anaphylactic transfusion reaction

1.Boonthorn
6 November 2009
Anaphylactic transfusion reaction

2. Case
66
CC: 2
PI: 3 .. 3 admit .
2 .. ..
PH:Atrial fibrillation on warfarin 2545 , Hx of gastritis,gouty arthritis on colchicine,herbal medicine 20 d ,Hx of blood transfusion 20yrs.ago (due to TAH operation ,no complication)

3. Physical examination
PE: BP 100/70, PR 70 irreg
Skin : no ecchymosis
HEENT: moderately pale ,not icterus ,no mucosal bleed
Heart:increase S 2 ,PSM gr IV at LLPSB , totally irreg
Lung: normal breath sound ,no adventitious sound
Abd: liver 1 FB below RCM
Ext.: no edema , no ecchymosis
PR : no melena
4. Lab (22/09)
Hct 20% wbc 6890 Plt 356,000 N52 L29 E10
PT 17.9 INR 1.6 PTT 27.9
BUN 48 Cr 2.1 uric 11
TB 0.45 DB 0.19 AST 14 ALT 9 ALP 74
UA : normal
CXR : cardiomegaly
EKG : atrial fibrillation
Echo : moderate pulmonary HT,severe TR
5. Hospital course
1.acute anemia R/O internal organ bleeding
EGD : clean based ulcer
LP PRC transfusion
Offwarfarin
2. acute renal failure
Hydration
Urine
Cr 1.3
pre renal azothemia
6. Hospital course
7. Hospital course
Serum tryptase =?
Repeat G/M => no mismatch
Coombs test : negative
IgA level= 311 ( 70 -400 )
single donor PRC 1 u
Hct stable ,.. blood transfusion Fe replacement D/C
underlying AF on warfarin bleeding GU with post hemorrhagic anemiaand prerenalazothemia Acute transfusion reaction ward
8. Acute transfusion reaction
Epidemiology
Type of reaction
Cause of anaphylactic transfusion reaction
Management ofIgA anaphylactic transfusion reaction
9. 7.9
5.1
0.2
Cumulative numbers of cases reviewed by SHOT, the UK hemovigilance system 1996-2007 (n = 4335) (Before 2006 the HTR category was referred to as delayed transfusion reactions.) ATR, acute transfusion reactions; HTR, hemolytic transfusion reaction; IBCT, incorrect blood component; PTP, post-transfusion purpura; TA-GVHD, transfusion-associated graft-versus-host disease; TRALI, transfusion-related acute lung injury; TTI, transfusion-transmitted infection
Transfusion alternatives in transfusion medicine 2008
10. Transfusion Medicine Reviews ,vol 20,No4,2006:273-82
11. Acute transfusion reactions in the pediatric intensive care unit
Transfusion.vol. 46 ,nov 20006.
12. 13. Allergic transfusion reaction
Allergictransfusion reactions are reported to complicate ~1- 3% of all blood transfusions.1
Severe allergic reactions ( anaphylactic shock ) incidence of 1 per 20 000 to 47 000 units of blood and components.1
Retrospective review 9 yrs.period (Cleveland)
allergic reactions 273/1613 adverse reactions (17%). 2
151 male and 122 female patients. (1.2:1)
14 (5.1%) allergic reactions associated withtemperature increase of1C or greater
26 (9.5%) not have skin manifestations
Transfusion Reactions. 2nd ed. Bethesda, Md: AABB Press; 2001:83127.
arch Patho Lab med vol 127,March 2003
14. arch Patho Lab med vol 127,March 2003
15. Severe allergic reactions
21/273 patients (7.7% of allergic reaction).
Overall incidence 21/1613 (1.3% of all transfusion reaction)
reactions : anaphylaxis or anaphylactoid signs and symptoms and/or hypotension ordecrease in oxygen saturation.
14 males and 7 females
red blood cell transfusions(33.3%)platelet or FFP transfusions (66.7%)
9pts. (42.9%) associated hypotension.
16. 9-year study period1,125,846 blood component transfusion
Transfusion alternatives in tranfusion medicine 2008
21. Possible Mechanisms Producing Allergic Transfusion Reactions
Preexisting IgE or IgGAb inrecipient reacts with allergens or proteins in transfused blood (eg, drugs or chemicals [ethylene oxide, plastics]).
Class- or subclass-specific anti-IgAAb in recipient reacts against IgA in transfused blood.
Preexisting IgG or IgE in recipient that reacts against allotypic serum protein forms in transfused blood (eg, albumin, haptoglobin, and complement component).
