Letter to the Editor Defining risk factors and presentations of allergic reactions to platelet transfusion To the Editor: Allergic transfusion reactions (ATRs) are a frequent complication of blood transfusion, occurring in at least 2% of platelet transfusions.1,2 The mechanisms of most ATRs are not understood. Antibodies to plasma proteins such as IgA,3,4 haptoglobin,5 and C46 in blood transfusion recipients are reported but rarely identified. Furthermore, individuals react sporadically to transfusions, which is inconsistent with a recipient having hypersensitivity to a ubiquitous plasma protein. We hypothesized that understanding the epidemiology and clinical presentation of ATRs will elucidate the underlying mechanism and guide strategies to prevent ATRs. We developed a cohort of platelet donors and the platelet transfusion recipients who received their donated products. The goals of this study were to (1) identify risk factors for ATRs, using platelet transfusion as a paradigm, and (2) define the clinical and biochemical presentation of ATRs. We conducted a longitudinal cohort study of patients receiving single donor apheresis platelet transfusions and their platelet donors. We defined an ATR as an acute transfusion reaction that included pruritus, urticaria, or angioedema. We took an allergy history, measured allergic sensitization and tryptase on the ImmunoCAP platform, and measured urine eicosanoid metabolites by using mass spectrometry. Additional details of the study design, laboratory measures, and analysis are provided in this article’s Online Repository at www.jacionline. org. Recipients who did (n 5 124) and did not (n 5 44) experience ATRs were similar in terms of transfusion history (see Table E1 in this article’s Online Repository at www.jacionline.org). A primary oncology diagnosis was present in 92.9% of platelet recipients. Including transfusions before enrollment, 36 subjects had 2 or more ATRs to platelet transfusion. ATRs manifested during or within 1 hour after platelet transfusion in 95% of ATRs. Diphenhydramine premedication was given in 27.9% of control transfusions and 42.3% of transfusions that resulted in an ATR. For 2 transfusions in the ATR group (1.4%), angiotensin-
converting enzyme inhibitor medication was given in the 24 hours before transfusion. Urticaria and pruritus were the most common symptoms (see Table E2 in this article’s Online Repository at www.jacionline. org). Criteria for anaphylaxis were met in 26 ATRs (18.2%). Diphenhydramine was used to treat 77 ATRs (53.9%), an H2 receptor antagonist in 22 ATRs (15.4%), and glucocorticoids in 19 ATRs (13.3%). Epinephrine was given in 1 case (0.7%). A typical cutaneous reaction is shown in Fig E1 in this article’s Online Repository at www.jacionline.org. A history of hay fever and food allergy was more frequent in platelet recipients experiencing an ATR (Table I). Reported grass sensitivity was more prevalent among ATR recipients than among never ATR recipients (37% vs 18%; P 5 .02; see Table E3 in this article’s Online Repository at www.jacionline.org). When we defined hay fever and food allergy as reporting symptoms plus a positive Phadiatop or fx5, respectively, the association of atopy with ATRs persisted for hay fever but not for food allergy. In contrast, there was no association between Phadiatop concentrations and ATRs in donors. Among recipients, total and aeroallergen-specific IgE concentration was higher in those with ATRs than in those without (Fig 1). IgE concentrations in platelet donors are not associated with ATRs. For platelet recipients, each quartile increase in Phadiatop concentrations was associated with a 43.5% increase in ATR incidence (95% CI, 27.2% to 62.0% increase; P < .001), controlling for the number of transfusions. Similarly, there was a 44.9% increase in ATR incidence for each quartile increase in total IgE (95% CI, 21.7% to 72.5% increase; P < .001). No ethylene oxide–specific IgE was detected in 25 platelet recipients with a high incidence of ATRs (data not shown). To validate the IgE results, we studied archived samples from the Trial to Reduce Alloimmunization to Platelets7 (see Fig E2 in this article’s Online Repository at www.jacionline.org). As in the present cohort, there was a direct relationship between incident ATRs and concentrations of aeroallergen-specific and total IgE. Older subjects tended to have milder ATRs. For the risk of anaphylaxis versus mucocutaneous reaction, the odds ratio is 0.75 for each 10-year increase in age (95% CI, 0.61-0.91; P 5 .004). The association of ATR severity with age remained statistically
