Liver cirrhosis is the end point of a broad spectrum of progressive chronic liver diseases and is an important cause of morbidity and mortality worldwide [1]. On the histological level, it is defined by regenerative nodules, which are surrounded by fibrotic tissue and leads to progressive distortion of the normal hepatic architecture and liver function impairment [2]. It is possible that as cirrhosis advances, the patient can develop portal hypertension, liver failure and various systemic complications that can significantly impact prognosis and quality of life [3]. Hematological changes are especially frequent due to the liver's role in synthesizing and regulating many of the components that are crucial to hemostasis [4]. One of the most common hematological disturbances seen in patients with CLD and cirrhosis is thrombocytopenia [5]. It is generally accepted as being a peripheral platelet count of less than 150,000/µL, and can be anywhere from mild reduction to severe thrombocytopenia [6]. As liver disease progresses, the incidence of thrombocytopenia also increases, and previous studies have indicated that many patients with established cirrhosis have low platelet levels [7]. This is clinically significant because patients that need an invasive diagnostic or therapeutic procedure may have to have their platelet count supplemented with blood transfusion during the procedure to maintain the desired count, especially in the case of severe thrombocytopenia [8].

The mechanisms involved in the pathogenesis of thrombocytopenia in liver cirrhosis are multiple. Portal hypertension can cause splenomegaly and hypersplenism that can cause a rise in the number of platelets sequestered and destroyed in the spleen [9]. Furthermore, the synthesis of thrombopoietin is impaired in the liver, which leads to less stimulation of megakaryocyte proliferation and platelet production in the bone marrow [10]. Thrombocytopenia may be accentuated by chronic viral hepatitis, alcohol hepatitis, iron overload and some drugs, which directly affect the bone marrow [11]. Chronic hepatitis B (HBV) and chronic hepatitis C (HCV) are still significant etiological causes of cirrhosis, especially in areas with ongoing high prevalence of viral hepatitis [12]. Liver cirrhosis continues to be a significant health problem worldwide, and chronic viral hepatitis, alcohol abuse and metabolic liver disease are among the most important underlying causes of liver cirrhosis [13]. There are significant differences in the epidemiological pattern between populations and geographical regions [14]. In addition, obesity, metabolic syndrome and alcohol misuse have contributed to the changing pattern of chronic liver disease in today's world [15]. These changes highlight the importance of considering specific complications of cirrhosis in specific populations. Repeated blood count monitoring, platelet transfusion, deferring procedures, and hospitalization for extended periods of time are potential sources of healthcare utilization that can be exacerbated by thrombocytopenia. Previous research has reported thrombocytopenia in approximately 78% of patients with liver cirrhosis.

Objective

To determine the frequency of thrombocytopenia in patients with liver cirrhosis.

This cross-sectional study was conducted at the Department of Medicine Unit-B, Saidu Group of Teaching Hospitals, Swat, from 15 June 2022 to 15 December 2022. A total of 104 patients with diagnosed liver cirrhosis were enrolled using a non-probability consecutive sampling technique. The sample size was calculated using the WHO sample size calculator with a 95% confidence level, 8% absolute precision, and a previously reported frequency of thrombocytopenia of 78% in patients with liver cirrhosis. Patients aged 40–70 years of either gender with a confirmed diagnosis of liver cirrhosis were included. Patients who had received platelet transfusion during the preceding two weeks or were receiving thrombopoietin agonists were excluded. Data Collection After approval from the hospital ethical review board, eligible patients admitted to the medical unit were enrolled after written informed consent. Demographic and clinical information, including age, gender, etiology of cirrhosis, and duration of liver cirrhosis, was recorded. A complete clinical history was obtained and physical examination was performed. Complete blood count with peripheral smear was sent to the hospital hematology laboratory for determination of platelet count. Thrombocytopenia was defined as a platelet count <150,000/µL. The frequency of thrombocytopenia was recorded, and affected patients were managed according to hospital protocols. All information was entered into a specially designed data collection proforma. Statistical Analysis Data were entered and analyzed using SPSS version 22.0. Quantitative variables including age, duration of cirrhosis, and platelet count were expressed as mean±standard deviation. Categorical variables including gender, etiology of cirrhosis, and presence of thrombocytopenia were presented as frequencies and percentages. Effect modifiers including age, gender, duration of cirrhosis, and etiology of liver cirrhosis were controlled through stratification. Post-stratification Chi-square test was applied, and a p-value ≤0.05 was considered statistically significant.

