Bleeding disorder linked to poor clinical outcome in COVID-19 patients

The novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is the pathogen responsible for the ongoing coronavirus pandemic of 2019 (COVID-19). About 20 to 55% of hospitalized patients with COVID-19 are said to have disturbed hemostatic laboratory parameters, suggesting coagulopathy.

These abnormalities include a slightly prolonged prothrombin (PT) time, a higher concentration of D-dimer, mild thrombocytopenia and, in advanced stages, a decrease in fibrinogen. Studies suggest that a high concentration of D-dimer is linked to poor clinical outcomes, such as the need for intensive care or even death. Available data shows that COVID-19 is characterized by a pro-thrombotic state caused by massive thromboinflammation, which may originate from diseased lung endothelial cells.

A better understanding of COVID-19-related coagulopathy is crucial for healthcare professionals to mitigate the risk of thrombosis and bleeding by changing treatment options.

Transmission electron micrograph of SARS-CoV-2 virus particles isolated from a patient. Image captured and enhanced with color at the NIAID Integrated Research Center (IRF) in Fort Detrick, Maryland. Credit: NIAID

Systematic review of link between hemostatic parameters and poor COVID-19 outcomes

Recently, a team of researchers from Canada and the United States systematically demonstrated the link between hemostatic laboratory parameters and key clinical outcomes in adult patients with COVID-19. They analyzed hemostatic parameters such as the concentration of PT and D-dimer in COVID-19 patients and their association with important clinical outcomes such as bleeding, thrombosis, severe illness and death. The study is published on the pre-print server, withRxiv*.

The team performed a systematic review of observational studies, randomized clinical trials, and case series published in PubMed (Medline), CENTRAL, and EMBASE between December 1, 2019 and March 25, 2020. Studies in adult patients with COVID -19 reporting at least one hemostatic laboratory parameter was included in the analysis.

High concentration of D-dimer is the best predictor of adverse clinical outcomes

The researchers extracted data from 57 studies, including more than 12,000 patients who met their inclusion criteria. 45% of the patients in the studies were female, and the average age of the patients was 52 years. Of the studies included in the review, 92.7% (N = 38/41) of the studies reported an average platelet count greater than 150 x 10⁹/ L, 68.2% (N = 15/22) of studies reported a mean PT of 11-14 s, 55% (N = 11/20) of studies reported a mean activated partial thromboplastin (TCA) time of the order of
25 to 35 s and 34.4% (N = 11/32) of the studies reported a concentration of D-dimer above the upper limit of normal (ULN).

Eight studies, including 7 cohorts and 1 case series, reported hemostatic laboratory values ​​for survivors compared to non-survivors. D-dimer concentrations were reported in 4 studies in non-survivors, and all reported an average level of D-dimer greater than ULN.

Based on the results, the researchers concluded that most of the patients hospitalized with COVID-19 had normal platelet counts, PT and aPTT values ​​in the upper reference range, and increased D-dimer concentrations. However, there was no explanation for how these hemostatic parameters were related to poor outcomes. Elevation of D-dimers appeared to be the best predictor of poor clinical outcomes.

“COVID-19-associated coagulopathy has been hypothesized to be due to pulmonary vascular endotheliopathy, which may contribute to the risk of thromboembolism and death in hospitalized patients with COVID-19.”

Findings Could Help Doctors Triage Severe COVID-19 Patients With Coagulopathy

The authors believe these findings provide a framework to guide healthcare professionals who care for patients with COVID-19. The results are consistent with data from COVID-19 hospital patients in Wuhan, China, which showed that patients requiring intensive care had a median D-dimer concentration of 2.4 mg / L versus 0.5 mg / L in those who did not need it. care.

Likewise, a New York study reported that a 4-fold higher D-dimer concentration was associated with an approximately 5-fold higher likelihood of severe disease compared to a normal D-dimer concentration.

This information may help doctors triage severe COVID-19 patients with coagulopathy and support the recommendation for close monitoring of COVID-19 in patients with elevated D-dimer concentrations. According to the authors, further studies are essential to confirm this correlation between hemostatic parameters and the risk of adverse clinical outcomes such as bleeding and thrombosis.

“This information will help frontline healthcare professionals use hemostatic laboratory settings for prognosis as well as triage of patients to the appropriate disposition, which is especially critical during a pandemic if resources are depleted.

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as established information.