Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series

Abstract

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

Keywords: COVID-19; COVID-19 vaccine AstraZeneca; ChAdOx1 nCoV-19; SARS-CoV-2 virus; cerebral venous thrombosis; complication; sinus vein thrombosis; thrombocytopenia.

Figure 1

Axial and coronal CT from patient 1 (A), 2 (B) and 5 (C). These patients presented with large parenchymal hemorrhages. Note the fluid-fluid levels [arrows, (A,C)], the subarachnoid hemorrhage [arrowheads, (A,C)] and the heterogeneous appearance of all hematomas.

Figure 2

MRI of patient 4 (upper row) and patient 2 (lower row), axial T2-weighted images (A,D), axial T1-weighted images (B,E) and contrast-enhanced axial T1-weighted images (C,F). A complex signal in hematomas of venous infarctions in the right cerebellar hemisphere (patient 4) and left temporal lobe (patient 2) is seen. Multiple fluid-fluid levels (arrows) and sedimentation indicate not fully coagulated blood. Multifocal areas of high signal intensity within the hematoma represents extravasated contrast agent [arrow heads, (F)]. An acute thrombus in the right transverse and sigmoid sinus [open arrow, (C)] cause a well-defined filling defect on the contrast-enhanced T1-MPRAGE. The round lesion with low signal intensity on T2-weighted image [thick arrow, (D)] was tubular on consecutive slices, showed lack of contrast enhancement and is compatible with a cortical vein thrombosis.

Figure 3

MRI, CT, and CT venography of patient 3. Thrombosis in a cortical vein (thin arrows) is possible to spot with high signal intensity on axial FLAIR (A) and filling defect on contrast enhanced axial T1-MPRAGE (B). Corresponding temporo-occipital hemorrhage (open arrow), cerebellar hemorrhage and high attenuation from thrombus in transverse and sigmoid sinuses can be seen on coronal CT (E). 3D phase-contrast MR venography demonstrates loss of flow signal in left transverse and sigmoid sinus (D). The thrombus in sigmoid sinus (thick arrows) is also evident on contrast enhanced axial T1-MPRAGE (C) and CT venography (F).

Figure 4

Autopsy findings in patient 5: (A) Coronal section of the formalin-fixed brain. Extensive hemorrhagic infarction (red arrows) in both hemispheres and major hemorrhage with communication to the brain surface and ventricular system. (B) Posterior sagittal sinus with a white thrombus. (C) Formalin fixed dura. Sagittal sinus with thrombus formation (arrow). (D) Cross-section of formalin fixed right transverse sinus with white thrombus (arrow).