Introduction
According to the International Society of Blood Transfusion, febrile nonhemolytic transfusion reaction (FNHTR) is characterized by a posttransfusion rise of more than 1°C or chills and rigor unrelated to the underlying condition.[1 1 2 3 3 4 5 6 7
Materials and Methods
It was an observational retrospective study in which all the details of FNHTRs reported to the department of transfusion medicine from July 2018 to July 2019 were analyzed. Patient demographic details, type of component transfused, and posttransfusion clinical presentations were analyzed to identify various factors affecting the severity of FNHTRs. A compatibility report is provided with every blood component issue. The clinicians were asked to follow the bedside transfusion instructions, i.e. red cell transfusions to be transfused within 30 min of the issue and completed within 4 h and for platelet concentrate and fresh frozen plasma transfusion to be started at the earliest after the receipt of blood components at the patient bedside and to be completed in 20–30 min. Clinical residents from all the clinical specialties of our institute are trained for reporting data to the pretransfusion testing laboratory of our department. When adverse transfusion reaction is identified by a clinician/nursing officer, transfusion is stopped immediately. Then, it is informed telephonically to the doctor on call in transfusion services. Complete details of the transfusion reaction are recorded and sent to the pretransfusion testing laboratory along with the used component bag, blood transfusion set, and posttransfusion sample taken from the site other than the implicated for transfusion reaction. Reported reactions were evaluated. To rule out wrong sampling/bedside error, the patient's identification details such as name, age, sex, and hospital registration number are rechecked both on the pre- and posttransfusion sample vials and requisition form. A gross examination of blood bag and transfusion set was done for any discoloration, clot, and hemolysis. Any evidence for thermal injury was looked upon by inspecting the bedside storage conditions of blood component after it was released from the blood bank. Pre- and posttransfusion samples of the patient were checked for hemolysis. Results of blood typing were compared with the previous records if the patient was transfused previously. The reconfirmation of ABO and Rh typing of the patient and blood product was done with repeat compatibility testing on both the samples. Clinical signs and symptoms were evaluated. Investigations such as direct antiglobulin test and indirect antiglobulin test were done. A sample from blood bag was taken in a blood culture bottle for microbiological examination. Other details which include storage conditions between component issue and transfusion were also noted.
Flowchart 1: Flowchart for Reporting Adverse Transfusion Reactions
Adverse transfusion reaction observed by a bedside physician/nursing officer
↓
Informed telephonically to the department of transfusion medicine and documentation on compatibility report is done
↓
Blood bag with transfusion set, posttransfusion sample along with filled form, is sent to the department of transfusion medicine
↓
Other relevant investigations are sent to various laboratories from the ward
↓
Requisition form is checked for any clerical errors
↓
Further investigations such as repeat blood grouping – ABO and Rh (D), direct antiglobulin test, cross-matching, and antibody screen are done with posttransfusion sample. Blood culture is sent to the microbiology laboratory
↓
Any further investigations required to diagnose the type of transfusion reaction are done
↓
Imputability of transfusion reaction is assessed in coordination with a clinical physician
↓
Reactions are reported to the national nodal center for hemovigilance
Results
A total of 52,289 PRBCs and 16,559 buffy coat-depleted PRBCs were distributed with an incidence of 0.11% transfusion reaction during our study period from July 2018 to July 2019. A total of 76 reactions were reported in our study period. Out of 76 reactions [Figure 1 ] reported, 34 (44.7%) were febrile reactions. Other adverse reactions reported were allergic reactions 28 (36.8%), followed by pulmonary reactions 7 (9.2%), transfusion-associated hypotension 3 (3.9%), hemolytic transfusion reactions (2.7%), and others (2.7%). Other reactions included transfusion-transmitted bacterial infection and transfusion-associated anxiety.
Figure 1: Incidence of various transfusion reactions in our study
Thirty-four FNHTRs were reported in our study period. Eighteen reactions were reported in males and 16 were reported in females. The mean age of patients is of 40.71 years. Four patients had only chills and rigor with no increase in temperature. Twelve patients had a 1° rise in temperature and the rest of the patients presented with severe FNHTR (>2°C). Among the patients with severe FNHTR, 10, 5, and 3 patients had a 2°, 3°, and 4° rise in fever, respectively [Figure 2 ]. Staphylococcus hominis growth was seen in culture in one case. Among 34 FNHTRs, imputability in 24 reactions was probable, possible in 5 reactions, definite in 3 reactions, and unlikely in 2.
