Study of clinical presentation, laboratory profile, transfusion requirements and transfusion-related infectious complications in adult patients of congenital hemolytic anemia in a tertiary care center

Abstract

Congenital hemolytic anemia (CHA) especially hemoglobinopathies is quite prevalent in certain ethnic groups in India and commonly seen in pediatric age group. Adult presentations are being seen due to better treatment options and increased life span. This study was conducted to determine the clinical profile, laboratory parameters, transfusion requirements, and transfusion-related infectious complications of adult patients with CHA. A total of 84 patients of CHA aged more than 12 years were enrolled and studied over 18 months period. 63% patients were males with mean age of 19.98+4.99 SD years and maximum (57%) in the age group of 13-20 years. Family history of CHA was present in 19 (22.61%) patients and consanguinity in 16 (19.04%) cases which were statistically significant (P<0.05). Easy fatigability (76.19%) was the most common symptom followed by dyspnea on exertion (36.19%), whereas pallor (98.80%) was the commonest finding on examination followed by spleenomegaly (40.47%). The mean average (mean+SD) values for hemoglobin was 7.37+1.23gm/dl, Red blood cell count was 4.7110.44 million/pL, Mean Corpuscular Volume was 77+5.05 fL, Mean Corpuscular Hemoglobin concentration was 3311.38 g/dl, Mean Corpuscular Hemoglobin was 23+1.22 pg and mean Mentzer's index was 16.59+2.24. The most common type of CHA in our study was ß thalassemia major (58%), followed by ß thalassemia intermedia (17%) and Sickle cell homozygous (13%). 45% of CHA patients required monthly transfusion (p <0.05) especially sickle cell homozygous (90%) and thalassemia major (65%) patients. 24 (28.57%) patients were Hepatitis C virus-positive and 1 was HIV virus-positive. Among adult patients with CHA, ß thalassemia major, intermedia and sickle cell anemia were predominant diagnoses. Consanguinity played a role in one-fifth of patients. A majority of the patients had monthly blood transfusion requirements. The high prevalence of hepatitis C virus infection is a major concern.

Headnote

Abstract

Congenital hemolytic anemia (CHA) especially hemoglobinopathies is quite prevalent in certain ethnic groups in India and commonly seen in pediatric age group. Adult presentations are being seen due to better treatment options and increased life span. This study was conducted to determine the clinical profile, laboratory parameters, transfusion requirements, and transfusion-related infectious complications of adult patients with CHA. A total of 84 patients of CHA aged more than 12 years were enrolled and studied over 18 months period. 63% patients were males with mean age of 19.98+4.99 SD years and maximum (57%) in the age group of 13-20 years. Family history of CHA was present in 19 (22.61%) patients and consanguinity in 16 (19.04%) cases which were statistically significant (P<0.05). Easy fatigability (76.19%) was the most common symptom followed by dyspnea on exertion (36.19%), whereas pallor (98.80%) was the commonest finding on examination followed by spleenomegaly (40.47%). The mean average (mean+SD) values for hemoglobin was 7.37+1.23gm/dl, Red blood cell count was 4.7110.44 million/pL, Mean Corpuscular Volume was 77+5.05 fL, Mean Corpuscular Hemoglobin concentration was 3311.38 g/dl, Mean Corpuscular Hemoglobin was 23+1.22 pg and mean Mentzer's index was 16.59+2.24. The most common type of CHA in our study was ß thalassemia major (58%), followed by ß thalassemia intermedia (17%) and Sickle cell homozygous (13%). 45% of CHA patients required monthly transfusion (p <0.05) especially sickle cell homozygous (90%) and thalassemia major (65%) patients. 24 (28.57%) patients were Hepatitis C virus-positive and 1 was HIV virus-positive. Among adult patients with CHA, ß thalassemia major, intermedia and sickle cell anemia were predominant diagnoses. Consanguinity played a role in one-fifth of patients. A majority of the patients had monthly blood transfusion requirements. The high prevalence of hepatitis C virus infection is a major concern.

Key words: Beta-thalassemia, Congenital hemolytic anemia, Hemoglobin E disease

DOI: 10.5455/jmas.49972

© 2023 Deccan College of Medical Sciences. All rights reserved.

