D-dimer-driven anticoagulation strategy of help for hospitalized COVID-19 patients

An anticoagulation strategy based on blood D-dimer level as a biomarker for clotting risk may help improve survival of patients hospitalized with COVID-19, according to a study presented during the ASH 2020 Meeting.

As SARS CoV-2 infection is known to put patients at high risk of thrombotic complications, anticoagulant use, particularly heparin, was believed to be of potential benefit.

“However, the optimal dose of anticoagulant for patients with COVID-19 is unknown,” said presenting author Dr Anastasia Martynova from the University of Southern California in Los Angeles, California, US. “Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19.”

The single-centre retrospective cohort study, which is part of an ongoing Quality Improvement programme on the use of heparin for anticoagulation, included 263 patients hospitalized with COVID-19. [ASH 2020, abstract 893] 

Under the D-dimer driven anticoagulation protocol, patients with no venous thromboembolism (VTE) were treated with a standard prophylactic dose of anticoagulant if blood D-dimer levels were <6 FEU/mL or an escalated prophylactic dose* of anticoagulant if their D-dimer levels were >6 FEU/mL. For those with known or suspected VTE, a standard therapeutic dose of anticoagulant was given instead.

Among the participants, 68.44 percent received a standard prophylactic dose, 12.55 percent were treated with an escalated prophylactic dose, and 19.01 percent were on a therapeutic dose. Almost half of the participants (49 percent) were under ICU care.

Overall, 12.6 percent of the cohort had died. Of note, D-dimer-driven use of therapeutic dose heparin was associated with better survival compared with the other two lower doses (standard and escalated prophylactic doses) during hospitalization (hazard ratio [HR], 0.13, 95 percent confidence interval [CI], 0.04–0.44). 

In addition, use of high-flow nasal cannula was also associated with improved survival based on a multivariate analysis (HR, 0.23, 95 percent CI, 0.07–0.72).

By contrast, increasing age (HR, 1.10, 95 percent CI, 1.05–1.15) and being under ICU care (HR, 20.42, 95 percent CI, 2.84–146.72) were factors associated with significantly greater risk of mortality.

Following the D-dimer driven anticoagulation protocol for COVID-19 inpatients appeared to be safe, noted Martynova.

“In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH** prophylaxis. By multivariate analysis, implementation of a D-dimer-titrated anticoagulation strategy was not associated with increased CRNMB,” she reported.

The primary outcome of ISTH-defined clinically relevant non-major bleeding (CRNMB) occurred in 4.56 percent of the overall cohort, with no difference between the groups receiving escalated prophylactic dose vs therapeutic dose (12 percent vs 12.12 percent).

By comparison, the incidence of CRNMB was less frequent in patients given the standard prophylactic dose (1.11 percent), although the difference did not reach statistical significance after adjusting for potential confounding factors including age, sex, ethnicity, comorbidities, BMI, sepsis-induced coagulopathy score (SICS) and HASBLED*** bleeding risk score.

There were no major bleeding events reported.

Nonetheless, the researchers also acknowledge the retrospective observational nature of the study and lack of a standardized diagnostic protocol for defining suspected VTE as limitations.

“Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population,” suggested Martynova.

*escalated prophylactic dose: Low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1–0.3 anti-Xa units or enoxaparin 0.5 mg/kg subcutaneously every 12 hours
**LMWH: Low-molecular-weight heparin
***HASBLED: Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly