Coagulation

Genetic thrombophilias predispose to COVID-related VTE


Inherited thrombophilias are associated with a higher risk of COVID-19–associated VTE, an Australian study has shown.

Researchers from the Baker Heart and Diabetes Institute in Melbourne say their finding that genetic thrombophilias such as Factor V Leiden (FVL) mutation may predispose to COVID-19 VTE may help identify patients who are more likely to benefit from higher-dose antithrombotic regimens.

In a paper in Circulation the researchers analysed data from a large UK cohort of more than 13,712 individuals aged 45-69 years who tested positive to COVID-19 between January 2020 and May 2021.

COVID-19 VTE was identified in 197 cases (1.4%), and there were 890 deaths from COVID-19 (6.5%) after a median follow-up time of 146 days. The median time to COVID-19 VTE diagnosis was 12 days.

The presence of rs6025, synonymous with the FVL mutation, was associated with an approximate 1.8-fold odds of COVID-19 VTE.

Moreover, both the fibrinogen gamma gene rs2066865 (Odds Ratio, 1.35) and the VTE polygenic risk score PRS-VTE (OR, 1.26) mutations were also associated with a higher risk of COVID-19 VTE.

In contrast, neither the ABO polygenic risk score nor the presence of coagulation factor XI (rs4253416), and ABO blood group (rs2519093 and rs8176645) mutations, or prothrombin mutation rs1799963 were associated with COVID-19 VTE.

Consistent with previous reports, COVID-19 VTE was associated with higher COVID-19 mortality (OR, 2.77), but no association was seen between either the SNPs or PRS with COVID-19 mortality.

The researchers, led by haematologists Drs Hannah Stevens and Associate Professor James McFadyen, said there was significant ongoing interest in the optimal antithrombotic regimen for the prevention of COVID-19 thrombotic complications.

“To date, studies evaluating the benefit of anticoagulation in patients with COVID-19 have been conflicting, and these regimens have consistently been associated with higher bleeding complications,” they wrote.

“Therefore, the identification of novel risk factors, such as genetic thrombophilias, may stratify patients with a higher risk of COVID-19 VTE, and ultimately help identify patients with COVID-19 who are more likely to benefit from higher-dose antithrombotic regimens.”

However, they acknowledged that timely access to genetic testing remained an outstanding issue.

They are also involved in clinical trials to understand more about treatments for COVID-19 related thrombosis, such as the ASCOT clinical trial, which aims to generate clinical evidence about new treatments to reduce death or the need for mechanical ventilation in hospitalised patients.

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