Analysis of Patterns of Adverse Transfusion Reactions and Management: A Novel Initiative toward Hemovigilance in a Teaching Hospital of South India

Introduction

Blood transfusion remains as a mainstay of treatment among clinical disciplines in the process of managing elective and crucial cases.¹ Appropriate and adequate access to safe uneventful blood transfusion resources is considered as an integral part to any basic health care delivery system.¹ Researchers quote an efficient blood banking system serves as a mirror of the hospital quality system.^1,2 Transfusion medicine often takes a frontline lead serving as a lifesaving process especially among critically ill patients.³ However, transfusion of blood and its components is inherent with its own risks ranging from minor complications to life threatening fatal conditions which are broadly coined as “adverse transfusion reactions (ATRs).”¹ Rationale selection of patient with pragmatic assessment of pretransfusion parameters aids to reduce the incidence rate of adverse reactions. ^1,4 It also provides scope to analyze risk versus beneficiary outcome of transfusion thereby picking up potential recipient to contain transfusion-related adverse reactions.⁵ This continuous monitoring of ATR serves as an effective modality in promoting quality control in terms of safety and patients care.

Adequate knowledge with regard to ATRs and its various patterns of presentation will guide for prompt identification with subsequent management and appropriate measures to prevent ATR in future as well.^1,6 Hemovigilance being a quality indicator of transfusion medicine, functions as a continuous system of data collection for analysis of transfusion-related adverse reactions.^6,7 It provides a platform to investigate their underlying etiopathogenesis and clinical outcomes and prevent their occurrence as well as recurrence in long term.^7,8 Thus hemovigilance process is directed with a purpose to ensure safety and efficacy of blood transfusion procedure covering the sequential chain of donors to recipients.^9,10

Hemovigilance based on its core principle includes proper identification, reporting, reverting, repeating investigations, and tracking various chain of events between donors and recipients.^11,12 It also interrogates incidents occurred in manufacturing level and consequent errors and “near misses.”^13,14 In the year 2012, “the Haemovigilance Programme of India” was commissioned by the Indian Pharmacopoeia Commission in collaboration with the National Institute of Biologicals under the auspices of Pharmacovigilance Programme of India, with an objective to track ATR due to transfusion of blood and its components in all affiliated blood banks across the country.^6,15

Hemovigilance system serving as a backbone of quality assurance, the present study was carried out with a novel aim of determining incidence of adverse transfusion-related reactions and to substantiate its patterns encountered in our teaching hospital blood bank located in remote South-Eastern part of the Country. The study owns an objective to enlighten knowledge and insights into patterns of ATR in the study domain which is not yet documented with special emphasis on root cause analysis with appropriate corrective and preventive actions.

Materials and Methodology

Categorization of ATR Patterns

The adverse reactions were classified into acute (within 24 hours) and delayed (onset after a period of 24 hours from cessation of transfusion). With regard to clinical presentation, febrile nonhemolytic transfusion reactions (FNHTR) constituted majority of the ATR commonly associated with PRBC transfusion followed by allergic reactions and hypotension. The distribution of adverse reaction patterns observed with respect to transfusion of blood and its components is depicted in ►Table 5

Table 5 Incidence of patterns of ATR in respect to transfusion of blood products

Number of transfusion		Patterns of ATR (n = 189)
Blood derivatives	FNHTR	Allergic reactions	Hypotension	AHTR	Total ATR with blood/components	Risk ratio
WB (n = 18)	3	2	–	4	09	0.50
PRBC (8,910)	90	20	9	2	126	0.02
PC (n = 4,410)	18	14	9	–	36	0.009
FFP (6,300)	11	7	–		18	0.004
Total	122	43	18	06	189

Abbreviations: AHTR, acute hypotensive transfusion reaction; ATR, adverse transfusion reaction; FFP, fresh frozen plasma; FNHTR, febrile nonhemolytic transfusion reactions; PC, platelet concentrates; PRBC, packed red blood cells; WB, whole blood.