Among 104 patients with liver cirrhosis, the mean age was 55.18±8.21 years, mean duration of cirrhosis was 4.95±1.48 years, and mean platelet count was 143,335.09±17,068.85/µL. Most patients were aged 51–60 years (39, 37.5%), followed by 61–70 years (33, 31.7%) and 40–50 years (32, 30.8%). Males accounted for 60 (57.7%) and females for 44 (42.3%) patients. Hepatitis C was the most common etiology in 59 (56.7%), followed by hepatitis B in 45 (43.3%).

Table I. Baseline Demographic and Clinical Characteristics of Patients with Liver Cirrhosis

The age distribution, gender, and etiological data are reported directly in the synopsis. 

Thrombocytopenia was present in 78 (75.0%) of the 104 patients, while 26 (25.0%) had a normal platelet count. Thus, approximately three-fourths of patients with liver cirrhosis had thrombocytopenia.

Table II. Frequency of Thrombocytopenia among Patients with Liver Cirrhosis

Thrombocytopenia was therefore present in three-quarters of the study population. 

Thrombocytopenia was observed in 25/32 (78.1%) patients aged 40–50 years, 28/39 (71.8%) aged 51–60 years, and 25/33 (75.8%) aged 61–70 years, with no significant association with age (p=0.82). It was present in 48/60 (80.0%) males and 30/44 (68.2%) females, but the gender difference was also not statistically significant (p=0.16).

Table III. Association of Thrombocytopenia with Age and Gender

Thrombocytopenia occurred in 35/45 (77.8%) patients with hepatitis B-related cirrhosis and 43/59 (72.9%) with hepatitis C-related cirrhosis, with no significant association with etiology (p=0.56). Among patients with cirrhosis duration of 3–5 years, 49/62 (79.0%) had thrombocytopenia compared with 29/42 (69.0%) of those with duration >5 years; this difference was also not statistically significant (p=0.24).

Table IV. Association of Thrombocytopenia with Etiology and Duration of Cirrhosis

The present study showed that thrombocytopenia was common in patients with liver cirrhosis with 78 patients (75.0%) having lower platelets < 150,000/µL and 26 patients (25.0%) having higher platelets ≥ 150,000/µL. The mean platelet count of this population was at 143,335.09±17,068.55/µL, which suggests that platelet reduction was a frequent hematological abnormality in this population. A high prevalence of thrombocytopenia was also found by previous studies, which showed that 64% of those with non-alcoholic cirrhosis or severe fibrosis also had thrombocytopenia, reflecting a strong relationship between advanced chronic liver disease and thrombocytopenia [17]. In a previous study, the thrombocytopenia rate in liver cirrhosis was 61%, which was also a very similar rate to that seen in the present study [18]. The multiple mechanisms that impact platelet production and survival in cirrhosis help to explain the high incidence of thrombocytopenia. Portal hypertension leads to splenic enlargement and sequestration of circulating platelets and progressive hepatic failure leads to decreased production of thrombopoietin. Viral infections, alcohol, drugs, and other causes can also cause bone marrow suppression, which can decrease platelet production. Minimization of thrombopoietin, impaired marrow production, sequestration in the spleen, and immune-mediated destruction of platelets also are highlighted as important mechanisms in the synopsis. In the past, it was also shown that splenomegaly was associated with a decrease in platelet count in liver disease patients, which reaffirms the role of portal hypertension and hypersplenism [19]. The mean age of patients in the present study was 55.18±8.21 years, with the largest proportion aged 51–60 years (37.5%), followed by 61–70 years (31.7%) and 40–50 years (30.8%). The proportion of thrombocytopenia was 78.1%, 71.8% and 75.8% in these three age groups, respectively, and was not statistically different by age (p=0.82). A mean age of about 57 years was reported in previous studies with liver disease and thrombocytopenia which was similar to the age profile observed in the present study [19]. There was no significant age association, indicating that cirrhosis-induced pathological changes may be more important than age per se in determining platelet count. The male population was 57.7% and the female population was 42.3% of the total study population. Thrombocytopenia was seen in 48/60 (80.0%) males and 30/44 (68.2%) females and a statistically significant difference was not demonstrated (p=0.16). The previous studies that assessed liver disease as a cause of thrombocytopenia also had a predominately male population, with 64% males and 36% females [19]. The results of the present study thus indicate that gender did not play an important independent role in this population but that thrombocytopenia was numerically more common in males. Etiology, hepatitis C was the most common cause of cirrhosis with 59 (56.7%) patients and hepatitis B was 45 (43.3%). Forty-three of 59 (72.9%) patients with hepatitis C-related cirrhosis and 35 of 45 (77.8%) patients with hepatitis B-related cirrhosis developed thrombocytopenia (p=0.56). Previous studies also have shown that both HBV and HCV infected individuals were thrombocytopenic, and cirrhosis and splenomegaly were significant co-factors [20]. In another previous study on chronic hepatitis C, the most frequent hematological finding was thrombocytopenia and its prevalence was found to be associated with progressive hepatic fibrosis [21]. There was no statistically significant relationship between the length of cirrhosis and thrombocytopenia. Thrombocytopenia was present in 49/62 (79.0%) of patients with cirrhosis for 3-5 years, and 29/42 (69.0%) of those >5 years of cirrhosis (p=0.24). This result indicates that length of time may not be the best indicator of the severity of the liver dysfunction or portal hypertension. Platelet reduction was found to be more closely correlated with some factors, including splenomegaly, fibrosis, bilirubin levels and the severity of hepatic disease, than just the duration of diagnosis, as previously reported [19]. The clinical significance of the high incidence of thrombocytopenia is that it can make invasive procedures for diagnosis and therapy more difficult in patients with cirrhosis. Note also in the attached synopsis that thrombocytopenia can contribute to the delay of procedures, and to greater concerns about bleeding, especially if platelets are severely depleted. Abnormal haematological indices, especially thrombocytopenia, have been reported to occur early and often in the development of liver cirrhosis, and to have a prognostic value in the advanced stages of the disease [22]. There were a few drawbacks in this study. The findings may have limited generalisability due to the single-center cross sectional study design and small sample size. Selection bias can also be caused by non-probability consecutive sampling. The study has the limitation of evaluating thrombocytopenia primarily based on platelet count and not the association of thrombocytopenia with severity of cirrhosis, portal hypertension, splenomegaly, or long-term clinical outcomes. However, causal relationships and prognostic implications could not be determined.