Hemolytic anemia is a condition characterized by premature destruction and a shorter life span of red blood cells (RBCs) due to various intrinsic defects as well as extrinsic factors predisposing to hemolysis and leading to clinical manifestations like severe anemia, jaundice, and splenomegaly. Hemoglobinopathies constitute the major part of (74%) disorder with a global prevalence of about 4.5%1'2. Studies in India have shown that the prevalence of ß thalassemia trait in the general population is approximately 3-4% (3545 million) with 10000 children born per year with ß thalassemia major (10% of global prevalence)34. There are about 2.5 million sickle cell carriers in India with approximately 1.25 lakh cases of sickle cell anemia3. The prevalence of sickle cell carriers varies from 0 to 40 percent in different Indian ethnic tribes especially in states of Gujarat, Madhya Pradesh, Maharashtra, and Odisha56. Hb E disease is more predominantly seen in north-eastern states of India whereas Hb D is predominant in Punjab (2% population).

In India, ß thalassemia major patients still have a very high under five (7 times) mortality with only 50% reaching adulthood despite the availability of blood transfusion services and provision of chelation therapy7. In contrast 30-year survival of transfusion dependent thalassemia patients is more than 80% in most of the developed countries8. Sickle cell disease patients used to have very high mortality (50-90% under-five mortality) and low life expectancy (<20 years) until 1970, after which the introduction of robust neonatal screening, penicillin prophylaxis, and pneumococcal vaccination has drastically reduced mortality with most people living beyond 45 years of age particularly in developed countries9. In India patients with sickle cell disease have a mortality rate of 1.24 cases per 100 person-years10.

With the availability of optimal treatment modalities, many patients with CHA are now reaching adulthood. In India, most of the studies on CHA are done in the pediatric population with scanty similar data in adult patients. Patients may present with clinical manifestation only during episodes of hemolysis. The diagnosis of CHA may often be overlooked till adult age, especially in the mild variety. In addition, adult CHA patients may have different clinical presentation and complication profiles. This study was conducted to determine clinical features, laboratory profile, transfusion requirements, and transfusion-related infectious complications of patients with congenital hemolytic anemia in a tertiary care center located in Mumbai which serves as a zonal referral center.

Material and methods

This was a prospective observational study conducted in the Medicine department on patients following up in the outpatient department and admitted in medical wards over a period of 18 months in a tertiary care center in western India. Patients who fulfilled the inclusion criteria were enrolled in the study.

Aims and objective

1. To study the clinical profile of adult patients with congenital hemolytic anemia

2. To study the investigation profile of adult patients with congenital hemolytic anemia

3. To study the transfusion-related infections in adult patients with congenital hemolytic anemia

4. To assess the requirement of blood and blood products in adult patients with congenital hemolytic anemia

Inclusion criteria

1. Age 12 years and above with proven congenital hemolytic anemia following up in medicine outpatient department and/or admitted in the medical ward after taking valid informed consent.

Exclusion criteria

1. Those having hemolytic anemia due to acquired causes.

2. Unable to provide informed consent.

Study procedure

Patient's demographic data (age, sex, religion, address, occupation, marital status), family history including consanguinity, relevant history (history of blood transfusion, frequency of transfusion, splenectomy), associated co-morbid conditions (Human Immunodeficiency Virus, Hepatitis B and C status) and presenting clinical features were noted. All patients underwent detailed general examination (vitals-pulse, blood pressure, respiratory rate, pallor, icterus, hemolytic faces, edema), a detailed examination of the abdominal system for hepatomegaly/spleenomegaly and cardiovascular system examination for evidence of congestive heart failure/cardiomegaly along with a routine assessment of other systems. Relevant routine laboratory investigations like complete blood count (CBC) with peripheral smear estimation/Mentzer's index calculation, Liver Function test, serum Lactate dehydrogenase (LDH) level and serology for Human Immunodeficiency Virus, Hepatitis B and C were done for all patients. Patients' Hemoglobin electrophoresis reports were noted to determine the type of congenital hemolytic anemia.

Factors like religion, age, family history, history of consanguinity, frequency of blood transfusion, serum LDH level, serum Indirect Bilirubin level, and Mentzer's index were correlated for association with different types of congenital hemolytic anemia using appropriate statistical tests.

