key: cord-0802121-m3cb8yij
authors: Zhang, Yanhong; He, Liwei; Chen, Huixin; Lu, Shuangyan; Xiong, Yongfen; Liu, Juan; Zheng, Yao; Wang, Shun; Liu, Lei
title: Manifestations of blood coagulation and its relation to clinical outcomes in severe COVID‐19 patients: Retrospective analysis
date: 2020-06-27
journal: Int J Lab Hematol
DOI: 10.1111/ijlh.13273
sha: 445907beabeeb9244da64d982c60c8fc0d491823
doc_id: 802121
cord_uid: m3cb8yij

INTRODUCTION: Characteristics of blood coagulation and its relation to clinical outcomes in COVID‐19 patients are still rarely reported. We aimed to investigate the blood coagulation function and its influences on clinical outcomes of patients with syndrome coronavirus 2 (SARS‐CoV‐2) infection. METHODS: A total of 71 severe patients with confirmed SARS‐CoV‐2 infection who were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled. The blood coagulation data in these patients and in 61 healthy controls were collected. The patients with COVID‐19 were divided into two groups: the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission. RESULTS: Compared with healthy controls, patients with COVID‐19 had significant performances with coagulation dysfunction, including dramatically elevated values of FIB, PT, APTT, INR, FDP, and D‐Dimers but markedly reduced AT value (P < .05). Importantly, more noteworthy coagulation disorders similar to the differences between patients and controls were found in the aggravated patients with conditions deterioration after admission than those in the nonaggravated patients without conditions deterioration (P < .05). Moreover, the aggravated patients possessed a longer hospital stay and a higher mortality compared with the nonaggravated patients (P < .001). The coagulation parameters of COVID‐19 patients were widely and closely related to the indexes of liver function and inflammation (P < .05), indicating the coagulation dysfunction of these patients may be caused by liver injury and inflammatory storm. CONCLUSION: Severe patients with SARS‐CoV‐2 infection often possess coagulation dysfunction on admission. A certain correlation exists in coagulation disorder and adverse clinical outcome among severe COVID‐19 patients.

Since early December 2019, pneumonia cases with unknown cause emerged in Wuhan 1 ; then, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of this mysterious pneumonia. 2 At the time of writing this paper, a total number of more than two million confirmed cases with coronavirus disease 2019 have been identified, spanning 181 countries and regions of the whole world.

Patients infected by SARS-CoV-2 are generally classified as mild, severe, and critical types in accordance with the severity of clinical symptoms. 3 According to previous study, 1,4-6 the severe or critical patients with COVID-19 markedly appear to have clinical manifestations of coagulation dysfunction. However, the correlations between coagulation and clinical outcomes, and the factors leading to coagulation dysfunction of COVID-19 patients were not fully elaborated. In this study, the complete coagulation parameters of severe COVID-19 patients and its influence on clinical outcomes were shown and analyzed, which may be helpful for formulating appropriate therapeutic strategy on coagulopathy of COVID-19.

All consecutive severe patients (N = 71) with confirmed SARS-CoV-2 infection who had been tested by real-time RT-PCR for viral infection and had conducted a test of coagulation function within 3 days on admission and were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled.

The study was approved by the Hospital Ethics Committee, and oral informed consent was obtained from each of the patients.

The patients enrolled in this study were treated according to WHO interim guidance, 7 and patients' conditions and clinical outcomes were determined by reference to the notice on the issuance of strategic guidelines for diagnosis and treatment of COVID-19. 8 (c) complication of organ functional failure and need intensive care unit support. All enrolled patients were severe cases with COVID-19 on admission and then were divided into two groups, the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission.

The general information (age, sex, initial symptoms, coexisting disorders), clinical, laboratory, and radiological characteristics data of the enrolled patients on admission were extracted from electronic medical records. For coagulation data, the first results of patients within 3 days on admission were shown and analyzed. The measurement process of coagulation function was conducted with Sysmex CS5100 Automatic Blood Coagulation Analyzer (Sysmex) using corollary reagents 

Continuous variables were described as the means and standard deviations or medians and interquartile ranges (IQR) values.

Categorical variables were expressed as the counts and percentages. Independent group t tests were applied to continuous variables that were normally distributed; otherwise, the Mann-Whitney test was used. Categorical variables were compared using the Chisquare tests, while the Fisher exact test was used when the data were limited. Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 software. A two-sided α of less than 0.05 was considered statistically significant.

The clinical characteristics of the 71 patients with COVID-19 enrolled in this study are shown in Table 1 

Vomiting 

The differences of hemostasis function between COVID-19 patients and healthy controls were shown on account of the assessment of eight parameters ( 

To make clear the relationship between blood coagulation on admission and clinical outcomes of severe COVID-19 patients, several hematological findings in laboratory were shown and compared between the aggravated and nonaggravated patients ( For liver function test and diagnostic enzyme indexes, the values of AST, TBiL, DBiL, LDH, and CRP of patients in the aggravated group were significantly higher than those of patients in the nonaggravated group (P < .05), but no difference was observed in the ALT value between two group patients. Moreover, the percentage values of AST, LDH, and CRP above their normal ranges were, respectively, higher in the aggravated patients than those in the nonaggravated patients (P < .05). The percentage values of ALT, TBiL, and DBiL above their normal ranges in the aggravated patients were, respectively, equal to those in the nonaggravated patients (P > .05). 

Correlation analysis results of coagulation function parameters with liver function parameters and diagnostic enzyme indexes in COVID-19 patients are displayed in Table 4 . The liver is responsible for the synthesis and transport of many coagulation factors and anticoagulants, 11, 12 and inflammation also acts as a significant role in coagulation regulation cascade network. 13, 14 CRP is a kind of acute protein which rises sharply in the plasma when the body is infected or damaged, and it is a nonspecific and momentous marker of inflammation. LDH widely exists in human organs and tissues, and it is able to reflect the inflammation and injury residing in liver. The correlation analysis results demonstrated that all of the coagulation parameters had a direct connection with CRP value, prompting inflammation existing in COVID-19 patients probably, and primarily lead to coagulation disorders. Furthermore, the close correlation between liver function indexes, LDH, and coagulation function parameters also indicates that coagulation dysfunction may be related to liver injury of COVID-19 patients. Therefore, we speculate that different clinical outcomes caused by coagulation function may be due to the different degree of organ damage (especially liver) and the different intensity of inflammatory response in COVID-19 patients. 1, 15, 16 Unfortunately, the number of patients infected by SARS-CoV-2 is globally exhibiting a rapid and constant progression. Although the mortality of this emerging infectious disease seems not high, severe 

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Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention

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Office of State Administration of Traditional Chinese Medicine. Notice on the issuance of strategic guidelines for diagnosis and treatment of novel coronavirus (2019-nCoV) infected pneumonia

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Manifestations of blood coagulation and its relation to clinical outcomes in severe COVID-19 patients: Retrospective analysis

The authors declare that no conflict of interest exists.

LL, SW, and YH.Z. conceived the study and designed experimental procedures; LH, HC, SL,YX, JL, and YZ collected patients' data and performed statistical analysis. LL, SW, YH.Z., and LH wrote the paper. All authors reviewed and approved the final version.

https://orcid.org/0000-0001-6764-3260