Hindawi

Anemia
Volume 2018, Article ID 9492303, 8 pages
https://doi.org/10.1155/2018/9492303

Clinical Study
Efficacy of Oral Acetaminophen and Intravenous
Chlorpheniramine Maleate versus Placebo to Prevent Red Cell
Transfusion Reactions in Children and Adolescent with
Thalassemia: A Prospective, Randomized, Double-Blind
Controlled Trial

Piya Rujkijyanont ,1 Chalinee Monsereenusorn,1 Pimpat Manoonphol,2

and Chanchai Traivaree 1
1
Division of Hematology-Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
2
Department of Pediatrics, Thungsong Hospital, Nakhon Sri Thammarat, Thailand

Correspondence should be addressed to Chanchai Traivaree; [email protected]

Received 17 May 2018; Accepted 16 September 2018; Published 1 October 2018

Academic Editor: Duran Canatan

Copyright © 2018 Piya Rujkijyanont et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Background. Thalassemia is a common congenital hemolytic disorder. In severe cases, regular blood transfusion is essentially
required. The role of premedications to prevent transfusion reactions is varied among institutions with no standard guideline.
Objective. To prospectively compare the risk of transfusion reactions in thalassemia patients premedicated with acetaminophen
and chlorpheniramine maleate (CPM) versus placebo prior to blood transfusion. Material and Method. A randomized, double-
blinded, placebo-controlled transfusion reaction study of 147 eligible patients was analyzed. All administered red blood cell (RBC)
products were leukoreduced blood products. Patients were monitored and followed for the development of transfusion reactions for
24 hours after RBC transfusion. Results. A total of 73 patients randomized to receive active drugs consisting of acetaminophen and
CPM were compared to 74 patients receiving placebo. The overall incidences of febrile reaction and urticarial rash were 6.9% and
22% in the patients randomized to receive active drugs comparing with 9.5% and 35.2% in the patients receiving placebo with no
significant differences between two groups. However, delayed development of urticarial rash at 4-24 hours after RBC transfusion
was significantly higher in female and patients receiving placebo. Conclusion. Administration of premedications in thalassemia
patients receiving RBC transfusion without a history of transfusion reactions does not decrease the overall risk of transfusion
reactions. However, the use of CPM might be beneficial to prevent delayed urticarial rash in those patients especially in females
(Thai Clinical Trial Registry (TCTR) study ID: 20140526001).

1. Introduction beta-globin chain production is affected [4]. The unique char-

acteristics of thalassemia include chronic hemolytic anemia,
Thalassemia is a group of congenital hemolytic anemia hepatosplenomegaly, failure to thrive, and other complica-
commonly found worldwide. The pathophysiology of anemia tions with a wide range of clinical spectrum depending on
in thalassemia resulted from reduced or absent synthesis of the disease’s severity. In severe cases, these complications
the alpha- or beta-globin chains of hemoglobin molecule can be fatal if the patients are not treated appropriately [4–
leading to abnormal hemoglobin production [1–3]. The dis- 6]. The clinical and hematological spectrum of thalassemia
ease can be classified according to the affected globin chains disease has been simply categorized according to transfusion
of hemoglobin into alpha thalassemia in which alpha-globin requirement into transfusion dependent thalassemia (TDT)
chain production is affected and beta thalassemia in which and nontransfusion dependent thalassemia (NTDT) [7–9].
2 Anemia

