Elevated D-dimer levels common months after COVID-19 diagnosis
More than one-quarter of patients with COVID-19 had elevated D-dimer levels up to 4 months after diagnosis, according to study results published in Journal of Thrombosis and Haemostasis.
“Elucidating the biological mechanisms responsible for sustained D-dimer increases may be of relevance in long COVID-19 pathogenesis and has implications for clinical management of these patients,” Liam Townsend, PhD candidate in the department of infectious diseases at St. James’s Hospital in Dublin, and colleagues wrote. “Persistent fatigue, breathlessness and reduced exercise tolerance have been reported after acute COVID-19 infection. Although immunothrombosis has been implicated in acute COVID-19 pathogenesis, the biological mechanisms underpinning long COVID-19 remain unknown.”
Townsend and colleagues examined clinical parameters combined with coagulation and inflammation biomarkers of 150 patients (mean age, 47.3 years; 56.7% women; 71.3% white) with COVID-19 who received care at St. James’s Hospital Dublin between May and September 2020.
More than half (54%) of patients had underlying comorbidities, including hypertension (18%), type 2 diabetes (9.3%), asthma (9.3%), hyperlipidemia (8%), ischemic heart disease (6.7%) and malignancy (6.7%). About 15% of patients had obesity (BMI 30 kg/m2) and 18.7% had overweight (BMI 25 kg/m2-30 kg/m2). Most (n = 81) were managed solely in the outpatient setting, whereas 69 patients underwent hospitalization during initial illness.
Standard doses of low-molecular-weight heparin prophylaxis were administered to all hospitalized patients throughout admission. Inpatient thromboprophylaxis dose was adjusted according to weight and renal function, but not according to D-dimer levels or level of care, according to the researchers.
Patients underwent clinical examinations, chest X-ray and 6-minute walk tests. Researchers also assessed coagulation and inflammatory markers.
Median time to follow-up was 80.5 days after initial diagnosis.
Results showed a median D-dimer level of 327 ng/mL, considered within the normal local range. However, 25.3% of patients had D-dimer levels higher than 500 ng/mL up to 4 months after diagnosis, with a median D-dimer level of 744 ng/mL among this group.
Researchers also noted that 8% of patients assessed during the recovery phase had D-dimer levels more than twice the upper limit of normal.
Increased D-dimer levels appeared more common among patients with COVID-19 who required hospitalization, as well as those aged older than 50 years (P < .001 for both).
Nearly one-third (29%) of patients with increased convalescent D-dimer levels received care exclusively in the outpatient setting. Other coagulation and inflammation markers returned to normal levels among more than 90% of convalescent patients.
“Despite ongoing symptoms and elevated D-dimers, CT pulmonary angiogram screening in eight patients failed to demonstrate pulmonary embolism,” the researchers wrote. “Further adequately powered studies will be required to elucidate the mechanisms underlying elevated D-dimer levels during COVID-19 convalescence. ... Furthermore, it seems likely that extravascular pulmonary fibrinolysis may be important in the etiology of elevated D-dimers during COVID-19 recovery. Given emerging data regarding post-infection long COVID-19 syndrome, as well as ongoing discussions regarding optimal duration of thromboprophylaxis in [patients with COVID-19] following discharge, defining these mechanisms may be of direct clinical relevance.”