Thrombocytopenia was a common hematological abnormality among patients with liver cirrhosis, occurring in 78 (75.0%) of 104 patients. No statistically significant association was observed with age, gender, etiology of cirrhosis, or duration of disease. These findings support routine monitoring of platelet counts in patients with liver cirrhosis to facilitate early recognition and appropriate clinical management.

Among 104 patients with liver cirrhosis, the mean age was 55.18±8.21 years, mean duration of cirrhosis was 4.95±1.48 years, and mean platelet count was 143,335.09±17,068.85/µL. Most patients were aged 51–60 years (39, 37.5%), followed by 61–70 years (33, 31.7%) and 40–50 years (32, 30.8%). Males accounted for 60 (57.7%) and females for 44 (42.3%) patients. Hepatitis C was the most common etiology in 59 (56.7%), followed by hepatitis B in 45 (43.3%).

Table I. Baseline Demographic and Clinical Characteristics of Patients with Liver Cirrhosis

The age distribution, gender, and etiological data are reported directly in the synopsis. 

Thrombocytopenia was present in 78 (75.0%) of the 104 patients, while 26 (25.0%) had a normal platelet count. Thus, approximately three-fourths of patients with liver cirrhosis had thrombocytopenia.

Table II. Frequency of Thrombocytopenia among Patients with Liver Cirrhosis

Thrombocytopenia was therefore present in three-quarters of the study population. 

Thrombocytopenia was observed in 25/32 (78.1%) patients aged 40–50 years, 28/39 (71.8%) aged 51–60 years, and 25/33 (75.8%) aged 61–70 years, with no significant association with age (p=0.82). It was present in 48/60 (80.0%) males and 30/44 (68.2%) females, but the gender difference was also not statistically significant (p=0.16).

Table III. Association of Thrombocytopenia with Age and Gender

Thrombocytopenia occurred in 35/45 (77.8%) patients with hepatitis B-related cirrhosis and 43/59 (72.9%) with hepatitis C-related cirrhosis, with no significant association with etiology (p=0.56). Among patients with cirrhosis duration of 3–5 years, 49/62 (79.0%) had thrombocytopenia compared with 29/42 (69.0%) of those with duration >5 years; this difference was also not statistically significant (p=0.24).

