Platelet count and coagulation profiles of adult hypertensive patients at Felege Hiwot comprehensive specialized hospital, Northwest Ethiopia: A comparative cross-sectional study

TL;DR

This study compares blood clotting profiles of hypertensive patients and healthy controls in Ethiopia, finding significant differences in clotting times.

Contribution

The study provides new regional evidence on coagulation abnormalities specifically in hypertensive patients from Northwest Ethiopia.

Findings

Hemostatic abnormality was observed in 69.2% of hypertensive patients.

Median values of activated partial thromboplastin time, prothrombin time, and international normalized ratio were significantly higher in hypertensive patients compared to controls.

Significant differences were found in coagulation parameters between both newly diagnosed and treated hypertensive patients versus healthy controls.

Abstract

Hypertension is a global public health problem and associated with metabolic, cellular, and blood disturbances. Hematological and hemostatic disturbance have been documented in individuals with hypertension, playing a pivotal role in hypertension associated vascular complications. Despite this, there is a scarcity of evidence and reports regarding the coagulation profiles are contradicting among hypertensive patients. Thus, this study aimed to compare the platelet count and coagulation profiles of adult hypertensive patients with those of normotensive controls at Felege Hiwot Comprehensive Specialized Hospital in Northwest Ethiopia, from June to August, 2023.

A comparative cross-sectional study was conducted among a total of 180 study participants (120 hypertensive patients and 60 healthy individuals) recruited by consecutive sampling technique. Socio-demographic, clinical and anthropometric data were collected using structured questionnaires and checklist. A total of six milliliters of venous blood (3 ml in EDTA tube and 3 mL in citrate tube) was collected for platelet count and coagulation profile determination. Platelet count and coagulation profile were determined using Uni Cel DxH800 hematology analyzer and Huma cue due plus coagulation analyzer, respectively. One-way ANOVA, Kruskal Wallis test, and correlation analysis was used during data analysis. A p-value of <0.05 was considered statistically significant.

In the present study, the median (interquartile range) age was 42.5 (36.0–50.0) years for newly diagnosed, 50.0 (45.0–65.0) years for treatment and 40.0 (35.0–45.7) years for the control group (P < 0.001). The overall hemostatic abnormality in hypertensive patient was 83 (69.2%), and significant difference was found in the median of activated partial thromboplastin time, prothrombin time and international normalized ratio between hypertensive patients as compared to control. Statistically significant difference was observed in the median (interquartile range) of activated partial thromboplastin time (P = 0.041), prothrombin time (P < 0.001), and international normalized ratio (P < 0.001) results between newly diagnosed hypertensive patients and healthy controls. Moreover, there was also a significant difference in activated partial thromboplastin time (P = 0.020), prothrombin time (P = 0.011), and international normalized ratio (P = 0.012) results between hypertensive patients undergoing treatment and healthy controls.

Hemostatic abnormality was observed in majority of hypertensive patients. Compered to healthy controls, the median values of activated partial thromboplastin time, prothrombin time and international normalized ratio were significantly higher in hypertensive patients. This finding highlights the importance of assessing coagulation parameters in hypertensive patients in order to prevent complications related to abnormal blood clotting. However, further longitudinal studies are necessary to gain better understanding of the changes in coagulation observed in hypertensive patients.

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Introduction

Hypertension (HTN) is the state of having high blood pressure (blood pressure of ≥140 mmHg systolic or ≥90 mmHg diastolic or on medication) [1]. Worldwide, the number of people living with HTN doubled between 1990 and 2019, from 650 million to 1.3 billion [2]. Uncontrolled HTN is the leading cause of cardiovascular disease and premature death across the globe [3]. Although it is a preventable and controllable risk factor for cardiovascular disease, many developing nations have not yet given it that much attention [4]. The rate of HTN increases with age and it is highly prevalent among adults aged 30–79 years, with two third of them residing in low- and middle-income nations [1, 2]. Recent epidemiological data indicate that the burden of hypertension accounts for 36% in Africa [1], and 25.9% in sub-Saharan Africa [5]. In Ethiopia, it is estimated that about 19.6% of the population has hypertension [6]. A study conducted in Bahir Dar city indicated that 24.3% of the population has hypertension and of these, 44.4% are unaware of having the condition [7].

