The clinical and laboratory diagnosis of vaccine-induced immune thrombotic thrombocytopenia

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious adverse syndrome occurring 5-30 days after adenoviral vector COVID-19 vaccination. Therefore, a practical evaluation of clinical assessments and laboratory testing for VITT is needed to prevent significant adverse outcomes as the global use of adenoviral vector vaccines continues. We received the clinical information and blood samples of 156 patient samples with a suspected diagnosis of VITT between April to July 2021 in Canada. The performance characteristics of various diagnostic laboratory tests were evaluated against the PF4-SRA including a commercial anti-PF4/heparin IgG/A/M enzyme immunoassay (EIA, PF4 Enhanced; Immucor), in-house IgG-specific anti-PF4 and anti-PF4/heparin-EIAs, the standard SRA, and the PF4/heparin-SRA. Of those, 43 (27.6%) had serologically confirmed VITT based on a positive PF4-SRA result and 113 (72.4%) were negative. The commercial anti-PF4/heparin EIA, the in-house anti-PF4-EIA, and anti-PF4/heparin-EIA were positive for all 43 VITT-confirmed samples (100% sensitivity) with a few false-positive results (mean specificity 95.6%). These immunoassays had specificities of 95.6% [95% confidence interval (CI) 90.0-98.6], 96.5% (95% CI 91.2-99.0), and 97.4% (95% CI 92.4-99.5), respectively. Functional tests, including the standard SRA and PF4/heparin-SRA, had high specificities (100%), but poor sensitivities for VITT [16.7% (95% CI 7.0-31.4); and 46.2% (95% CI 26.6-66.6), respectively]. These findings suggest EIA assays that can directly detect antibodies to PF4 or PF4/heparin have excellent performance characteristics and may be useful as a diagnostic test if the PF4-SRA is unavailable.

Vaccine-induced immune thrombotic thrombocytopenia: Updates in pathobiology and diagnosis

“…The median age of this cohort was 52 years old (ranging from 29 to 73 years old) with no apparent sex-related differences ( 5 ). Patients present with thrombocytopenia and the majority have concurrent thrombosis (85.7%) ( 5 ). Rarely, patients can present without thrombocytopenia, as occurred in 2/35 patients in the Canadian cohort.…”

“…Examples of these include the ChAdOx1 nCoV-19 [AstraZeneca-Oxford] and Ad21.COV2.S [Johnson & Johnson/Janssen] vaccines. VITT patients have a medium time to symptom onset of 15 days post-vaccination (ranging from 7 to 61 days) based on a Canadian cohort of 43 patients ( 5 ). The median age of this cohort was 52 years old (ranging from 29 to 73 years old) with no apparent sex-related differences ( 5 ).…”

“…VITT patients have a medium time to symptom onset of 15 days post-vaccination (ranging from 7 to 61 days) based on a Canadian cohort of 43 patients ( 5 ). The median age of this cohort was 52 years old (ranging from 29 to 73 years old) with no apparent sex-related differences ( 5 ). Patients present with thrombocytopenia and the majority have concurrent thrombosis (85.7%) ( 5 ).…”

Vaccine-induced immune thrombotic thrombocytopenia

“…In two extensive VITT studies, the median time from vaccination to presentation of VITT was 14 days after ChAdOx1 nCOV-19 vaccination and nine days after Ad26.COV2.S vaccination [ 8 , 12 ]. Patients frequently presented with unremitting head or abdominal pain, abnormal breathing, tachycardia, chest pain, limb swelling, ischemia, or more severe cardiopulmonary complications [ 12 , 36 ]. Classical cases present with both thrombosis and thrombocytopenia, although patients with isolated thrombosis [ 37 , 38 ] or isolated thrombocytopenia [ 17 , 39 , 40 ] have been noted.…”

“…Rare cases of VITT have been reported after administration of mRNA-1273 (Moderna) or BNT162b2 (Pfizer) mRNA-based vaccines [ 8 ] [ 36 , [59] , [60] , [61] , [62] ]. The incidence of mRNA vaccine-associated VITT is extremely infrequent, with an estimated incidence rate of less than one case per 100 million vaccine doses [ 8 ].…”