Vaccine-induced immune thrombotic thrombocytopenia may worsen the severity of cerebral venous thrombosis

1. The primary outcome of mortality or dependency was greater in patients with VITT-associated CVT compared to non-VITT CVT (p=0.0061).

2. Better prognosis was seen in VITT-associated CVT for patients treated with non-heparin anticoagulants (p=0.0031) and intravenous immunoglobulins (p=0.022).

Evidence Rating Level: 2 (Good)

Study Rundown: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event thought to be associated with the receipt of adenovirus vector COVID-19 vaccines. Proposed diagnostic criteria for VITT include symptom onset 4-28 days from vaccination, low platelet count, presence of anti-PF4 antibodies, and elevated D-dimer. This study analyzed data from patients who experience cerebral venous thrombosis (CVT) following COVID-19 vaccination with the aim of better understanding VITT-associated CVT. When comparing VITT-associated CVT versus non-VITT-associated CVT, patients with VITT were more likely to die or be dependent on others following hospitalization. Patients with VITT were also more likely to have extracranial thrombosis. Further analysis performed on the VITT-associated CVT patients demonstrated better outcomes in patients treated with non-heparin anticoagulants and intravenous immunoglobulins (IVIG). Limitations of this study include the small number of patients due to the rare condition. Nevertheless, this study provides important data regarding the clinical features of VITT-associated CVT, including potential treatment strategies and recommendations to clinicians.

Click to read the study in the Lancet

Click to read an accompanying editorial in the Lancet

Relevant Reading: Prognosis of Cerebral Vein and Dural Sinus Thrombosis

In-Depth [retrospective cohort]: In this study, cases of patients with cerebral venous thrombosis after COVID-19 vaccination were sought out via communications to physicians in the United Kingdom. Clinical and demographic data was included from 95 patients across the United Kingdom who had a CVT event after vaccination. VITT was determined by a recorded platelet count below 150×10⁹ per L, elevated D-dimer levels (≥2000 µg/L), and the presence of anti-PF4 antibodies on ELISA. In total, of 95 patients presenting with CVT following a COVID-19 vaccination, 70 patients were met the criteria for VITT and 25 did not. Demographic differences showed that patients with VITT were generally younger than those without VITT (median age [IQR] 47 years [32-55] vs. 57 years [41-62], respectively; p=0.0045). There was no significant difference in sex of VITT between non-VITT patients.

Between patients with VITT and those without, there were a few notable differences. All VITT patients (n=70) were vaccinated with one dose of ChAdOx1 (Oxford-AstraZeneca) vaccine. In contrast, 85% of non-VITT patients (n=21) received one dose of ChAdOx1 before the CVT event, whereas the rest (n=4 [16%]) had either one or two doses of BNT162b2 (Pfizer-BioNTech). While there were no clinical differences in CVT symptomatology between the two groups, there were some notable differences in disease severity. For example, the number of veins thrombosed, intracerebral hemorrhages and venous infarctions was greater in patients with VITT. In addition patients with VITT were more likely to present with extracranial thrombosis compared.

To measure disease morbidity, the modified Rankin scale (where 0 is no symptoms, 5 is severe disability and 6 is death during admission) was used at patient discharge. The primary outcome of mortality or dependency was significantly increased in patients with VITT-associated CVT (31 of 70 patients [44%] compared to non-VITT (4 of 25 [16%]; p=0.0003). Patients with VITT had better outcomes if they were treated with non-heparin anticoagulants (p=0.0031) or IVIGs (p=0.022).

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