Coagulopathy in elderly patients with coronavirus disease 2019

Abstract Background Since the outbreak of coronavirus disease 2019 (COVID‐19), clinical features have been analyzed in detail. However, coagulopathy in elderly COVID‐19 patients has been scarcely reported. Methods Coagulation parameters of 189 patients with COVID‐19 in Tongji hospital were retrospectively analyzed among age groups. Results Patients were divided into 2 groups: older group (≥65 years, n = 87) and younger group (<65 years, n = 102). The proportion of patients with elevated fibrinogen (79.0% vs 59.6%, p = .005) and D‐dimer (78.0% vs 55.2%, p = .001) shows the significant difference between the groups. The elderly patients revealed significantly longer prothrombin time (14.0 [13.4–14.4]s vs 13.6 [13.2–14.1]s, p = .026), higher D‐dimer (1.00 [0.5–1.9] μg/mL vs 0.6 [0.3–1.6] μg/mL, p = .013) and fibrinogen (5.2 [4.1–6.2] g/L vs 4.4 [3.4–5.7] g/L, p = .004) levels, compared to the younger group. A positive correlation was observed between the coagulation parameters and inflammatory markers including high‐sensitivity C‐reactive protein and interleukin‐6 (p < .05). Conclusions The hypercoagulable state is more common in elderly COVID‐19 patients, and coagulopathy is associated with excessive systemic inflammation.

with SARS-CoV-2 infection, and to investigate the relations between coagulopathy and systemic inflammation in COVID-19 patients.

| Data collection
The clinical data, including demographics information; underlying diseases; laboratory results and clinical outcomes were extracted from electronic medical records. Coagulation tests included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), platelet count (PLT) and D-dimer. High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) as inflammatory markers were also detected. The data above were recorded in the first 24 hours after diagnosis. The end point was written of discharging from hospital or death. All the data were reviewed by experienced physicians separately and checked by two physicians independently.

| Statistical analysis
All measurements were expressed as median (interquartile range [IQR]) or number (%). Continuous variables were compared using the Mann-Whitney U test. Categorical variables were compared using the Chi-squared test. Correlations between variables were analyzed using the Spearman's rank correlation. A p-value < .05 was considered statistically significant. Data was analyzed using SPSS software (version 25.0).

| The grade of disseminated intravascular coagulation
According to the Consensus of Chinese experts on the diagnosis of disseminated intravascular coagulation (version 2017), 13

| D ISCUSS I ON
Coagulation system plays a crucial role in the innate immunity. 14 Multiple inhibitory pathways regulate the coagulation process, such as tissue factor pathway inhibitor (TFPI), antithrombin (AT), and protein C system. 15 The imbalance between coagulation and anticoagulation systems is responsible for abnormalities. Current evidence points to an extensive cross-talk between coagulation and inflammation systems. 16 COVID-19 infection has a heterogenous disease course, majority of patients only have mild symptoms, while some severe patients have immunologic complications, resulting in cytokine storm. 17 Inflammatory factors such as IL-1 and IL-6 promote a hypercoagulable state through excess thrombin generation and fibrinolysis shutdown. 18 Previous studies have asserted that advanced age is a risk factor in the development of VTE and that the incidence of VTE increases significantly with increasing age. 19,20 COVID-19 patients with coagulation dysfunction have a higher risk of death. 21 Therefore, coagulopathy in elderly COVID-19 patients need more clinical concern.
Klok FA et al reported a VTE rate of 27% in severe COVID-19 patients, and pulmonary embolism (PE) was the most frequent thrombotic complication. 22 Elderly patients always have reduced physical mobility and high hospitalization rates for illnesses that contribute to the development of VTE. 20 In our study, we found higher D-dimer and FIB levels in the older group, which indicated that elderly COVID-19 patients tend to be in a hypercoagulable state and have higher risks of thromboembolism. Besides, longer PT was also observed in the older group compared to the younger group but both groups were within the normal reference range and did not belong to the pathological state of the disease, which Only 189 patients were included in our cohort due to the time and condition constraints. Nonetheless, our study has shown that the hypercoagulable state is more common in elderly COVID-19 patients, with the longer PT, higher D-dimer and FIB levels. HsCRP and IL-6 levels had significant correlations with coagulation parameters, which confirmed that coagulopathy is associated with excessive systemic inflammation. The monitoring of the coagulation function may be helpful to evaluate early prognosis in the elderly.

CO N FLI C T O F I NTE R E S T
The authors report no conflicts of interest related to the submitted work.

DATA AVA I L A B I L I T Y S TAT E M E N T
All the data from electronic medical records in Tongji Hospital were reviewed by experienced physicians separately and checked by 2 physicians independently.