Figure 2: Rise in temperature in 34 cases of FNHTR. FNHTR: Febrile nonhemolytic transfusion reaction
Out of the 34 reported febrile reactions, one was due to apheresis platelet transfusion and the remaining reactions were due to red cell transfusion. The incidence of FNHTR in buffy coat-depleted PRBC and PRBC is 0.03% and 0.05%, respectively. FNHTRs are seen more in females with prior history of transfusion (87.5%) as compared to males (66.67%) (P = 0.046). Eighty-five percent of total febrile reactions were due to PRBC transfusion (nonbuffy coat depleted) transfusion and approximately 12% were due to buffy coat-depleted PRBC transfusion. It is a known fact that the incidence of FNHTR decreases with buffy coat depletion and we observed the same in our study also. A decrease in the incidence of FNHTR decreases the need for other biochemical and microbiology tests and its associated cost. However, one interesting finding in our study is that the FNHTR is less severe with buffy coat-depleted PRBC transfusion than PRBC. Table 1 shows the characteristics of FNHTR with respect to the rise in temperature during the reaction, the volume of blood component transfused, and the time gap between initiation of transfusion and transfusion reaction.
Table 1: Characteristics of febrile nonhemolytic transfusion reactions with respect to rise in temperature during the reaction, the volume of blood component transfused, and the time gap between initiation of transfusion and transfusion reaction
It was found that the temperature rise was higher with PRBC transfusion [Figure 3 ]. Temperature rise with buffy coat-depleted PRBC was 1.3 ± 0.8 and PRBC was 1.74 ± 1.13. Although the results were not statistically significant, yet it implies that buffy coat depletion in a certain group of patients may decrease the severity of febrile reaction in terms of rise in temperature. Thus Buffy coat depletion can help in preventing any sequelae to transfusion reaction in predisposed patients. The other concern with transfusion reactions is the inability to transfuse due to transfusion reaction as transfusion needs to be stopped immediately after transfusion to rule out any hemolytic cause of transfusion reaction. FNHTRs are generally benign reactions, but these blood units are discarded and it adds to the financial burden on the hospital. We found that febrile response to buffy coat-depleted PRBC transfusion occurred at higher mean volume (145 ml) transfusion than PRBC transfusion (87.2 ml), and this difference between PRBC and buffy coat-depleted PRBC was statistically significant. Furthermore, the transfusion reaction with buffy coat-depleted PRBC occurred later than PRBC transfusion, as shown in Table 1 . The mean time gap between initiation of transfusion and transfusion reactions was 80 min and 115 min with PRBC and buffy coat-depleted PRBC, respectively. Hence, more red cell volume is transfused with more benefit to the patient and may help in the reduction of patient cost for the hospital authorities.
Figure 3: Box plot chart shows the mean ± SD rise in temperature in buffy coat depleted and PRBC transfusion. It highlights the higher increase in temperature in a patient receiving PRBC transfusion as compared to buffy coat-depleted PRBC transfusion. SD: Standard deviation, PRBC: Packed red blood cell
Discussion
This study was done from July 2018 to July 2019 in a tertiary care hospital. Transfusion of blood and blood components can sometimes lead to adverse events in the form of adverse transfusion reactions which are then reported online to form a national database. Coordination between the clinical and transfusion teams is of utmost importance for timely identification of events and hence its clinical management.
Total transfusion reactions reported in our study was 76 with an incidence of 110 transfusion reactions per lakh of red cell component transfused. The rate of occurrence of transfusion reaction in our study was less as compared to other studies in which the incidence varies from 0.18% to 0.42%.[8 9 10 11 et al .,[8 et al .,[12 et al .,[13 et al .[14
Eighty-five percent of FNHTR was due to PRBC transfusion (nonbuffy coat depleted) and the reason was that the components were not leukoreduced which results in the interaction of antibodies in a patient with antigens on donor leukocytes resulting in febrile reactions. In addition, the level of pro-inflammatory cytokines also increases in nonleukoreduced blood components during storage which can also lead to febrile reactions. Various studies have shown that the incidence of FNHTR to red cell transfusion can be decreased with universal leukoreduction. The incidence of FNHTR with nonleukoreduced red cell components and leukoreduced red cell components was 0.24% and 0.05%, respectively, as shown in a retrospective analysis from India.[15 et al ., the incidence of FNHTR due to red cell transfusion significantly decreased from 0.37% to 0.19% after the introduction of leukoreduction in their center.[3 et al . from India.[16
Interesting findings we found in our study were that FNHTRs are less severe with buffy coat-depleted PRBC transfusion than PRBC transfusion which was evident mainly from two factors, i.e. temperature and volume. Temperature rise (mean ± standard deviation) was less severe with buffy coat-depleted PRBC transfusion. The rise of temperature with buffy coat-depleted PRBC was 1.3 ± 0.8, and the rise of temperature with PRBC was 1.74 ± 1.129. Febrile response to buffy coat-depleted PRBC transfusion occurred at higher volume (145 ml) transfusion and later than PRBC transfusion (87.2 ml). Hence, we can say that no doubt leukoreduction is the main modality to prevent FNHTR, but in developing countries like India, the use of buffy coat-depleted PRBC over PRBC can reduce both incidence and severity of FNHTR.