Thailand is known as one of the endemic areas of tha- 2. Materials and Methods
lassemia disease. The prevalence of thalassemia traits in Thai
population was reported to be 20–30% for 𝛼-thalassemia, 2.1. Patient Selection. One hundred and fifty-three tha-
3-9% for 𝛽- thalassemia, and 20-30% for Hb E [10, 11]. lassemia patients receiving RBC transfusion and attending
The diverse thalassemia genotypes found in this population the Hematology Clinic at Department of Pediatrics, Phra-
results in different phenotypic characteristics and variation mongkutklao Hospital, Bangkok, Thailand, from November
in transfusion requirements comparing to other diseases [12, 1, 2014, to October 31, 2017, were enrolled in the study.
13]. Given the clinical severity of ineffective erythropoiesis The informed consent and assent form were written and
in patients with thalassemia disease, red blood cell (RBC) obtained from all participants as well as their parents or
transfusion is considered as the mainstay of treatment in legal guardians prior to the enrollment in the study. The
order to prolonged overall survival in most of the patients study protocol was approved by the Institutional Review
[14, 15]; however, a risk of developing reactions from RBC Board of Phramongkutklao Hospital and Phramongkutklao
transfusion is commonly reported and quite challenging College of Medicine, Bangkok, Thailand, following the ethical
since the reactions are difficult to predict in each individual principles of the Declaration of Helsinki of 1975 and its
patient [16, 17]. revision. Inclusion criteria in this study included all children
Acute transfusion reactions can be categorized into and adolescents with thalassemia aged between 1 and 22
immune-mediated, involving antigen-antibody complex years who required RBC transfusion. Patients were excluded
formation, or nonimmune-mediated reactions. Immune- from the study if they developed fever with body temperature
mediated reactions can be further divided into hemolytic of greater than 38∘ C prior to RBC transfusion or received
and nonhemolytic reactions consisting of febrile and allergic antiallergic drugs within 24 hours or antipyretic drugs within
reactions. Febrile reaction occurs at a rate of 0.3 to 6 percent 4 hours prior to the transfusion. The additional exclusion
of RBC transfusions in which fever usually occurs during criteria included patients with a known history of allergy
the first 4 hours of transfusion with or without chills. The to either oral acetaminophen or IV CPM or those who
risk of febrile reaction is reduced to 0.2 percent when had documented history of febrile or allergic transfusion
patients receive prestorage leukoreduced blood products but reactions.
increased to 2 percent for poststorage leukoreduction [18].
Contrarily, the prevalence of allergic reactions occurs at a 2.2. Study Design and Clinical Assessment. This study was
rate of 0.4 to 3 percent of all transfusions and is not mitigated a randomized, double-blind, placebo-controlled trial. All
by leukoreductions. Signs and symptoms of allergic reactions patients were randomly assigned to receive either active drugs
usually appear within 2 hours of transfusions consisting or placebo in a double-blinded fashion with equal probability
of urticarial rash, facial edema, airway edema, and lower using randomization (block of four) to ensure approximately
respiratory tract symptoms, which are responsive to equal accrual over time. The dose of oral acetaminophen (500
antihistamines. However, the symptoms might turn to be mg tablet) was given at 250 mg (1/2 tablet) for patients who
more severe such as hypotension or anaphylaxis. Patients weighed less than 25 kg and 500 mg (1 tablet) for patients
who have experienced febrile or allergic reactions are at who weighed more than 25 kg. The dose of IV CPM was
increased risk of recurrence of reactions with subsequent given at 0.35–0.4 mg/kg/dose with a maximum dose of 10
transfusions although the overall likelihood of reactions mg. The dispensing pharmacist, an individual not otherwise
remains low [19]. involved in the study, was aware of treatment allocation and
Acetaminophen and chlorpheniramine maleate (CPM) dispensed either placebo or active drugs. Study medications
are commonly used as premedications to prevent transfusion were given 15 minutes before the RBC transfusion. All
reactions from prestorage leukoreduced, poststorage leuko- transfusions were closely monitored per standard practice
reduced, or nonleukoreduced blood products in most of guideline by the thalassemia clinic service for 4 hours during
the developing countries with variable practice guidelines RBC transfusion and additional 20 hours at home. All other
among different institutions even though the literatures caregivers, members of the study team, and patients were
support that idea that pretransfusion medication is required blinded throughout the study duration and data collection
only when transfusion reactions occur [18, 20–23]. The until the study was completed. Transfusion reactions were
previous study [24, 25] suggested that there is no medical evaluated using medical record review by the same investiga-
benefit of administering pretransfusion medication and also tors during the first 4 hours then parents were given a follow-
questioned the cost benefits of the practice. However, most up phone call by the research coordinator in order to assess
of the studies were conducted on adult population with no patient’s clinical status. Demographic data including patient’s
specific disease type especially certain diseases that require specific characteristics, age, sex, type of thalassemia, type
regular transfusion. The aim of this study was to evaluate the of RBC products, and reported development of transfusion
need for pretransfusion medication prior to RBC transfusion reactions were collected. A febrile reaction was defined
specifically in children and adolescent with thalassemia as a body temperature of greater than 38∘ C. Urticarial
disease. The primary objective of this study was to prospec- reactions were classified as hives with or without itching.
tively compare the risk of febrile and allergic reactions in Other reactions, such as hemolytic transfusion reactions,
those thalassemia patients who received oral acetaminophen facial edema, airway edema, and lower respiratory tract
and intravenous (IV) CPM versus placebo prior to RBC symptoms, were documented as described in the medical
transfusion. record.
Anemia 3