Passive transfer of IgE antibodies from donor to the recipient.
Transfusion of complement-derived anaphylatoxins (C3a and C5a) produced during blood storage.
Transfusion of cytokines, bradykinin, histamine, or other biological mediators produced during blood storage.
22. IgA anaphylactic transfusion reaction
Incidence : no reliable estimate ( nonstandardized diagnostic criteria, lack of laboratory based F/U for severe allergic transfusion reaction)
occur in 1 in 20,000 to 47,000 transfusions3
patients with a history of anaphylactic transfusion reactions, anti-IgA was detected in only 65 of 359 (18%) ofpatients2
Screened 32,376 healthy blood donors for registry of IgA-deficient donors, 1 in 1200 donors was found to be IgA-deficient (75 % of the case reports of IgA anaphylactic transfusion reactions were published before 1985 when TRALI was first recognized
1.Blood 1994;84:2031-5.
2.Current Opinion in Hematology 2003, 10:419423
3. Transfus Med Rev. 1995 Jan;9(1):1-8
23. Diagnosis of IgA deficiency in managinganaphylactic transfusion reactions
diagnosis : show IgA-antibody in patient's serum
Anti-IgA and anaphylactictransfusion reactions first described by Vyaset al. in 1968
AABB Press textbook on transfusion reactions :when pt. experience anaphylacticor severe anaphylactoid transfusion reaction for first time, pretransfusion serum must be screened for anti-IgA and If an anti-IgA is detected, a lifelong commitment to transfusion with only IgA-deficient blood components is made
Current Opinion in Hematology 2003, 10:419423
24. Vyaset al.:Two groups of patients with anti-IgA
class specific
suffered severe anaphylactic reactions
No detectable serum IgA
very high titers ofanti-IgA
reacted with all IgAparaprotein-coated red blood cells
limited specificity
generally multiple transfused patients
only suffered urticaria or other milder reactions to blood products
detectable levels of serum IgA
low titers of anti-IgA
Reacted with only some IgAparaprotein coats and not others
Current Opinion in Hematology 2003, 10:419423
25. prevalence of IgA deficiency in north India.
Methods: A sensitive enzyme linked immunosorbent assay developed in-house was used to detect IgA deficiency in a total of 3818 blood donors. Complete IgA deficiency was defined as value less than 5 mg/dl whereas partial IgA deficiency was defined as value between 5-30 mg/dl.
Results: Of the 3818 blood donors screened, 3640 (95.3%) were males with a mean age of 31.2 yr. No donor was found to have complete IgA deficiency; however, 257 (6.7%) had partial IgA deficiency
INDIAN J MED RES, MAY 2006
26. IgA DEFICIENCY
Relative IgA deficiency
plasma IgA concentrationless than labs reference range ( wash RBC and PLT componentsor locate components fromIgA deficient donor.
TRANSFUSION Volume 46, January 2006
32. 3. Patients withHx ofsevere anaphylactic transfusion reaction andlaboratory-confirmed diagnosis of IgA deficiency.
safest option is transfusing IgA deficient blood components (IgA selective IgA deficiency(1 in 30,000)
prevalence of haptoglobin deficiency among patients who experienced immediate-onset anaphylactic NHTRs ~ 1 in 60
TRANSFUSION 2007;47:2315-2321.
41. Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions
Blood. 2000; 95:1138-1143
42. Identification of haptoglobin deficiency with simplified ELISA among 200 Thais.
TRANSFUSION 2007;47:2315-2321.
43. Detection of 6 subjects heterozygous for the Hpdel allele among 200 Thais. (A) Determination of Hpdel allele with Hpdel -specific PCR (B) Determination of haptoglobin phenotype by Western blotting
TRANSFUSION 2007;47:2315-2321.
44. - no haptoglobin-deficient subjects detected among 200 Thais
- haptoglobin phenotypes : Hp 1-1 (10), Hp 2-1 (81),
and Hp 2-2 (109)

