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The magnitude and associated factors of coagulation abnormalities among liver disease patients at the University of Gondar Comprehensive Specialized Hospital Northwest, Ethiopia, 2022

Thrombosis Journal volume 21, Article number: 35 (2023) Cite this article

Abstract

Background

Liver disease is any condition that affects the liver cells and their function. It is directly linked to coagulation disorders since most coagulation factors are produced by the liver. Therefore, this study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients.

Methods

A cross-sectional study was conducted from August to October 2022 among 307 consecutively selected study participants at the University of Gondar Comprehensive Specialized Hospital. Sociodemographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 2.7 mL of venous blood were collected and analyzed by the Genrui CA51 coagulation analyzer. Data were entered into Epi-data and exported to STATA version 14 software for analysis. The finding was described in terms of frequencies and proportions. Factors associated with coagulation abnormalities were analyzed by bivariable and multivariable logistic regression.

Result

In this study, a total of 307 study participants were included. Of them the magnitude of prolonged Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were 68.08% and 63.51%, respectively. The presence of anaemia (AOR = 2.97, 95% CI: 1.26, 7.03), a lack of a vegetable feeding habit (AOR = 2.98, 95% CI: 1.42, 6.24), no history of blood transfusion (AOR = 3.72, 95% CI: 1.78, 7.78), and lack of physical exercise (AOR = 3.23, 95% CI: 1.60, 6.52) were significantly associated with prolonged PT. While the presence of anaemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of vegetable feeding habit (AOR = 2.64; 95% CI: 1.34, 5.20), no history of blood transfusion (AOR = 2.28; 95% CI: 1.09, 4.79), and a lack of physical exercise (AOR = 2.35; 95% CI: 1.16, 4.78) were significantly associated with abnormal APTT.

Conclusion

Patients with liver disease had substantial coagulation problems. Being anemic, having a transfusion history, lack of physical activity, and lack of vegetables showed significant association with coagulopathy. Therefore, early detection and management of coagulation abnormalities in liver disease patients are critical.

Background

Liver diseases are various disorders that can affect liver cells and impair normal liver function [1]. It is one of the world's most critical public health problems. The most common causes of the rising burden of liver disease are chronic viral hepatitis, mainly hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease, caused by obesity, diabetes, autoimmunity, and hemochromatosis, damage from medication or chemicals are the other most common causes and types of liver disease [2, 3]. The liver has more than 5,000 separate bodily functions, including the synthesis of coagulation factor proteins to control bleeding within a damaged blood vessel and the production of blood coagulation inhibitors to prevent blood clots in normal circulation. Furthermore, the liver is involved in the reticuloendothelial system, which plays an important role in the clearance of active coagulation products. Liver disease affects both primary and secondary hemostasis by impairing the synthesis of all blood coagulation factors, activators, and inhibitors; which are essential to the blood coagulation pathway and fibrinolytic systems [4]. Consequently, patients with liver disease will suffer from the consequences of prolonged coagulation time, decreased clearance of activated factors, low platelet count, hyperfibrinolysis, and accelerated intravascular coagulation [5].

The PT and the APTT are both affected by cirrhosis because in liver disease there is reduced production of clotting factors and anticoagulants that are dependent on and independent of vitamin K [6]. The laboratory values of several coagulation tests are used to manage the bleeding problem in liver disease patients [7]. Up to 60% of chronic and active liver disease patients have prolonged PT, an independent predictor of poor survival in individuals with advanced cirrhosis [8]. In patients with cirrhosis, considerable amounts of fresh frozen plasma are necessary to enhance clotting factor levels [9]. Additionally, for patients with cirrhosis and abnormal coagulation screening tests, supplementation of vitamin K also corrects abnormal coagulation results [10].

Hemorrhagic complications due to liver disease patients are a major consequence and significant reason for intensive care unit admission, which varies from 15 to 61%, with 17–20% of cirrhotic patients experiencing a new commencement of substantial bleeding [11]. Around one‐third of patients with acute liver failure died from bleeding consequences [12]. Liver disease primarily causes upper gastrointestinal bleeding, portal hypertension caused by coagulation defects results in death in up to 2–6.7% of cases. Acute upper gastrointestinal bleeding is still a major cause of death in liver disease, accounting for up to 48% of cases [13]. Despite its consequences, there is a scarcity of information on the magnitude and associated factors of coagulation abnormalities among liver disease patients in the study area. Therefore, the current study aimed to assess the magnitude and associated factors of coagulation abnormalities among liver disease patients.