Conclusion
Maximum number of transfusion reaction reported were FNHTR, followed by allergic reaction. Reporting every transfusion reaction is a must for medical education and strengthening of Indian hemovigilance system. In developing countries where universal leukoreduction is difficult to achieve, the use of buffy coat-depleted PRBC (SAGM-PRBC) over PRBC can reduce the intensity and severity of FNHTR.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. International Society of Blood Transfusion Working Party on Hemovigilance. Proposed Standard Definitions for Surveillance of Non Infectious Adverse Transfusion Reactions. July 2011, Incorporating TRALI Definition 2013 and TACO Definition. 2018
2. King KE, Shirey RS, Thoman SK, Kennedy DB, Tanz WS, Ness PM. Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs Transfusion. 2004;44:25–9
3. Pomper GJ Rossi's Principles of Transfusion Medicine. 2009 AABB Press Bethesda MD:826–46
4. Cohen R, Escorcia A, Tasmin F, Lima A, Lin Y, Lieberman L, et al Feeling the burn: The significant burden of febrile nonhemolytic transfusion reactions Transfusion. 2017;57:1674–83
5. Wang RR, Triulzi DJ, Qu L. Effects of prestorage vs. poststorage leucoreduction on the rate of febrile nonhemolytic transfusion reactions to platelets Am J Clin Pathol. 2012;138:255–9
6. Bisht A, Marwaha N, Kaur R, Gupta D, Chhabra R. Haemovigilance Programme of India: Comparative analysis of transfusion reactions reported over a 5-year period through two reporting formats and key recommendations for blood safety Asian J Transfus Sci. 2020;14:103–16
7. Eder AF, Chambers LA. Noninfectious complications of blood transfusion Arch Pathol Lab Med. 2007;131:708–18
8. Bhattacharya P, Marwaha N, Dhawan HK, Roy P, Sharma RR. Transfusion-related adverse events at the tertiary care center in North India: An institutional hemovigilance effort Asian J Transfus Sci. 2011;5:164–70
9. Michlig C, Vu DH, Wasserfallen JB, Spahn DR, Schneider P, Tissot JD. Three years of haemovigilance in a general university hospital Transfus Med. 2003;13:63–72
10. de Sousa Neto AL, Barbosa MH. Analysis of immediate transfusion incidents reported in a regional blood bank Rev Bras Hematol Hemoter. 2011;33:337–41
11. Callera F, Silva AC, Moura AF, Melo DB, Melo CM. Descriptions of acute transfusion reactions in a Brazilian Transfusion Service Rev Bras Hematol Hemoter. 2004;26:78–83
12. Chowdhury FS, Biswas J, Siddiqui MA, Hoque MM, Adnan SK. Transfusion reaction among the blood recipient: A study of 120 cases J Dhaka Med Coll. 2008;17:67–71
13. Khalid S, Usman M, Khurshid M. Acute transfusion reactions encountered in patients at a tertiary care center J Pak Med Assoc. 2010;60:832–6
14. Bassi R, Aggarwal S, Bhardwaj K, Thakur KK. Patterns of adverse transfusion reactions in a tertiary care centre of north India: A step towards hemovigilance Indian J Hematol Blood Transfus. 2017;33:248–53
15. Rajesh K, Harsh S, Amarjit K. Effects of prestorage leukoreduction on the rate of febrile nonhemolytic transfusion reactions to red blood cells in a tertiary care hospital Ann Med Health Sci Res. 2015;5:185–8
16. Dutt N, Sidhu M, Sharma S, Parihar R, Kumar D. Effectiveness of buffy coat leucoreduced packed red blood cells in decreasing febrile non hemolytic transfusion reactions in thalassemic patients Int J Res Med Sci. 2017;5:1756–9
