CMAAO
CORONA FACTS and MYTH BUSTER 108 Thrombo-inflammation
Dr K K Aggarwal
President CMAAO
With inputs from Dr Monica Vasudev
930: Complete
Fibrinolysis Shutdown in Severe COVID-19
COVID-19
causes not only hypercoagulability, but also "fibrinolysis
shutdown," which is associated with venous thromboembolism (VTE), stroke,
and renal failure.
Complete
lack of clot lysis at 30 minutes on a thromboelastogram (TEG) assay, coupled
with a D-dimer value above 2600 ng/mL, identifies high-risk individuals who will potentially
require more aggressive anticoagulation.
Patients
with COVID-19 are at high risk of blood clots, both in small and large blood
vessels.
The study
was published online May 7 in the Journal of the
American College of Surgeons.
Wright
and colleagues did a retrospective study of 44 COVID-19 patients (28 male;
median age, 54 years).
The primary
study outcomes were VTE events and new-onset renal failure requiring dialysis.
Forty-one (93%) patients required mechanical ventilation, 16 (36%)
had acute renal failure requiring dialysis, 11 (25%) had a VTE, and
six (14%) had a thrombotic stroke.
Derangements
in coagulation laboratory values included an elevated D-dimer level and
elevated fibrinogen, with normal platelet counts in the majority of
patients and mildly elevated prothrombin time (PT) and partial
thromboplastin time (PTT), with median values at or slightly above the
upper limits of normal.
The
median International Society on Thrombosis and Haemostasis (ISTH) disseminated
intravascular coagulation (DIC) score was 0, with no patient having a
score higher than 4. TEG variables were consistent with a hypercoagulable state
with an elevated maximum amplitude and low lysis at 30 minutes.
On TEG
testing, more than half of patients (57%) had a complete lack of clot lysis at
30 minutes (LY30), and this was a significant predictor of VTE, with an
area under the receiver operating characteristic curve (AUROC) of 0.742 (P =
.021).
A D-dimer
cutoff of 2600 ng/mL was a significant predictor of need for dialysis,
with an AUROC of 0.779 (P = .005).
Overall, patients with no clot lysis at
30 minutes on TEG assay and a D-dimer value above 2600 ng/mL had a
rate of VTE of 50%, compared with 0% for patients with neither risk factor (P =
.008). The time to VTE was also significantly shorter in patients with
fibrinolysis shutdown.
The hemodialysis rate was 80% with these
two coagulation risk factors, compared with 14% without (P = .004).
This cohort of critically ill COVID-19
patients was clearly hypercoagulable, despite high normal or frankly elevated
PT and PTT levels, demonstrating the importance of using whole blood coagulation
assays (which more closely approximate in vivo conditions including the
presence of cells and platelets) such as the TEG for improved risk
stratification."
1.
Coronavirus disease 2019 (COVID-19) is
associated with a hypercoagulable state associated with acute inflammatory
changes and laboratory findings that are distinct from acute disseminated
intravascular coagulation (DIC), save for those with very severe disease.
2.
Fibrinogen and D-dimer are increased,
with typically only modest prolongation of the prothrombin time (PT) and
activated partial thromboplastin time (aPTT) and mild thrombocytosis or
thrombocytopenia.
3.
The presence of a lupus anticoagulant
(LA) is common in individuals with a prolonged aPTT.
4. The
risk for venous thromboembolism (VTE) is markedly increased, especially in
patients in the intensive care unit (ICU), with case series reporting
prevalences of 25 to 43 percent in ICU patients, often despite
prophylactic-dose anticoagulation.
5. The risk for other thrombotic events (stroke,
microvascular thrombosis) is less clear.
6. All
patients admitted to the hospital for COVID-19 should have a baseline complete
blood count (CBC) with platelet count, PT, aPTT, fibrinogen, and D-dimer.
Repeat testing is done according to the patient's clinical status.
7. Outpatients do not require coagulation
testing.
8. All
inpatients should receive thromboprophylaxis unless contraindicated. Low
molecular weight (LMW) heparin is preferred, but unfractionated heparin can
be used if LMW heparin is unavailable or if kidney function is severely impaired.
Some institutional protocols include more aggressive anticoagulation with
intermediate-dose or even therapeutic-dose anticoagulation for
thromboprophylaxis.
9. Therapeutic-dose
(full-dose) anticoagulation is appropriate to treat deep vein thrombosis (DVT)
or pulmonary embolism (PE), unless contraindicated.
10. Bleeding
is unusual but can occur. If it occurs, treatment is similar to non-COVID-19
patients and may include transfusions, anticoagulant reversal or
discontinuation, or specific products for underlying bleeding disorders.
What’s
new
COVID-19
hypercoagulable state (May 2020): Many reports have described a hypercoagulable state associated with
COVID-19. The prevalence of venous thromboembolism (VTE) is increased,
especially in critically ill individuals, often despite prophylactic
anticoagulation. Arterial thrombosis has also been reported but the prevalence
is not known. Some individuals have markedly elevated D-dimer, which correlates
with worse prognosis. Unlike disseminated intravascular coagulation (DIC), the
fibrinogen is often elevated, and clotting times and platelet counts are
typically normal.
Causes
of death from COVID-19 (May 2020)
Two new autopsy studies, together including a total
of 33 individuals who died of COVID-19, have revealed common causes of death to
be pneumonia and pulmonary embolism.
Lung histology also showed diffuse alveolar damage
consistent with early acute respiratory distress syndrome, and inflammatory
infiltrates consistent with viral or bacterial pneumonitis. In both studies,
the average age was in the mid-70s, most were men, and most had preexisting
conditions, especially heart disease, hypertension, diabetes, and obesity. While
both studies were small, they emphasize the contributions of lung inflammation
and hypercoagulability to fatal illness in this disease. [uptodate]
RV dilatation
Respiratory distress and myocarditis common in patients hospitalized with COVID-19 have an impact on the right ventricle (RV), but the acute effects and whether they create longer-lasting damage is less well understood as per a pair of recent reports in JACC: Cardiovascular Imaging.
In the retrospective study, 31% of more than 100 such patients with a
clinical indication for echocardiography were found to have RV dilation, a
feature that didn't track with myocardial inflammation or injury or with pulmonary embolism (PE). But it did
independently predict more than a fourfold increase in in-hospital mortality.
The RV dilation wasn't continuous, typically. These changes were dynamic. We saw patients moving in either
direction, going from normal ventricle to enlarged and going from enlarged to
normalized.
All of the people who had RV enlargement underwent CT angiography to
look for pulmonary embolisms, and only 50% of them had PE
The echocardiography study, was published May 15.
The other report included findings on postdischarge MRI in 26
consecutive patients from one center in Wuhan, China, who had recovered from
COVID-19 but later experienced cardiac symptoms, such as chest pain or
palpitations; none had a pre-COVID-19 history of myocarditis or other heart
disease.
Fifteen of the cohort, or 58%, showed MRI signatures for diffuse
myocardial edema and for fibrosis by late-gadolinium enhancement (LGE), or for
both along with impaired RV cardiac index and ejection fraction, despite preserved
LV function.
That was compared with 20 recent historical control subjects without
documented cardiovascular or inflammatory disease who underwent the same MRI
examinations.
The presence of myocardial tissue abnormalities in otherwise healthy subjects
suggests cardiac involvement as a lasting consequence of SARS-CoV-2 infection
Lu Huang, MD, PhD, Tongji Medical College and Huazhong University of
Science and Technology, Wuhan, in their report published May 11.
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