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

Date:
September 8, 2020
Source:
Massachusetts General Hospital
Summary:
New research points to disturbances in blood clotting protein factor
V activity as both a potential cause of blood clotting disorders
with COVID-19, and to potential methods for identifying at-risk
patients with the goal of selecting the proper anticoagulation
therapy.



FULL STORY ========================================================================== Patients hospitalized with severe COVID-19 infections who have high
levels of the blood clotting protein factor V are at elevated risk
for serious injury from blood clots such as deep vein thrombosis or
pulmonary embolism, investigators at Massachusetts General Hospital
(MGH) have found.


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

Their findings, based on studies of patients with COVID-19 in MGH
intensive care units (ICUs), point to disturbances in factor V activity
as both a potential cause of blood clotting disorders with COVID-19,
and to potential methods for identifying at-risk patients with the goal
of selecting the proper anticoagulation therapy.

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

"Aside from COVID-19, I've never seen anything else cause markedly
elevated factor V, and I've been doing this for 25 years," Van Cott says.

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



==========================================================================
In March 2020, in the early days of the COVID-19 pandemic in
Massachusetts, Van Cott and colleagues found 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, a potentially fatal blood clot
occurring at the junction of the left and right pulmonary arteries.

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 levels were significantly elevated among patients
with COVID-19 compared with controls, and that the association between
high factor V activity and COVID-19 was the strongest among all clinical parameters studied.

In all, 33 percent of patients with factor V activity well above the
reference range had either deep vein thrombosis or a pulmonary embolism, compared with only 13 percent of patients with lower levels. Death rates
were significantly higher for patients with lower levels of factor V (30 percent vs. 12 percent), with evidence that this was due to a clinical
decline toward a DIC-like state.

Van Cott and colleagues also found that the clinical decline toward
DIC was foreshadowed by a measurable change in the shape or "waveform"
of a plot charting light absorbance against the time it takes blood
to coagulate (waveform of the activated partial thromboplastin time,
or aPTT).



==========================================================================
"The waveform can actually be a useful tool to help assess patients as
to whether their clinical course is declining toward DIC or not," Van
Cott explains. "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.

"This investigation was spurred by the surprising case we encountered,
and was conducted rapidly by an interdisciplinary pathology team at
MGH during the peak of the pandemic," said Jonathan Stefely, MD, PhD,
one of the study's co- authors.

Other co-authors of the study include Bianca B. Christensen, MD,
MPH; Tasos Gogakos, MD, PhD; Jensyn K. Cone Sullivan, M.D; Gabriella
G. Montgomery, BS; and John P. Barranco, BS, all of MGH and Harvard
Medical School.

The study was internally funded. All authors reported no conflicts of
interest to disclose.


========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jonathan A. Stefely, Bianca B. Christensen, Tasos Gogakos, Jensyn
K. Cone
Sullivan, Gabriella G. Montgomery, John P. Barranco, Elizabeth
M. Van Cott. Marked factor V activity elevation in severe
COVID‐19 is associated with venous thromboembolism. American
Journal of Hematology, 2020; DOI: 10.1002/ajh.25979 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200908131122.htm

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