TABLE I. Atopic phenotype of platelet recipients and donors Platelet recipient, n (%) Never ATR (n 5 44)
Reported atopic history* Hay fever Asthma/albuterol use Eczema Food allergy Symptoms in last week Specific IgE screen Phadiatop positive fx5 positive Confirmed hay feverà Confirmed food allergyà
ATR (n 5 124)
Platelet donor, n (%) P value
No ATR (n 5 46)
ATR (n 5 87)
P value
23 17 7 1 2
(53.5) (38.6) (15.9) (2.3) (4.8)
86 38 16 18 10
(71.7) (31.7) (13.1) (14.6) (8.9)
.04 .46 .62 .03 .52
36 10 13 3 6
(78.3) (21.7) (28.3) (6.5) (13)
60 15 10 8 7
(69) (17.2) (11.5) (9.2) (8.0)
.31 .64 .03 .75 .37
10 2 7 0
(28.6) (10.5) (18.9) (0)
62 4 51 2
(55.9) (5.8) (47.7) (2.9)
.006 .61 .002 1
9 3 8 0
(40.9) (15) (29.6) (0)
23 7 22 1
(41.8) (14.6) (34.4) (1.5)
1 1 .81 1
*Responses have kUa/L) and responded affirmatively to either ‘‘Have you ever had hay fever’’ or ‘‘Have you ever suffered, in the absence of a cold, from an itchy, stuffy, or runny nose and/or swollen, itchy eyes?’’ Subjects were considered to have food allergy if they reported a food allergy with convincing symptom history _0.35 kUa/L). and had a positive fx5 result (> Donors and recipients were asked whether they ate any soy, peanut, tree nut, cow dairy, seafood, wheat, or eggs in the 24 hours before donating or receiving platelets. There were complete food and food allergy histories of 106 donor-recipient pairs. There were 105 complete donor-recipient pairs of donor drug allergy history and recipient drug exposure. To perform validation of plasma IgE results, subjects from an independent cohort were evaluated. Plasma samples from subjects who experienced a ‘‘severe urticarial reaction’’ in the Trial to Reduce Alloimmunization to Platelets (NCT00000589)E4 were obtained from the National Heart, Lung, and Blood Institute BioLINCC repository. The Trial to Reduce Alloimmunization to Platelets protocol did not define criteria for a ‘‘severe urticarial reaction.’’
Study population During the study period, 179 ATRs were reported; 36 patients (20.1%) were unable to provide consent or refused consent, resulting in 143 ATRs being evaluated. These ATRs occurred in 111 unique subjects with ATR. A total of 133 platelet donors were enrolled, representing 65.5% of the platelet products transfused to the cases and controls.
J ALLERGY CLIN IMMUNOL nnn 2014
Laboratory testing Total and allergen-specific IgE levels were analyzed using the ImmunoCAP platform (ThermoFisher Scientific/Phadia, Kalamazoo, Mich). Phadiatop uses a CAP with weed, grass, and tree pollen; pet epidermal; dust mite; and mold allergens. The fx5 uses a CAP with allergen from 6 foods (cow’s milk, chicken egg, peanut, soybean, wheat, and cod). Phadiatop and fx5 tests were considered clinically significant (ie, positive) for values of 0.35k Ua/L or more. Fx5 tests were performed on samples from the Johns Hopkins Hospital cohort only (n 5 89 recipients and n 5 69 donors); an interim analysis indicated that additional testing would likely not be informative. Phadiatop tests were performed on plasma samples that were available from 144 recipients (85.7%) and 78 donors (58.6%). As an exploratory analysis, ethylene oxide–specific IgE was screened in 25 subjects using ImmunoCAP. Total tryptase was measured using ImmunoCAP. Urine was collected without additive and frozen at 2808C until analysis. Eicosanoid metabolites prostaglandin (PG) E-M (9,15-dioxo-11a-hydroxy13,14-dihydro-2,3,4,5-tetranor-prostan-1,20-dioic acid), 2 metabolites of PGD2 (tetranor PGD-M, 9a-hydroxy-11,15-dioxo-13,14-dihydro-2,3,4,5tetranor-prostan-1,20-dioic acid, and PGD-M, 9a,11 b-dihydroxy-15oxo-2,3, 18,19-tetranorprost-5-ene-1,20-dioic acid), and leukotriene E4 were measured using mass spectrometry with deuterated internal standards as previously described.E5,E6 Metabolite concentrations were normalized to urine creatinine concentrations. Urine was collected 3 to 6 hours after an ATR for peak measurement and more than 24 hours later for a baseline sample. Urine was collected on 2 control transfusions immediately before transfusion and 3 hours after transfusion.
