Elevated D-dimer and Adverse In-hospital Outcomes in COVID-19 Patients and Synergism with Hyperglycemia

Abstract

Aim: One of the most common laboratory findings in COVID-19 patients has been observed to be hypercoagulability with elevated D-dimer levels. An activation of thrombosis may be generated by hyperglycemia. We aimed to explore the association between D-dimer and in-hospital outcomes, and evaluate the synergistic effect between elevated D-dimer and hyperglycemia on COVID-19 prognosis.

Methods: A retrospective cohort study was undertaken with 2467 COVID-19 inpatients. D-dimer and fasting blood glucose (FBG) on admission and adverse in-hospital outcomes (events of death and aggravated severity) were collected. Cox proportional risk model was performed to assess the association of D-dimer and adverse in-hospital outcomes, and the combined effects of D-dimer and FBG.

Results: Among these COVID-19 patients, 1100 (44.6%) patients had high D-dimer (≥0.50 mg/L). Patients with high D-dimer were older, with higher FBG (≥7.00 mmol/L), and had significantly higher adjusted risk of adverse in-hospital outcomes when comparing with those who with D-dimer<0.50 mg/L (hazard ratio, 2.73; 95% confidence interval, 1.46-5.11). Moreover, patients with high FBG and D-dimer levels had an increasing risk (hazard ratio, 5.72; 95% confidence interval: 2.65-12.34) than those with normal FBG and D-dimer.

Conclusion: Risk of adverse in-hospital outcomes is higher among patients with high D-dimer levels. Additionally, this study found for the first time that elevated D-dimer and hyperglycemia had a synergistic effect on COVID-19 prognosis, and this risk was independent of diabetes history.

Keywords: COVID-19; D-dimer; cohort study; hyperglycemia; in-hospital outcomes.

Figure 1

Flowchart for selection of the study patients.

Figure 2

Cox regression analysis of combined subgroups of D-dimer and FBG levels on the risk of adverse in-hospital outcomes. All substantial models are additionally adjusted for age, gender, disease type of admission, history of hypertension, diabetes, respiratory and cardiovascular and cerebrovascular disease, white blood cell count, hemoglobin, hs-CRP, creatinine, albumin and AST. *P<0.05. The subgroup with D-dimer<0.50 mg/L and FBG<7.00 mmol/L was defined as the reference group. There were 12(1.0%), 66(7.4%), 2(1.3%), and 38(18.3%) adverse in-hospital outcomes in the subgroup with D-dimer <0.50 mg/L and FBG <7.00 mmol/L, the subgroup with D-dimer ≥0.50 mg/L and FBG <7.00 mmol/L, the subgroup with D-dimer <0.50 mg/L and FBG≥7.00 mmol/L and the subgroup with D-dimer ≥0.50 mg/L and FBG≥7.00 mmol/L, respectively.