The Impact of COVID-19 on Blood Coagulation Profile among Sudanese Hospitalized Adult Patients

Malaz Salah Taha, Malaz Eltayb Elbasheir, Mudathir A.A. Abakar, Elharam Ibrahim Abdallah, Mohamed Mobarak Elbashier, Alaa Eltayeb Omer, Lienda Bashier Eltayeb^*

Abstract

Covid-19 is a severe acute respiratory syndrome, the disease presents with a ranging from asymptomatic to severe symptomatic illness with multiple organ failure and death, and can cause a severe effect on the coagulation system. This study aimed to determine the effect of the covid 19 on the extrinsic and intrinsic pathway of coagulation [prothrombin time(PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT)] and to determine the association of age and gender with the severity of COVID-19 in Sudan in order to improve the outcome. A cross-sectional study carried out among 487 COVID-19 patients attending Khartoum State. COVID-19 patients were confirmed by RT-PCR. For all patients, the prothrombin times (PT), International normalized ratio (INR), and Activated partial thromboplastin (APTT) were estimated by using a semi-automated coagulometer analyzer. Patients were divided into three subclass groups according to the Severity of COVID-19 (mild, severe in the emergency room (ER) and intensive care unit (ICU), and the clotting factors values were compared between the groups. The results were statically analyzed by spss version 21 for data analysis. These results showed statistically significant increased Levels of PT, INR, and APTT for all (P. value = 0.000), compared to the control group. Also, the levels of coagulation tests were higher in ICU COVID-19 patients (P. value = 0.000) compared to mild and severe subgroups. This study concluded that:  coagulation clotting times were increased in COVID-19 patients, especially among patients in ICU which could be a marker for DIC and even death.

Keywords: Coagulation profile, COVID-19, PCR, INR.

Introduction

The Coronaviruses is severing acute respiratory syndrome (Lu et al., 2020) emerged in Wuhan (China) at the end of 2019 with an unknown cause (Di Gennaro et al., 2020), in January 2020, after a few weeks later, take a sample from the lower respiratory tract for analysis, identified a novel virus severe acute respiratory syndrome coronavirus as a causative agent for that observed pneumonia cluster (Huang et al., 2020). the disease named SARS-CoV-2 “COVID-19” by Dr. Tedros Adhanom Ghebreyesus, in 2020 (March 11th) when there was an increased number of countries involved (114), with more than 118,000 cases and over 4000 deaths, then the WHO declared the pandemic status (Llitjos et al., 2020). The disease ranges from asymptomatic to severe symptomatic illness with multi-organ failure and death (World Health Organization Director-General’s Opening Remarks at the Media Briefing on COVID-19–11, 2020). Respiratory droplet transmission is the main route and it can also be transmitted through asymptomatic carriers by person-to-person contacts (Abou-Ismail et al., 2020). COVID -19 can cause severe effects on coagulation systems. The complication of coagulation activation can be leading to the formation of disseminated intravascular coagulation (DIC) and death (Lupia et al., 2020). The systemic inflammatory response by COVID -19 can cause severe effects in coagulation systems leading to endothelial damage, coagulation activation, and intravascular fibrin deposition (Yang et al., 2020). the complication of coagulation activation can be leading to the formation of thrombus and even disseminated intravascular coagulation (DIC) (Qiu et al., 2020). The coagulation blood cascade is start when the sub-endothelial tissue factor is exposed to the blood flow followed either by activation or damage of the endothelium. It may happen as a result of the activation of endothelium or perforation of the vessel wall by cytokines, chemicals, or inflammatory processes by extrinsic pathway (PT and INR) and extrinsic pathway (APTT) (Bikdeli et al., 2020).

Materials and Methods

This was a cross-sectional study, conducted among 487 COVID-19 patients. Information about gender, age, COVID -19 symptoms, Ethical permission was taken from Ethical Research Committee, faculty of Medical Laboratory Sciences, Alzim Alazhari University, certainly an informed consent was taken from selected subject before participation in the study The primary data was gathered using a self-administered questionnaire; this was particularly designed to obtain data that would support in the study. The isolation hospitals use a real-time polymerase chain reaction device AccuPower® COVID-19 RT-PCR kit to confirm the diagnosis of COVID-19 patients (Bioneer Corporation, Daejeon, South Korea) following the manufacturer guidance; all cases were positive for COVID-19 by RT-PCR. PT, INR, and APTT clot analysis were performed for patients and 302 healthy individuals as a control group using Stago semi-automated analyzer. Patients were further subdivided into three subgroups [77 mild COVID-19,137 severe COVID -19 (ER) and 273   patients in ICU], subject-categorized according to the following: the first group with or without clinical evidence of pneumonia but without oxygen requirements (“mild” group), the second group with oxygen requirements ("severe” group (ER) and the last group under mechanical ventilation (ICU group). The study was approved by the University of Alzaeim Alazhari committee.

Statistical Data Analysis

Statistical analysis was performed by Statistical Package for Social the Sciences (SPSS software version 16) for windows. P. values equal or less than 0.05 was considered statistically significant.

