A Study on Adverse Transfusion Reactions in a Secondary Care Hospital of Rural India

Aims: The study aims to assess the incidence, causality, and severity of adverse transfusion reactions in patients transfused with blood or blood components at a secondary care referral hospital. Study Design: A prospective observational study was conducted in the secondary care referral hospital located in rural settings of Anantapur district, Andhra Pradesh, India. The study was conducted for a period of six months from May 2019 to October 2019 Methodology: All the patients transfused with blood or blood components in the hospital located in Andhra Pradesh during those six months study period were included. The transfusion reactions were reported to the blood bank in the Adverse Transfusion Reaction Report Form (ATRRF). Descriptive statistics were used to represent the adverse transfusion reactions. Results: From 2549 transfusions, 30 adverse transfusion reactions were reported (1.17%).Most of the reactions reported were febrile non-hemolytic transfusion reactions FNHTRs (73.3%) followed by allergic reactions (20.0%). Transfusion reactions were predominant in females 21 (70.0%) than males 9 (30.0%). Most of the reactions were confirmed/definite (46.6%) in causality assessment and moderate (63.3%) in severity assessment. The incidence of adverse transfusion reactions was found to be 1.17%. Conclusion: The study concludes that there was a low incidence of adverse transfusion reactions indicating probably underreporting in the healthcare system. This would be due to lack of knowledge regarding importance of surveillance and reporting of adverse transfusion reactions by blood or blood components. There was a need to conduct continuous educational programs (CEP) on hemovigilance system towards healthcare providers to improve the reporting practice. The study provides insights about type of adverse transfusion reactions and their causality and severity. This data helps in motivating the healthcare staff to report ATRs and also to develop strategies to handle preventable ATRs.


INTRODUCTION
Transfusion of blood or blood components is essential to improve the clinical condition of the patient [1]. Even though blood transfusion was considered a life-saving intervention, it was associated with a wide range of complications from minor fever to severe anaphylactic reaction [2]. Haemovigilance is "systematic surveillance of adverse reactions and adverse events related to transfusion" intending to improve transfusion safety [3]. The hemovigilance system involves identifying, monitoring, reporting, investigating, and analyzing Adverse Transfusion Reactions (ATR) of Blood and Blood components [4]. This approach was developed by the French Blood Agency in 1994 with the implementation of Blood Transfusion Committees and setting a National Hemovigilance System [4]. This system is essential for quality control, prompting preventive measures, and advancing the quality and safety of blood products [5].

Indian
Pharmacopoeia Commission, in collaboration with the National Institute of Biologicals, Noida, Uttar Pradesh, has launched a Hemovigilance Programme of India (HvPI) on 10th December 2012 under its Pharmacovigilance Programme of India (PVPI), underthe Ministry of Health and Family Welfare, Government of India [6]. About 3,027 transfusions were reported through hemovigil software in a period of 3 years from 2013 to 2016 [7].
Hemolytic transfusion reactions are the most common non-infectious complications. Ten million units of RBCs were given to 30 million patients in 10 years. So, the risk of hemolytic transfusion reactions is 1:55,000 per unit [8].The occurrence of transfusion reactions has been increasing day by day, which poses a burden on the health and economy of individual patients. Thorough knowledge of the incidence and ATR profile can help prevent and treat adverse transfusion reactions of blood or blood components.For this purpose, the study aims to assess the incidence, causality, and severity of adverse transfusion reactions in patients transfused with blood or blood components at a secondary care referral hospital.

MATERIALS AND METHODS
A prospective observational study was performed over a period of six months, from May 2019 to October 2019, in a secondary care referral hospital located in rural settings of Anantapur district, Andhra Pradesh, India. All the patients transfused with blood or blood components during the study period were considered for inclusion. After transfusion of blood or blood products, all reactions were reported to the respective blood bank in the Adverse Transfusion Reaction Report Form (ATRRF).
The data collection form comprises IP admission number, age, gender, current diagnosis, treatment drugs, type of blood component transfused (number, frequency, volume), laboratory investigations, reaction observed (onset time, duration, and characteristics), history of the patient, and management of the transfusion reaction.

Investigation of Adverse Transfusion Reactions
1. The patient's name and identification number were checked in the blood request form and blood bag to rule out manual administration errors.
2. The identifiers were rechecked before transfusion of the blood or blood components. 3. A Blood bag along with the transfusion set was observed for any deterioration before transfusion.
4. Records of ABO compatibility and Rh typing were checked before transfusion.
5. Compatibility tests and cross-matching were repeated both on pre-transfusion and posttransfusion samples.
6. Medical and medication history of the patient, including transfusions and transfusion reactions, were considered.
7. In case of sepsis or other infections patient's post-transfusion sample and blood bag were cultured.
8. In the case of non-hemolytic transfusion reactions, lab tests were done based on the symptoms.
9. Post-transfusion sample was checked for hemolysis; bilirubin levels and antibody screening were done.
10. The observed reactions were assessed for causality and severity based on the scales developed by the World Health Organization.

