Q) What do we know about cerebral venous thrombosis (CVT) in COVID-19 patients?

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A) There are a few points that we would like to share here.

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1. Although venous thrombosis is very common in patients with severe COVID infection (approximately 30%), prothrombotic state from this virus can occur in milder infection.

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2. There are 21 individual case reports (as of October 25th, 2020) of CVT associated with COVID-19 infection. Interestingly, deep CVT was common (40%) in COVID-19 patients. Generally, deep CVT was found in less than 10% of all CVT before the pandemic.

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3. Most patients were diagnosed with CVT approximately 2 weeks after a COVID-19 diagnosis. However, some patients presented with CVT after receiving a negative COVID status or as their first manifestations of the disease.

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4. CVT presentations are not specific and usually patients have risk factors for it. However, COVID-19 is a possible risk factor for CVT. CVT should be ruled out when patients present with headache, altered mental status, seizure or acute focal neurological deficits or intubated patients who are not waking up and have increasing D-dimers level.

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5. All three CVT cases who had lumbar puncture done, had elevated WBC (10-40 cells/mm3) and high protein (616 & 1104 mg/dl) which imply that even though CSF profile is consistent with encephalitis profile, it does not exclude CVT.

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6. How do we explain the mechanisms of venous thrombosis in COVID-19? COVID-19 can cause endothelial injury, cytokine storm which leads to COVID-19 associated coagulopathy and hemodynamic instability and ACE2 depletion (Please see figure) and elevated antiphospholipid antibodies.

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7. All patients (15 patients) had elevated D-Dimers (median: 2876 ng/ml and mean: 6397; normal range < 500 ng/ml)

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8. The mortality rate of CVT in COVID-19 patients is 52% (9/17) in contrast to the general population (5%).

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9. Low-molecular-weight heparin (LMWH) is preferred instead of unfractionated heparin (UFH). Current evidence reveals that using LMWH decreased mortality, new associated hemorrhage, and improved thrombus regression and recovery of symptoms. Moreover, the concerns of time to achieve therapeutic aPTT and increased health care worker exposure for frequent blood draws when using UFH should be kept in mind.

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10. White et al. shows heparin resistance (LMWH & UFH) was observed in 80% of COVID patients in ICU. Therefore, anti-Xa level monitoring for patients on LMWH is reasonable

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Reference

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2) Klein DE, Libman R, Kirsch C, Arora R. Cerebral venous thrombosis: A typical presentation of COVID-19 in the young. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104989.

3) Hughes C, Nichols T, Pike M, Subbe C, Elghenzai S. Cerebral Venous Sinus Thrombosis as a Presentation of COVID-19. Eur J Case Rep Intern Med. 2020 Apr 29;7(5):001691.

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