Predictors of mortality in thrombotic thrombocytopenia after adenoviral COVID-19 vaccination: the FAPIC score

Abstract

Aims The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality. Methods and Results PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732–0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration. Conclusions Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants.

Post COVID-19 Vaccination-Associated Neurological Complications

“…The scores depend on the age, platelet count, fibrinogen level, and intracranial hemorrhage, in addition to CVT. 15 It is important to note that the two deceased patients had the highest D-dimers readings overall among our 18 studied cases. Thus, in the current study, D-dimer elevation indicates the severity of the coagulopathy and its related complications, including CVT and its association with poor outcomes in COVID-19-vaccinated individuals, especially those receiving the Vaxzevria vaccine, in a similar way to COVID-19 patients.…”

“…We applied the FAPIC predictive scoring model for mortality 15 to our first three patients. If any of the following was applicable, a point was scored: age less than or 60 years, platelet count of less than 2510 9 /mL, fibrinogen less than 150 mg/dL, intracranial hemorrhage (ICH), and CVT.…”

A case report of vaccine-induced immune thrombocytopenia and thrombosis syndrome after Ad26.COV2.S vaccine (Janssen/Johnson & Johnson)

“…Mortality reported in the literature varied from 23% to 72% depending on the existence or not of intracranial bleeding and thrombocytopenia < 30 G/L [4] , [5] , and also associated with early diagnosis and rapid initiation of appropriate treatment. A predictive mortality score has been developed: the FAPIC score [9] . It includes fibrinogen (< 1,5 g/L), age (≤ 60 years), platelet count (< 25 G/L), intracerebral hemorrhage and cerebral venous thrombosis, and can be used to predict mortality of VITT syndrome [9] .…”

“…A predictive mortality score has been developed: the FAPIC score [9] . It includes fibrinogen (< 1,5 g/L), age (≤ 60 years), platelet count (< 25 G/L), intracerebral hemorrhage and cerebral venous thrombosis, and can be used to predict mortality of VITT syndrome [9] .…”

“…Occurrence of serious adverse events attributable to the vaccine therefore remains difficult to interpret. VITT syndrome has only been reported very few times in the literature [1] , [4] , [6] , [8] , [9] , [10] , around 474 cases for the ChAdOx1 nCov-19 in European Union and United Kingdom on October 9, 2021, and 28 cases for the Ad26.COV2.S vaccine in USA on July 19, 2021. Risk-benefit ratio remains in favor of vaccination, in particular since SARS-CoV-2 infection is more thrombogenic than vaccination [6] .…”