Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis

Abstract

The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral based vaccines, associated with the presence of antibodies to a PF4/polyanion neoepitope, measured by ELISA assays. Presented are serial anti-PF4/polyanion antibodies, platelet and D-dimer measurements in a large cohort of patients and their relation to relapse. 51% of patients using the Stago assay had a persistently positive anti-PF4/polyanion levels 100 days post diagnosis whilst 94% of patients monitored using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days with 72% of patients remaining positive after a median duration of follow up of 105 days. The use of plasma exchange appeared to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6% with all relapsed cases showing persistently positive PF4 antibodies and falling platelet counts. Only one case had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse is low and does not appear to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid definition of the natural history of this novel condition.

Mechanisms of Thrombosis in Heparin-Induced Thrombocytopenia and Vaccine-Induced Immune Thrombotic Thrombocytopenia

“…50 Interestingly, it appears that anti-PF4 antibodies may persist for several months postdiagnosis and treatment of VITT, and in most cases, this is not associated with any relapse of thrombosis. 51 52…”

Vaccine-induced immune thrombotic thrombocytopenia

“…IgG heavy chains paired exclusively with lambda light chains likely highlight a common developmental pathway in VITT antibody production [ 13 , 24 ]. Lastly, antibodies in VITT appear to be more persistent relative to HIT, with anti-PF4 antibodies capable of stimulating platelet activation for several months after acute presentation and remaining detectable by enzyme-linked immunosorbent assay (ELISA) up to nine months or more [ [25] , [26] , [27] , [28] , [29] ] ( Fig. 2 ).…”

“…Another critical question relates to how long a VITT patient should be anticoagulated given the extended persistence of anti-PF4 antibodies in diagnostic ELISA assays. Considering that the rate of recurrence of thrombocytopenia or thrombosis was found to be 12.6% in a study of ∼150 VITT patients and that all recurrences were within 90 days of presentation [ 29 ], it may be appropriate for anticoagulation to be continued for at least three months after VITT is diagnosed.…”

Potential mechanisms of vaccine-induced thrombosis

“…Relevant to the laboratory issues on the diagnosis of VITT, Craven et al., in a large cohort of 148 VITT patients from United Kingdom, reported substantial differences between two different ELISA tests in terms of time to normalization of anti-PF4 antibodies [52] . They found a median duration of positivity of the PF4 assay of 87 days, with 72% of patients remaining positive after a median duration of follow up of 105 days.…”