Methods and materials

Study design, area, and period

A hospital-based cross-sectional study was conducted from August to October 2022 at the University of Gondar Comprehensive Specialized Hospital (UoG-CSH). The hospital is located in Gondar town. Gondar is found at a distance of 727 km from Addis Ababa, the capital city of Ethiopia, in the northwest direction, and at a distance of 175 km from Bahir Dar, the capital city of the Amhara National Regional State. According to the 2015 report of the central statistical agency of Ethiopia, Gondar has a population of 323,900 [14]. The town has one public comprehensive specialized hospital, which is one of the oldest teaching hospitals in the country and provides health services for more than 7 million people in Gondar town and surrounding catchment areas [15].

Operational definitions

Habit of drinking tea or coffee

Habitual tea/coffee drinkers are defined by tea/coffee consumption of 120 mL/day or more for at least 1 year [16].

Physical exercise

Participant who performs the daily active exercise for about 30 min a day [17, 18].

Habit of feeding vegetables

It is a consistent action to integrate a variety of vegetables into one's diet or meal plan [19].

Habit of feeding meat

It is the consumption of animal-derived proteins such as beef, poultry, pork, fish, or other meats as a primary source of nutrition in one's daily diet [20].

Population, variables, and sampling techniques

Liver disease patients who were attending the UoG-CSH during the data collection period and who fulfilled the inclusion criteria were considered as a study population. Although the coagulation parameters (PT and APTT) were taken as dependent variables, the socio-demographic variables (age, gender, marital status, educational level, and residence), clinical variables (comorbidity, nutritional characteristics, blood transfusion history, smoking, habit of alcohol consumption, types of liver disease, and habit of physical exercise), and behavioural related variables (smoking, habit of alcohol consumption, and habit of physical exercise) were taken as independent variables. A total of 307 consecutively selected liver disease patients were included in this study. Study participants with a history of hereditary coagulation disease, critically ill patients, pregnant women, patients who took oral contraceptives, and patients who took drugs such as aspirin, heparin, and warfarin were excluded from the study.

Data collection methods and data quality management

The socio-demographic, lifestyle, and nutritional data were collected using a pretested structured questionnaire through a face-to-face interview, and the clinical data were collected using a data extraction sheet from the patient’s medical charts. Coagulation tests were carried out by a Genrui CA51 coagulation analyzer. To maintain the quality of the data, quality control testing was performed for each procedure. Furthermore, standard operating procedures were strictly followed. Training was given to all data collectors prior to the actual data collection. During the data collection period, there was close supervision by the investigators.

Statistical analysis

Epidata version 3.1 software was used to enter, code, clean, and sort data. The data were then exported to STATA version 14.0 software for analysis. Frequencies, proportions, and summary statistics were used to summarize the data. Pearson rank chi-square assumption fulfillment was checked for categorical variables. Bivariable and multivariable logistic regression were used to determine factors associated with coagulation abnormalities. The Hosmer–Lemeshow goodness of fit test with a p-value greater than 0.5 was used to validate the model fitness assumption. Finally, the odds ratio with a 95% confidence interval was used to express the strength of the association. Variables with a p-value < 0.05 from the multivariable analysis were considered to have a significant association with the outcome.

Results

Socio-demographic and clinical characteristics of study participants

In this study, a total of 307 study participants were included. Of them, 220 (71.66%), 213 (69.38%), 181 (59.28%), and 143 (46.58%) were males, from rural residences, married, and unable to read and write, respectively. Besides, the mean age of the study participants was 38.38 ± 15.13 years, ranging from 6 to 82 years (Table 1).

Table 1 Socio demographic of Liver disease patients at UoG-CSH, Northwest Ethiopia, 2022. (n = 307)
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From a total of study participants, 157 (51.14%), 37 (12.05%), 87 (28.34%), and 26 (8.47%) of study participants had chronic liver disease (CLD), acute liver disease, viral hepatitis, and ALD, respectively. Among viral hepatitis study participants, about 62/87 (71.26%) and 25/87 (28.74%) had HBV and HCV, respectively. On the other hand, about 86 (28.01%) of the study participants had taken medication rather than liver disease drugs. About 51 (16.61%), 39 (12.70%), and 33 (10.75%) were anemic, had a history of blood transfusions, and had heart disease, respectively (Table 2).