Enrollment

Assessed for eligibility

(n=153)

Excluded (n=6)
Not meeting inclusion
criteria (n=4)
Declined to participate (n=2)

Randomized
(n=147)

Allocation

Allocated to active drugs (n=73) Allocated to placebo (n=74)

Received allocated Received allocated
intervention (n=73) intervention (n=74)
Follow-Up in 24
hours
Loss follow-up (n=0) Loss follow-up (n=0)

Analysis

Analyzed (n=73) Analyzed (n=74)

Figure 1: Study flow diagram.

2.3. Statistical Analysis. This study was designed to accrue or placebo (n=74). The entire patients well complied with the
140 patients, which would have provided 90 percent power study operation with no loss follow-up reported.
for detecting a difference risk of a transfusion reaction Patients’ demographic data were shown in Table 1. The
of 0.27 (treatment relative to placebo) at the two-sided patients’ age ranged between 1.50 and 21.17 years and all of
level of significance. Baseline values of selected variables them received RBC transfusion. Upon entering the study, the
were calculated as the mean, standard deviation, minimum, patients were randomized to receive either active drugs or
maximum, frequency, and percentage. Differences between placebo. Seventy-three patients were randomized to receive
the two treatment groups with respect to age, sex, type of active drugs consisting of oral acetaminophen and IV CPM
thalassemia, and type of RBC products were analyzed using prior to RBC transfusion, and 74 patients were randomized to
Independent sample t-test for continuous variables and Chi- receive placebo. Of 73 patients randomized to receive active
square test for the categorical variables. Variables used in drugs, 37 patients (50.7%) were male and 36 (49.3%) were
the binary logistic regression model included age, sex, type female. Among 74 patients receiving placebo, 45 patients
of thalassemia, and type of RBC products, in addition to (60.8%) were male and 29 (39.2%) were female. The mean
a treatment indicator (active drugs or placebo). Statistical ages of the patients randomized to receive active drugs and
Package for the Social Science (SPSS) version 23 software placebo were 12.49±4.84 and 11.32±4.72 years, and the mean
(IBM, NY, USA) was used for data analysis and p values of ages at diagnosis of those patients were 24.93±23.84 and
<0.05 were considered statistically significant. 25.08±24.36 months, respectively.
Beta thalassemia/hemoglobin E (ß thal/HbE) was the
3. Results most common type of thalassemia disease in the study. The
disease was noted in 99 patients in which 49 (67.1%) and
3.1. Patients’ Demographic Data. As shown in Figure 1, one 50 (67.5%) of those were randomized to receive active drugs
hundred and fifty-three patients were assessed for eligibility. and placebo, respectively. The second most common type
Two patients refused to participate in the study and 4 of thalassemia disease was homozygous beta thalassemia (ß
patients were excluded due to a known history of allergy (2 thal/ß thal), which was noted in 19 patients, and 12 (16.4%)
patients) and taking antihistamine for upper respiratory tract and 7 (9.5%) of the patients received active drugs and placebo,
symptoms (2 patients). One hundred and forty-seven patients respectively. AE Bart disease was noted in 16 patients, and 6
met our inclusion criteria, and their parents or legal guardians (8.2%) and 10 (13.5%) of those were randomized to receive
provided informed consent to enroll in the study over 3 years active drugs and placebo, respectively. The rest of thalassemia
beginning in November 2014. The patients were randomized type found in the study was Hemoglobin H disease with
according to the study protocol to receive active drugs (n=73) constant spring (Hb H with CS).
4 Anemia

Table 1: Patients’ demographic data.

