Association of D-dimer elevation with inflammation and organ dysfunction in ICU patients with COVID-19 in Wuhan, China: a retrospective observational study

Abstract

Coronavirus disease 2019 (COVID-19)-associated coagulation dysfunction is gaining attention. In particular, dynamic changes in the D-dimer level may be related to disease progression. Here, we explored whether elevated D-dimer level was related to multiple organ failure and a higher risk of death. This study included 158 patients with COVID-19 who were admitted to the intensive care unit (ICU) at Jinyintan Hospital in Wuhan, China between January 20, 2020 and February 26, 2020. Clinical and laboratory data were collected. The relationship between D-dimer elevation and organ dysfunction was analyzed, as were dynamic changes in inflammation and lipid metabolism. Approximately 63.9% of patients with COVID-19 had an elevated D-dimer level on ICU admission. The 14 day ICU mortality rate was significantly higher in patients with a high D-dimer level than in those with a normal D-dimer level. Patients with a D-dimer level of 10-40μg/mL had similar organ function on ICU admission to those with a D-dimer level of 1.5-10μg/mL. However, patients with higher levels of D-dimer developed organ injuries within 7 days. Furthermore, significant differences in inflammation and lipid metabolism markers were observed between the two groups. In conclusion, the D-dimer level is closely related to COVID-19 severity and might influence the likelihood of rapid onset of organ injury after admission.

Keywords: COVID-19; D-dimer; coronavirus disease 2019; critical care; organ dysfunction; retrospective study.

Figure 1

Heat maps of the correlation between the D-dimer level and laboratory results. (A) The number of patients with abnormalities in 46 parameters varied according to D-dimer level at the time of ICU admission. (B) The number of patients with abnormalities in 52 parameters varied according to D-dimer level during ICU treatment. D0: D-dimer<1.5μg/mL, D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL, D3: D-dimer≥40μg/mL. Normal: the result is within the normal range, High: the result is beyond the normal range, Low: the result is below the normal range. *P<0.05, **P<0.01, ***P<0.001 among these 4 groups, abbreviation and range of normal values can be found in Supplementary Table 3, Supplementary files.

Figure 2

The 7- and 14-day mortality rates in patients with different D-dimer levels at ICU admission. Survival curves of patients with different D-dimer level within 7 and 14 days. D0: D-dimer<1.5μg/mL, D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL, D3: D-dimer≥40μg/mL.

Figure 3

Dynamic changes in organ function in patients with different D-dimer levels within 14 days after ICU admission. (A) liver injury (B) kidney injury (C) myocardial injury (D) severe ARDS (E) thrombocytopenia (F) DIC (ISTH criteria), D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL, D3: D-dimer≥40μg/mL. ^▼P<0.05 with D1 group vs. D2 group, ^#P<0.05, ^##P<0.01 with D2 group vs. D3 group, *P<0.05, **P<0.01 with D1 group vs. D3 group. ARDS: acute respiratory distress syndrome, DIC: disseminated intravascular coagulation, ISTH: international society of thrombosis and hemostasis.

Figure 4

Growth rate of the number of patients with organ dysfunction after ICU admission. (A) liver injury (B) kidney injury (C) myocardial injury (D) severe ARDS (E) thrombocytopenia (F) DIC (ISTH criteria). D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL, D3: D-dimer≥40μg/mL. ARDS: acute respiratory distress syndrome, DIC: disseminated intravascular coagulation, ISTH: international society of thrombosis and hemostasis.

Figure 5

Dynamic changes in the SOFA score and inflammation markers in patients with different D-dimer levels. (A) SOFA score (B) CRP (C) PCT (D) IL-6 (E) Ferritin (F) Neutrophil. (G)Lymphocyte (H) LDH. D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL. SOFA: sequential organ failure assessment, CRP: c-reactive protein, PCT: procalcitonin, IL-6: Interleukin-6, LDH: Lactate dehydrogenase. *P<0.05, **P<0.01 with D1 group vs. D2 group.

Figure 6

Dynamic changes in lipid metabolism markers in patients with different D-dimer levels. (A) CHOL (B) HDL (C) LDL (D) CHE (E) APOA (F) APOB. D1: 1.5≤D-dimer<10μg/mL, D2: 10≤D-dimer<40μg/mL. CHOL: Cholesterol, HDL: High density lipoprotein, LDL: Low density lipoprotein, CHE: Cholinesterase, APOA: Apolipoprotein A, APOB: Apolipoprotein B. *P<0.05, **P<0.01 with D1 group vs. D2 group.