DHM COVID-19 Clinical Dispatch

Bite-sized, weekly clinical updates

Issue #3: Hypercoagulability in COVID-19

This week we bring you a discussion on hypercoagulability in COVID. Does COVID-19 induce a unique thrombophilic state distinct from other infections? It is a fascinating topic with potentially big implications for management, but so far with minimal data of variable quality.

We start with a series of pathology images from Varga et al. showing endothelial cell dysfunction in autopsy specimens suggesting endotheliitis may be induced by COVID-19.

We then present data from two Tang et al. articles, showing the association of coagulation abnormalities with poor outcomes in COVID and a potential benefit from full dose anticoagulation in severe disease. These and other data have led many to believe that a hypercoagulable state may play a role in the pathogenesis of severe COVID.

Our Big Takeaways for the week?
We think there is compelling evidence that endothelial dysfunction and coagulopathy play a role in severe COVID disease but it’s unclear at this point precisely how this should impact management, and specifically whether we should change our approach to anticoagulation in these patients.

- The COVID Clinical Working Group

Pathology of endothelial cell dysfunction in COVID-19
(A, B) Electron microscopy of kidney tissue shows viral inclusion bodies in a peritubular space and viral particles in endothelial cells of the glomerular capillary loops. Aggregates of viral particles (arrow) appear with dense circular surface and lucid centre. (C) Small bowel resection specimen of patient 3, stained with haematoxylin and eosin. Arrows point to dominant mononuclear cell infiltrates within the intima along the lumen of many vessels. (D) Post-mortem lung specimen stained with haematoxylin and eosin showed thickened lung septa, including a large arterial vessel with mononuclear and neutrophilic infiltration (arrow in upper inset).

The Big Question

Does COVID uniquely predispose patients to Hypercoagulability?

Dynamic profile of coagulation parameters in patients with COVID-19 (survivors in BLUE, non-survivors in GREEN). (Tang et al. 2020)

Last week in our dispatch on predictors of severe disease, we highlighted the association of D-dimer and poor clinical outcomes. Similarly, a retrospective study showed that compared with survivors, non-survivors of COVID-19 had abnormal D-dimer and Fibrin Degradation products and developed DIC at much higher rates. Though the study is small, it is supported by a growing body of evidence that a COVID induces a prothrombotic state, especially in severe disease.

Quick Lit - One-Page Literature Review

Within Our Walls - What is Happening at UCSF?

We expect official guidance to come from our clinical working groups shortly. In the interim, Dr. Andy Leavitt from hematology suggested the following best practices:

All patients, ICU or otherwise, at admission get PT, aPTT, fibrinogen and D-dimer
Repeat q2-3 days regardless of clinical course
ALL COVID+ patients on VTE ppx (at standard dosing)
No plan yet for higher dose AC or empiric full AC, though this may change

What We're Reading

Here are the articles that our team is reading this week, which are particularly relevant to this issue. To see more in-depth summaries please head over to our Literature Database!

“Hematological findings and complications of COVID-19” (Am J Hem, April 13): This review article notes that abnormal hematologic findings are common in patients with COVID-19 and correlate with severe disease, disease complications, and mortality. Disordered coagulation is a significant concern in this patient population, and elevated D-dimer and prolonged PT and aPTT are associated with worse outcomes.
“Prominent changes in blood coagulation of patients with SARS-CoV-2 infection” (Clin Chem and Lab Med, Mar 16): This prospective study of 94 COVID+ patients in a single Chinese hospital finds evidence of significant coagulation dysfunction in patients with COVID-19, and this is worse in patients with severe disease - most notably with higher D-dimer and fibrin degradation products.
“COVID-19-Related Severe Hypercoagulability in Patients Admitted to ICU for Acute Respiratory Failure” (Thromb Haemost, April 21): This single-center retrospective study detected high fibrinogen, high D-dimer and markedly hypercoagulable thromboelastography profiles in 22 ICU patients with COVID-19 and ARDS in Italy.
“Incidence of thrombotic complications in critically ill ICU patients with COVID-19” (J Thromb Res, April 10): This multi-center, retrospective review describes a 31% incidence of venous or arterial thrombotic events (PE, VTE, ischemic stroke, MI or systemic arterial embolism) of 184 ICU patients with COVID-19 in Denmark
"Endothelial cell infection and endotheliitis in COVID-19” (Lancet, April 20): This correspondence in the Lancet describes 3 patients who died of COVID-19 with multiorgan failure. In each case, pathologic evaluation revealed viral presence and dysfunction of endothelial cells in affected organs (kidney, lung, intestine, liver, heart), suggesting a possible, direct viral effect on the endothelium and impaired microcirculatory function.
“Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2” (J Thromb and Thrombolysis, April 3): This retrospective analysis of 449 COVID and 104 non-COVID patients with severe pneumonia found no differences in use of heparin or in baseline coagulation parameters. However, in the COVID+ group the use of heparin was associated with a decrease in 28-day mortality for those with significantly elevated D-dimers, suggesting that some COVID patients have a hypercoagulable state that may benefit from full dose anticoagulation.
“Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia” (ISTH, Feb 18): This is an early retrospective analysis of 183 consecutive patients with confirmed COVID-19 for coagulation parameters, stratified by survival. On admission, non-survivors were found to have higher Prothrombin Time, D-dimer and Fibrin Degradation Products - these continued to rise over the course of hospitalization, and non-survivors developed DIC at markedly higher rates.

Test Yourself!

Can you answer this question from last issue’s article of the week?

In the Zhou et al retrospective cohort study reviewed last week, which of the following was not a co-morbidity found to be significantly associated with mortality among confirmed COVID patients?

Hypertension
Coronary heart disease
Obesity
Diabetes

See the answer here!

Links

Questions, thoughts, insights? Share them here! Clinical Knowledge Portal

Prior Dispatches:

Issue 1: GI symptoms in COVID

Issue 2: Predictors of Severe COVID Disease