Cerebral venous sinus thrombosis and thrombocytopenia after COVID-19 vaccination - A report of two UK cases

Abstract

Recent reports have highlighted rare, and sometimes fatal, cases of cerebral venous sinus thrombosis (CVST) and thrombocytopenia following the Vaxzevria vaccine. An underlying immunological mechanism similar to that of spontaneous heparin-induced thrombocytopenia (HIT) is suspected, with the identification of antibodies to platelet factor-4 (PF4), but without previous heparin exposure. This unusual mechanism has significant implications for the management approach used, which differs from usual treatment of CVST. We describe the cases of two young males, who developed severe thrombocytopenia and fatal CVST following the first dose of Vaxzevria. Both presented with a headache, with subsequent rapid neurological deterioration. One patient underwent PF4 antibody testing, which was positive. A rapid vaccination programme is essential in helping to control the COVID-19 pandemic. Hence, it is vital that such COVID-19 vaccine-associated events, which at this stage appear to be very rare, are viewed through this lens. However, some cases have proved fatal. It is critical that clinicians are alerted to the emergence of such events to facilitate appropriate management. Patients presenting with CVST features and thrombocytopenia post-vaccination should undergo PF4 antibody testing and be managed in a similar fashion to HIT, in particular avoiding heparin and platelet transfusions.

Keywords: COVID-19; Cerebral venous sinus thrombosis; Cerebrovascular disease; Immunology; Neurology; Stroke; Thrombocytopenia; Vaccine.

Fig. 1

A. Upper panel: volumetric coronal non-contrast CT brain study (left image) and volumetric axial CT venogram brain study (right image) was performed at the time of hospital admission. There is a heavy burden of clot expanding the middle to anterior third of the superior sagittal sinus, seen as an area of hyperdensity in the non-contrast study (white arrow in left image) and as a filling defect in the contrast study (red arrow in right image). There is extension into the superficial cortical venous system, most prominently the right superficial anastomotic vein which is seen to be thrombosed and dilated in the non-contrast study (yellow arrowheads in left image). There is significant cortical oedema with sulcal crowding. There is subarachnoid haemorrhage along the right central sulcus and a small subcortical intraparenchymal haematoma inferomedial to this (blue arrow in right image). Lower panel: volumetric axial and sagittal non-contrast CT brain imaging 3 days post-admission demonstrates extensive parietal haemorrhage in a typical venous distribution with evidence of cerebellar tonsillar descent (white arrow in right image). B. Upper panel: volumetric coronal and axial non-contrast CT brain imaging at time of hospital admission demonstrates large volume clot within the superior sagittal sinus (white arrow in left image) and its supplying cortical venous tributaries (examples shown with red arrowheads in right image). In addition, there are focal areas of venous haemorrhage in the subcortical parietal lobes (yellow arrowheads in left image), and subarachnoid haemorrhage along the right central and post-central sulci (blue arrow in right image). Lower panel: Volumetric sagittal and axial CT venogram study performed 3 hours later highlights a large filling defect in the anterior two thirds of the superior sagittal sinus (white arrow in left image). Extensive parenchymal acute haemorrhage is seen in the right frontal and parietal lobes with marked oedema and midline shift. There is also extensive subarachnoid haemorrhage within the frontoparietal convexity sulci bilaterally (examples shown with blue arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)