The liver weighing between 1-1.5 kg and constituting 1.5-2.5% of lean body mass, is the largest and one of the most complex organs in the body. It plays crucial roles in carbohydrate, protein and lipid metabolism; detoxification of various substances; metabolism and conjugation of bilirubin; production of bile; drug and hormone metabolism; plasma protein synthesis; and immunity maintenance through Kupffer cells ^1,2.

From serving as the primary site of hematopoiesis during fetal development to maintaining hematological parameters in postnatal life, the liver is vital for blood homeostasis. It stores iron, folic acid, and vitamin B12 and secretes clotting factors and inhibitors. Consequently, liver diseases often result in a range of hematological abnormalities³.

Chronic liver disease (CLD) cause significant morbidity and mortality worldwide. CLD means disease of the liver which lasts for more than 6 months.  It is characterized by progressive destruction and regeneration of parenchyma of liver causing fibrosis and cirrhosis⁴ .

Common etiological factors for CLD are alcohol, chronic hepatitis B & C and non-alcoholic fatty liver disease (NAFLD).

Alcohol is a frequent cause of chronic liver disease and is directly toxic to bone marrow. Individuals with alcoholism often suffer from secondary malnutrition, which can result in anemia due to deficiencies in vitamin B12 and folate.

In chronic liver disease (CLD), various factors such as jaundice, liver cell failure, portal hypertension, hypersplenism, and reduced red blood cell lifespan impact the peripheral blood profile. Additionally, liver cell failure and cholestasis can lead to disruptions in the coagulation system^5,6.         

Dietary deficiencies, bleeding, alcoholism and hepatic synthesis abnormalities of blood-forming or coagulation proteins exacerbate liver disease complications. Hematological abnormalities in CLD increase morbidity and mortality, necessitating investigations into these issues to reduce comorbidities.

Hematological abnormalities are frequently associated with chronic liver diseases and since liver is the major site for erythropoiesis, anemia of various etiologies is one of the common finding⁷. About 75% of patients with chronic liver disease develop anemia, predominantly normocytic normochromic anemia due to chronic inflammation. Blood loss from esophageal and rectal varices, portal hypertensive gastropathy, and antral vascular ectasia can lead to iron-deficiency anemia (microcytic hypochromic anemia)⁸. Additionally, defects in red blood cell membranes result in acanthocytes and reduced lifespan, while hypersplenism and hepcidin deficiency further contribute to anemia. A frequent hematological issue in CLD patients is macrocytosis, with multifactorial causes.

This study aimed to assess the hematological abnormalities with coagulation abnormalities in patients of decompensated chronic liver disease so that corrective measures could be taken to reduce morbidity and mortality.

AIMS AND OBJECTIVES

• Evaluate hematological abnormalities in decompensated chronic liver disease.
• Determine the severity, morphology, and most common type of anemia in chronic liver disease.
• Assess PT/INR levels in patients with decompensated chronic liver disease.

Inclusion Criteria

1. All patients with liver disease whose symptoms and signs persists for more than 6 months.
2. Alcoholic cirrhosis, viral cirrhosis, autoimmune hepatitis, metabolic causes of liver diseases were taken.
3. Diagnosis was supported by ultrasonography finding of small nodular liver with splenomegaly and intra- abdominal collaterals or presence of ascites

Exclusion Criteria

1. Patients with underlying malignancy or known case of primary hepatocellular carcinoma.
2. Patients with primary coagulation disorder or primary abnormalities of haemostatic function.
3. Acute hepatic failure.
4. Patients with pre-existing anaemia due to other causes.
5. Patients on drugs causing bone marrow suppression.
6. Patients suffering from end stage medical diseases like COPD, coronary artery disease, cardiac failure and CKD.
7. Those with history of recent transfusion (within 3 months) with blood or blood products.