Table 2 Clinical characteristics of liver disease patients at UoG-CSH Northwest, Ethiopia, 2022 (n = 307)
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Nutritional and life style characteristics of study participants

About 269 (87.91%), 287 (93.49%), and 237 (77.1%) of the study participants had a habit of drinking tea/coffee, habit of feeding meat, and habit of vegetable, respectively. However, most of the study participants 262 (85.34%) had no habit of physical exercise, and about 11 (3.58%) had a smoking habit (Table 3).

Table 3 Lifestyle characteristics of liver disease patients at UoG-CSH Northwest, Ethiopia, 2022 (n = 307)
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Magnitude of coagulation abnormalities

From the total study participants, 209 (68.08%, 95% CI: 62.8%, 73.3%) had a prolonged PT. On the other hand, 195 (63.51%; 95% CI: 58.1%, 68.9%) of the study participants had abnormal APTT. From the abnormal APTT, 184 (94.4%) patients had prolonged APTTs, and 11 (5.6%) had shorter APTTs. Furthermore, 161 (52.44%) study participants had both prolonged PT and abnormal APTT (Table 4, Fig. 1).

Table 4 Coagulation abnormalities tabulated with PT and APTT among liver diseased study participants at the UoG-CSH, Northwest Ethiopia, 2022 (n = 307)
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Fig. 1
figure 1

Magnitude of coagulation abnormalities among liver disease patients at the UoG-CSH, Northwest Ethiopia, 2022 (n = 307)

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Factors associated with coagulation abnormalities

Bivariable and multivariable logistic regressions were performed to determine the association between PT abnormality and independent variables. Bivariable and multivariable logistic regressions were done for variables that fulfilled the chi-square assumption. The presence of anemia, physical exercise, a history of blood transfusion, the type of liver disease, the habit of feeding vegetables, and the frequency of feeding vegetables were associated with prolonged PT in bivariable analysis. Variables with a p-value of less than 0.25 in the bivariable analysis were selected for multivariable logistic regression. After multivariable logistic regression analysis, the history of anaemia (AOR = 2.97; 95% CI: 1.26, 7.03), the absence of a history of blood transfusion (AOR = 3.72; 95% CI: 1.78, 7.78), the absence of a vegetable feeding habit (AOR = 2.98; 95% CI: 1.42, 6.24), and the lack of physical exercise (AOR = 3.23; 95% CI: 1.60, 6.52) are significantly associated with prolonged PT (Table 5).

Table 5 Bivariable and multivariable logistic regression of PT among liver disease patients attending at the UoG-CSH, Northwest, Ethiopia, 2022 (n = 307)
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To determine the association between APTT abnormality and independent variables, both bi-variable and multi-variable binary logistic regression were done. The analysis includes independent variables that satisfy the chi square assumption. The presence of anemia, physical exercise, a history of blood transfusion, a type of liver disease, the feeding habits of vegetables, and age group were associated with APTT abnormalities in bivariable analysis. Variables with a p-value of less than 0.25 in the bivariable analysis were selected for multivariable logistic regression. After multivariable logistic regression analysis, young adult (18–45) (AOR = 5.22; 95%CI: 1.26, 21.63), old adult (> 45) (AOR = 5.49; 95%CI: 1.21, 24.82), presence of anemia (AOR = 3.02; 95% CI: 1.34, 6.76), lack of blood transfusion history (AOR = 2.28; 95%CI: 1.09, 4.79), lack of vegetable feeding habit (AOR = 2.64; 95%CI: 1.34, 5.20), and not doing physical exercise (AOR = 2.35; 95%CI: 1.16, 4.78) remained significantly associated with APTT abnormality ( \* MERGEFORMAT Table 6).

Table 6 Bivariable and multivariable logistic regression of abnormal APTT among liver disease patients attending at the UoG-CSH, Northwest, Ethiopia, 2022 (n = 307)
Full size table

Discussion

Liver disease is a global public health problem that results in mortality and morbidity. It is one of the main causes of coagulopathy both in developed and developing countries [21]. Thus, the magnitude and associated factors of coagulation abnormalities in liver disease patients attending UoG-CSH were investigated in this study.

