Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Risk of venous thromboembolism after COVID-19 vaccination.

BACKGROUND: COVID-19 vaccinations in the United States are effective in preventing illness and hospitalization yet concern over post-vaccination venous thromboembolism (VTE) risk has led to vaccine hesitancy. METHODS: The aim of this study was to compare VTE rates before and after COVID-19 vaccination. COVID-19 vaccinated patients ≥18 years between November 1, 2020 through November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE (upper or lower deep vein thrombosis or pulmonary embolism) occurring 90 days before and after the date of first vaccine dose. RESULTS: A total of 792 010 patients with at least one COVID-19 vaccination were identified (Pfizer, n = 452 950, Moderna, n = 290 607, and Janssen [Johnson & Johnson], n = 48 453). A total of 1565 VTE events occurred in the 90 days before (n = 772) and after (n = 793) COVID-19 vaccination. VTE post-vaccination occurred in 326 patients receiving Moderna (0.11%, incidence rate [IR] 4.58 per 1000p-years), 425 patients receiving Pfizer (0.09%, IR 3.84 per 1000p-years), and 42 receiving Janssen (0.09%, IR 3.56 per 1000p-years). Compared to the pre-vaccination timeframe, the adjusted hazard ratio (aHR) for VTE after the Janssen vaccination was 0.97 (95% confidence interval [CI] 0.63-1.50), aHR 1.02 (95% CI 0.87-1.19) for Moderna, and aHR 1.00 (95% CI 0.87-1.15) for Pfizer. CONCLUSION: In this large cohort of COVID-19 vaccinated patients, no increased risk for acute VTE post-vaccination was identified for the authorized vaccines in the United States.

Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies.

Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT. Here we demonstrate that while Ad26.COV2.S-associated VITT patients are uniformly strongly positive in PF4-polyanion enzyme-linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4-dependent p-selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150 x 103 /µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4-polyanion ELISAs and functional assay are non-specific and detect all three conditions. Here, we report that a novel un-complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV-19, from both spontaneous HIT, HIT and commonly-encountered HIT-suspected patients who are PF4/polyanion ELISA-positive but negative in functional assays. In summary, Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.

Timing of venous thromboembolism diagnosis in hospitalized and non-hospitalized patients with COVID-19.

BACKGROUND: The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort. METHODS: COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise. Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms. RESULTS: A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients. CONCLUSION: We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.