Prevalence of transfusion-transmitted infections in multiple blood transfused thalassemia patients: A report from a tertiary care center in North India

Aims: The present study was undertaken to estimate the prevalence of transfusion-transmitted infections (TTIs) in multitransfused patients of thalassemia major and to determine the association with relation to the number of blood units being transfused in Jammu province. Materials and Methods: The study was conducted on 138 beta thalassemia patients registered for regular blood transfusions at the Department of Blood Transfusion Medicine, Shri Maharaja Gulaab Singh Hospital, Government Medical College, Jammu in the period July-December 2014. The tests for TTIs, i.e., human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), were performed by using third-generation enzyme-linked immunosorbent assay (ELISA) kits. Statistical Analysis: The data were analyzed as proportions. The statistical significance of the results was evaluated using the chi-squared test/Fisher’s exact test. A P value of <0.05 was considered significant. Results : Out of 138 patients, 13.7% (19/138) were seroreactive for TTIs. Of these seroreactive patients, 13.04% (18/138) were positive for anti-HCV and 0.72% (1/138) positive for anti-HIV. Of the anti-HCV reactive cases, 66.66% were >15 years of age. Of the anti-HCV positive cases, 94.4% (17 out of 18) had received more than 100 transfusions. Anti-HCV seroreactivity was noted to increase with increase in the age of the patient and the number of transfusions. Conclusion: HCV is the main TTI in multitransfused thalassemic patients. HBV vaccination must be done before starting the transfusion regimen or as soon as otherwise possible.

Keywords: Enzyme-linked immunosorbent assay (ELISA), multitransfused, thalassemia, transfusion-transmitted infections (TTIs)

Thalassemias are hereditary hemolytic anemias characterized by the deficient synthesis of one or more globin chains in the hemoglobin. They are the most common genetic disorder worldwide: About 1.5 million people, i.e., 3% of the world population carry the beta thalassemia gene. ^[1] It is estimated that there are about 65,000-67,000 beta thalassemia patients in India, with around 9,000-10,000 cases added every year. ^[2] Beta thalassemia major, also called Cooley’s anemia, is a severe form and is transfusion-dependent.

The conventional treatment for patients suffering from beta thalassemia is regular blood transfusion and chelation therapy in view of constraints in bone marrow transplantation. Current guidelines recommend a pretransfusion hemoglobin threshold not exceeding 9.5 gm/dL, which seems to be associated with adequate marrow inhibition and low iron burden. ^[3] The blood transfusions required by such patients expose them to the serious hazard of transfusion-transmitted infections (TTIs) such as human immunodeficiency virus (HIV) and hepatitis B and C (HBV and HCV, respectively) viral infections. The risk of these patients acquiring TTIs through multiple transfusions can be overcome by better donor screening, voluntary donations rather than replacement, and implementing better technologies to detect these infections. ^[4] The present study was undertaken to estimate the prevalence of TTIs in multitransfused patients of thalassemia major and to determine the association with relation to the number of blood units transfused in Jammu province.

The study was conducted on 138 beta thalassemia patients registered for regular blood transfusions at the Department of Blood Transfusion Medicine, Shri Maharaja Gulaab Singh Hospital, Government Medical College, Jammu. The study was undertaken after obtaining consent from the patients or their guardians. Clinical data, including age, number and duration of transfusions received, and history of HBV vaccination, were collected from the patients enrolled in the study. When the patients appeared for blood transfusion, 5 mL of venous sample was collected from each patient in a plain Vacutainer (Hebei Xinle Sci & Tech Co. Ltd, Made in China), along with the sample for pretransfusion testing. Serum was separated and stored at -80°C until all the samples of all the patients on regular transfusion were collected. The tests for TTIs, i.e., HIV, HBV, and HCV, were performed by using third-generation ELISA kits. The tests were strictly performed as per manufacturers’ instructions.

The data were analyzed as proportions. Statistical significance of the results was evaluated by using the chi-squared test/Fisher’s exact test. A P value of <0.05 was considered as significant.

The population of the present study consisted of 138 thalassemic patients, of whom 86 were males and 52 females. The ages of these patients ranged from 18 months to 32 years, and 33.33% patients were >15 years old. Of all the patients, 64.4% (89/138) had received more than 100 transfusions. All the patients had received vaccination against HBV. Out of 138 patients, 13.7% (19/138) were seroreactive for TTIs. Of these seroreactive patients, 13.04% (18/138) were positive for anti-HCV and 0.72% (1/138) positive for anti-HIV. None of the cases were reactive for HBV surface antigen (HBsAg). Of the study population, 15% of males were reactive for HCV (13/86), whereas 9.6% of females were reactive for HCV.

