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Blood Viscosity Enters the Equation in COVID Mortality

— Its association with death may be unrelated to inflammation

Ƶ MedicalToday
A computer rendering of red and white blood cells.

People with thicker blood were less likely to survive hospitalization for COVID-19, according to an observational study.

As estimates of whole blood viscosity at different shear rates, estimated high-shear and low-sheer blood viscosity (eHSBV and eLSBV) were associated with increased in-hospital mortality, such that one unit increases in each were associated with 36.0% and 7.0% greater risks of death, respectively (P<0.001).

After adjustment for interleukin-6 and other inflammatory biomarkers, only the high-sheer measure remained significantly associated with mortality, reported Robert Rosenson, MD, a cardiologist at Mount Sinai Medical Center, New York City, and colleagues in the July 26 issue of the .

Study results supported a link between hyperviscosity and the immune-mediated thrombosis of acute COVID-19 illness.

"This study demonstrates the importance of checking for blood viscosity in COVID-19 patients early in hospital admission, which is easily obtained through routine lab work. Results can help determine the best treatment course for at-risk patients and help improve outcomes," said Rosenson in a press release.

"We are currently investigating the effects of therapeutic heparin to reduce the risk of complications during acute COVID-19 infections, which may greatly benefit those with high blood viscosity," he added.

In the large platform trials, therapeutic-dose heparin improved survival for hospitalized COVID-19 patients but . However, those trials did not incorporate blood viscosity as a factor.

Rosenson's observational study included 5,621 COVID-19 patients hospitalized across six hospitals in the Mount Sinai Health System.

Study authors noted that whole blood viscosity (WBV) is a validated measure of blood rheology and established predictor of cardiovascular risk. WBV is largely determined by hematocrit, plasma viscosity, erythrocyte aggregation, and erythrocyte deformability.

The study did not directly measure WBV, however, and instead relied on estimated BV (eBV) calculated from hematocrit, albumin, and total protein levels per the Walburn-Schneck model.

"Following the introduction of novel antiviral agents for COVID-19 to be administered especially in the community setting, refining risk stratification strategies to identify subjects with COVID-19 at elevated risk for disease progression is of utmost importance. The assessment of the prognostic role of eBV in the larger population of COVID-19 outpatients shall therefore be desirable," commented Aldo Bonaventura, MD, PhD, of Ospedale di Circolo e Fondazione Macchi in Varese, Italy, and Nicola Potere, MD, of G. d'Annunzio University of Chieti-Pescara, also in Italy.

"While still requiring adequate -- both external and prospective -- validation, eBV is likely to represent an attractive biomarker, as it was shown to be an early and robust predictor of mortality, and it is widely available and relatively inexpensive. In light of the translational potential associated with eBV, further investigation is eagerly warranted to confirm and expand the present findings, in order to advance eBV into the clinical scenario," the pair wrote in an .

COVID-19 patients included in the study had been hospitalized at some point from early 2020 to late 2021.

Participants with higher eHSBV tended to have higher inflammatory markers at baseline. Those in the highest quartile of eHSBV were more likely to be men, of Black or Hispanic race or ethnicity, have a history of diabetes, and require oxygen support at the time of presentation.

The highest quartile of eHSBV (range 4.53-9.86 centipoise [cP]) had significant excess mortality compared with lowest quartile in the 3.01-4.00 cP range (adjusted HR 1.53, 95% CI 1.27-1.84). The difference was consistent across subgroups with the exception of Asian people, who showed no difference in mortality between highest and lowest quartiles.

"While it has been reported that hyperviscosity may increase the risk of developing thrombotic events in critically ill patients with COVID-19, a clear, direct link between the proposed mechanism (i.e., hyperviscosity) and the putative ensuing clinical event (i.e., thrombosis) is still lacking," Bonaventura and Potere said.

Study authors noted the study's limitations in its retrospective nature and lack of direct measurement of WBV. Patients from later stages of the pandemic -- with the advent of new variants and vaccines -- were also not included in the study.

"The impact of distinct SARS-CoV-2 variants and vaccines on blood viscosity still remains to be elucidated," according to Bonaventura and Potere.

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    Nicole Lou is a reporter for Ƶ, where she covers cardiology news and other developments in medicine.

Disclosures

Rosenson's group had no disclosures.

Bonaventura disclosed a travel grant from Kiniksa Pharmaceuticals and honoraria from Effetti srl.

Potere reported a training fellowship from the International Society on Thrombosis and Haemostasis.

Primary Source

Journal of the American College of Cardiology

Choi D, et al "Association of blood viscosity with mortality among patients hospitalized with COVID-19" J Am Coll Cardiol 2022; DOI: 10.1016/j.jacc.2022.04.060.

Secondary Source

Journal of the American College of Cardiology

Bonaventura A, Potere N "Blood hyperviscosity: a novel link between hyperinflammation and hypercoagulability in COVID-19" J Am Coll Cardiol 2022; DOI: 10.1016/j.jacc.2022.04.061.