Thrombotic Events in Symptomatic COVID-19: New Data Suggest Potentially Attenuated Risk

Cleveland Clinic’s initial experience with thrombotic events in symptomatic patients with COVID-19 reveals a lower incidence of thrombosis than in prior published reports, although it was substantially higher than in the general population of hospitalized patients. The health system’s experience was recently published online as a research letter in Arteriosclerosis, Thrombosis, and Vascular Biology.

The observational study sought to quantify and characterize thrombotic outcomes among symptomatic adults with COVID-19 managed at Cleveland Clinic facilities in Northeast Ohio and South Florida from March 13 to May 13, 2020. Clinical and lab data were analyzed to identify predictors of thrombotic events, which were defined as venous thromboembolism (VTE), acute ischemic stroke or acute myocardial infarction (MI).

Findings by the numbers

Of 3,678 adults testing positive for SARS-CoV-2 during this two-month period, 892 (24.3%) were hospitalized and 296 (8.0%) required ICU admission.

Acute thrombotic events occurred in 46 of the 892 hospitalized patients (5.2%) and consisted of 24 VTEs, 11 acute ischemic strokes and 11 acute MIs.

Among the 296 ICU patients, thrombotic events developed in 26 (8.8%) and consisted of 15 VTEs, five strokes and seven acute MIs.

Key findings regarding risk and outcomes of thrombotic events included the following:

• Older age was the only demographic or comorbidity factor associated with an elevated risk of a thrombotic event (P = 0.05).
• Among hospitalized patients, those with a thrombotic event had higher C-reactive protein levels and higher WBC counts on admission compared with the rest of the cohort, but D-dimer levels did not differ between the groups. C-reactive protein was a significant predictor of thrombotic events on univariable analysis, and WBC count was a significant predictor on both univariable and multivariable analyses.
• Patients with thrombotic events were significantly more likely to require ICU admission, respiratory support, pressors and hemodialysis. In-hospital mortality was higher among those with versus those without a thrombotic event (17.5% vs. 12.0%), but the difference was not statistically significant.

The results in context

The researchers note that the incidence of thrombotic events in their study — 5.2% among hospitalized patients and 8.8% among ICU patients — is markedly lower than the rates in previously published reports of hospitalized patients with COVID-19, which ranged from 16% to nearly one-third and came from hospitals in New York City and the Netherlands. “This may reflect nonquantifiable risk factors that were perhaps absent in the regions we serve but present in COVID-19 epicenters such as New York City earlier this year,” observes senior author Scott Cameron, MD, PhD, Section Head of Vascular Medicine at Cleveland Clinic.

He adds that while some of the prior reports detected an association between D-dimer levels and thrombotic events, the Cleveland Clinic experience did not. “Notably, however, the elevation in white blood cells observed in our study was driven by neutrophilia rather than by lymphocytosis,” Dr. Cameron says. “This intriguing finding suggests a potential for in situ pulmonary immunothrombosis through mechanisms that remain to be defined and which merit further investigation.”

“These results point us away from using D-dimer to exclude thrombus in patients with COVID-19 and increase our index of suspicion for thrombosis in the setting of high inflammatory biomarkers,” adds Cleveland Clinic cardiologist Mina Chung, MD, Director of the American Heart Association’s COVID-19 Rapid Response Research Grants Coordinating Center.