Active drugs Placebo

p-value
(N=73) (N=74)
Gender
Male 37(50.7) 45(60.8) 0.216
Female 36(49.3) 29(39.2)
Types of Thalassemia
ß thal/ß thal 12(16.4) 7(9.5) 0.353
ß thal/Hb E 49(67.1) 50(67.5)
AE Bart disease 6(8.2) 10(13.5)
Hb H with CS 6(8.2) 7(9.5)
RBC products
LPRC 49(67.1) 50(67.6) 0.954
LDPRC 24(32.9) 24(32.4)
Weight (kg)
Mean±SD 37.7±15.81 33.45±15.07 0.138
Min-Max 10.3-62.3 10.7-61.5
Age (years)
Mean±SD 12.49±4.84 11.32±4.72 0.097
Min-Max 1.58-18.5 1.5-21.17
Age at diagnosis (months)
Mean±SD 24.93±23.84 25.08±24.36 0.970
Min-Max 0.0-87.0 0.0-122
Note: Data were shown as number (%), mean±SD, min-max; p values were analyzed by Chi-square test for categorical data and independent sample t-test for
continuous data. p<0.05 is statistically significant.
Abbreviations. ß thal/ß thal: homozygous beta thalassemia; ß thal/HbE: beta thalassemia/hemoglobin E; Hb H with CS: hemoglobin H disease with constant
spring; RBC: red blood cell; LPRC: leukocyte poor packed red cell; LDPRC: leukocyte depleted packed red cell.

Table 2: The associated risk between premedications and transfusion reactions.

Active drugs Placebo

p-value OR 95%CI
(N=73) (N=74)
Fever 0 - 4 hrs
Yes 4(5.5) 6(8.1) 0.527 1.522 0.411-5.634
No 69(94.5) 68(91.9)
Fever 4 - 24 hrs
Yes 1(1.4) 1(1.4) 0.992 1.014 0.062-16.521
No 72(98.6) 73(98.6)
Rash 0 - 4 hrs
Yes 8(11) 7(9.5) 0.764 1.178 0.404-3.435
No 65(89) 67(90.5)
Rash 4 - 24 hrs
Yes 8(11) 19(25.7) 0.021∗ 0.356 0.145-0.877
No 65(89) 55(74.3)
Note. Data were shown as number (%), and associated risks between treatment groups were analyzed by binary logistic regression; ∗: p<0.05 is statistically
significant.

Among the different types of transfused RBC products, were no statistically significant differences in the patients’
leukocyte poor packed red cell (LPRC) was transfused to demographic data between 2 groups as described in Table 1.
49 (67.1%) and 50 (67.6%) patients randomized to receive
active drugs and placebo, respectively. In addition, leukocyte 3.2. The Incidence of Transfusion Reactions and Correlation
depleted packed red cell (LDPRC) was transfused to 24 with Premedications. As shown in Table 2, the overall rate
(32.9%) patients randomized to receive active drugs and to of febrile reaction during the first 24 hours after RBC
the same numbers of patients who received placebo. There transfusion was 6.9% in the patients randomized to receive
Anemia 5

Table 3: Risk factors for development of urticarial rash at 4 to 24 hours post-RBC transfusion.