6 individuals heterozygous for Hpdel were detected

45. frequency of Hpdelallele was calculated to be 0.015- prevalence of haptoglobin deficiency caused by Hpdelhomozygosity ~1 in 4000. (similarin Japan )
TRANSFUSION 2007;47:2315-2321.
46. Posttransfusion anaphylactic reactions in patient with severe vWD: role of complement and alloAb to vWF
Serial plasma samples were collected from a patient with severe vnWillebrand disease, IgGalloAb against vWF , and a history of posttransfusion anaphylaxis.
During an 18-day period the patient was treated with factor VIII-vWF concentrate and with recombinant factor VIII.
Symptoms of anaphylaxis and signs of complement activation were present only when IgGAb to vWF were measurable during replacement with factor VIII-vWF concentrate (days 1 and 6).
IgE, IgA, and IgM antibodies to vWF were not detectable in plasma at any time.
This study indicates cause-effect relationship between formation of IgG-vWF complexes and massive complement activation in posttransfusion non-IgE-mediated anaphylactic reactions
J Lab Clin Med. 1995 Mar;125(3):348-55.
47. infusion of vWF-containingpreparations into patients C.K. andG.T. led to formation of IgG-vWF complexes, release of complementanaphylatoxins
The journal of Immunology, 1996, 156: 1256-1 261.
48. Adverse transfusion reactions associated with precipitating anti-C4 antibody of anti-Rodgers specificity.
patient suffer from chronic hepatitis exhibited severe transfusion reactions after administration ofFFP andprothrombin complex conc.
1 month before these reactions, she received FFP
patient's serum obtained 1 wk and 6 mo.
IgG class present in sera reacted with purified preparation of C4
Ab limited specificity and reacted only with C4 of Rodgers specificity
Phenotype ofpatient's C4 group : Chido positive and Rodgers negative.
patient had neither detectable anti-IgA nor other anti-IgAb
coexistence of precipitating anti-C4 Ab and adverse transfusion reactions to plasma fractions containing large amounts of C4 indicates that in the absence of Ab of other specificities, this Ab can be considered as the cause of the transfusion reaction.
Vox Sang. 1984;47(3):242-9
49. Severe anaphylactic reactions following transfusions of platelets to patient with anti-Ch
Report : anti-Ch (and anti-Rg) not cause hemolytic transfusion reactions
Ab did not cause red cell destruction, but did cause a life-threatening anaphylactic reaction during transfusion of plasma proteins in pooled platelets.
Ab was of the IgG4 subclass and might have caused a short-term, sensitizing anaphylactic response.
This case (transfusion reaction caused by anti-Ch ), and one previously reported in whichpatient with anti-Rg experienced a severe reaction to FFP and plasma derivative
these Ab can cause severe, life-threatening reactions in patients who receive plasma-containing components
Transfusion. 1992 Jul-Aug;32(6):576-9.
50. Activated platelet membranes orplatelet-derived microparticles as possiblecause of anaphylactic transfusion reactions
platelet membrane-derived microparticles (PMPs) may be responsible for high incidence of reactions to platelet concentrates
study of acute reactions in pediatric patients, there was a 5% incidence of allergic reactions to standard platelets and a 6% incidence to pre-storage WBC-reduced platelets1
study in adult patients there was a 4.1 and 4.8% incidence of allergic reactions to pre-storage WBC reduced whole blood derived and apheresis platelets respectively2
negatively charged surfaces ( externalized phosphatidyl serine and phosphatidyl ethanolamine on surface ) like ionic contrast media
management option for patients who need FFP would be solvent-detergent treated plasma (SD Plasma)
Transfusion 2002, 42:753758
Transfusion 2002, 42:556566
51. Platelets expressing P-selectin and platelet-derivedmicroparticles in stored platelet concentrates bind to PSGL-1 on filtrated leukocytes.
levels of IL-6 & platelet-derived microparticles (PMPs) were measured in 137 patients with SE from PC transfusion with leukocyte removal filtration
203 transfusions
84 patients with hematologic disease
53 patients with nonhematologic disease
urticaria (75.9%), erythema (18.7%), and fever (17.2%), but no anaphylactic reactions.
levels of interleukin-6 and PMP correlated in both groups, and were significantly higher in the hematologic disease group than in the nonhematologic disease group.
The level of PMP, but not interleukin-6, was significantly higher for patients testing positive for allergic reaction than for those testing negative. In the stored PC prior to filtration, the level of interleukin-6 was normal. The level of P-selectin-expressing platelets and PMPs was elevated before filtration, but was significantly lower after filtration. Taken together, the results suggest that PMP is involved in the generation of transfusion reactions, and indicate that both platelets and PMP displaying P-selectin bind to P-selectin glycoprotein ligand-1 of leukocytes retained by the leukocyte filter.
ClinApplThrombHemost. 2000 Oct;6(4):213-21.
52. Conclusion
Anaphylactic transfusion reactions are rare
Possible mechanisms are Ab to plasma donor (eg.IgA,haptoglobin,complement,coagulation factor)
Management :
Treatment of anaphylaxis
Exclude other cause of acute transfusion reaction
prevention for recurrent anaphylaxis by special blood component ( IgA blood donor,not available in Thailand?) , washed Rbc

anaphylactic transfusion reaction

Health & Medicine