Analysis Undetectable Phadiatop/fx5 results and total serum IgE results were reported as 0.01 kUa/L and 1 IU/mL, respectively. Binary data were compared using the Fisher exact test. Continuous variables and their transformations were assessed for normality by using the skewness-kurtosis and ShapiroFrancia tests. Normally distributed variables were compared using Student t tests. For non-normally distributed data, a Mann-Whitney U test was used. A nonparametric test for trend was used to compare ATR rates across ordinal independent variables. Retrospective evaluation of control subjects revealed that 13 of 57 (22.8%) subjects had experienced ATRs to prior transfusions before enrollment. For the primary analyses, platelet recipients were categorized as ‘‘Never ATR’’ or ‘‘Any ATR.’’ There were 17 transfusions in which the recipient received 2 sequential platelet products from 2 different donors. In these cases, the analysis was restricted to the donor of the first product. Logistic regression with robust variance estimation was used to estimate the relationship between continuous independent variables and binary outcomes. Odds ratios using exact CIs were used for binary independent variables. Poisson regression with robust variance estimation was used to relate independent variables with the frequency of ATRs. Analyses were conducted with Stata v13.1 (StataCorp, College Station, Tex). REFERENCES E1. Sanders RP, Geiger TL, Heddle N, Pui CH, Howard SC. A revised classification scheme for acute transfusion reactions. Transfusion 2007;47:621-8. E2. Arshad SH, Karmaus W, Matthews S, Mealy B, Dean T, Frischer T, et al. Association of allergy-related symptoms with sensitisation to common allergens in an adult European population. J Investig Allergol Clin Immunol 2001;11:94-102. E3. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report–Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006;117:391-7. E4. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 1997;337:1861-9. E5. Sheikh SI, Nestorov I, Russell H, O’Gorman J, Huang R, Milne GL, et al. Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther 2013;35:1582-94.e9. E6. Duffield-Lillico AJ, Boyle JO, Zhou XK, Ghosh A, Butala GS, Subbaramaiah K, et al. Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway. Cancer Prev Res (Phila) 2009;2:322-9.
LETTER TO THE EDITOR 3.e2
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
FIG E1. A typical urticarial transfusion reaction.
3.e3 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
FIG E2. Validation of IgE results in the Trial to Reduce Alloimmunization to Platelets (TRAP). ‘‘Severe urticarial reactions’’ (n 5 31) were prospectively recorded in 8769 platelet transfusions in TRAP. Archived baseline samples were tested for total IgE (A) and Phadiatop (B). The reference line at 0.35 kUa/L indicates a likely clinically significant Phadiatop test.
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
FIG E3. ATR incidence decreases with increasing transfusion number. Platelet transfusions for subjects with complete platelet transfusion histories (n 5 120) were categorized into bins of 5 transfusions. The incidence of ATRs in each bin was calculated. Numbers above indicate the number of platelet transfusions in each bin.
LETTER TO THE EDITOR 3.e4
3.e5 LETTER TO THE EDITOR
FIG E4. Total tryptase level increases with more severe ATRs. Plasma total tryptase level was measured before and 25 to 90 minutes after an ATR. Concentrations are presented as the change in total tryptase level. The reference line at 2 ng/mL indicates a threshold for clinically relevant change.
J ALLERGY CLIN IMMUNOL nnn 2014
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
LETTER TO THE EDITOR 3.e6
FIG E5. Urinary eicosanoid metabolites are increased in ATRs. Urine PGE-M (A), tetranor PGD-M (B), PGD-M (C), and LTE4 (D) were measured at baseline and 3 to 6 hours after transfusion in 2 control platelet transfusions without an ATR, 4 subjects with urticarial reactions, and 2 subjects with urticaria and angioedema. Fold changes in metabolite levels after transfusion are shown. PGD-M and PGE-M results were not available for ATR ‘‘Urticaria 4.’’ LT, Leukotriene.
3.e7 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
TABLE E1. Demographic characteristics of platelet transfusion recipients Characteristic
Age (y) Males (%) Total platelet transfusions Total platelet ATRs Total RBC transfusions Total RBC ATRs
Never ATR (n 5 44)
ATR (n 5 124)
P value
58 (3-82) 55 12 (1-176) 0 (0-0) 12 (0-241) 0 (0-1)
57 (2-86) 60 9 (1-224) 1 (1-8) 12 (0-121) 0 (0-2)
.44 .59 .99 — .64 .68
Note. Data are median (range) unless otherwise indicated.
