Complete Fibrinolysis Shutdown Seen in Severe COVID-19

Megan Brooks

May 28, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

COVID-19 causes not only hypercoagulability, but also "fibrinolysis shutdown," which is associated with venous thromboembolism (VTE), stroke, and renal failure, clinicians from Colorado have observed.

They have found that the 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.

"Our findings support a growing body of evidence that patients with COVID-19 are at high risk of blood clots, both in small and large blood vessels," Frank Wright, MD, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, told | Medscape Cardiology.

The study also suggests a method to identify patients at highest risk for these complications "with a goal of providing more aggressive blood-thinning medications to attempt prevent these complications," said Wright.

The study was published online May 7 in the Journal of the American College of Surgeons.

Coagulation Derangements

Wright and colleagues did a retrospective study of 44 COVID-19 patients (28 male; median age, 54 years) admitted to the intensive care unit who had at least one TEG assay performed early in the course of illness, as well as other conventional coagulation assays.

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 (= .021).

A D-dimer cutoff of 2600 ng/mL was a significant predictor of need for dialysis, with an AUROC of 0.779 (= .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).

"Of note," write the researchers, "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."

"These study results suggest there may be a benefit to early TEG testing in institutions that have the technology to identify COVID-19 patients who may need more aggressive anticoagulation therapy to prevent complications from clot formation," Wright said in a news release.

"TEG testing is certainly not universally available," he told | Medscape Cardiology. "However, many larger hospitals, especially those with major trauma centers, transplant programs, or high-volume cardiothoracic surgical activity may have access to this tool to more comprehensively understand blood clotting issues in critically ill patients."

Commenting on the study for | Medscape Cardiology, Anu Lala, MD, assistant professor of medicine (cardiology), Icahn School of Medicine at Mount Sinai, New York City, noted that thromboembolic disease is now recognized as a "frequent and concerning complication" among patients hospitalized with COVID-19.

This study, she added, suggests there is also a degree of "fibrinolysis shutdown," as evidenced by the TEG results and elevated D-dimer levels.

"We are in desperate need of prospective randomized clinical trials to inform 1) predictors of which patients will benefit from anticoagulation and 2) optimal anticoagulation regimens, including which agents, what doses, and what duration, for specific populations infected with COVID-19," Lala said.

Support for the study was provided by the Colorado Clinical & Translational Sciences Institute (CCTSI). Wright and Lala have no relevant disclosures.

J Am Coll Surg. Published online May 7, 2020. Full text


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