Of COVID-19’s hallmark symptoms, clotting may not rank high in the
national consciousness. But it has made quite an impression in-hospital.
“I have never, ever, ever seen such high levels of D-dimer in any of
the hundreds of other patients with venous thrombosis that I’ve seen
over the past 15 years,” said Behnood Bikdeli, MD, of
NewYork-Presbyterian Hospital/Columbia University Irving Medical Center
in New York City. “It’s just mind-blowing.”
Clinicians treating COVID-19 patients have described
pervasive clots in the lungs on autopsy, breakthrough clotting
clogging dialysis lines despite antithrombotic medication, and even
clots forming in real-time during mechanical thrombectomy for ischemic stroke.
“At this point, even though our knowledge is limited, what we know is
highly suggestive of a prothrombotic milieu — an excess of thrombotic
events in the setting of COVID-19, specifically severe COVID-19,” said
Bikdeli.
Whether coagulopathy in COVID-19 is a
consequence or cause of what’s happening in the lungs remains unclear. However, consensus has formed on
anticoagulation treatment for hospitalized patients and sending them home with an empiric regimen.
Guidelines
from Bikdeli’s consensus group of the International Society on
Thrombosis and Haemostasis (ISTH) and other professional societies
recommended risk stratifying COVID-19 patients in the hospital for
venous thromboembolism (VTE) prophylaxis using the normal risk tools,
noting that once-daily dosing of unfractionated heparin gives it the leg
up on other options for reducing personal protective equipment use and
healthcare worker exposure.
Previously, ISTH had recommended prophylactic-dose low molecular
weight heparin (LMWH) for all hospitalized COVID-19 patients, even those
not in the ICU, unless they have contraindications such as active
bleeding or low platelet count (<25×10
9/L).
New guidance out last week from the National Institute for Public Health of the Netherlands, released in a report in
Radiology, advocated prophylactic-dose LMWH
for all hospitalized patients with or suspected to have COVID-19, irrespective of risk scores.
“One of the big questions… is whether when we see such elevated
D-dimer levels, do we have to empirically up our game and give more
intense antithrombotic agents or do we have to routinely screen for deep
vein thrombosis? There is no good answer at the moment,” Bikdeli told
MedPage Today.
Some centers are going ahead with full therapeutic dosing or
intermediate doses, based on subgroup analysis from a single
retrospective study from China suggesting high D-dimer predicted VTE
with over 85% specificity and sensitivity.
“The majority of [consensus group] panel members consider
prophylactic anticoagulation, although a minority consider
intermediate-dose or therapeutic dose to be reasonable,” Bikdeli’s group
wrote in the Journal of the American College of Cardiology.
The University of North Carolina at Chapel Hill is one such center
that has been using intermediate or full-dose anticoagulation for
COVID-19 patients, depending on their risk factors. Those with D-dimer
over 2,500 ng/mL get an intermediate dose, and full dose is used for
those with high suspicion of VTE without objective documentation
possible or who have repetitive clotting of dialysis tubing.
The Dutch group proposed a more nuanced algorithm for anticoagulation
dosing based on initial and rising D-dimer levels in hospital.
Elevated D-dimer levels, while common with COVID-19, do “not
currently warrant routine investigation for acute VTE in absence of
clinical manifestations or other supporting information,” Bikdeli’s
group argued, although urging a high index of suspicion in case of
typical deep vein thrombosis symptoms, hypoxemia disproportionate to
known respiratory pathologies, or acute unexplained right ventricular
dysfunction.
How long inflammation and
thrombotic derangements last after recovering from the symptoms of COVID-19 remains unclear as well.
Bikdeli’s consensus group’s recommendations advocated extended
prophylaxis with LMWH or direct oral anticoagulants (DOACs) as
reasonable after hospital discharge, with individualized risk
stratification for thrombotic and hemorrhagic risk.
Up to 45 days of prophylaxis could be considered for
low-bleeding-risk patients at elevated VTE risk due to reduced mobility
or comorbidities such as active cancer. Elevated D-dimer more than twice
the upper limit of normal was also suggested as a high-risk group to
get post-discharge extended prophylaxis, although without full consensus
from the writing group.
UNC’s algorithm calls for 30 days of DOAC use after discharge with
COVID-19. However, “our outpatient management in the algorithm is purely
empiric and non-evidence based!” cautioned Stephen Moll, MD, who helped
design the algorithm there.
Bikdeli agreed that the evidence isn’t solid, which is why it had to
be an international collaborative to form some interim consensus-based
guidance rather than the standard guideline process. “It wasn’t easy to
address.”
Still, “to some extent we can extrapolate to people with milder
COVID-19 who are homebound or people who have multiple risk factors for
venous thrombosis who are homebound,” Bikdeli noted, acknowledging that
the evidence was even scarcer for them.
For quarantined patients with mild COVID-19 but significant
comorbidities or who are being less active because of quarantine,
prophylaxis is uncertain, according to Bikdeli’s group: “These patients
should be advised to stay active at home. In the absence of high-quality
data, pharmacological prophylaxis should be reserved for those highest
risk patients, including those with limited mobility and history of
prior VTE or active malignancy.”
VTE can be challenging to diagnose for many reasons in hospitalized
COVID-19 patients, particularly for those in prone positioning. It’s
likely underdiagnosed, Bikdeli and colleagues noted.
Research letters from France in
Radiology recently reported
that 23% to 30% of pulmonary CT angiograms performed for COVID-19
patients showed acute pulmonary embolus (PE) — much higher than the 1.3%
typical for critically ill patients without COVID-19 infection or 3% to
10% seen in emergency department patients. Notably,
D-dimer over 2,660 µg/L had 100% sensitivity and 67% specificity for PE on CT angiography. Patients with PE were
more likely in the ICU and on mechanical ventilation.
Longer-term outcomes for such patients, incidence of events during
recovery outside the hospital, and other important questions haven’t
been looked at yet, Bikdeli noted.
“We are currently in a war zone,” he said, so it’s hard to follow-up
patients longitudinally. “It’s a critically important part of the care,
but just because of the priorities, many of the cardiology and critical
care-trained people in institutions across the country are being asked
to take care of those priorities in critically ill patients. But
addressing the thrombotic events in the inpatient and outpatient setting
are similarly important.”
https://www.medpagetoday.com/infectiousdisease/covid19/86230