LETTER TO THE EDITOR 3.e8
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
TABLE E2. ATR manifestations to platelet transfusion (n 5 143) Mucocutaneous Pruritus Urticaria Flushing Angioedema Respiratory Dyspnea Wheezing Gastrointestinal symptoms Emesis Nausea/abdominal pain Cardiovascular Shock Note. Values are n (%).
123 120 49 36
(86.0) (83.9) (35.0) (25.1)
15 (10.5) 5 (3.5) 6 (4.2) 3 (2.1) 1 (0.7)
3.e9 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
TABLE E3. Hypersensitivity history in platelet recipients and donors* Platelet recipient, n (%) Allergen
Grass Weed Tree Mold Animals Dust mites Penicillin Sulfa Aspirin Vancomycin
Never ATR (n 5 44)
6 2 12 9 7 5 7 4 1 1
(13.6) (4.6) (27.2) (20.5) (15.9) (11.6) (16.3) (9.3) (2.3) (2.3)
*Responses have
converting enzyme inhibitor medication was given in the 24 hours before transfusion. Urticaria and pruritus were the most common symptoms (see Table E2 in this article’s Online Repository at www.jacionline. org). Criteria for anaphylaxis were met in 26 ATRs (18.2%). Diphenhydramine was used to treat 77 ATRs (53.9%), an H2 receptor antagonist in 22 ATRs (15.4%), and glucocorticoids in 19 ATRs (13.3%). Epinephrine was given in 1 case (0.7%). A typical cutaneous reaction is shown in Fig E1 in this article’s Online Repository at www.jacionline.org. A history of hay fever and food allergy was more frequent in platelet recipients experiencing an ATR (Table I). Reported grass sensitivity was more prevalent among ATR recipients than among never ATR recipients (37% vs 18%; P 5 .02; see Table E3 in this article’s Online Repository at www.jacionline.org). When we defined hay fever and food allergy as reporting symptoms plus a positive Phadiatop or fx5, respectively, the association of atopy with ATRs persisted for hay fever but not for food allergy. In contrast, there was no association between Phadiatop concentrations and ATRs in donors. Among recipients, total and aeroallergen-specific IgE concentration was higher in those with ATRs than in those without (Fig 1). IgE concentrations in platelet donors are not associated with ATRs. For platelet recipients, each quartile increase in Phadiatop concentrations was associated with a 43.5% increase in ATR incidence (95% CI, 27.2% to 62.0% increase; P < .001), controlling for the number of transfusions. Similarly, there was a 44.9% increase in ATR incidence for each quartile increase in total IgE (95% CI, 21.7% to 72.5% increase; P < .001). No ethylene oxide–specific IgE was detected in 25 platelet recipients with a high incidence of ATRs (data not shown). To validate the IgE results, we studied archived samples from the Trial to Reduce Alloimmunization to Platelets7 (see Fig E2 in this article’s Online Repository at www.jacionline.org). As in the present cohort, there was a direct relationship between incident ATRs and concentrations of aeroallergen-specific and total IgE. Older subjects tended to have milder ATRs. For the risk of anaphylaxis versus mucocutaneous reaction, the odds ratio is 0.75 for each 10-year increase in age (95% CI, 0.61-0.91; P 5 .004). The association of ATR severity with age remained statistically
TABLE I. Atopic phenotype of platelet recipients and donors Platelet recipient, n (%) Never ATR (n 5 44)
Reported atopic history* Hay fever Asthma/albuterol use Eczema Food allergy Symptoms in last week Specific IgE screen Phadiatop positive fx5 positive Confirmed hay feverà Confirmed food allergyà
ATR (n 5 124)
Platelet donor, n (%) P value
No ATR (n 5 46)
ATR (n 5 87)
P value
23 17 7 1 2
(53.5) (38.6) (15.9) (2.3) (4.8)
86 38 16 18 10
(71.7) (31.7) (13.1) (14.6) (8.9)
.04 .46 .62 .03 .52
36 10 13 3 6
(78.3) (21.7) (28.3) (6.5) (13)
60 15 10 8 7
(69) (17.2) (11.5) (9.2) (8.0)
.31 .64 .03 .75 .37
10 2 7 0
(28.6) (10.5) (18.9) (0)
62 4 51 2
(55.9) (5.8) (47.7) (2.9)
.006 .61 .002 1
9 3 8 0
(40.9) (15) (29.6) (0)
23 7 22 1
(41.8) (14.6) (34.4) (1.5)
1 1 .81 1
*Responses have kUa/L) and responded affirmatively to either ‘‘Have you ever had hay fever’’ or ‘‘Have you ever suffered, in the absence of a cold, from an itchy, stuffy, or runny nose and/or swollen, itchy eyes?’’ Subjects were considered to have food allergy if they reported a food allergy with convincing symptom history _0.35 kUa/L). and had a positive fx5 result (> Donors and recipients were asked whether they ate any soy, peanut, tree nut, cow dairy, seafood, wheat, or eggs in the 24 hours before donating or receiving platelets. There were complete food and food allergy histories of 106 donor-recipient pairs. There were 105 complete donor-recipient pairs of donor drug allergy history and recipient drug exposure. To perform validation of plasma IgE results, subjects from an independent cohort were evaluated. Plasma samples from subjects who experienced a ‘‘severe urticarial reaction’’ in the Trial to Reduce Alloimmunization to Platelets (NCT00000589)E4 were obtained from the National Heart, Lung, and Blood Institute BioLINCC repository. The Trial to Reduce Alloimmunization to Platelets protocol did not define criteria for a ‘‘severe urticarial reaction.’’