All the cases in the study (n = 189 cases) were acute transfusion reactions, where 122 (69%) cases showed FNHTR, 43 cases (21%) showed allergic reactions, 18 cases (8%) showed hypotension, and six (2%) cases showed AHTR. Majority of transfusion reaction occurred in patients with anemia as indicated (90 cases) followed by dialysis (59 cases), elective surgical procedures (27 cases), and others (13 cases) as shown in ►Fig. 1.

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Fig. 1

Distribution of frequency clinical indications for blood transfusion.

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Discussion

Quality assurance being an integral part of efficient blood banking system, prompt reporting by clinicians on information related to any adverse events encountered during or post transfusion is the main source to document ATRs.^1-5 In the present study, the adverse reactions were of acute nature with a transfusion to ATR ratio of 10:0.1 (0.9%), concording with prior studies performed in Northern parts of Chandigarh and Punjab where the incidence of ATR was noted to be 1.09%.^6,7 Observations from two long-term studies conducted in the domain of New Delhi and Chandigarh documented much lower frequency of ATR (0.05 and 0.19%, respectively).⁷ Similar studies conducted in European Nations reported lower reaction rates ranging between 0.035 and 0.02%.⁸ Thus it is evident that adverse transfusion events at our study place was modestly higher when compared with studies performed at national and international centers.^7-9 The reason for higher incidence could be altered immune system, medication history, circumstantial evidences for oncotic imbalance, thermal conditions, osmotic injuries, storage conditions of the blood unit issued, mode of transfusion, increased number of reporting and reverting, and high frequency of transfusion.⁷

Surprisingly, the frequency of adverse events was commoner among females compared with males with an approximate ratio of 1.5:1. Studies carried out in Indian domain predominantly showed male preponderance for ATR with an average percentage ranging between 54 and 59%, whereas studies done in Middle–East region showed female preponderance almost concurring with ratio observed in the present study.^7,8 It had been estimated that the frequency of ATR varies between 0.2% and a maximum of 10% with a mortality rate of two in 2, 00,000.^9,10 The present study correlated and varied with prior studies on ATR performed among Indian population conducted in other parts of the country including premier institutions like All India Institute of Medical Sciences, is elaborated in ►Table 7.

The concept of biosafety and hemovigilance had been evolved in later part of 19th century and gained popularity since its time of inception.^1,11 The term “hemovigilance” is now recognized as a quality indicator and practiced worldwide as an essential component of quality assurance in transfusion medicine.^12,13 It functions as a system on an ideal objective directed to detect, document, and evaluate undesirable events encountered with transfusion of blood and its components, thereby enabling to perform root cause analysis and setting up or reframing policies and improvisation of standard operating procedures.^13,14

Data collected from different studies on the incidence of FNHTR, correlate and vary in equal proportion in the literatures.^6,7 FNHTR is defined as a reaction otherwise unexplained with a rise in body temperature of minimum 1ºC while the transfusion is ongoing or shortly after cessation of transfusion.^1,15 The potential reason for this variations is attributed to several possible factors such as monitoring clinical signs and symptoms by the bedside clinical staff nurses and residents, alteration of internal temperature due to pretransfusion of medicines, case ascertainment, environment, geographical distributions, and racial inheritance.^7,16 In the present study, the incidence of FNHTR was high (64%) especially in cases with PRBC transfusion. The association between FNHTR with preceding PRBC transfusion showed significant statistical analysis (p-value < 0.05) concurring with prior studies as well.^7,17 The reason attributed for high adverse events with PRBC association is higher frequency of transfusion compared with other components and majority of cases had prior transfusion leading to antigenic exposure.¹⁸ PRBC being non-leukodepleted component, has higher potential for ATR as evident from our study. To manage the high incidence of FNHTR, the study proposes to first rule possibility of hemolysis, to inject antihistamines and in case if reaction occurs for second time, usage of leukodepleted blood components must be encouraged.^1,18

In reference to audit of requests from clinical departments, Obstetrics and Gynecology topped the table in claiming for maximum requests with an overall issue rate of 8,100 among which issue for PRBC with anemia as a common underlying indication. ¹⁵ Most of the cases had multiple transfusions leading to adverse reaction due to varied antigenic exposure and same is the factor for adverse reactions among females.