Hypertension is a silent disease and it is diagnosed at a delayed stage in the majority of patients when complications develop and require immediate treatment [8, 9]. Despite the fact that lowering blood pressure is essential in the treatment of hypertension, it is also crucial to effectively control other cardiovascular risk factors such as dyslipidemia, diabetes, glucose intolerance, obesity, smoking as well as hematological and coagulation disturbances [10, 11]. Both cellular and non-cellular components can contribute to the viscosity, volume, and coagulability of the blood which significantly influence blood pressure regulation [12]. Platelet parameters and basic coagulation profile tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) are used to evaluate systemic inflammatory response, hemostatic function, identify coagulopathies, and monitor anticoagulant therapy in different group of patients [13–19].

Hemostatic abnormality indicated by change in PT and APPT was observed in patients with diabetes [20, 21], heart disease [22], bleeding diathesis [14] and HIV/AIDS [23]. Moreover, it has been documented that a significant change was observed in platelet count and coagulation profiles such as PT, APTT, and INR in hypertensive patients as compared to normotensive individuals [24–28]. In addition, the PT and APTT of hypertensive patients’ show a positive correlation between systolic blood pressure and duration of hypertension [27]. Thus, assessment of these parameters at the earlier stage is crucial for preventing severe complication of hypertension due to hemostatic dysfunction.

Hemostatic dysfunction primarily thrombotic coagulopathy play a key role in the development of atherosclerosis, which is the most common complications of hypertension, resulting in an increased morbidity and mortality [29, 30]. It has been reported that hypertensive patients have an increased risk of deep vein thrombosis, pulmonary embolism, and stroke, which are all related to abnormal blood clotting [31]. The pathophysiological change of hemostasis and/or coagulation irregularities in patients with hypertension is thrombogenic rather than hemorrhagic [32–36]. In the light of several evidences, patients with hypertension have shown endothelial dysfunction, platelet hyperactivation, dysregulation of the coagulation and fibrinolytic pathways, which help to promote the induction and the maintenance of prothrombotic state [37–42]. Additionally, evidences from empirical studies suggests that larger platelets are escape from the bone marrow due to increased consumption at the site of a damaged blood vessel, which accelerates thrombotic diseases such as coronary artery disease, cerebrovascular illness [39], and myocardial infarction [38, 43].

Generally, hematologic and hemostasis disturbances are major changes in hypertension, with significant contribution to morbidity and mortality. In Ethiopia, the current guidelines on the management of chronic medical conditions including hypertension don’t include routine assessment of hematological and coagulation parameters unless the patients experience serious complications [22, 44]. Although some studies on the coagulation profiles of hypertension patients have been done in different corner of the world, they came up with a range of contradictory findings. Some studies showed that patients with hypertension have significantly higher value of PT [24-28, 40], APTT [24, 25] and, INR [24], while other studies reported no significant difference in APTT between the hypertensive and normotensive groups [26, 40]. Regarding the result of platelet count, few studies reported that there was significant increase in platelet count among hypertensive patients compared to normotensive group [25, 28], while others reported there is no statically significant difference in platelet count between the groups [45, 46]. To the best of our knowledge, no published studies exist in Ethiopia in particular and the coagulation profile of hypertensive patients is not well studied in general. To assure this claim, common indexation databases such as PubMed/Medline, Web of Sciences, and Scopus was searched. Therefore, this study was intended to compare platelet count and coagulation profile among treatment naïve and treatment experienced hypertensive patients with apparently healthy normotensive group at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia.

Materials and methods

Study design, period, and area

A comparative cross-sectional study was carried out from June to August 2023 at Felege Hiwot Comprehensive Specialized Hospital (FHCSH). The hospital is found in Bahir Dar city, located 565 km northwest to Addis Ababa, the capital city of Ethiopia at an average elevation of 1840 meters [47]. The hospital provides comprehensive healthcare services to a catchment population of more than 7 million. The hospital has been providing teaching, research, and community service. At the time of the study, the hypertension follow-up clinic at Hospital gives service to more than 665 hypertensive patients on regular follow‒up.

