Factor V activity a key feature in COVID-19 outcomes

Patients with severe COVID-19 infections who have elevated factor V activity are at high risk for coagulopathy such as deep vein thrombosis and pulmonary embolism, US researchers have shown.

Subsequent decreases in factor V were also linked to progression toward disseminated intravascular coagulation (DIC) and death, according to findings published in the American Journal of Hematology.

Researchers at Massachusetts General Hospital say their findings point to disturbances in factor V activity as both a potential cause of coagulation disorders in COVID-19 disease, and to potential methods for identifying at-risk patients with the goal of selecting the proper anticoagulation therapy.

They started their investigation after noticing in the early days of the COVID-19 that a blood sample from a patient with severe COVID-19 on a ventilator contained factor V levels high above the normal reference range.

Four days later, this patient developed a saddle pulmonary embolism. This pointed the investigators to activity of factor V as well as factor VIII and factor X, two other major clotting factors.

They studied the levels of these clotting factors and other parameters in a group of 102 consecutive patients with COVID-19, and compared the results with those of current critically ill patients without COVID-19, and with historical controls.

They found that factor V activity was significantly elevated in COVID‐19 patients (median 150 IU/dL, range 34–248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22–161 IU/dL) (P < 0.00001) – the strongest association with COVID‐19 of any parameter studied, including factor VIII, fibrinogen, and D‐dimer.

In all, 33% of patients with factor V activity well above the reference range had either deep vein thrombosis or a pulmonary embolism, compared with only 13% of patients with lower levels.

Death rates were significantly higher for patients with lower levels of factor V (30% vs. 12%), with evidence that this was due to a clinical decline toward a DIC-like state.

“Aside from COVID-19, I’ve never seen anything else cause markedly elevated factor V, and I’ve been doing this for 25 years,” said study co-investigator Dr Elizabeth Van Cott of the Coagulation Laboratory at MGH.

She said the research also found that the clinical decline toward DIC was foreshadowed by a measurable change in the waveform of  the activated partial thromboplastin time (PTT).

“The waveform can actually be a useful tool to help assess patients as to whether their clinical course is declining toward DIC or not,” Dr Van Cott said. “The lab tests that usually diagnose DIC were not helpful in these cases.”

Importantly, the MGH investigators note that factor V elevation in COVID-19 could cause misdiagnosis of some patients, because under normal circumstances factor V levels are low in the presence of liver dysfunction or DIC.

Physicians might therefore mistakenly assume that patients instead have a deficiency in vitamin K.

“Together, these data reveal marked perturbations of factor V activity in severe COVID‐19, provide links to SARS‐CoV‐2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID‐19,” the study authors concluded.

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