The findings of this study showed that the overall prevalence of prolonged PT and abnormal APTT test results was 68.08% (95% CI: 62.8%, 73.3%) and 63.51% (95% CI: 58.1%, 68.9%), respectively. This value represents a high public health problem for patients with liver disease. The magnitude of abnormal PT and APTT in this study is significant. This high result is due to liver disease, which reduces the production of clotting factors, particularly vitamin K-dependent factors. Hence, patients with liver disease experience a range of hemostatic problems, including reduced production of clotting factors and coagulation inhibitor proteins [5, 6]. In contrast, the shorter APTT finding might be associated with inflammation, which may initiate clotting and decrease the activity of natural anticoagulant mechanisms. Additionally, inflammatory cytokines are also the major mediators involved in coagulation activation [22]. The prolonged PT in this study was consistent with a study reported by Bohania N et al. 68.33% [23], and Yatish PA et al. 63% [24]. In contrast, the finding of this study was lower than a study by Chetali Rupela et al. 86.6% [25], Parashat Patel et al. 85% [26], and Siddiqui SA et al. 88% [27]. The differences could be due to the variety of the study population or the way the tests were done. However, it is higher than that of Garg RP et al. 4.90% [28], Shobhaha P et al. 42.22% [29], Bhatia G et al. 62% [30]. The possible reason for the high coagulation abnormality in this study may be associated with the presence of other comorbidities in this study; mainly, 16.61% were anaemic and 10.75% had cardiac disease; additionally, 86 (28.01%) patients had treatment other than liver disease drugs.

The magnitude of abnormal APTT in this study was 63.51% (95% CI: 58.1%, 68.9%); it was in line with a study conducted by Bohania et al., which found a 61.67% prevalence of abnormal APTT [23]. In contrast, the magnitude of the abnormal APTT was lower than that of Chetali R. et al. (82.2%) [25], Siddiqui SA et al. (71%) [27]. The differences could be in the study population or the way the tests were done, but this study finding was higher than a study reported by Shobhaha. P et al. (26.66%) [29], Bhatia G et al. (39.3%) [30], Yatish PA et al. (56%) [24], Parashat P. et al., (52%) [26]. The possible reason may be associated with the presence of other comorbidities; mainly, 51 (16.61%) patients were anaemic and 33 (10.75%) had heart disease; additionally, 86 (28.01%) patients had treatment other than liver disease drugs. Additionally, possible reasons for the difference might be associated with differences in the study population, geographical variability, or the way the test was done.

Anemia was statistically associated with prolonged PT and abnormal APTT. In the current study, study participants has history of anaemia were 2.97 times (95% CI: 1.26, 7.03) more likely to have prolonged PT and 3.02 times (95% CI: 1.34, 6.76) more likely to have APTT abnormalities when compared with those without anemia. This is due to an anaemic patients' delayed response in the initiation of the coagulation cascade [31].

Types of liver disease were statistically associated with prolonged PT. Study participants with CLD had a 3.01-fold (95% CI: 1.10, 8.21) higher likelihood of being associated with prolonged PT; study participants with ALD had a 4.97-fold (95% CI: 1.27, 17.41) higher likelihood of being associated with prolonged PT; and study participants with viral hepatitis had a 3.56-fold (95% CI: 1.19, 10.63) higher likelihood of being associated with prolonged PT when compared to acute liver disease. Scientific explanations suggest that the liver plays a central role in the clotting process and is invariably associated with coagulation disorders due to decreased synthesis of clotting and inhibitory factors. Additionally, liver disease causes decreased synthesis of clotting factors, mainly vitamin K-dependent factors [6].

In this study, the young adult age (18–45) class has a 5.22-fold (95% CI: 1.26, 21.63) higher likelihood of being associated with abnormal APTT, whereas study participants in the old adult (> 45) age class have a 5.49-fold (95% CI: 1.21, 24.82) higher likelihood of being associated with abnormal APTT when compared with children (< 18). According to research, as one gets older, the liver's proliferative and metabolic functions may decline [32]. Since the regenerative capacity of the liver correlates with liver function [33].

Physical exercise was statistically associated with coagulation abnormalities. Study participants who did not do physical exercise had 3.23 times (95% CI: 1.60, 6.52) more likely associations with prolonged PT and 2.35 times (95% CI: 1.16, 4.78) more likely associations with APTT abnormalities when compared with those who did. This is due to the fact that physical exercise enhances the activation of both the coagulation and fibrinolytic cascades and increases the activity of several components of the coagulation cascades [34]. Additionally, it is suggested that short-term exercise activates blood coagulation, enhances blood fibrinolysis, and maintains the delicate balance between clot formation and clot dissolution [35].

