Appelbaum et al.: "SARS-CoV-2 spike-dependent platelet activation in COVID-19 vaccine-induced thrombocytopenia"
by Paul Alexander
'Our serologic investigations highlight a potential mechanism for COVID-19 VIT involving SARS-CoV-2 spike-dependent FcγRIIa-mediated platelet activation.'
“Our patient was a 25-year-old woman who presented to the hospital 10 days after receiving the Moderna mRNA COVID-19 vaccine with fatigue, petechiae, and wet purpura. The initial platelet count was 1 × 109/L 1000/mm3 without evidence of schistocytes on blood smear (Figure 1A). Coagulation studies were within the normal range, including prothrombin time of 13.6 seconds (normal, 10.7-15.6 seconds), international normalized ratio of 1.1 (normal, 0.8-1.3), and partial thromboplastin time of 30 seconds (normal, 22-35 seconds). The presence of a lupus anticoagulant was likely excluded, given the use of a lupus-sensitive reagent for partial thromboplastin time testing. Anti-PF4/heparin antibodies were not detected (optical density [OD], 0.221) and the SRA tests, with or without heparin or exogenous PF4, were negative. Assays for drug-induced immune thrombocytopenia with washed donor platelets as above were also negative for platelet binding with vaccine, PEG2000, or SARS-CoV-2 spike protein.
Our serologic investigations highlight a potential mechanism for COVID-19 VIT involving SARS-CoV-2 spike-dependent FcγRIIa-mediated platelet activation. Similar immune complex–mediated platelet activation has also been observed with severe COVID-19 infection.2,4 The mechanism described here resembles platelet activation seen in HIT but does not involve anti-PF4/heparin antibodies. HIT serves as a useful analogy, but certain key differences were noted in our patient. Notably, our patient presented with bleeding symptoms as opposed to thrombosis; however, in parallel to HIT, not all patients with platelet-activating antibodies develop thrombosis.10
Finally, it is unclear why only a minority of patients with anti-spike antibodies exhibit thrombocytopenia and platelet activation. One hypothesis is that platelet activation is dependent on unique spike protein epitopes, which are recognized by only a minority of identified antibodies, as seen in HIT.11 Therefore, using our knowledge of platelet activation from studying HIT, we propose this mechanism for COVID-19 VIT involving SARS-CoV-2 anti-spike antibodies.’