A cross-sectional analytical study was conducted in patients attending the department of Hepatology in Mahatma Gandhi Medical College and Hospital, Jaipur from January 2024 to December 2024, satisfying the inclusion and exclusion criteria. After obtaining Institutional Ethics Committee approval, oral and written informed consent from patients, they were enrolled for study, to assess hematological abnormalities and hemostatic derangements to guide treatment and reduce morbidity.

CLD patients with one or more features of decompensation in the form of ascites, jaundice, hepatic encephalopathy or bleeding varices were included. Cirrhosis with Child Pugh score of 7 or more also included as decompensated chronic liver disease.

 A total of 100 patients were selected for the investigation. All participants of CLD were evaluated for hematological abnormalities upon admission to the ward.

A prestructured performa was prepared after collecting the demographic data. A detailed past, present, personal and family history was recorded. Blood samples were collected and routine all investigations [complete blood count (CBC), clinical biochemistry, liver function test] was analyzed. Peripheral blood smear was assessed to find the morphological type of anemia.

A cross -sectional analytical study was conducted at Mahatma Gandhi Medical College and Hospital, Jaipur from January 2024 to December 2024 to assess hematological abnormalities in chronic liver disease.

TABLE 1: COMMON ETIOLOGIES IN CHRONIC LIVER DISEASE

FIGURE 1: ETIOLOGY vs % OF PATIENTS

In patients with chronic liver disease, alcohol emerges as the leading etiology, accounting for 64% of cases. Hepatitis B virus is the second most common cause, responsible for 15% of cases, while cryptogenic cases make up 14%. Other less common causes include Hepatitis C virus (2%), autoimmune conditions (3%), drug-induced liver disease (1%), and Wilson’s disease (1%). This distribution underscores the predominance of alcohol-related and viral etiologies in chronic liver disease.

TABLE 2: HEMOGLOBIN LEVELS IN CHRONIC LIVER DISEASE

FIGURE 2: HEMOGLOBIN LEVELS vs % OF PATIENTS

In patients with chronic liver disease, anemia is a predominant hematological abnormality. Among 100 patients studied, 92% have haemoglobin levels below 10 gm%, with 42% falling in the 6–8 gm% range and 50% in the 8.1–10 gm% range. Only 8% exhibit haemoglobin levels above 10 gm%, reflecting the rarity of normal levels in this group. These findings underscore the high prevalence of anemia in chronic liver disease and the critical need for targeted interventions.

TABLE 3: WHITE BLOOD CELL COUNT IN PATIENTS WITH CHRONIC LIVER DISEASE

FIGURE 3: WBC COUNT vs % OF PATIENTS

In patients with chronic liver disease, abnormalities in white blood cell counts are noted. Among the 100 patients studied, 13% exhibit leucopenia (WBC < 4000), while 26% show leucocytosis (WBC > 11000). The majority, 61%, fall within the normal range of 4000–11000. These variations highlight immune system disturbances commonly associated with chronic liver disease.

TABLE 4: PLATELET COUNT IN PATIENTS WITH CHRONIC LIVER DISEASE

FIGURE 4: PLATELET COUNT vs % OF PATIENTS

In patients with chronic liver disease, platelet abnormalities are commonly observed. A significant proportion (70%) of patients exhibit thrombocytopenia with platelet counts below 1 lakh. Specifically, 36% have counts below 50,000, and 34% fall in the range of 50,000–1 lakh. Moderate levels of 1–1.5 lakh are seen in 26% of cases, while only 4% have platelet counts exceeding 1.5 lakh, indicating normal levels are rare. These findings highlight the prevalence of platelet dysfunction in chronic liver disease.

TABLE 5: TYPE OF RED BLOOD CELLS (RBCs) IN CHRONIC LIVER DISEASE

FIGURE 5: RBC PICTURE vs % OF PATIENTS

The study indicates that normocytic RBCs are the most prevalent type, seen in 72% of patients. Microcytic RBCs account for 13%, while macrocytic RBCs are observed in 15%, showcasing the varying red blood cell morphology in chronic liver disease.

