Factor V activity in severe coronavirus disease 2019 (COVID-19) was associated with rates of venous thromboembolism and mortality, suggesting it may be a useful biomarker to guide anticoagulation therapy among this patient population, according to results of a study published in the American Journal of Hematology.

It is now well-established that many patients with COVID-19 experience morbidity and mortality caused by coagulopathy, and investigators have been attempting to characterize the underlying mechanisms and to identify relevant biomarkers.

In March 2020, Jonathan Stefely, MD, PhD, and colleagues at the Coagulation Laboratory of Massachusetts General Hospital observed markedly elevated factor V activity in a patient with COVID-19. “This was the highest factor V activity level ever observed in our high-volume coagulation laboratory,” wrote the authors.

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This led them to hypothesize that venous thromboembolism, and possibly other complications of severe COVID-19, is associated with factor V activity.

In addition to factor V, they also measured factor VIII and X activity, and D-dimer and fibrinogen levels in 102 consecutive inpatients with COVID-19 admitted to Massachusetts General Hospital in Boston. The also measured samples from contemporaneous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (17 patients) and historical prepandemic controls (factor V, 44 patients; factor X, 346 patients; D-dimer, 373 patients; fibrinogen, 260 patients).

The patients with COVID-19 all had severe illness. During hospitalization, the majority of patients (92%) required ventilator use, and nearly half of patients experienced line clots (47%). Deep vein thrombosis (DVT) or pulmonary embolism (PE), and mortality occurred in 23% and 22% of patients, respectively.

Among the measured factors, factor V activity was significantly elevated in patients with COVID-19 (median, 150 IU/dL; range, 34-248 IU/dL) compared to contemporaneous SARS-CoV-2-negative controls (median, 105 IU/dL; range 22-161 IU/dL; P <1´10–5), and it was the factor most strongly associated with COVID-19.

Like previous studies, D-dimer was significantly elevated in patients with COVID-19 (median, 2849 ng/mL; 101 patients) compared with the reference range (<500 ng/mL) and historical controls (median, 546; 373 patients; P <1´10–7). Fibrinogen was also significantly elevated in patients with COVID-19 (median, 763 mg/dL; 91 patients) compared with the reference range (150-400 mg/dL), historical controls (median 349, P <1´10–23), and contemporaneous SARS-CoV-2-negative controls (median, 212 mg/dL; 9 patients; P <1´10–4).

Within the COVID-19 cohort, patients with COVID-19 and elevated factor V activity (>150 IU/dL) had a significantly higher rate of DVT/PE (16/49, 33%) compared with those with lower factor V activity (≤150 IU/dL; 7/53; 13%; P =.03). Similarly, patients with COVID-19 and elevated factor V activity had significantly a higher mortality rate (16/53; 30%) than those with lower factor V activity (6/49; 12%; P <.05).

Limitations of the study included small sample size for the contemporaneous SARS-CoV-2-negative controls and a lack of patients with mild COVID-19 illness.

“Our study reveals factor V perturbations as a previously unrecognized feature of severe COVID-19, adds a mechanistic candidate to ongoing investigations of COVID-19 coagulopathy with potential links to SARS-CoV-2 disease biology, and provides a foundation for future studies of COVID-19 coagulopathy diagnosis and biomarkers for guiding anticoagulation therapy in severe COVID-19,” the authors concluded.


Stefely JA, Christensen BB, Gogakos T, et al. Marked factor V activity elevation in severe COVID‐19 is associated with venous thromboembolism. Am J Hematol. Published online August 24, 2020. doi:10.1002/ajh.25979