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Hemostatic Biomarkers Predictive of COVID-19 Outcomes in Patients With Cancer

December 5, 2022

Mid-January 2023

Hemostatic biomarkers were predictive of thromboembolism (TE), severe COVID-19, and death in patients with cancer and acute COVID-19 infection, according to a report from the National Cancer Institute’s COVID-19 in Cancer Patients Study (NCCAPS) presented at the 64th ASH Annual Meeting and Exposition.1 Alok A. Khorana, MD, of Cleveland Clinic in Ohio, pointed out that people with cancer have a higher risk of poor outcomes from COVID-19, though prospective data have been limited.

“The inflammatory response of SARS CoV-2 infection [the virus that causes COVID-19] causes both an acute phase response and endothelial dysfunction, and together these processes contribute to COVID-19-associated coagulopathy,” Dr. Khorana said.

Certain inflammatory and hemostatic biomarkers, such as D-dimer, have been associated with worse COVID-19 outcomes in the general population.2 “But it has not been known if these biomarkers can also predict COVID-19 outcomes in people with cancer,” Dr. Khorana added.

The NCCAPS study used a longitudinal cohort of patients with hematologic or solid malignancy within 14 days of a positive COVID-19 test. Eligible patients were within 14 days of initially testing positive and had history of a hematopoietic cell transplant or chimeric antigen receptor T-cell therapy or had received anticancer treatment within the past six weeks.

Of the 1,619 patients studied, 23% experienced severe disease. Within 30 days of a positive COVID test, 3% experienced a thromboembolic event. Within 90 days, 8% of patients in the cohort had died.

Biomarkers, assessed at initial COVID-19 diagnosis, were available for only a fraction of patients (193 to 227, depending on assay), which Dr. Khorana noted was a limitation of the study. Moreover, not all biomarkers thought to be associated with severe COVID-19 or mortality were available for assessment.

Baseline levels of two biomarkers were strongly associated with an increased risk of future TE: von Willebrand factor (VWF) and factor VIII (FVII; odds ratio [OR] = 1.18 per 10% above normal when measured as a continuous variable and 1.16 per 10% above normal, respectively).

Dr. Khorana added, “von Willebrand was associated with severe COVID-19, with a strong adjusted [OR] of 8.02 when measured as a categorical variable.”

Similarly, FVIII had an adjusted OR of 3.56 for severe COVID-19.

Dr. Khorana continued, “Ninety-day mortality was astoundingly high: an adjusted hazard ratio of 12.4 for elevated VWF when measured as a categorical variable.”

Looked at another way, patients with a normal VWF had a 98% chance of survival at 90 days, but patients who had elevated VWF during acute COVID-19 illness had an increased absolute risk of dying of about 13%. Similarly, having an increased FVIII at baseline testing resulted in an 8% increased risk of dying (96% survival to 88%).

Elevated D-dimer levels and high-sensitivity C-reactive protein were also both associated with increased mortality over 90 days and increased COVID-19 disease severity. Dr. Khorana said this finding confirms previous reports of an association between both tests and severe COVID-19 and mortality.

“Our findings provide insight into pathophysiological mechanisms of COVID-19 associated coagulopathy,” Dr. Khorana said. He speculated that this information might be used in clinical settings to identify patients with cancer and COVID-19 who are at high risk of poor outcomes.

Any conflicts of interest declared by the authors can be found in the original abstract.

References

  1. Khorana AA, Denicoff A, Bowman M, et al. Hemostatic biomarkers predict risk of thromboembolism (TE), severe COVID-19 and mortality: A report from the National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS). Abstract #136. Presented at the 2022 American Society of Hematology Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana.
  2. Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous thromboembolism: biological mechanismsThorax. 2021;76(4):412-420.

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