TABLE 6: PROTHROMBIN TIME (PT) IN CHRONIC LIVER DISEASE

FIGURE 6: PROTHROMBIN TIME (PT) vs % OF PATIENTS

Prolonged prothrombin time was observed in 86% of patients, reflecting significant coagulation abnormalities in chronic liver disease. Only 14% of patients had normal PT values, indicating widespread clotting impairment.

TABLE 7: INTERNATIONAL NORMALIZED RATIO (INR) IN CHRONIC LIVER DISEASE

FIGURE 7: INTERNATIONAL NORMALIZED RATIO (INR) vs % OF PATIENTS

In patients with chronic liver disease, coagulation abnormalities are evident, as reflected by INR values. Among the patients studied, 42% have an INR between 1.6 and 2, and 31% fall in the 2.1–2.5 range, indicating significant coagulopathy. Lower INR values are observed in 15% of patients (<1.1) and 12% within the range of 1.2–1.5. These findings emphasize the prevalence of impaired coagulation in chronic liver disease.

                                    Table 8: TOTAL PROTEINS IN CHRONIC LIVER DISEASE

FIGURE 8: TOTAL PROTEIN vs % OF PATIENTS

In patients with chronic liver disease, significant hypoproteinemia is observed. Among the 100 patients studied, 83% have total protein levels below 4 gm%, while 17% fall in the range of 4–6 gm%. Notably, none of the patients have protein levels above 6 gm%, highlighting the widespread protein deficiency associated with chronic liver disease.

In our study, alcohol-induced liver disease emerges as the leading etiology, accounting for 64% of cases, likely due to its direct bone marrow toxicity. Hepatitis B virus is the second most common cause, observed in 15% of cases. Autoimmune and drug-induced liver diseases are relatively rare, contributing to 3% and 1% respectively, as do Wilson’s disease (1%). Cryptogenic cases constitute 14%, where the etiology remains unknown.

These findings align with the study by Jasmine Kaur et al.⁹, which identified alcohol as the most common etiology in 57.8% of patients, followed by hepatitis C in 17.8%, alcohol combined with hepatitis C virus in 11.1%, and hepatitis B in 6.6%. Similar observations were made by Varun Shetty et al¹⁰, where alcohol-induced liver disease was the predominant cause, followed by viral hepatitis.

Suresh Moothezhathu Kesavadas⁴ reported comparable results, with alcoholism being responsible for 61.3% of cases, followed by alcohol combined with viral hepatitis (8%) and viral hepatitis alone (12%, comprising 6.7% hepatitis B and 5.3% hepatitis C). NASH-related chronic liver disease (CLD) accounted for 5.3%. In the study by Gautam Ray et al.¹¹, alcohol was identified as the most common etiology in 42% of cases, viral hepatitis in 31% (21% hepatitis B and 10% hepatitis C), and cryptogenic causes in 25%. These comparisons reinforce the predominance of alcohol-induced liver disease and viral hepatitis as major contributors to chronic liver disease across different populations.

In the present study, anemia is a common finding among patients with chronic liver disease.  92% have haemoglobin levels below 10 gm%, with 42% falling in the 6–8 gm% range having moderate anemia and 50% exhibits mild anemia with hemoglobin levels in the range of 8.1–10 gm%. Only 8% exhibit haemoglobin levels above 10 gm%, reflecting the rarity of normal levels in this group.  No patients are observed with hemoglobin levels below 6 gm%.

These results differ from Jasmine Kaur et al.⁹, where 43.3% of patients had severe anemia, and moderate anemia was observed in 32.2%. Anbazhagan et al. noted anemia in 80% of their study population, with 30% having hemoglobin below 6 gm%. Similarly, E. Halleys Kumar et al.⁸ found 86% of cases to be anemic, with 16% having severe anemia with hemoglobin levels below 6 gm%.

