Immune thrombocytopenia and thrombosis mortality predictors following SARS-CoV-2 vaccine
1. Low baseline platelet count and intracranial hemorrhage were shown to be prognostic mortality markers due to vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the adenoviral vector SARS-CoV-2 vaccine.
2. Other correlated factors of mortality associated with VITT thrombosis were shown to be increased D-dimer levels and decreased baseline fibrinogen levels.
Evidence Rating Level: 2 (Good)
Study Rundown: Following adenoviral vector SARS-CoV-2 vaccination (ChAdOx1 nCoV-19), vaccine-induced immune thrombocytopenia and thrombosis (VITT) is possible side-effect with fatal outcomes. As such, this study described patient characteristics of the initial cases of definite or probable VITT following vaccination. The analysis found that baseline platelet count and the presence of intracranial hemorrhage were independent predictors of death. Furthermore, the presence of cerebral venous sinus thrombosis, increased baseline D-dimer, and decreased baseline fibrinogen level were all found to have significant odds of death. The study was limited by case-ascertainment bias, given the global attention on the topic of VITT amongst SARS-CoV-2 vaccines. Furthermore, analysis of this study was carried out before the vaccine was made available to younger populations, which potentially skewed the cohort composition towards older patients. Together, this data supports increased surveillance and supportive measures for patients who exhibit a constellation of features suggesting susceptibility to VITT.
Click to read the study in NEJM
Relevant Reading: Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine–Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis
In-Depth [prospective cohort]: A prospective cohort of 220 patients suspected of having vaccine-induced thrombocytosis and thrombopenia (VITT) were identified in the United Kingdom. Patients were confirmed to have VITT if they met the following 5 criteria: symptoms arising 5-30 days after the first dose of the ChAdOx1 nCoV-19 vaccine, presence of thrombosis, thrombocytopenia, increased D-dimer levels (< 4000 fibrinogen-equivalent units), and presence of anti-PF4 antibodies. Patients who did not meet these five criteria were assumed to have probable, possible, or unlikely VITT. Patients who met the criteria thrombofor increased D-dimer levels but not one of the remaining four criteria were classified as probable VITT. Of the 220 patients, 170 patients were classified as definite cases of VITT and 50 patients were determined to have probable cases of VITT. The median age of the cohort was 48 years (interquartile range, 38 to 56) and the median time to presentation was 14 days post-vaccination (interquartile range, 10 to 16). There was no sex predominance. The most common site of thrombosis (50%) at presentation was in the cerebral veins, followed by deep veins of the legs and pulmonary arteries. At the time of analysis, 22% of patients died. Odds of death increased for presence of cerebral venous sinus thrombosis (factor, 2.7; 95% confidence interval [CI], 1.4 – 5.2), increased for platelet count (factor, 1.7 for every 50% decrease from baseline; 95% CI, 1.3 – 2.3), increased for D-dimer level (factor, 1.2 for every increase of 10,000 FEU; 95% CI, 1.0 – 1.3), and increased for fibrinogen level (factor, 1.7 for every 50% decrease, 95% CI, 1.1 – 2.5). Multivariate analysis identified baseline platelet count (< 30,000 / mm3) and presence of intracranial hemorrhage as independently associated factors with mortality. Together, this data supports that increased surveillance and supportive measures should be in place for patients exhibiting lower platelet counts, low fibrinogen levels, and higher D-dimer levels following the ChAdOx1 nCoV-19 vaccine.
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