Results and Discussion

This cross-sectional study was carried out on 487 COVID-19 patients (304 males and 183 females), aged between 20-88 years old in Sudan hospitals in Khartoum State during the period from April 2020 to December 2020. PT, INR, and APTT results were statically analyzed by SPSS version 21 to obtain descriptive statistics (mean (±) SD, minimum and maximum results) also one-way ANOVA test was used for the comparison of more than two parameters, and an independent T-test used to compare between two parameters to obtain the P-value (P-value less than 0.05 was considered significant). These results showed statistically significant increased Levels of PT, INR, and APTT among patients with COVID-19 when compared with the control (for all P-value = 0.000) Table 1. Also, the levels of coagulation tests were higher in ICU COVID-19 patients compared to mild and severe subgroups Table 2. No statistical significant was revealed between PT, APTT, and INR among mild Covid-19 patients and control group (p value 0.987, 0.990, 0.137) respectively. Data were summarized in Table 3.

In this study (56% of a patient admitted into the ICU unit, 28.1% were admitted to ER unit, and 15.8% of covid 19 patients with mild symptoms), male was more affected by the disease than female; 303 versus 184, respectively. Also, males were mainly represented in the ICU unit (male 183 (67.3%) versus female 90 (32.7%) Table 5. This study showed that ages up to 60 years (97.5%) with COVID-19 and mainly represented in the ICU unit Table 4.

Table 1. Comparison of PT, APTT, and INR between Covid-19 patients and control group

Mann-Whitney test was used to calculate the P-value

A p-value less than 0.05 is considered significant

Table 2. Comparison of PT, APTT, and INR between Covid-19 patients’ subgroups and control group

* Kruskal Wallis Test was used to calculate the P-value

** Mann-Whitney test was used to calculate the P-value

A p-value less than 0.05 is considered significant

Table 3. Comparison of PT, APTT, and INR between mild Covid-19 patients and control group

Table 4. Distribution of age groups among COVID-19 subgroups

Table 5. Distribution of gender among COVID-19 subgroup

Recently the whole world affected by the pandemic COVID-19 which become rapidly spreading, and dangerous and may lead to death especially for the old aged, also with time there is wide heterogeneity regarding clinical remark for the disease, due to the virus diversity. The dangerous COVID-19 complications are to induce severe acute respiratory distress syndrome and multiple organ failure (MOF), which are at risk of DIC and death (Chang, 2019). Mortality of the covid 19 seems to be relatively low among patients with the critical disease or at high risk of developing acute respiratory distress syndrome and being admitted to ICU (Han et al., 2020). This study was conducted to determine the effect of COVID-19 on the extrinsic and intrinsic pathway of coagulation (PT, INR, and APTT) and to determine the severity of COVID-19 in Sudan regarding age and gender in order to improve the outcome. This study showed that significantly increased in PT, INR, and APTT among covid-19 patients when compared to control groups (P Value 0.000).

As mentioned in previous studies, COVID -19 can lead to disturbance in coagulation systems. The most dangerous outcome is the activation of coagulation which can be leading to the formation of disseminated intravascular coagulation (DIC) and death (Lupia et al., 2020). PT and APTT are simple and first-line investigations for patients with coagulation disturbance and their results can predict the occurrence of DIC.

This study showed that there was no significant difference in PT, INR, and APTT results between patients in ER (severe) and mild subgroups (P.value > 0.05) but it was highly significantly increased among ICU patients (p.value 0.000). This current study agreed with the (Yongwei et al., 2020) report that significantly increased PT, INR, and APTT among patients with COVID-19 than healthy controls (p-value <0.05) (Sayad & Rahimi, 2020) and agreed with (Sayad & Rahimi, 2020) showed statistically significant in PT, INR and APTT result in ICU patient [pv<0.05] (Jin et al., 2020) also this study was in concordance with (You et al., 2020) showed a significant increase in PT (P.value 0.000, INR (P.value 0.000) in COVID-19 patient (Luo et al., 2020), but This study was disagreed with (Micco et al., 2020), showed statistically insignificant in PT, INR, and APTT (P.value > 0.05), this variation may relate to the low sample size of their study (67 patient). This recent study included (303) males and (184) females (56% of a patient admitted to the ICU unit, 28.1% were admitted to ER unit, and 15.8% of covid 19 patients with mild symptoms), this study revealed that males are more affected (60.3%) than female (48.9%) mainly represented in ICU unit, this study was similar to (Mahajan & Kaushal, 2020); the incidence in male =76%, and female =46% (Mahajan & Kaushal, 2020). This study showed that aged up to 60 years (97.5%) are more likely to get COVID-19 and represented in the ICU unit, the study was in agreement with (Pastor-Barriuso et al., 2020); demonstrated that the old age individuals up to 60 years more likely to get COVID-19 infection with more complicated symptoms.

Conclusion

This study concluded that significant increase in PT, INR, and APTT in covid 19 patients, especially among ICU covid 19 subgroups compared to mild and severe subgroups, which may indicate a risk of bleeding and or thrombosis that could lead to death (Adiga, 2019)^. Old age is more likely to increase the severity of covid 19 infection (Abd Elwahaab et al., 2019).

Acknowledgments: This publication was supported by the Deanship of scientific research at Prince Sattam Bin Abdul Aziz University. Authors appreciated to Faculty of Medical Laboratory Sciences, Alzaeim Alazhari University, Sudan.

Conflict of interest: None

Financial support: None

Ethics statement: Ethical permission was taken from Ethical Research Committee, faculty of Medical Laboratory Sciences, Alzim Alazhari University, certainly an informed consent was taken from selected subject before participation in the study

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