Varun Shetty et al.¹⁰ reported a higher prevalence of severe anemia, where 17% had hemoglobin levels below 6 gm%, 38% between 6–8.9 gm%, and only 20% above 13 gm%. Bibhu Prasad Behera’s study showed severe anemia in 53.62% of patients, with a mean hemoglobin level of 7.99 ± 2.18 g/dL. Mild anemia accounted for 5.8%, and only 4.35% of patients had normal hemoglobin levels.

In comparison to these studies, our findings demonstrate a lower prevalence of severe anemia, possibly due to differences in patient characteristics or the inclusion criteria. This emphasizes the need for early detection and management of anemia in chronic liver disease to improve patient outcomes.

In our study, abnormalities in white blood cell (WBC) counts are observed among patients with chronic liver disease. The majority of patients (61%) has normal WBC counts (4,000–11,000 cells/µL), while 13% exhibits leukopenia (<4,000 cells/µL), which may be attributed to hypersplenism, and 26% shows leukocytosis (>11,000 cells/µL), potentially due to infections.

These findings are consistent with the study by E. Halleys Kumar⁸, which reported that leucocytosis was more prevalent than leucopenia in decompensated chronic liver disease patients, with 36 patients having leucocytosis due to infections and 4 with leucopenia. Similarly, Jasmine Kaur et al.⁹   found that 45.6% of patients had leukocytosis and 15.6% had leukopenia. Poornachandra R.N et al.¹² observed leucocytosis in 32% of cases, associated with nosocomial infections, spontaneous bacterial peritonitis, and secondary bacterial peritonitis, while 6% of patients had leucopenia, with the majority having normal WBC counts.

In the study by Varun Shetty et al.¹⁰, 7% of patients had WBC counts below 4,000 cells/µL, 15% between 4,000–5,999 cells/µL, 35% between 6,000–7,999 cells/µL, 23% between 8,000–11,000 cells/µL, and 20% above 11,000 cells/µL. Similar trends were observed in Selvamani et al., where leucopenia was present in 6% of patients and leucocytosis in 22%. Viney Sambyal et al¹³. reported that among 546 patients, 7.7% had leucopenia and 3.3% had leucocytosis.

Overall, our findings are in line with other studies, highlighting the prevalence of leukopenia and leukocytosis as hematological abnormalities in chronic liver disease, with infections and hypersplenism being the probable underlying mechanisms.

In the present study, thrombocytopenia is a common hematological abnormality among patients with chronic liver disease.  A significant proportion (70%) of patients exhibits thrombocytopenia with platelet counts below 1 lakh. Specifically, 36% has moderate thrombocytopenia with counts below 50,000 and 34% of patients exhibits mild thrombocytopenia with counts between 50,000–1 lakh. Platelet levels of 1–1.5 lakh is seen in 26% of cases, while only 4% have platelet counts exceeding 1.5 lakh, indicating normal levels are rare. However, severe thrombocytopenia (<20,000) is not observed in this study.

As highlighted in Tody L Kujovich MD’s article "Hemostatic Defects in End Stage Liver Disease," mild to moderate thrombocytopenia occurs in 49–64% of decompensated chronic liver disease (DCLD) cases, with platelet counts rarely falling below 30,000–40,000/mm.¹⁴ Kumar et al. and E. Halleys Kumar⁸ similarly reported that thrombocytopenia is prevalent in patients with DCLD, with most patients presenting with mild to moderate thrombocytopenia and severe cases being less common.

In another study, 51% of patients had thrombocytopenia, with the majority (34%) falling within the mild range of 70,000–1.5 lakh/mm³, 9% in the moderate range of 20,000–70,000/mm³, and 8% in the severe range (<20,000/mm³)¹⁵. Varun Shetty et al.¹⁰ observed that 10% of patients had platelet counts below 100,000/mm³, while 47% ranged between 100,000–150,000/mm³, 35% between 150,001–200,000/mm³, and 8% had counts above 200,000/mm³.