Rash 4 - 24 hrs
Yes No p-value Crude OR 95%CI Adjusted OR 95%CI
N = 27 N = 120
Thalassemia types
ß thal/ß thal 5(26.3) 14(73.7) 0.159 3.095 0.643-14.906
ß thal/Hb E 19(19.2) 80(80.8) 0.275 2.058 0.563-7.519
Others 3(10.3) 26(89.7) 1
RBC products
LPRC 19(19.2) 80(80.8) 0.711 1.187 0.478-2.947
LDPRC 8(16.7) 40(83.3)
Age
13.22±4.58 11.61±4.81 0.118 1.079 0.981-1.187 1.103 0.993-1.225
Gender
Male 10(12.2) 72(87.8) 1 1
Female 17(26.2) 48(73.8) 0.033∗ 2.55 1.077-6.04 2.990∗ 1.204-7.426
Premedications
Active drugs 8(11) 65(89) 0.025∗ 0.356 0.145-0.877 0.263∗ 0.101-0.689
Placebo 19(25.7) 55(74.3) 1 1
Note. Data were shown as number (%), and associated risks between treatment groups were analyzed by binary logistic regression; ∗: p<0.05 is statistically
significant.
Abbreviations. ß thal/ß thal: homozygous beta thalassemia; ß thal/HbE: beta thalassemia/hemoglobin E; RBC: red blood cell; LPRC: leukocyte poor packed red
cell; LDPRC: leukocyte depleted packed red cell.

active drugs comparing with 9.5% in the patients receiving randomized to receive placebo comparing to those receiving
placebo as pretransfusion medications (p value = 0.565). A active drugs consisting of oral acetaminophen and IV CPM
febrile reaction within 4 hours of RBC transfusion was noted as premedications prior to RBC transfusion, we further
in 4 (5.5%) and 6 (8.1%) patients randomized to receive active analyzed other associated risk factors which could potentially
drugs and placebo, respectively (p value = 0.527). Fever at 4 contribute to the delayed posttransfusion urticarial rash by
to 24 hours post RBC transfusion was reported in 1 patient using binary logistic regression analysis (Table 3). We found
(1.4%) randomized to receive active drugs and in 1 patient that types of thalassemia, type of RBC products, and patients’
(1.4%) receiving placebo (p value = 0.99). The overall rate age were not associated with the development of posttransfu-
of development of urticarial rash during the first 24 hours sion urticarial rash at 4 to 24 hours (p-value > 0.05). However,
after RBC transfusion was 22% in the patients randomized patients’ gender and premedications were noted to be risk
to receive active drugs comparing with 35.2% in the patients factors for the development of post-transfusion urticarial
receiving placebo as pretransfusion medications (p value = rash. The development of delayed posttransfusion urticarial
0.111). The development of urticarial rash within 4 hours of rash at 4 to 24 hours was statistically significantly higher in
RBC transfusion was noted in 8 (11%) and 7 (9.5%) patients female (17 patients, 26.2%) than male (10 patients, 12.2%) with
randomized to receive active drugs and placebo, respectively a p value of 0.03 (adjusted OR = 2.9, 95%CI: 1.204-7.426).
(p value = 0.764). Interestingly, the delayed development Additional risk factor found to have statistical significant
of urticarial rash at 4 to 24 hours post RBC transfusion association with delayed posttransfusion urticarial rash was
was reported in 19 patients (25.7%) randomized to placebo, the use of IV CPM as premedication prior to RBC transfusion
which was statistically significantly higher than 8 patients with a p-value of 0.025 (adjusted OR = 0.26, 95%CI: 0.101-
(11%) receiving active drugs with a p value of 0.02 (OR = 0.689).
0.35, 95%CI: 0.145-0.877,). There were no other transfusion
reactions such as hemolytic transfusion reactions or other 3.4. Risk Factors for Development of Febrile Reaction Post
allergic reactions such as facial edema, airway edema, lower RBC Transfusion. We found that types of thalassemia, RBC
respiratory tract symptoms, and hypotension noted in all products, patients’ age, gender, and premedications were not
thalassemia patients enrolled in our study. Moreover, none associated with the development of febrile reaction (p value
of the patients developed adverse effects from IV CPM > 0.05) (Table 4).
including drowsiness and thickening of bronchial secretions.
4. Discussion
3.3. Risk Factors for Development of Urticarial Rash at 4 to 24
Hours Post-RBC Transfusion. Since the delayed development Thalassemia is a common inherited blood disorder character-
of urticarial rash at 4 to 24 hours post RBC transfusion ized by decreased or absent hemoglobin production causing
was statistically significantly higher in thalassemia patents chronic hemolysis. The severity of the disease depends on
6 Anemia

Table 4: Risk factors for development of febrile reaction post RBC transfusion.