Study participants

This study encompasses three distinct groups: All adult hypertensive patients attending at the chronic care clinic of FHCSH, consisting drug naïve group, who are not currently receiving any anti-hypertensive treatment; the drug experienced group, comprising hypertensive patients who are actively undergoing anti-hypertensive treatment; and the control group, which includes individuals serving as nonremunerated voluntary blood donors at the Bahir Dar blood bank were involved in the current study. On the other hand, hypertensive patients with documented bleeding and clotting disorders, patients who were taking anticoagulant therapy, patients with a known chronic condition like heart, liver, or kidney disease, patients with secondary hypertension, pregnant women, patients diagnosed with diabetes, hepatitis B or C, tuberculosis, HIV/AIDS, hematological malignancies, and patients below the age of 18 and above 65 years were excluded from participation. The health condition of the control groups was evaluated according to the national blood bank service blood donor questionnaire, and screening was done for transfusion-transmitted infectious diseases (HIV, Hepatitis, Syphilis, and malaria).

Operational definition

Coagulation abnormalities: is an abnormality of one of the hemostasis compartments; thrombocytopenia, abnormal high PT/INR or APTT.

Thrombocytopenia**:** is defined as a platelet count lower than 150 x10^3^ cells/µl [48].

Prolonged PT: is described by a coagulation time that surpasses 16 seconds [49].

Prolonged APTT: is identified as a coagulation time that exceeds 36 seconds [49].

Abnormal high INR: INR value of greater than 1.2 [49]

Sample size and sampling technique

The determination of the sample size was based on the commonly accepted principle of the rules of thumb, which advises a minimum of 30 participants per group to effectively detect differences between groups with a statistical power of 80% [50]. To bolster the statistical robustness and reliability, we decided to increase the number of participants by twofold. This decision resulted in a total of 180 participants being included in the study. Specifically, this total comprised 60 drug-naïve hypertensive patients, 60 drug-experienced hypertensive patients, and 60 normotensive controls. The study participant was recruited consecutively until the desired total number of participants was achieved.

Data collection and laboratory methods

Information pertaining to socio-demographic and behavioral characteristics was collected using pre-tested structured questionnaire. These data were collected through face-to-face interviews conducted by a trained nurse, ensuring consistency and reliability in the data collection process. Clinical, blood pressure and anthropometric data were collected using structured checklist. Blood pressure (BP) was taken by clinical nurses using an analog sphygmomanometer. Measurements were taken from the upper arm with the hand at the heart level after the patient had been rest for more than 5 minutes. The data regarding anthropometric variables such as height (to the nearest centimeter without shoes), and weight (to the nearest 0.1 kg), were collected according to the anthropometric measurements protocol. Body mass index (BMI) was computed by dividing the weight in kilograms by the square of the height in meters, providing a standardized measure of participants’ body composition [51].

Six-milliliter (ml) of venous blood specimen (3 ml in K2EDTA tube and 3 ml in sodium citrate tube) was collected from the median cubital vein of each study participant by medical laboratory professionals by adhering to standardized operational procedures. Following the collection process, platelet count was analyzed using Unicel DXH 800 (Beckman Coulter, USA) automated hematology analyzer by employing impedance principle [52]. The remaining 3 ml of blood in 3.2% sodium citrate tube was used for assessment of the coagulation profiles from platelet poor plasma (PPP). Coagulation profiles including PT, INR and APTT were determined using the Huma cue due plus coagulation analyzer, by following the turbidity meter principle [53].

Data quality assurance and management

The English version of questionnaire was translated to local language, Amharic, and then translated back to English to check the consistency. A pre-test was conducted on 5% of the sample size at Tibebe Gione Comprehensive Specialized University Hospital to ensure the validity of the questionnaires. Training was given for the data collectors prior to data collection. Blood pressure and anthropometric measurements was measured twice during each assessment, and the average of the two readings was recorded for analysis. Manufacturer instructions and standard operating procedures were strictly followed during specimen collection and all other laboratory procedures. Blood in K2EDTA and sodium citrate tube was gently mixed 6–8 times to prevent blood clotting. Visual inspection of the collected blood samples was conducted, with gentle mixing to observe for clots as an indicator of sample quality. Daily internal quality control procedures were performed for the hematology and huma cue due plus analyzer. Wright-stained peripheral blood film examination was performed to figure out any suspected pseudo thrombocytopenia. Completion, and clarity of the collected data were checked regularly and the results were properly recorded, transcribed, and reviewed.

