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.

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

“…A recent study to evaluate the effect of hyperglycemia and hypercoagulability on COVID-19 prognosis has shown that elevated hyperglycemia and D-dimer had a synergistic effect on COVID-19 prognosis, and this risk was independent of diabetes history [ 109 ]. In the case of COVID-19, in which physiopathology is characterized by hyperinflammatory response with cytokine overproduction and cardiovascular disorder, it is not yet clear whether the diabetes condition increases the risk of infection or its severity [ 110 ], magnifying the pathogenicity of SARS-CoV-2 since both COVID-19 and diabetes share some pathological mechanisms.…”

Prothrombotic status in COVID‑19 with diabetes mellitus (Review)

“…In a recent review presenting the relationship between DM and COVID-19, it was emphasized that ever since the emerging of the virus, it was observed that patients with DM had a worse outcome when contracting SARS-CoV-2, presenting statistically higher rates of ARDS, organ damage, necessity of hospitalization in ICUs and higher mortality rates, regardless of the geographical area where the studies were performed (53). Some of the most relevant studies regarding the association between DM and COVID-19 that demonstrated the prothrombotic state observed in these patients are summarized in Table I (5,(54)(55)(56)(57)(58)(59).…”

Pathophysiological and laboratory aspects of hemostatic disorders in patients with COVID-19

“…Han et al estimated that D-dimer and fibrinogen were elevated in all COVID-19 patients, so that the concentrations were higher in patients with severe SARS-CoV-2 infection than those in patients with milder forms (46). Similarly, Nopp pointed out that COVID-19 patients developing venous thromboembolism had higher D-dimer levels (47). Several studies described that elevated D-dimer levels correlate with adverse outcomes, and that COVID-19 patients with high values of this parameter should be hospitalized, even if they have no other symptoms, because of the potential risk of thrombosis (48 -50).…”