Statistical analysis

In this study, all the data was entered in Microsoft excel sheet and was analyzed using the latest statistical software SPSS (Version 20.0). All the continuous variables were summarized using various summary statistics (number of observations, mean and standard deviation) and frequencies and percentages were used for categorical variables. Association between various variables was demonstrated by using the Chi-square test with a P-value of <0.05 considered statistically significant.

Results

A total of 84 patients meeting the inclusion criteria were enrolled in the study conducted over 18 months from March 2018 to September 2019.

Demographic data, family history, consanguinity, and splenectomy history in the study population are shown in Table 1.

The age of patients ranged from 13 to 35 years with a median age of 19.98 years. The majority of the patients were males (63.09%) and belonged to the Hindu religion (74%). About 19 (22.61%) patients had a family history of CHA and 16 (19.04%) patients were born of a consanguineous marriage. 20 (23.80%) patients had a history of splenectomy done in the past.

Figure 1 is showing the graphic distribution of presenting symptoms of the patients. The most common symptoms on presentation were easy fatigability present in 64 (76.19%) followed by dyspnea on exertion present in 31 (36.90%) of the total patients. Other common symptoms were fever (27.38%), jaundice (22.61%), joint pain (14.28%), abdominal pain (4.76%) and abdominal lump (1.19%). The examination findings are given in Figure 2. Pallor, splenomegaly, icterus, hemolytic facies, and hepatomegaly were seen in 98.8, 40.5, 35.7, 19.04, and 17.85 percent respectively.

Figure 3 is showing a graphical presentation of various types of congenital hemolytic anemia found in the study as per hemoglobin electrophoresis analysis, ß thalassemia major was present in 58.33% (49) patients followed by ß thalassemia intermedia in 16.66 % (14) patients. Other types of hemolytic anemia seen were sickle cell homozygous (13.09%), sickle cell heterozygous (9.52%), and homozygous Hb E disease (2.38%).

Table 2 is showing the association of various tors like religion, family history, consanguinity, frequency of blood transfusion, and Mentzer's index with different types of congenital hemolytic anemia. Statistically significant correlation (p value <0.05) was seen between various types of CHAs and frequency of blood transfusions, history of consanguinity and family history of CHA.

Table 3 shows the association of serum LDH values with various types of CHA. The difference between mean serum LDH values for five groups (Hb electrophoresis) was statistically significant (pvalue < 0.05).

Table 4 shows the association between serum indirect bilirubin with various types of CHA. The difference between mean serum indirect bilirubin values for five groups (Hb electrophoresis) was statistically significant (p-value < 0.05).

Table 5 summarizes the various laboratory findings of various CHAs with statistics (mean, standard deviation, and range), and Table 6 is showing the overall statistics of different laboratory parameters. The mean values for hemoglobin (g/dl) was 7.3711.24 (Range 2.7-12), RBC count (million/pL) was 4.7110.44 (Range 3.6-5.4), Mean Corpuscular Volume (fL) was 77.37+5.05 (range 64-86), Mentzer's index was 16.59+2.24 (range 12.2-21.3), serum LDH (U/L) was 522.78+237.66 (range 1401955) and serum indirect bilirubin (mg/dl) was 2.28+0.79 (range 0.8-5.8). The test for a statistical association between different types of CHA with laboratory parameters was applied for serum LDH, indirect bilirubin, and Mentzer's index (ANOVA). It was statistically significant for LDH and indirect bilirubin but not for Mentzer's index.

In our study, Human Immunodeficiency Virus (HIV) infection was found in 1 patient, Hepatitis C virus infection was present in 24 patients, and no one was found to be infected with Hepatitis В virus (Table 7).

Discussion

Most studies done on congenital hemolytic anemia in the past involved only the pediatric population (age <12 years). However, as the life expectancy is increasing in these patients, focusing on patients age >12 years is also important. This study was conducted on 84 patients with congenital hemolytic anemia to evaluate demographic data, family and consanguinity history, clinical profile, laboratory parameters, associated co morbid blood transfusion-related infections, frequency of blood transfusions, and to correlate the above parameters with different types of CHA.

The median age of the patients in our study was 19.98 years with the majority of the patients being male (63%). These findings are similar to a study conducted by Prakash et al on 19 adult ß thalassemia patients (>18 years) in North India where their mean age was 21.6 years with 58% males11.

