worsened, which led to a repeated cerebral imaging, showing a large intraparenchymal hemorrhage in the left temporal lobe (arrow in E), causing midline shift (arrowhead in E), caused by a thrombosis of the transverse and sigmoid sinus (arrows in F), as well as of the adjacent tentorial veins. In case #4, a thrombus in the right pulmonary artery was observed (arrows in E; coronal reconstruction shown in the right lower corner of G). Further imaging also revealed thrombi in the femoral veins on both sides (arrows in H).

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