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Complications of Transfusion
M2 Hematology/Oncology Sequence Robertson Davenport, MD
Winter 2009
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Transfusion Reactions!• Acute (intravascular) hemolytic reaction • Delayed (extravascular) hemolytic reaction • Febrile non-hemolytic reaction • Allergic (urticarial) reaction • Bacterial contamination • Transfusion-related acute lung injury • Transfusion-associated circulatory overload • Post-transfusion purpura • Graft-vs.-host disease
4
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Hemolytic Transfusion Reactions
• Acute – Presentation within 24 hrs – Intravascular hemolysis – Prototype: ABO incompatibility
• Delayed – Presentation > 24 hrs – Typically extravascular but may be
intravascular – Prototype: Rh 5
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Clinical Presentation of HTR
• Intravascular – Fever, chills, pain, hemoglobinemia, hemoglobinuria,
dyspnea, vomiting, shock – Complications: renal failure, DIC, ARDS, death – Mortality: ~10%
• Extravascular – Fever, chills, leukocytosis, anemia – Complications: renal failure, DIC, sickle cell crisis – Mortality: rare
6
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Recognition of HTR
• Free serum hemoglobin, positive DAT • New red cell antibody • Patient or sample misidentification • Bleeding, hemoglobinuria in an
anesthetized patient
7
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Febrile Non-Hemolytic Transfusion Reactions
• Incidence – 1:250 transfusions
• Presentation – Fever and/or chills
• Mechanisms – Leukocyte antibodies in recipient – Cytokines released in unit during storage
8
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Allergic Reactions
• Incidence 1-3:100 transfusions • Presentation
– Hives, flushing, dyspnea, vomiting • Mechanisms
– Antibody to allergen or plasma protein – Passive transfer of donor antibody
9
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Anaphylaxis
• Presentation – Hypotension, bronchospasm, stridor, shock
• Mechanism – IgA deficiency with anti-IgA – Haptoglobin deficiency with anti-haptoglobin
• Prevention – IgA deficient plasma, washed RBC & platelets
10
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Bacterial Contamination • Incidence in platelet concentrates
– 1:5000 culture positive – 1:10,000 cause reactions – 1:75,000 cause mortality
• Organisms involved – Platelets: Gram neg. rods, Gram pos. cocci – RBC: Yersinia, Pseudomonas
• Sources – Contaminated equipment, nonsterile procedure – Donor skin – Donor blood
11
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Bacterial Contamination
• Symptoms: fever, chills, rigors, hypo-tension, shock, DIC
• Differential: hemolytic transfusion reaction, sepsis
• Work-up: Gram stain, culture
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Transfusion Related Acute Lung Injury (TRALI)
• Incidence 1:5000 transfusions • Presentation: non-cardiogenic pulmonary edema • Mechanisms
– Donor antibody to recipient neutrophil-specific or HLA antigen – Production of platelet activating factor-like lipid during storage – Release of CD40L from platelets during storage
• Mortality: 10 - 20% • Differential: Hemolytic reaction, allergic reaction, fluid
overload, acute lung injury • Reduction strategy
– Plasma components from male donors – Antibody screening
13
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Transfusion Associated Graft-vs.-Host Disease
• Incidence: rare • Presentation: rash, fever, diarrhea, liver
dysfunction, cytopenia • Mechanism: engraftment of transfused T-
cells • Mortality: very high • Differential: viral infection, drug reactions
14
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Patients at risk for TA-GVHD
• Severe cellular immuodeficiency – Congenital immunodeficiency – Intrauterine transfusion – Bone marrow transplantation – Hodgkin’s disease, NHL, high dose chemotherapy
• Homogenous populations • Recipients of donations from first degree
relatives 15
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Mechanism of Engraftment in Normal Recipients
• HLA homozygous donor
• HLA heterozygous recipient
• Shared haplotype A1 A1 A1
B8 B8 B8
A2
B44
Donor Recipient
Different
Same
16
R. Davenport
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Transfusion-Associated Circulatory Overload (TACO)
• Incidence: Variable • Presentation: Dyspnea, hypoxemia,
pulmonary edema • At-risk patients: heart disease, renal failure • Mortality: ~double underlying disease • Differential: Hemolytic reaction, allergic
reaction, TRALI, cardiac or pulmonary disease
17
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Other Adverse Effects of Transfusion
• Iron overload • Alloimmunization • Non-immune hemolysis • Hypotensive reaction • Acute pain reaction
18
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Transfusion-Transmitted Diseases!
• Hepatitis (B, C, G) • HIV/AIDS • Cytomegalovirus • HTLV • Parvovirus • Chagas’ disease • Malaria • Babesiosis • Leishmania • Variant CJD
19
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Hepatitis B !