Data Analysis
Data analysis was performed using Epi-Info 7 statistical software given by the Centre for Disease Control, USA. Descriptive statistics like proportion, frequency, mean, and standard deviation were used to represent the adverse transfusion reactions.

RESULTS AND DISCUSSION
During the study period, 2549 blood and blood components were transfused. Among them, 30 adverse transfusion reactions were reported. The majority of the reactions were seen in adults, i.e., 43.3%, and mainly observed in females 21 (70%), as shown in Table 1.
Among all transfusion reactions reported, 26 (86.6%) occurred in Packed Red Blood Cells transfusions, and 4 (13.3%) occurred in platelet transfusions. Though the blood transfusions are done for the blood group of O+Ve(899) and B+Ve(874) were almost nearer, the reactions were primarily observed in B+Ve(17) than in O+ve (3).   The reactions were primarily observed in transfusions done for the patients with anemia (9); Thalassemia (7); During labor (4), and aplastic anemia (4), followed by pancytopenia (2); surgery (2); pure red cell aplasia (1) and dengue (1). Most of the symptoms the patients experienced include fever, chills, and itching.  As the number of transfusion reactions has been increasing, which may endanger the health and economic burden on individual patients and the nation, monitoring the occurrence of transfusion reactions is necessary to prevent and for the early management of those reactions. To know the incidence of transfusion reactions, reporting is the only source of information. In our study, all the reactions reported were acute. No delayed reactions were reported, though recipients were advised to visit the hospital for follow-up.
The incidence of adverse transfusion reactions in our study was found to be 1.17%. The incidence obtained in our study may not be the true incidence due to underreporting of some mild reactions. Underreporting was also found in a study conducted by Surekha K et al., Incidence in our study was found to be 1.17% which was different from a study conducted by Surekha  [8,9,10]. A hemovigilance study conducted in Portuguese among elderly people shown a high rate of adverse transfusion reactions compared to the current study [11].
In our study, transfusions were predominant in females (70%) than males (30%). These results coincide with the study done by Vidya Shree M (females-53.8% & males-46.1%). In our research, most of the reactions were confirmed (46.6%) in causality assessment which was different from observations of Vidya Shree M, where most of the reactions were probable [12].
Our study's principal reason for transfusions was anemia, which was found to be similar to the observations of study conducted byVidya Shree Met al. Among all the transfusion reactions, most of the transfusion reactions have occurred in patients who received Packed Red Blood Cells (86.6%). These results coincide with the study done by Vidya Shree M and Praveen Kumar et al., [8,12].  [16,17,18].
Our study has shown that B-Positive (56.5%) had a higher incidence of transfusion reactions among all blood groups than other groups, which are different from the study conducted by the Vikram Kumar Gente in which B-Negative had a higher incidence of transfusion reactions [2].
Our study was correlated with the study conducted by Venkatachalapathy TS, Praveen Kumar et al., RajiniBassi et al., their results also showed a higher incidence of FNHTRs. FNHTRs occur due to interaction between antibodies of recipient and antigens on leukocytes of the donor. The use of leuko-reduced blood products can control these reactions. Packed Red Blood Cells were more frequently involved in acute transfusion reactions. These results were correlated with the study done by Rajini Bassi et al. [8,13,20].
The limitations of our study were dependent on the reporting of transfusion reactions. Reporting was not done for some mild reactions and delayed reactions. In our study, risk factors that increase the incidence of transfusion reactions were not evaluated.

CONCLUSION
The study concludes that there was a low incidence of adverse transfusion reactions indicating probably underreporting in the healthcare system. This would be due to lack of knowledge regarding importance of surveillance and reporting of adverse transfusion reactions by blood or blood components. There was a need to conduct continuous educational programs (CEP) on hemovigilance system towards healthcare providers to improve the reporting practice. The study provides insights about type of adverse transfusion reactions and their causality and severity. This data helps in motivating the healthcare staff to report ATRs and also to develop strategies to handle preventable ATRs.

CONSENT
Before data collection, informed consent was obtained from the patients who received blood or blood component transfusions.

ETHICAL APPROVAL
As per international standard or university standard written ethical approval has been collected and preserved by the author(s).