Fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) post Ad26.COV2.S: first documented case outside US

Abstract

Purpose: We reported the first described post Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine-induced immune thrombocytopenia (VITT) case outside US. CASE DESCRIPTION: CA young woman without any medical history presented association of deep vein thrombosis and thrombocytopenia at day 10 after vaccine injection. The patient was treated with low-molecular weight heparin at a first medical institution. Twelve days post Ad26.COV2.S vaccination, the patient was admitted at our hospital for neurological deterioration and right hemiplegia. Medical imaging using MRI showed thrombosis of the major anterior part of the sagittal superior sinus with bilateral intraparenchymal hemorrhagic complications. Screening tests for antibodies against platelet factor 4 (PF4)-heparin by rapid lateral flow immunoassay and chemiluminescence techniques were negative. Platelet activation test using heparin-induced multiple electrode aggregometry confirmed the initial clinical hypothesis. Despite immediate treatment with intravenous immunoglobulin, dexamethasone, danaparoid and attempted neurosurgery the patient evolved toward brain death.

Conclusion: Even though it is an extremely rare complication of vaccination physicians should maintain a high index of suspicion of VITT in patients who received an adenovirus-vector-based SARS-CoV-2 vaccine within the last 30 days with persistent complains compatible with VITT or thromboembolic event associated with thrombocytopenia. The diagnosis should not be excluded if the rapid anti-PF4 immunological nor chemiluminescence techniques yield negative results. An adapted functional assay should be performed to confirm the diagnosis. Early treatment with intravenous immunoglobulin and non-heparin anticoagulants is essential as delayed diagnosis and administration of appropriate treatment is associated with poor prognosis.

Keywords: Ad26.COV2.S; COVID-19; Cerebral venous sinus thrombosis; TTS; Thrombosis; Thrombosis with thrombocytopenia syndrome; VITT; Vaccine; Vaccine-induced thrombotic thrombocytopenia.

Fig. 1

Magnetic resonance imaging on day #12 post-vaccination. The sagittal view of the 3D Phase contrast venous angiography a shows the thrombosis of the major anterior part of the sagittal superior sinus (arrows). As the consequence of it, on B0 Diffusion weighted image b multiple bilateral hemorrhagic collections are seen and on apparent diffusion coefficient map c the extensive cytotoxic oedema involves almost the whole left hemisphere and partly the right one

Fig. 2

Time line summarizing the evolution, findings and management of the case

Fig. 3

Results of the functional assay (HIMEA): aggregation of platelets (from a good responder) after incubation with plasma from the patients was measured by whole-blood impedance aggregometry. The measurements were performed in absence of added heparin (left side) and in the presence of low (1 IU/ml middle) or high (385 IU/ml right side) heparin concentrations. The red and blue lines represent duplicate measurements. AU denotes arbitrary units, and AUC the area under the curve