Elevated clotting issue V ranges linked to worse outcomes in extreme COVID-19 infections

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Elevated clotting factor V levels linked to worse outcomes in severe COVID-19 infections

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Patients hospitalized with severe COVID-19 infections and high levels of clotting protein factor V are at increased risk of serious blood clot injuries, such as deep vein thrombosis or pulmonary embolism, researchers at Massachusetts General Hospital (MGH) have found.

On the other hand, critically ill patients with COVID-19 and low factor V levels appear to be at increased risk of death from a coagulopathy that resembles disseminated intravascular coagulation (DIC), a devastating, often fatal abnormality in which small blood clots form Vessels throughout the body that lead to depletion of clotting factors and proteins that control clotting, report Dr. Elizabeth M. Van Cott, researcher for the Department of Pathology at MGH and colleagues.

Their results, which are based on studies of patients with COVID-19 in MGH intensive care units (ICUs), point to disturbances in factor V activity as both a possible cause of blood clotting disorders with COVID-19 and possible methods of identifying at-risk patients with the aim of choosing the right anticoagulation therapy.

The study results are published online in the American Journal of Hematology.

"Aside from COVID-19, I have never seen anything else that causes a significantly increased factor V and has for 25 years," says Van Cott.

Patients with severe COVID-19 illness caused by the SARS-CoV-2 virus may develop blood clots in medical lines (intravenous lines, catheters, etc.) as well as in arteries, lungs, and extremities, including the toes. However, the mechanisms underlying coagulation disorders in patients with COVID-19 are still unknown.

In March 2020, in the early days of the Massachusetts COVID-19 pandemic, Van Cott and colleagues found that a ventilator blood sample from a patient with severe COVID-19 had factor V levels well above the normal reference range . Four days later, this patient developed a saddle pulmonary embolism, a potentially fatal blood clot that occurs at the junction of the left and right pulmonary arteries.

This pointed the researchers to the activity of factor V as well as factor VIII and factor X, two other major clotting factors. They examined the levels of these coagulation 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 levels were significantly increased in patients with COVID-19 compared to controls and that the association between high factor V activity and COVID-19 was strongest among all clinical parameters examined.

Overall, 33 percent of patients with factor V activity well above the reference range had either deep vein thrombosis or pulmonary embolism, compared with only 13 percent of those with lower levels. Mortality rates were significantly higher in patients with lower Factor V scores (30 percent versus 12 percent), suggesting that this was due to a clinical decline towards a DIC-like condition.

Van Cott and colleagues also found that the clinical decline towards DIC was caused by a measurable change in the shape or "waveform" of a graph showing light absorption versus the time it took for the blood to coagulate (waveform of activated partial thromboplastin time, or aPTT ), was predicted).

"The waveform can actually be a useful tool for patients to judge whether or not their clinical progression is decreasing towards DIC," explains Van Cott. "The laboratory tests that normally diagnose DIC have not been helpful in these cases."

Importantly, the MGH researchers note that an increase in factor V in COVID-19 can lead to a misdiagnosis in some patients because factor V levels are low under normal circumstances in the presence of liver dysfunction or DIC. Doctors may therefore mistakenly assume that patients are deficient in vitamin K instead.

"This investigation was fueled by the surprise case we witnessed and was quickly conducted by an interdisciplinary pathology team at MGH during the height of the pandemic," said Dr. Jonathan Stefely, one of the co-authors of the study.

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More information:
Jonathan A. Stefely et al., Marked Increase in Factor V Activity in Severe COVID-19 Is Associated with Venous Thromboembolism, American Journal of Hematology (2020). DOI: 10.1002 / ajh. 25979

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Massachusetts General Hospital

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