Similarly, Rajkumar Solomon T et al.³ found that 50% of patients had thrombocytopenia (<1 lakh), of which 80% had mild to moderate thrombocytopenia (50,000–1 lakh) and 20% had severe thrombocytopenia (<50,000). These findings align with our study, which underscores the prevalence of platelet dysfunction and its role in the pathology of chronic liver disease.

In the present study, normocytic RBCs are the most common type, observed in 72% of patients. This predominance is likely due to the chronic inflammatory state associated with liver disease. Macrocytic RBCs are found in 15% of patients, while microcytic RBCs are present in 13%, highlighting the varied impact of chronic liver disease on red blood cell morphology.

These findings align with the study by Jasmine Kaur et al.⁹, where 64.4% of patients had normocytic anemia and 21.1% had microcytic anemia. According to Sherlock's and Oxford Textbook of Hepatology, normocytic normochromic anemia is the most common type observed in cirrhosis. Similar results were seen in the study by Selvamani et al., where 52% of patients had normocytic normochromic anemia, 30% had microcytic anemia, and 16% had macrocytic RBCs⁹.

Additional comparisons include Varun Shetty et al.¹⁰, where normocytic anemia was reported in 17% of patients, microcytic anemia in 42%, macrocytic anemia in 28%, and dimorphic anemia in 13%. E. Halleys Kumar et al.⁸ observed normocytic normochromic anemia in 52.3%, followed by microcytic anemia in 27.9%, and macrocytic RBCs in 17.44%. Similarly, Poornachandra R.N et al.¹² found normocytic anemia in 48% of patients, microcytic anemia in 28%, and macrocytic anemia in 26%.

Overall, these results emphasize the prevalence of normocytic RBCs as the most common hematological abnormality in patients with chronic liver disease, while also highlighting the presence of microcytic and macrocytic RBCs in a subset of cases. These observations are consistent across various studies, supporting the findings of this study.

In the present study, prolonged prothrombin time (PT) is observed in 86% of patients, indicating significant coagulation abnormalities. Only 14% of patients has normal PT values. These findings are consistent with the study by Varun Shetty et al.¹⁰, where 82% of patients had prolonged PT, and Jasmine Kaur et al.⁹, in which 80% of patients had prolonged PT by more than 6 seconds with a mean INR of 1.40. Similarly, Suthar et al. reported that 72% of patients had prolonged PT, with a mean prolongation of 5.6 seconds⁹. Poornachandra R.N et al.¹² also found 80% of patients had prolonged PT, and 88% had a prolonged activated partial thromboplastin time (APTT).

International Normalized Ratio (INR) values in the present study reveals that 42% of patients has INR levels between 1.6–2, and 31% are within the range of 2.1–2.5. Lower INR values are less common, with 15% of patients having values below 1.1 and 12% between 1.2–1.5. These findings align with Varun Shetty et al.¹⁰, who reported INR distributions similar to ours, with 32% of patients having values between 1.6–2 and 15% between 2.1–2.5. Additionally, Jasmine Kaur et al.⁹noted that INR values exceeded 1.5 in 77.8% of patients, highlighting the prevalence of impaired coagulation in chronic liver disease.

Regarding total protein levels, severe hypoproteinemia is noted in 83% of patients with levels below 4 gm%, while 17% fall within the range of 4–6 gm%. No patients have total protein levels above 6 gm%, emphasizing the widespread protein deficiency in this cohort. These observations are in concordance with findings from Jasmine Kaur et al.⁹, where mean albumin was 2.4 g/dL. Similarly, Nand et al. found mean albumin levels of 2.79 ± 0.62 g/dL, with severe hypoalbuminemia in 65% of patients.

