Early recognition and treatment of pre-VITT syndrome after adenoviral vector-based SARS-CoV-2 vaccination may prevent from thrombotic complications: review of published cases and clinical pathway

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but highly morbid complication after adenoviral vector-based SARS-CoV-2 vaccination. The pre-VITT syndrome is defined as vaccine-induced immune thrombocytopenia without thrombosis typically presenting with new-onset headache. This review aims to identify at-risk patients before complications such as cerebral venous sinus thrombosis occur. We review previously published reports of 19 patients (median age 35 years, range 23-74; 16 females) who met the diagnostic criteria for a pre-VITT syndrome. Seven patients progressed to VITT, 12 patients did not. Patients who experienced VITT received delayed treatment. The median interval between the onset of headache and VITT-treatment (i.e. anticoagulation, immune globulins, or corticosteroids) was 5 days (range 1-8 days) compared with 2 days (0-5 days) in those without subsequent VITT (P = 0.033). The interval from onset of headache to anticoagulation was longer in patients with VITT (median 7 vs. 2 days; range 3-9 vs. 0-7 days; P = 0.01). Anticoagulation was safe in all patients with a pre-VITT syndrome as no haemorrhagic complications occurred after anticoagulation was started despite low platelets. The transient decline of platelet count after admission was significantly more pronounced in patients who progressed to VITT (median 67 vs. 0 × 10³/µL; range 0-77 × 10³/µL vs. 0-10 × 10³/µL; P = 0.005). d-dimers did not differ between groups. Pre-VITT syndrome is a 'red flag' and allows to identify and preemptively treat patients at-risk of further progression to VITT. However, it must be distinguished from post-vaccination immune thrombocytopenia.

Keywords: Anticoagulation; Headache; Pre-VITT syndrome; TTS; Thrombocytopenia; VITT.

Graphical Abstract

Figure 1

Latencies from onset of headache to vaccine-induced immune thrombotic thrombocytopenia-specific treatment: latencies to vaccine-induced immune thrombotic thrombocytopenia-specific treatment of seven patients who developed subsequent vaccine-induced immune thrombotic thrombocytopenia are illustrated by straight arrows (blue), median time to start of vaccine-induced immune thrombotic thrombocytopenia-specific treatment was 5 days. Latencies of 10 patients who were prevented from subsequent vaccine-induced immune thrombotic thrombocytopenia are illustrated by dotted arrows (green), median time to start of VITT-specific treatment was 2 days (P < 0.05).

Figure 2

Suggested assessment, diagnosis, and treatment of pre-vaccine-induced immune thrombotic thrombocytopenia syndrome: a diagnostic approach to the patient presenting with headache after adenoviral vector-based immunization. A detailed explanation is provided in the text.