Table IV. Association of Thrombocytopenia with Etiology and Duration of Cirrhosis

The present study showed that thrombocytopenia was common in patients with liver cirrhosis with 78 patients (75.0%) having lower platelets < 150,000/µL and 26 patients (25.0%) having higher platelets ≥ 150,000/µL. The mean platelet count of this population was at 143,335.09±17,068.55/µL, which suggests that platelet reduction was a frequent hematological abnormality in this population. A high prevalence of thrombocytopenia was also found by previous studies, which showed that 64% of those with non-alcoholic cirrhosis or severe fibrosis also had thrombocytopenia, reflecting a strong relationship between advanced chronic liver disease and thrombocytopenia [17]. In a previous study, the thrombocytopenia rate in liver cirrhosis was 61%, which was also a very similar rate to that seen in the present study [18]. The multiple mechanisms that impact platelet production and survival in cirrhosis help to explain the high incidence of thrombocytopenia. Portal hypertension leads to splenic enlargement and sequestration of circulating platelets and progressive hepatic failure leads to decreased production of thrombopoietin. Viral infections, alcohol, drugs, and other causes can also cause bone marrow suppression, which can decrease platelet production. Minimization of thrombopoietin, impaired marrow production, sequestration in the spleen, and immune-mediated destruction of platelets also are highlighted as important mechanisms in the synopsis. In the past, it was also shown that splenomegaly was associated with a decrease in platelet count in liver disease patients, which reaffirms the role of portal hypertension and hypersplenism [19]. The mean age of patients in the present study was 55.18±8.21 years, with the largest proportion aged 51–60 years (37.5%), followed by 61–70 years (31.7%) and 40–50 years (30.8%). The proportion of thrombocytopenia was 78.1%, 71.8% and 75.8% in these three age groups, respectively, and was not statistically different by age (p=0.82). A mean age of about 57 years was reported in previous studies with liver disease and thrombocytopenia which was similar to the age profile observed in the present study [19]. There was no significant age association, indicating that cirrhosis-induced pathological changes may be more important than age per se in determining platelet count. The male population was 57.7% and the female population was 42.3% of the total study population. Thrombocytopenia was seen in 48/60 (80.0%) males and 30/44 (68.2%) females and a statistically significant difference was not demonstrated (p=0.16). The previous studies that assessed liver disease as a cause of thrombocytopenia also had a predominately male population, with 64% males and 36% females [19]. The results of the present study thus indicate that gender did not play an important independent role in this population but that thrombocytopenia was numerically more common in males. Etiology, hepatitis C was the most common cause of cirrhosis with 59 (56.7%) patients and hepatitis B was 45 (43.3%). Forty-three of 59 (72.9%) patients with hepatitis C-related cirrhosis and 35 of 45 (77.8%) patients with hepatitis B-related cirrhosis developed thrombocytopenia (p=0.56). Previous studies also have shown that both HBV and HCV infected individuals were thrombocytopenic, and cirrhosis and splenomegaly were significant co-factors [20]. In another previous study on chronic hepatitis C, the most frequent hematological finding was thrombocytopenia and its prevalence was found to be associated with progressive hepatic fibrosis [21]. There was no statistically significant relationship between the length of cirrhosis and thrombocytopenia. Thrombocytopenia was present in 49/62 (79.0%) of patients with cirrhosis for 3-5 years, and 29/42 (69.0%) of those >5 years of cirrhosis (p=0.24). This result indicates that length of time may not be the best indicator of the severity of the liver dysfunction or portal hypertension. Platelet reduction was found to be more closely correlated with some factors, including splenomegaly, fibrosis, bilirubin levels and the severity of hepatic disease, than just the duration of diagnosis, as previously reported [19]. The clinical significance of the high incidence of thrombocytopenia is that it can make invasive procedures for diagnosis and therapy more difficult in patients with cirrhosis. Note also in the attached synopsis that thrombocytopenia can contribute to the delay of procedures, and to greater concerns about bleeding, especially if platelets are severely depleted. Abnormal haematological indices, especially thrombocytopenia, have been reported to occur early and often in the development of liver cirrhosis, and to have a prognostic value in the advanced stages of the disease [22]. There were a few drawbacks in this study. The findings may have limited generalisability due to the single-center cross sectional study design and small sample size. Selection bias can also be caused by non-probability consecutive sampling. The study has the limitation of evaluating thrombocytopenia primarily based on platelet count and not the association of thrombocytopenia with severity of cirrhosis, portal hypertension, splenomegaly, or long-term clinical outcomes. However, causal relationships and prognostic implications could not be determined.

Thrombocytopenia was a common hematological abnormality among patients with liver cirrhosis, occurring in 78 (75.0%) of 104 patients. No statistically significant association was observed with age, gender, etiology of cirrhosis, or duration of disease. These findings support routine monitoring of platelet counts in patients with liver cirrhosis to facilitate early recognition and appropriate clinical management.

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