In conclusion, the present study highlights the significant abnormalities in coagulation parameters and protein levels in chronic liver disease. These findings are consistent with prior research, demonstrating prolonged PT, elevated INR, and severe hypoproteinemia as common complications in this patient population.

The data highlights the prevalence of various haematological abnormalities in patients with decompensated chronic liver disease. Anemia, leukopenia, leukocytosis, thrombocytopenia, hypoalbuminemia and prolonged PT are common hematological abnormalities. According to our study, most common anemia is normocytic normochromic. Leucocytosis is more common than leukopenia. Thrombocytopenia is common but prolonged PT and APTT in most of the patients.

These abnormalities can significantly impact the clinical management and prognosis of these patients. Early identification and appropriate management of these haematological abnormalities are crucial in reducing morbidity and improving the quality of life for patients with decompensated chronic liver disease.

Comparing our findings with other studies, we observe similar trends in the prevalence of haematological abnormalities. However, there are variations in the severity and distribution of these abnormalities, which may be attributed to differences in study populations, methodologies, and geographic locations.

1. Review of Medical Physiology: William F Ganong 22nd edition, Regulation of gastrointestinal function, page 500, Functions of liver.
2. Sherlocks textbook of liver diseases 12th edition; Haematological disorders of the liver, Pramod K Misry and Dhanpat Jain, Para 1.
3. Anand A, Joeimon JL, Mohanraj K, Karthikeyan RK, Kayalvizhi J. A Study on Hematological Abnormalities in Chronic Liver Diseases.
4. Kesavadas SM, Saraswathy SKT, Muhammed. A Study On Haematological Abnormalities In Decompensated Chronic Liver Disease. J. Evid. Based Med. Healthc. 2017; 4(35), 2099-2103.
5. Sherlocks textbook of liver diseases 12th edition; Chapter 1: Anatomy and Function, Jay H. Lekowitch, Anatomy of liver, page 1.
6. Boyd E. Normal variability in weight of the adult human liver and spleen. ArchPathology1933.
7. Tomar MSI, Melwani V, Trivedi A. Hematological abnormalities in chronic liver disease and their association with severity and types of chronic liver disease. Panacea J Med Sci 2023;13(3):681-686
8. Kumar EH, Radhakrishnan A. Prevalence Of Anaemia In Decompensated Chronic Liver Disease. World J Med Sci. 2014;10(1):56-60.
9. Kaur J, Kaur N, Kaur J, et al. A study on haematological manifestations in patients with chronic liver disease in a tertiary care hospital of North India. J Evid Based Med Healthc 2021;8(25):2222-2228. DOI: 10.18410/jebmh/2021/415
10. Shetty V, Yadav SS, Kothari S. Hematological Abnormalities In Decompensated Chronic Liver Disease–A Prospective Study From Navi Mumbai. Int J Acad Med Pharm. 2023;5(2):698-701.
11. Ray AN, Barman DC, Pandit N. Clinical Study On Haematological Profile Abnormalities In Alcoholic Liver Disease Patients In A Tertiary Teaching Hospital In North East India. J Evid Based Med Healthc. 2019;6:2455-60.
12. Poornachandra R.N And Rangaswamy L. (2023); Study Of Hematological Abnormalities In Chronic Liver Disease Int. J. Of Adv. Res. 11 (May). 202-207] (ISSN 2320-5407). www.Journalijar.Com
13. Sambyal V, Bharti D. A study of hematological abnormalities in chronic liver disease indian journal of applied research Vol 9, Issue-4, April-2019, PRINT ISSN No 2249-555
14. Chandra Jha S, Kumar Singh J, Kumar A. Hematological Abnormalities in Chronic Liver Disease: A Retrospective Study in North Bihar. J Medic Sci Clin Res. 2019;7(05):779-84.
15. Bhosle D, Aggarwal A. Haematological Profile in Chronic Liver Disease Patients in Geriatric Population: An Observational Study 2023;17(2): 21-24.