Clinical and Serological Characteristics of Vaccine-Associated Immune Thrombocytopenia Following COVID-19 Vaccination

Introduction: Vaccine-associated immune thrombocytopenia (VA-ITP) is a serious hematological complication that re-emerged during COVID-19 vaccination campaigns and continues to complicate vaccine safety. The mechanisms of VA-ITP are unknown, and the associated laboratory and patient outcomes have not been well characterized. In this study, we determined the association of VA-ITP with anti-platelet autoantibodies.

Methods: We conducted a retrospective cohort study of adult patients with VA-ITP following COVID-19 vaccination identified from the McMaster ITP Registry between December 2020 and January 2024. VA-ITP was defined as new-onset thrombocytopenia (platelet count <100 x10⁹/L) within 3 months of exposure to vaccination. We excluded patients with vaccine-induced immune thrombotic thrombocytopenia (VITT) and positive anti-PF4 antibodies. Platelet counts, vaccine type, and treatments were collected. Platelet antibody testing was performed using a direct monoclonal antibody immobilization of platelet antigens (MAIPA) assay to detect antibodies against platelet glycoprotein (GP) IIbIIIa and GPIbIX. Anti-PF4 antibodies were also measured in the enzyme-immunoassay (EIA) and in the PF4-enhanced serotonin release assay (PF4-SRA). The data were summarized using descriptive statistics.

Results: We identified 6 VA-ITP patients after COVID-19 vaccination from the McMaster ITP Registry. Mean age was 52 years (range 28–70), 2 (33.3%) were female. Culprit vaccines were the ChAdOx1 nCoV-19 adenoviral vector (n=3, 50%; first vaccine only), and the BNT16B2b2 mRNA vaccine [n= 3, 50%; after first (n=1), third (n=1) or fourth vaccine (n=1)]. Median platelet count pre-vaccination was 248 x10⁹/L (IQR 197 – 249 x10⁹/L), and median presenting platelet count was 12 x10⁹/L (IQR 9 – 82 x10⁹/L) at 19.5 days (median; IQR 14 – 23 days) post vaccination. Median lowest platelet count was 7 x10⁹/L (IQR 3 – 11 x10⁹/L), occurring 65 days (median; IQR 57 – 384 days) post vaccination. No patients had thrombosis.

Three (50%) of 6 patients had detectable platelet antibodies up to 156 days post-vaccination (range 70 – 247 days). Two patients had anti-GPIbIX only and 1 patient had both anti-GPIbIX and anti-GPIIbIIIa. Two patients had received the adenoviral vector vaccine, and one patient received the mRNA vaccine.

Treatments for VA-ITP included corticosteroids (n=6), IVIg (n=5), thrombopoietin receptor agonists (n=3), rituximab (n=2), and splenectomy (n=1). Median number of treatments was 3 (IQR 3 – 4). One patient (16.7%) achieved a durable platelet count response, and 5 patients (83.3%) achieved an initial platelet count response and subsequently relapsed, requiring ongoing treatment at the end of follow up (median, 29.5 months; IQR 21.5 – 31).

Among the 3 patients with anti-GPIbIX or anti-GPIIbIIIa antibodies, median number of treatments was 4 (range 3 – 5), median lowest platelet count was 6 x10⁹/L (range 3 – 8 x10⁹/L), and all had relapsed requiring ongoing treatment at the end of follow up. Among the 3 antibody-negative patients, the median number of treatments was 3 (range 2 – 3), median lowest platelet count was 11 x10⁹/L (range 1 – 71 x10⁹/L), and 2 (66.7%) required ongoing treatment at the end of follow up. All 6 patients received a median of 2.5 booster vaccines (IQR 1 – 4) during follow up; 2 patients (33.3%) experienced a decrease in platelet counts ≥20%, but none developed severe ITP.

Conclusion: We found that 3 (50%) of 6 patients with VA-ITP after adenoviral vector and mRNA COVID-19 vaccines had detectable anti-platelet antibodies, including 2 patients with anti-GPIbIX and one patient with both anti-GPIbIX and anti-GPIIbIIIa. Antibody-positive VA-ITP tended to be more severe and require more treatment.