The most common type of CHA observed in our study was ß thalassemia major (58%), followed by ß thalassemia intermedia (17%), Sickle cell homozygous (13%), Sickle cell heterozygous (10%), and Homozygous Hb E disease (2%). The incidence of ß thalassemia is very high in comparison to other varieties of congenital hemolytic anemia as seen in other studies12. Two cases of Hb E disease which is common in the northeast part of India were also detected in our study. This is because of population migrations and intermarriage between different ethnic groups in India. In our study, it was observed that 19 patients (22.61%) had significant positive family history especially in ß thalassemia major (20.40%), Sickle cell homozygous (50%), and sickle cell heterozygous (33.33%). A study done by Krushna Pani et al in West Bengal on 20 Hb E-ß thalassemia patients showed positive family history in 50% of the cases13. Another study done by Chattopadhay et al on 297 CHA patients from northeast India showed positive family history in 64.3% of sickle-ß thalassemia followed by 54.9% in Hb E-ß thalassemia14. Hence screening for congenital hemolytic anemia in relatives of thalassemia and sickle cell anemia can help in early diagnosis and prompt treatment adding life to one's years. History of consanguineous marriage was present in 16 (19.04%) patients in our study cially in cell heterozygous (33.33%), Sickle cell homozygous (30%), and ß thalassemia intermedia (14.28%). In a study done by Ebrahim et al 17.6 % of patients with congenital hemolytic anemia gave a history of consanguineous marriage15. Pre-marriage counselling particularly in consanguineous marriages can help to reduce the disease incidence.

The most common clinical symptom was easy fatigability (76.19%) and the clinical examination finding was pallor (98.80), followed by splenomegaly (40.47%). Hepatomegaly (18%), hemolytic facies (19%), and splenomegaly (40%) incidence were lower compared to other studies, most likely due to regular blood transfusion suppressing extramedullary hematopoiesis and above features12,13,16. Majority of the patients (45%) in our study required monthly transfusion especially sickle cell homozygous (90%) and thalassemia major (65%) which was higher compared to other studies13,16. The incidence of blood transfusion-related infections was higher for hepatitis C (24/84-28%) as compared to HIV infection (1 patient). An Italian study done by Daniele P et al on 1384 patients with congenital hemolytic anemia had 2.9% patients having HIV and none of the patients had Hepatitis B and C showing very high standards of pre-transfusion testing for the above viruses17. The incidence of Hepatitis C is much higher (28.57%) in our study population because previously in most health care centers, patients requiring blood transfusion were tested for Hepatitis C with anti HCV antibodies and not by PCR for HCV RNA. This implies that testing of blood by nucleic acid amplification (PCR for Hepatitis & HIV) before transfusion which is done now days would be a positive step towards the safety of patients. Laboratory investigations in our study showed higher mean hemoglobin (7.37 gm/dl), MCV (77 fL), MCH (23 pg), and MCHC (33 g/dl) compared to other studies18,19. In this study only 3 patients (3.57 %) show Mentzers index >13 (differentiating thalassemia from iron deficiency anemia) which is not consistent with other studies20, 21. This could be due to regular blood transfusion contributing to a higher MCV.

Study strength

Our study involved adult patients with congenital hemolytic anemia who came to our tertiary health care center for a routine visit or due to a medical emergency. Hence our patient sample is a fairly good representative sample of different clinical presentations.

Limitations of the study

It was a single-center study with moderate sample size. The diverse etiologies within CHA with their diverse presentations may differ from region to region. Hence such studies need to be conducted across multiple sites in India. A long-term followup study would contribute to a better understanding of adult patients with congenital hemolytic anemia including evaluation of the late complications. This will unravel an unbiased and comprehensive spectrum analysis of the patients.

Conclusion

Among adult patients with CHA, β thalassemia major, intermedia and sickle cell anemia were predominant diagnoses observed in the present study. Consanguinity played a role in one-fifth of patients, especially in sickle cell anemia cases. A majority of the patients had monthly blood transfusion requirements. The high prevalence of hepatitis C virus infection is a major concern.

Conflict of interest: None

Acknowledgments: None

Source of funding: Nil

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Article history

Received 02 June 2022

Accepted 24 September 2022

Online 31 January 2023

Print 31 January 2023

Corresponding author

Dhirendra Shivprasad Yadav

Assistant Professor, Department of Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai-400022, Maharashtra, India.

Phone: [phone]

Email: [email protected]

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