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.
- 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.
- Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms. Thorax. 2021;76(4):412-420.