The history of blood transfusion has been statistically associated with coagulation abnormalities. A study participant without a history of blood transfusion has a 3.72-fold (95% CI: 1.78, 7.78) more likely association with prolonged PT and a 2.28-fold (95% CI: 1.09, 4.79) more likely association with an APTT abnormality when compared with a participant with a history of blood transfusion. A scientific explanation suggests blood transfusions reintroduce blood clotting elements into the patient's blood. Additionally, whole blood contains approximately 150 mL of plasma, which provides the patient with non-labile clotting factors [36].

Vegetable feeding habits were statistically associated with coagulation abnormalities. Study participants with a lack of vegetable feeding habits had 2.98 times (95% CI: 1.42, 6.24) more likely associated with prolonged PT and 2.64 times (95% CI: 1.34, 5.20) more likely associated with APTT abnormality when compared with study participants who have a vegetable feeding habit. Scientific suggestions are that vitamin K and dependent coagulation factors such as FII, FVII, FIX, and FX are essential for regulating blood coagulation and comprise the coagulation factors. Vitamin K is found in the diet in two bioactive forms: phylloquinone (vitamin K1) and menaquinones (vitamin K2), both of which are abundant in leafy green vegetables [37, 38].

Strength and limitation of the study

This study has its strengths and limitations. The strength of this study is that it is the first study on the determination of the magnitude and associated factors of coagulation abnormalities in liver disease patients in Ethiopia. However, the limitation of this study was that we could not perform parasitic infection screening, which may interfere with the finding of the study.

Conclusion on recommendation

Coagulation abnormalities in liver disease were identified as a major public health issue. About half of liver disease patients had coagulation abnormalities (prolonged PT and abnormal APTT). Prolonged PT was associated with the presence of anemia, an absence of transfusion history, a habit of physical exercise, types of liver disease, and vegetable feeding habits. Abnormal APTT was associated with the presence of anemia, the absence of transfusion history, a habit of physical exercise, increased age, and vegetable feeding habits. Based on the high prevalence of coagulation abnormalities in patients with liver disease, it is recommended that healthcare providers should regularly monitor and assess coagulation function in these patients. This can help identify any potential bleeding and allow for timely intervention to prevent complications.

Availability of data and materials

All the data supporting these findings are contained within the manuscript.

Abbreviations

ALD:

Alcoholic Liver Disease

APTT:

Activated Partial Thromboplastin Time

CLD:

Chronic Liver Disease

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

PT:

Prothrombin Time

UoG-CSH:

University of Gondar Comprehensive Specialized Hospital

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Acknowledgements

We would like to thank the Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, and the University of Gondar. We also wish to extend our sincere thanks and gratitude to the University of Gondar Hospital for their willingness and efforts during this data collection. Finally, many thanks are given to all study participants for their willingness to participate and for providing the necessary information during the data collection.

Funding

The authors did not receive any funding for this work.

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Authors and Affiliations

  1. Department of Medical Laboratory Science, College of Medicine and Health Sciences, Debre Markos University, P.O. Box 269, Debre Markos, Ethiopia

    Abateneh Melkamu

  2. Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia

    Berhanu Woldu, Chomaw Sitotaw, Masresha Seyoum & Melak Aynalem

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Contributions

All authors participated in the data collection, feeding, performing the statistical analysis, drafting the manuscript, and reading and editing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Abateneh Melkamu.

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Ethics approval and consent to participate

An ethical clearance was obtained from the Ethics Review Committee of the School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar Research, with reference number SBMLS/384/2022. Then, a permission letter was secured from the UoG-CSH medical director. Before starting data collection, the data collectors were informed to ask permission, explain the purpose of the study and its importance and benefits, and offer to answer all the participants' questions to confirm their willingness. Then, written informed consent, or assent, was obtained. Participation in the study and refusals were possible. To ensure confidentiality of data, study participants were identified using codes, and unauthorised persons had no access to the data. All abnormal laboratory findings were linked to health professionals for proper management and treatment of patients.

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Melkamu, A., Woldu, B., Sitotaw, C. et al. The magnitude and associated factors of coagulation abnormalities among liver disease patients at the University of Gondar Comprehensive Specialized Hospital Northwest, Ethiopia, 2022. Thrombosis J 21, 35 (2023). https://doi.org/10.1186/s12959-023-00479-2

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Thrombosis Journal

ISSN: 1477-9560

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