Febrile reaction
Yes No p-value Crude OR 95%CI
N = 12 N = 135
Thalassemia
ß thal/ß thal 3(15.8) 16(84.2) 0.166 5.250 0.503-54.777
ß thal/Hb E 8(8.1) 91(91.9) 0.405 2.462 0.295-20.540
Other 1(3.4) 28(96.6) 1
RBC products
LPRC 9(9.1) 90(90.9) 0.557 1.500 0.387-5.814
LDPRC 3(6.2) 45(93.8) 1
Age
13.9±3.63 11.73±4.86 0.141 1.116 0.964-1.291
Gender
Male 7(8.5) 75(91.5) 1
Female 5(7.7) 60(92.3) 0.853 0.893 0.270-2.955
Premedications
Active drugs 5(6.8) 68(93.2) 0.565 0.704 0.213-2.328
Placebo 7(9.5) 67(90.5) 1
Note. Data were shown as number (%), mean±SD, and associated risks between treatment groups were analyzed by binary logistic regression; p<0.05 is statistically
significant.
Abbreviations. ß thal/ß thal: homozygous beta thalassemia; ß thal/HbE: beta thalassemia/hemoglobin E; RBC: red blood cell; LPRC: leukocyte poor packed red
cell; LDPRC: leukocyte depleted packed red cell

the type of thalassemia ranging from a silent carrier with after RBC transfusion was statistically significantly higher
no clinical anemia and normal hemoglobin level to a severe in the patients randomized to receive placebo comparing
case presenting with significant anemia requiring regular to those receiving active drugs. Furthermore, binary logistic
RBC transfusion. Although thalassemia disease can be cured regression analysis was used to investigate potential asso-
by hematologic stem cell transplantation or gene therapy ciated risk factors that could potentially contribute to the
[26], financial limitation is still a major issue especially delayed posttransfusion urticarial rash which confirm the
in developing countries where most of the patients ended requirement of pretransfusion antihistamine.
up with chronic RBC transfusion. The side effects of RBC There are many types of antihistamine available in the
transfusion include iron overload requiring iron chelation market and some of those were used as premedication prior
and more importantly posttransfusion reactions with each to RBC transfusion. Bennardello F et al. found that the
cycle of RBC transfusion, which could potentially be fatal. regimen of using oral loratadine taken by the patients at
The common transfusion reactions are febrile reaction and home for 3 consecutive days prior to transfusion could reduce
allergic reactions in which the patients could present with allergic reactions to 0.9% in patients receiving washing
urticarial rash, facial edema, airway edema, lower respi- and/or double filtration of RBC products [27]. However,
ratory tract symptoms or more severe symptoms such as the use of antihistamine in oral form and to give the drug
hypotension and anaphylaxis. The methods to minimize or for several days prior to transfusion might not be perfectly
prevent the development of transfusion reactions are different applicable in children and adolescent due to their reliability
among institutional practice guidelines ranging from close to take oral medication and potentially poor compliance
observation to the use of pharmacologic premedications especially in adolescent. In our study, we decided to use IV
prior to RBC transfusion. Herein, the aim of our study CPM as premedicated antihistamine and administered this
was to evaluate the role of using pretransfusion medication medication shortly prior to RBC transfusion in order to cut
consisting of oral acetaminophen and IV CPM comparing off those concerns. CPM is a H1-receptor antagonist, and
to placebo specifically in children and adolescent with tha- it blocks a certain kind of histamine receptor (H1 receptor)
lassemia disease. required for the uptake of histamine among the cells leading
Children and adolescent with thalassemia disease who to the prevention of allergic symptoms. Although Kennedy
required RBC transfusion were enrolled in our study and LD et al. used diphenhydramine which is the same first
blindly randomized to receive active drugs consisting of oral generation antihistamine as CPM and found no significant
acetaminophen and IV CPM versus placebo prior to RBC difference in the development of allergic reactions between
transfusion. Although there were no statistical differences patients receiving diphenhydramine and those receiving
in the overall development of febrile reaction and urticarial placebo, the study only looked at immediate reaction within
rash during 24 hours of RBC transfusion, we found that the 4 hours of transfusion [18]. According to the results from our
development of delayed urticarial rash from 4 to 24 hours study, there was no significant difference in the development
Anemia 7