• Jaundice 2 -3 months after transfusion • Chronic carrier rate 5-10% • 25% active hepatitis in carriers • Complications
– Cirrhosis – Hepatocellular carcinoma
20
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Hepatitis C!
• Acute infection usually nonicteric • 70% develop chronic hepatitis
– 10 - 20% progress to cirrhosis • 0.5% of first time blood donors are HCV+
21
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Sources of Infection for Persons With Hepatitis C
Sexual 15%
Other 1%*
Unknown 10%
Injecting drug use 60%
Transfusion 10% (before screening)
* Nosocomial; iatrogenic; perinatal
Occupational 4%
22
Centers for Disease Control and Prevention
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Posttransfusion Hepatitis C
0
5
10
15
20
25
30
1965 1970 1975 1980 1985 1990 1995 2000
Year
% o
f R
ecip
ient
s In
fect
ed
All volunteer donors HBsAg
Donor Screening for HIV Risk Factors Anti-HIV
ALT/Anti-HBc
Anti-HCV Improved HCV Tests
23
Source Undetermined
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Transfusion Transmitted HIV
0100200300400500600700800
78 79 80 81 82 83 84 85 86 87 88 89 90 91
Year of Transfusion
Inci
denc
e
24
Source Undetermined
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Estimated HIV/AIDS Cases 2006
MSM59%IDU
16%
MSM+IDU7%
Heterosexual17%
Other1%
CDC Cases of HIV infection and AIDS in the United States and Dependent Areas, 2006
25
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Outcome of Transfusion Transmitted HIV
• Rate of progression similar to other cohorts • Progression rate independent of donor status • Older recipients progress more rapidly than
younger recipients
26
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Estimated Current Risks
• Hepatitis C – 1:1,800,000
• HIV – 1:2,300,000
• Hepatitis B – 1:1,500,000
27
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Cytomegalovirus
• Enveloped DNA Herpes virus • Usually asymptomatic in immunocompetent
patients • Latent in monocytes and other cells • High prevalence in donor populations
28
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Patient Populations at Risk of CMV Disease
• Fetuses • Premature infants • Bone marrow transplantation • HIV infection • Congenital cellular immunodeficiency • Solid organ transplantation
29
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CMV and Blood Transfusion
• Transmission rate by seropositive cellular components: 0.4 - 10%
• Seronegative blood components equivalent to background rate
• Leukocyte reduced components are as effective as seronegative in prevention
30
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Parvovirus B19
• Non-lipid enveloped DNA virus • Clinical associations
– Erythema infectiosum (Fifth disease) – Arthritis – Red cell aplasia – Non-immune hydrops
31
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Parvovirus and Blood Transfusion
• Per unit risk 1:1,000 - 1:5,000 • Seroconversion rate: 80% • Detected in factor concentrates, pooled
plasma and donor sera by PCR • Seroprevalence 50%
32
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West Nile Virus
• Latent period 3-15 days • No chronic carrier state • Blood donor prevalence: ~1:10,000 • Transfusion risk: <1:1,000,000
33
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2008 WNV Blood Donor Viremia
34
Centers for Disease Control and Prevention
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Chagas Disease
• US prevalence: ~100,000 persons • Seroprevalence: ~1:5000 in Los Angeles • Infectivity: 60% of seropositive bloods are
PCR positive • Transfusion transmission: 9 cases in US and
Canada • Prevention: leukocyte reduction, antibody
screening 35
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Chagas Confirmed Positive Blood Donors
36 American Association of Blood Banks
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CJD
• UK vCJD experience – 18 donors with 66 components transfused – 3 recipients developed vCJD 5-10 years after
transfusion – Background mortality: 0.24/million/year
• US sCJD and fCJD experience – 32 donors with 395 components transfused – 1663 person-years follow-up – No evidence of transmission to date
37
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Other Transfusion-Transmitted Diseases
• Human T-Lymphotropic Virus • Hepatitis G • Epstein-Barr Virus • Malaria • Babesiosis • Leishmania
38
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Informed Consent for Transfusion
• Indications for the transfusion • Possible risks • Possible benefits • Alternatives • Possible consequences of not receiving the
transfusion
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Emergency Transfusion
• Judgement of patient’s preference • Implied consent • Do not delay transfusion in life-threatening
situations • Document circumstances in medical chart
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Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy
Slide 16: Robertson Davenport Slide 22: Centers for Disease Control and Prevention Slide 23: Source Undetermined Slide 24: Source Undetermined Slide 25: CDC Cases of HIV infection and AIDS in the United States and Dependent Areas, 2006 Slide 34: Centers for Disease Control and Prevention Slide 36: American Association of Blood Banks