Relationship of seroreactivity with age

23% of anti-HCV-positive cases were >15 years old, while 66.66% of total anti-HCV reactive cases were >15 years of age. X ² = 8.713, P < 0.01 [Table 1].

The relationship of seroreactivity with the number of blood transfusions was as follows: 94.4% (17/18) anti-HCV positive cases had received more than 100 transfusions until the time of writing. A single case of anti-HIV positivity was in a 9-year-old male who had received 96 transfusions [Table 2].

Regular blood transfusions are the mainstay of therapy in thalassemia major patients. A hemoglobin level of at least 9.5 gm/dL is necessary for maintaining the physical growth and development of such patients. ^[1] Adequate and safe blood transfusions improve the quality of life and survival of patients. However, they also expose the patients to the risk of acquiring TTIs. The probability of acquiring TTIs is related to the probability of being exposed to the infected units of blood. This probability depends on the prevalence of carriers among the blood donors in the population and the number of units transfused. ^[4] Thus, the infection rate of TTIs increases with age in subsequent years.

In the present study, seropositivity for TTIs was 13.7% (18/137). HIV seropositivity was 0.7% and that for HCV was 13.04%. None of the thalassemia patients in the study group was positive for HBV infection. [Table 3] shows comparison with recent studies. ^{[4],[5],[6],[7]}

On comparing rates of TTIs with studies from other part of India, HIV ranged 0-9%, HBV ranged 1.2-7.4%, and highest rate was seen for HCV transmission, ranging 2.2-44% ^{[8],[9],[10],[11]} Variations in the prevalence of TTIs amongst thalassemics even after serological screening could be related to geographical differences in prevalence of the viral infections among blood donors, nature of blood donors whether replacement or voluntary, and the nature of care individual thalassemics receive.

TTIs such as HBV, HCV, and HIV are dreaded consequences of transfusions, as these can result in long-term morbidity and mortality. In India, it is mandatory to screen donated blood for anti-HIV 1 and 2 (since 1991), anti-HCV (since 2001), HBsAg, syphilis, and malaria.

Studies conducted in and around 1988 showed a high prevalence of HIV, ranging 14-18%, while that of HCV remained at 14%. TTIs can still occur from blood donations negative for the markers for these infections, as reported by various Indian investigators and international studies. ^[8],[9],[10] This residual risk of acquiring a TTI from screened blood depends on the safety of the donor population, the sensitivity of the screening tests used, window-period donations, and other reasons, such as mutant strains. ^[12]

Liver disease is the leading cause of death in patients with beta thalassemia. Transfusion-associated hepatotropic viruses and hepatic siderosis can act either synergistically or independently in promoting chronic liver disease, and they may induce liver damage through a similar oxidative pathway. ^[5]

HBV infection can be prevented in these patients, as very effective HBV vaccine is available: This is evident from our study where all the patients were vaccinated against HBV infection and none were reactive for the HBsAg. Hence, all patients who require multiple transfusions should be vaccinated right from the beginning. Nucleic acid testing (NAT) is widely recommended for the screening of donor blood. Makroo et al. have shown that blood units negative for HIV 1+2, HBsAg, and HCV have 1:1000-1:1500 NAT positivity rate and that the majority of the positivity was due to HBV virus, underlining the need for HBV vaccination in thalassemic patients. ^[13] Now with the introduction of the fourth-generation ELISA test that detects p24 antigen along with antibodies, the window period can be reduced to 2 weeks, but NAT screening further shortens it to 2.93 days for HIV, to 10.24 days for HBV, and to 1.37 days for HCV. ^[14] Malhotra et al. found a significant increase in the detection of seroreactivity with fourth-generation ELISA kits compared to third-generation ones. ^[15]

In the present study, 66.66% cases positive for anti-HCV were >15 years of age, i.e., they have been receiving transfusions before 2001, when screening for anti-HCV became mandatory; this finding is comparable to other studies. ^[4],[6],[7] There is a reduction in the development of anti-HCV post 2001, but it has not been eliminated. All the cases of positive anti-HCV had received more than 100 transfusions, similar to other studies. ^[6],[7] Thus, patients have more chances of developing anti-HCV with increase in age, due to cumulative increase in the transfusions.

In the present study, HCV was the main TTI in multitransfused thalassemic patients, and one patient was reactive for HIV. Measures recommended are: Better donor-screening strategies; the promotion of voluntary blood donation; and the implementation of newer technologies such as fourth-generation ELISA and/or NAT screening for HIV, HBV, and HCV, which reduces the window period and thus reduces exposure to these infections via blood transfusion. HBV vaccination must be done before starting the transfusion regimen or as soon as otherwise possible.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.159849

[Table 1], [Table 2], [Table 3]