Data analysis and interpretation

The data underwent thorough cleansing and completeness checks, entered into Epi Info version 7 and subsequently exported to SPSS version 25 software for analysis. The normality of data distribution was assessed using the Shapiro wilk test and Kolmogorov-Smirnov test. The results were reported as frequency and percentages for categorical variables, mean ± SD for normally distributed continuous variable and median with interquartile range (IQR) for continuous variables with skewed distribution. Chi-square test were used to determine statistical differences for categorical variables between the study groups. One-way ANOVA and Kruskal-Wallis test supplemented by pairwise post hoc analysis were used to compare platelet count and coagulation profiles between the groups. On the other hand, correlation tests were utilized to examine the correlation of platelet and coagulation profile with BMI and duration of treatment. P < 0.05 determining statistical significance for all analyses.

Ethical consideration

The study was carried after ethical clearance was secured from the Research and Ethical Review Committee of the School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, with reference number SBMLS/508. An official permission letter was granted from Felege Hiwot Comprehensive Specialized Hospital, and informed written consent was obtained from each participant prior to data collection. Participants were thoroughly briefed on the study’s potential risks and benefits, and their right to withdraw at any stage. Confidentiality of participant information was strictly maintained, and cases involving coagulation abnormalities as well as individuals screening positive for malaria, syphilis, HIV and hepatitis were promptly communicated to physicians for appropriate management.

Results

Socio-demographic, clinical, and anthropometric characteristics of study participant

A total of 180 study participants, including 120 hypertensive patients which comprises 60 newly diagnosed, and 60 patients who are on treatment, as well as 60 healthy individuals as a control group, were enrolled in this study. The median (IQR) age was 42.5 (36.0–50.0) years for newly diagnosed, 50.0 (45.0–65.0) years for treatment and 40.0 (35.0–45.7) years for the control group (P < 0.001). In terms of sex distribution, there were no significance difference across the study groups. Significant difference was observed in the median (IQR) of systolic and diastolic BP among the study groups (P < 0.001). Regarding the anthropometric measurement, there were no significance difference in BMI across the study groups (P = 0.358). (Table 1).

Table 1: Socio-demographic, clinical characteristics and anthropometric measurements of the study participants at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2023, (n = 180).

Platelet count and coagulation profiles of study participants

In the present study, the median (IQR) of PT, APTT and INR values showed a significant difference across groups. Statistically significant difference was observed in the median (IQR) of PT (P < 0.001), APTT (P = 0.041), and INR (P < 0.001) results between newly diagnosed hypertensive patients and healthy controls. Moreover, there was also a significant difference in PT (P = 0.011), APTT (P = 0.020), and INR (P = 0.012) results between hypertensive patients undergoing treatment and healthy controls. However, the present study was not found a significant difference in any of the coagulation profiles between newly diagnosed and on treatment hypertensive patients (Table 2).

Table 2: Comparison of platelet count and coagulation profiles of study participants at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2023, (n = 180).

Coagulation profile abnormalities among the hypertensive patient

The overall hemostatic abnormality in hypertensive patient was 83 (69.2%). Of these, hemostatic abnormality was observed in 45 (75%) newly diagnosed and 38.0 (63.3%) treatment experienced hypertensive patients. Furthermore, thrombocytopenia, prolonged PT, APTT, and INR was found among 13.0 (10.8), 35.0 (29.2), 51.0 (42.5), and 66.0 (55.0) of the study participants, respectively (Table 3).

Table 3: Coagulation profile abnormalities among hypertensive patient participants at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Northwest Ethiopia, 2023, (n = 120).

Discussion

It has been documented that a significant change was observed in platelet parameters and coagulation profiles in hypertensive patients as compared to normotensive individuals [24–28]. In the present study, the overall hemostatic abnormality in hypertensive patient was 83 (69.2%), and significant difference was found in the median of APTT, PT and INR between hypertensive patients as compared to control. The median platelet count was higher in newly diagnosed hypertensive patients as compared to the control group, but the difference was not statistically significant. The findings indicated that newly diagnosed and treatment experienced hypertensive patients exhibited significantly higher median for PT and INR compared to the normotensive controls. This finding was coherent with the finding reported in Nigeria [25, 27, 28], Pakistan [24], Al Gezira state [26] and Khartoum State [40] of Sudan. The higher level of PT and INR among hypertensive patients could be attributed to endothelial damage caused by atherosclerosis, which is commonly associated with hypertension [54]. In addition, hypertension is related to low-grade inflammation along with the influence of inflammatory markers, which has an impact on the coagulation system, leading to prolonged PT and INR values [55].