of urticarial rash within 4 hours of RBC transfusion between adolescent patient) with specific type of disease (thalassemia
patients randomized to receive IV CPM and those receiving disease). Since thalassemia is the most common inherited
placebo which is also resemble to the study from Kennedy blood disorder especially in South East Asia and Mediter-
LD et al. However, we further followed up patients up to 24 ranean and most of the patients affected with this disease
hours and noted that the incidence of delayed development unfortunately require regular blood transfusion throughout
of urticarial rash at 4 to 24 hours post-RBC transfusion their life, many of them are suffered from transfusion compli-
was significantly lower in patients randomized to receive cations. In addition, in our study, we extended the duration
IV CPM than those receiving placebo. Our study affirms of observation and monitoring of transfusion reactions to
the role of IV CPM in preventing delayed development of 24 hours, and interestingly we found the higher incidence
urticarial rash which is important since during that time of delayed development of urticarial rash, which could
interval, the patients are at home where the close monitoring be successfully decreased by administration of intravenous
of transfusion reactions by healthcare professional is not chlorpheniramine maleate. We truly hope that the data from
feasible. This finding also confirms the need to monitor our study could be used and beneficial for other practitioners
patients for a longer period of time instead of discharging in order to improve the ways we manage and monitor those
patients immediately once the RBC transfusion is completed. patients in clinical practice.
In addition, we also found that delayed development of In conclusion, this study is a prospective, randomized,
urticarial rash was significantly higher in female than in double-blind placebo controlled trial. Based on the results of
male. This interesting finding could be from the effect of our study, we recommend that the use of oral acetaminophen
hormone estrogen in female on the enzyme lining the blood as pretransfusion medication to prevent febrile reaction is
vessels causing the increased production of nitric oxide not necessary in thalassemia patients who receive LPRC and
which results in prolonged and severe allergic reactions LDPRC transfusion. However, IV CPM might be beneficial
[28, 29]. Moreover, a combination of CPM (H1-receptor as premedication to prevent delayed urticarial rash in those
antagonist) and ranitidine (H2-receptor antagonist) provided patients especially in female. Furthermore, the patient should
a satisfactory result in urticarial treatment [30]. Therefore, be informed to observe signs and symptoms of delayed
it might be interesting to evaluate this combination of H1- development of allergic reactions and to contact healthcare
and H2-receptor antagonists as pretransfusion medication in professional if the symptoms occur.
order to prevent the development of urticarial rash in the
future study.
Compared to incidence reported in literatures, the higher
Data Availability
incidence of transfusion reactions in our study could be The data used to support the findings of this study are
from our patient population’s background. Since our study available from the corresponding author upon request.
was conducted on thalassemia patients who required regular
red cell transfusion every 3 to 4 weeks, frequent exposure
to antigens from different red cell products might cause Conflicts of Interest
increased alloreactivity to antigens expressed on donor cells
The authors declare that they have no conflicts of interest.
and be the reason for a higher risk of development of febrile
reaction as well as allergic reactions. In addition, our study
had monitored transfusion reactions for a longer period of Acknowledgments
time up to 24 hours after red cell transfusion using follow-
up phone call and was able to detect delayed development of This study was supported in part by grants from the Phra-
reactions. Therefore, this might be another reason for a higher mongkutklao Hospital and College of Medicine, Royal Thai
incidence of reactions in our study. Army. The authors would like to thank patients and families
The study done by KK Tan et al. reported the significant for participating in the study.
increase of transfusion reactions in patients receiving buffy
coat-poor packed red cell products comparing to filtered References
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