COVID-19 mRNA-1273 vaccine induces production of vaccine
A challenge in distinguishing between VITT and the “background rate” of thrombotic thrombocytopenia due to anti-PF4 antibodies (i.e., spontaneous HIT) is the lack of tests capable of differentiating between the two3; antibodies to both entities are detected in current ELISA and functional assays. In a report just published in the American Journal of Hematology4, Kanack and colleagues make the new discovery that antibody binding to uncomplexed PF4 can distinguish between these two syndromes.
Thus, post-mortem, the uncomplexed PF4 ELISA was used to further characterize our patient's anti-PF4 antibodies. To avoid confounding antibodies that may have developed after heparin exposure, the preheparin (first) blood sample was initially tested.
Figure 1 shows that this sample demonstrated an elevated OD of 3.3852, consistent with VITT antibodies, and was also shown to be a platelet activator in the PF4-dependent P-selectin (PEA) expression assay, a test that uses PF4-treated platelets for the sensitive detection of VITT4 and HIT antibodies.5 The follow-up sample continued to be strongly positive in the uncomplexed PF4 ELISA (OD 3.5883), also compatible with VITT.
These data are consistent with the possibility that non-adenovirus mRNA vaccines may induce VITT in rare cases. To add to this case, the CDC reports two additional patients with a clinical/laboratory picture consistent with VITT after mRNA-1273 vaccination, including thrombosis (at unusual sites: cerebral venous sinus in one and mesenteric artery thrombosis in the other), thrombocytopenia, very high d-dimers, and strongly positive HIT ELISAs (OD > 1.0) in both patients.2 To our knowledge, samples from these patients n have not been tested against uncomplexed PF4 targets.
Additionally, a recent case of VITT has been reported following vaccination against HPV (recombinant quadrivalent human papillomavirus vaccine), which uses non-adenovirus virus-like particle vaccine technology.6 Thus, we believe that emerging data on VITT after non-adenovirus vector vaccines evidenced by our case suggests that VITT should remain on the differential diagnosis of thrombocytopenic thrombotic reactions observed after several different types of vaccines so that an accurate diagnosis can be made and interventions appropriate therapies can be instituted quickly.