The American Heart Association/American Stroke Association (AHA/ASA) has released guidance to help physicians respond to, and understand, the reports of rare blood clots and low platelet counts after COVID-19 vaccination. This report was published in Stroke Journal this week. The report aims to heighten awareness of the apparent association between adenovirus SARS-CoV2 vaccinations and cerebral venous sinus thrombosis (CVST) with vaccine-induced immune thrombotic thrombocytopenia (VITT) and suggest approaches to management.

Few case reports of vaccine-induced immune thrombotic thrombocytopenia (VITT) leading to (CVST) resulted in temporary pauses in use of the vaccines in the United States and Europe, which have since been lifted. Regulators have determined that the benefits of receiving the shots outweigh any potential risks.

The document, published online in Stroke, focuses on the diagnosis and management of CVST arising from VITT, a condition that has been reported in people who have received the COVID-19 vaccines developed by Janssen/Johnson & Johnson and Oxford/AstraZeneca.

Mechanism behind hypercoagulability:

The Ad26.COV2.S (Janssen) and ChAdOx1 nCoV-19 (AstraZeneca) vaccines contain replication-incompetent adenoviral vectors, human Ad26.COV2.S and chimpanzee ChAdOx1, respectively, that encode the spike glycoprotein on SARS-CoV-2. It is believed that leakage of DNA from the adenovirus infected cells binds to platelet factor 4 (PF4) and triggers the production of auto-antibodies. This mechanism mirrors the one underlying Heparin induced thrombocytopenia syndrome (HIT) and thus management should be approached on similar lines.

Risk factors for CVST:

CVST most commonly affects young adults (mean age 35-40 years), predominantly women of childbearing-age. Risk factors for CVST are similar to those for venous thromboembolism; over 80% of patients with CVST have at least one identifiable risk factor for thrombosis and half have multiple predisposing factors. Most common transient risks factors include temporary medical conditions, such as pregnancy and puerperium, exposure to drugs (oral contraceptives, chemotherapy), central nervous system or ear and face infections, and head trauma.

To vaccinate or not to vaccinate?

The authors report that the risk of CVST is about eight to 10 times higher with COVID-19 than with any of the vaccines designed to protect against it, and about 100 times higher than in the general population. Thus the chances of getting CVST aree much higher after contacting COVID-19 infection than post-vaccination, hence these small case reports should under no circumstance deter the vaccination efforts for community.

How to pick up CVST early?

When it comes to recognizing CVST, headache is a major feature, occurring in 90% of patients. It's not unusual to have a headache in the first 24 hours after vaccination, Karen Furie, MD (Rhode Island Hospital, Brown University, Providence, RI), lead author of the new guidance) noted, but the pain that accompanies CVST develops several days later, is progressive, and doesn't respond to analgesics.

That type of headache should prompt a more-thorough evaluation that includes blood tests and a lower threshold for imaging of the venous system with MRI or CT, she advised. She highlighted the fact that these recent cases tend to be clustered in young-to-middle-age women, a population that is prone to migraine. "So clinicians shouldn't ignore symptoms of headache, particularly of the kind I just described, in this younger population," she said

How to manage if my patient gets CVST?

Once a diagnosis has been made, management recommendations are largely based on HIT treatment guidelines because of the dearth of information on treating CVST with VITT specifically. In the acute phase, "intravenous immunoglobulin 1 g/kg body weight daily for 2 days has been recommended after laboratory testing for PF4 antibodies has been sent," Furie et al say, adding that some experts recommend use of steroids.

Heparin products should be avoided, but "anticoagulation should be used in CVST even in the presence of secondary intracranial hemorrhage as it is necessary to prevent progressive thrombosis to control this bleeding," the authors advise. Anticoagulation therapy should follow HIT guidelines for alternatives to heparin. Once platelet counts have recovered, patients can be switched to an oral anticoagulant like warfarin or NOACs.

Vaccination should continue unabated

Reports of vaccine associated CVST may increase vaccine hesitancy, yet the risk of CVST associated with COVID-19 infection is far greater than that associated with vaccination. The particular co-morbidities that might predispose to CVST after vaccination are unknown. Although the presence of PF4 antibodies has been confirmed in cases of vaccine associated CVST with thrombocytopenia, the true prevalence and risk of this antibody are unknown

The major takeaway for now, according to Furie, is that "COVID-19 infection increases risk of thrombosis, and despite the reports of a small number of cases of CVST in the US and Europe, vaccination remains the best strategy for maintaining brain health."

• Source: Stroke Journal: Furie KL, Cushman M, Elkind MSV, et al. Diagnosis and management of cerebral venous sinus thrombosis with vaccine-induced immune thrombotic thrombocytopenia. Stroke. 2021;Epub ahead of print.