Study population During the study period, 179 ATRs were reported; 36 patients (20.1%) were unable to provide consent or refused consent, resulting in 143 ATRs being evaluated. These ATRs occurred in 111 unique subjects with ATR. A total of 133 platelet donors were enrolled, representing 65.5% of the platelet products transfused to the cases and controls.
J ALLERGY CLIN IMMUNOL nnn 2014
Laboratory testing Total and allergen-specific IgE levels were analyzed using the ImmunoCAP platform (ThermoFisher Scientific/Phadia, Kalamazoo, Mich). Phadiatop uses a CAP with weed, grass, and tree pollen; pet epidermal; dust mite; and mold allergens. The fx5 uses a CAP with allergen from 6 foods (cow’s milk, chicken egg, peanut, soybean, wheat, and cod). Phadiatop and fx5 tests were considered clinically significant (ie, positive) for values of 0.35k Ua/L or more. Fx5 tests were performed on samples from the Johns Hopkins Hospital cohort only (n 5 89 recipients and n 5 69 donors); an interim analysis indicated that additional testing would likely not be informative. Phadiatop tests were performed on plasma samples that were available from 144 recipients (85.7%) and 78 donors (58.6%). As an exploratory analysis, ethylene oxide–specific IgE was screened in 25 subjects using ImmunoCAP. Total tryptase was measured using ImmunoCAP. Urine was collected without additive and frozen at 2808C until analysis. Eicosanoid metabolites prostaglandin (PG) E-M (9,15-dioxo-11a-hydroxy13,14-dihydro-2,3,4,5-tetranor-prostan-1,20-dioic acid), 2 metabolites of PGD2 (tetranor PGD-M, 9a-hydroxy-11,15-dioxo-13,14-dihydro-2,3,4,5tetranor-prostan-1,20-dioic acid, and PGD-M, 9a,11 b-dihydroxy-15oxo-2,3, 18,19-tetranorprost-5-ene-1,20-dioic acid), and leukotriene E4 were measured using mass spectrometry with deuterated internal standards as previously described.E5,E6 Metabolite concentrations were normalized to urine creatinine concentrations. Urine was collected 3 to 6 hours after an ATR for peak measurement and more than 24 hours later for a baseline sample. Urine was collected on 2 control transfusions immediately before transfusion and 3 hours after transfusion.
Analysis Undetectable Phadiatop/fx5 results and total serum IgE results were reported as 0.01 kUa/L and 1 IU/mL, respectively. Binary data were compared using the Fisher exact test. Continuous variables and their transformations were assessed for normality by using the skewness-kurtosis and ShapiroFrancia tests. Normally distributed variables were compared using Student t tests. For non-normally distributed data, a Mann-Whitney U test was used. A nonparametric test for trend was used to compare ATR rates across ordinal independent variables. Retrospective evaluation of control subjects revealed that 13 of 57 (22.8%) subjects had experienced ATRs to prior transfusions before enrollment. For the primary analyses, platelet recipients were categorized as ‘‘Never ATR’’ or ‘‘Any ATR.’’ There were 17 transfusions in which the recipient received 2 sequential platelet products from 2 different donors. In these cases, the analysis was restricted to the donor of the first product. Logistic regression with robust variance estimation was used to estimate the relationship between continuous independent variables and binary outcomes. Odds ratios using exact CIs were used for binary independent variables. Poisson regression with robust variance estimation was used to relate independent variables with the frequency of ATRs. Analyses were conducted with Stata v13.1 (StataCorp, College Station, Tex). REFERENCES E1. Sanders RP, Geiger TL, Heddle N, Pui CH, Howard SC. A revised classification scheme for acute transfusion reactions. Transfusion 2007;47:621-8. E2. Arshad SH, Karmaus W, Matthews S, Mealy B, Dean T, Frischer T, et al. Association of allergy-related symptoms with sensitisation to common allergens in an adult European population. J Investig Allergol Clin Immunol 2001;11:94-102. E3. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. Second symposium on the definition and management of anaphylaxis: summary report–Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006;117:391-7. E4. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 1997;337:1861-9. E5. Sheikh SI, Nestorov I, Russell H, O’Gorman J, Huang R, Milne GL, et al. Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther 2013;35:1582-94.e9. E6. Duffield-Lillico AJ, Boyle JO, Zhou XK, Ghosh A, Butala GS, Subbaramaiah K, et al. Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway. Cancer Prev Res (Phila) 2009;2:322-9.