This study unveiled a statistically significant increase in median APTT value in hypertensive patients compared to their normotensive counterparts. These findings were similar to previously reported results in Pakistan [24] and Nigeria [25]. Several plausible explanations exist for this phenomenon. Chronic high blood pressure might wreak havoc on the endothelium of blood vessels, triggering the release of procoagulant factors and activating platelets, ultimately prolonging APTT. Another culprit could be hyperactive platelets, more prone to clumping together and altering APTT measurements. Additionally, the influence of antihypertensive medications, particularly diuretics and beta-blockers, on coagulation pathways [56]. It’s crucial to acknowledge conflicting evidence presented from Sudan by Merghani [40] and Eman [26] whose studies didn’t detect significant APTT differences between hypertensive and normotensive individuals. This discrepancy could be attributed to several factors, including smaller sample sizes, variations in patient characteristics and co-morbidities, or even methodological differences. Therefore, further research is warranted to solidify the link between hypertension and altered APTT. Ultimately, a comprehensive understanding of this potential association can pave the way for improved strategies in managing and preventing complications associated with hypertension.

Regarding coagulation abnormalities, higher prevalence of coagulation abnormalities among hypertensive participants was observed. The overall hemostatic abnormality in hypertensive patient was 83 (69.2%). Of these, hemostatic abnormality was observed in 45 (75%) newly diagnosed and 38.0 (63.3%) treatment experienced hypertensive patients. The higher prevalence among those newly diagnosed cases compared to on treatment suggests, suggesting potential initial effects and highlighting the increased coagulopathy risk associated with hypertension. High blood pressure in untreated patients can damage the inner lining of blood vessels, which might trigger abnormal platelet activation and coagulation changes. Conversely, antihypertensive medications might help normalize blood pressure, reducing stress on the endothelium and potentially lowering the risk of coagulopathy. Additionally, treating hypertension helps prevent atherosclerosis, further reducing the risk of abnormal clotting [57]. It’s important to acknowledge that other factors like age, co-morbidities, and lifestyle habits can also influence coagulation profiles independently, potentially impacting the observed trends [54, 58].

On the other hand, thrombocytopenia was slightly higher among hypertensive patients receiving treatment compared to those who were newly diagnosed. The possible reason for the high prevalence of thrombocytopenia among those hypertensive patients who are taking anti-hypertensive treatment could be certain anti-hypertensive medications such as thiazide diuretics have been associated with an increased risk of thrombocytopenia as side effects. It can affect the production of platelets in the bone marrow, leading to a decrease in platelet levels and an increased risk of thrombocytopenia [59, 60].

According to our extensive literature, there has been no comprehensive study assessing the coagulation profile of hypertensive patients in Ethiopia, specifically in the study area, which is addressed by the current study. However, a key limitation lies in its study nature, i.e., being a comparative cross-sectional study focusing on the comparison of specific coagulation tests. Additionally, while the study investigates coagulation profiles, its focus on specific tests might have overlooked other potentially crucial aspects of coagulation function, leaving a gap in understanding the full picture. While this study provides a valuable snapshot of associations, further research using longitudinal designs and a wider range of coagulation tests is needed to explore causal relationships between hypertension and coagulation.

Conclusion and recommendation

In the present study, hemostatic abnormality was observed in majority of hypertensive patients. In addition, there was a statistically significant variation in the APTT, PT, and INR values of hypertensive patients compared to normotensive controls. The platelet count of hypertensive patients is also higher than that of normotensive controls even if it is not statistically significant. Thus, the prediction of the coagulation changes enables the clinician to establish an effective and early therapeutic intervention to prevent the occurrence of major hypertensive complications. Based on the above findings, it is important to assess the changes in coagulation parameters because it may indicate a risk of developing complications before it becomes worse. Further longitudinal cohort studies are recommended to clarify the definitive pathophysiological mechanisms of hypertension regarding coagulation parameters.

Supporting information

S1 FileQuestionnaire.(DOCX)

S2 FileRaw data (HTN + control anonymized data set).(XLSX)