Allergic reaction was the second highest prevalence of adverse reaction observed to be associated with transfusion and it is noted in 43 cases (0.2% of overall transfusion) presenting as urticaria and rashes. Statistical analysis revealed insignificant difference between the frequency of allergic events and type of blood transfused (p-value > 0.05 for all blood components). Few studies had been conducted by Kumar et al in Northern part of India at AIIMS, New Delhi, which showed that overall incidence of allergic reaction is only 0.02% which is significantly lower than our observed value.⁷ Studies had showed that allergic reactions can occur in from 0.1 to 2% of transfusion at a given point of time concurring with the observations of the present study.⁷ The pathological sequence associated with allergic reactions is due to donor’s plasma interacting antigen/allergens in patient plasma and with subsequent triggering of histamine action and release of chemical mediators of inflammation. Another significant contributing factor for high allergic reaction assumed to the remnant plasma kept in PRBC to decrease the blood viscosity may expedite immune reactions.^8,18 The high incidence could be fixed by administering antihistamines at least 1 hour prior to transfusion.¹⁸ Platelet transfusions showed reactions with an incidence of 0.8% in overall transfusion which is still higher when compared with other Indian studies which showed an incidence of 0.04%.^7,11

The practice of whole transfusion should be restricted until it is absolutely indicated and NACO proposes that in a given year the utilization or issue of whole blood must be less than 10 percentage of overall issues of the blood bank.¹ In the present study hemolytic reaction was commonly associated with whole blood transfusion in four cases (22%, n = 18) and two cases with PRBC (0.02%). Laboratory investigations showed the presence of schistocytes on blood smear indicating evidence of hemolysis and with additional evidences for urine RBC cast and positive direct Coombs test. In the study, we re-emphasized the clinician regarding the management protocol in event of hemolytic reactions to inform the blood bank promptly to disconnect the entire infusion, to collect a post transfusion vial fresh blood, and to return the blood bag immediately to the blood bank.

Hypotension was encountered in 18 cases with PRBC and platelet concentration each with distribution of nine cases and the patients were already on treatment with ACE inhibitors and on dialysis. PC transfusion showed adverse events in 36 cases (0.8%) with FNHTR and allergic reactions and the study proposed administration of corticosteroids and also to monitor the platelet counts since, many a times thrombocytopenia is a self-limiting condition and platelet transfusion is nonbeneficial.¹⁹

Though not encountered in the study, as an additional novelty, the study proposes management protocol in instances of delayed transfusion reactions as it is neither feasible to follow-up patients once they get discharged nor prevent them from succumbing to delayed reactions. We propose that whenever RBC antibodies are detected in blood bank, the treating physician should be kept informed about the same and to counsel them to provide this vital information to the patients when they get hospitalized elsewhere to avoid delayed reactions. In the present study, delayed transfusion reactions were not encountered probably due to nonreporting, due to loss of follow-up, under diagnosis since the recipients get discharged with a time interval to visit for reviews.

Critical appraisal: The study claims novelty by advocating the practice of nonpunitive type of error management in managing events of adverse transfusion-associated reactions. Judicious selection of recipients and stringent follow-up after issue of blood units in wards especially ensuring optimal temperature, storage, transportation are essential. Hemovigilance provides scope for corrective and preventive action and gives referral guidelines to prevent future recurrence. It is believed that the practice of transfusing leukodepleted blood units in our hospital could enable to substantially retard the incidence of adverse events of transfusion as a general measure and febrile reactions in particular.

Conclusion

The present study is evident with a novelty in revealing the fact that the overall incidence of transfusion-associated reactions in the study domain is higher at very modest level when compared to more advanced centers in India. However, there were no significant variations observed with respect to cumulative incidence of ATRs based on the type of blood component transfused except for marginal association between packed cell transfusion and febrile reactions. There was neither delayed reaction nor mortality due to adverse reaction encountered in the study. The study analyzed the patterns of ATR with emphasis on management followed in treating adverse events as a unique aspect. The observations reiterate the use leukodepleted units in case of whole blood transfusion and packed cells to retard the incidence rate of adverse reactions. Hemovigilance assists toward inclination of quality assurance in blood bank and extends as a platform for fact finding rather than fault finding in analysis of ATRs.