LETTER TO THE EDITOR 3.e2
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
FIG E1. A typical urticarial transfusion reaction.
3.e3 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
FIG E2. Validation of IgE results in the Trial to Reduce Alloimmunization to Platelets (TRAP). ‘‘Severe urticarial reactions’’ (n 5 31) were prospectively recorded in 8769 platelet transfusions in TRAP. Archived baseline samples were tested for total IgE (A) and Phadiatop (B). The reference line at 0.35 kUa/L indicates a likely clinically significant Phadiatop test.
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
FIG E3. ATR incidence decreases with increasing transfusion number. Platelet transfusions for subjects with complete platelet transfusion histories (n 5 120) were categorized into bins of 5 transfusions. The incidence of ATRs in each bin was calculated. Numbers above indicate the number of platelet transfusions in each bin.
LETTER TO THE EDITOR 3.e4
3.e5 LETTER TO THE EDITOR
FIG E4. Total tryptase level increases with more severe ATRs. Plasma total tryptase level was measured before and 25 to 90 minutes after an ATR. Concentrations are presented as the change in total tryptase level. The reference line at 2 ng/mL indicates a threshold for clinically relevant change.
J ALLERGY CLIN IMMUNOL nnn 2014
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
LETTER TO THE EDITOR 3.e6
FIG E5. Urinary eicosanoid metabolites are increased in ATRs. Urine PGE-M (A), tetranor PGD-M (B), PGD-M (C), and LTE4 (D) were measured at baseline and 3 to 6 hours after transfusion in 2 control platelet transfusions without an ATR, 4 subjects with urticarial reactions, and 2 subjects with urticaria and angioedema. Fold changes in metabolite levels after transfusion are shown. PGD-M and PGE-M results were not available for ATR ‘‘Urticaria 4.’’ LT, Leukotriene.
3.e7 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
TABLE E1. Demographic characteristics of platelet transfusion recipients Characteristic
Age (y) Males (%) Total platelet transfusions Total platelet ATRs Total RBC transfusions Total RBC ATRs
Never ATR (n 5 44)
ATR (n 5 124)
P value
58 (3-82) 55 12 (1-176) 0 (0-0) 12 (0-241) 0 (0-1)
57 (2-86) 60 9 (1-224) 1 (1-8) 12 (0-121) 0 (0-2)
.44 .59 .99 — .64 .68
Note. Data are median (range) unless otherwise indicated.
LETTER TO THE EDITOR 3.e8
J ALLERGY CLIN IMMUNOL VOLUME nnn, NUMBER nn
TABLE E2. ATR manifestations to platelet transfusion (n 5 143) Mucocutaneous Pruritus Urticaria Flushing Angioedema Respiratory Dyspnea Wheezing Gastrointestinal symptoms Emesis Nausea/abdominal pain Cardiovascular Shock Note. Values are n (%).
123 120 49 36
(86.0) (83.9) (35.0) (25.1)
15 (10.5) 5 (3.5) 6 (4.2) 3 (2.1) 1 (0.7)
3.e9 LETTER TO THE EDITOR
J ALLERGY CLIN IMMUNOL nnn 2014
TABLE E3. Hypersensitivity history in platelet recipients and donors* Platelet recipient, n (%) Allergen
Grass Weed Tree Mold Animals Dust mites Penicillin Sulfa Aspirin Vancomycin
Never ATR (n 5 44)
6 2 12 9 7 5 7 4 1 1
(13.6) (4.6) (27.2) (20.5) (15.9) (11.6) (16.3) (9.3) (2.3) (2.3)
*Responses have
