Transcript Delayed Hemolytic TXRs

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‫اهواز‬
Non-infectious Risks of
Transfusion
If not Infectious, What are the Risks?
Delayed
Reaction
TRALI, 7%
Acute
Reaction
Post-Tx
Purpura
Non-Infectious Risks
• Human Error and
Clerical Errors
• Improper
Administration of the
Blood Product
GVHD
Infections, 2%
Mis-transfusion, 66%
SHOT DATA 1996-2003
How common are errors?
• Risk of an error occurring during
transfusion of a blood component is
1:16,500
• Risk of an ABO incompatible transfusion is
1:100,000
• Risk of death as a result of an 'incorrect
blood component transfused' is around
1:1,500,000
Clerical Errors
• Sample drawn on the wrong patient
– It is vital to check the name and patient ID number
every time you draw a blood sample for testing
• Blood is hung on the wrong patient
– It is vital to check that the name and patient ID
number on the unit of blood matches that on the
patient’s ID band
• Labeling error
– Label tubes as you draw or use them rather than
batch labeling. When batching, the risk of a tube
switch exists
– Sample tubes must be labeled at the patient’s
bedside/chairside
Sample Collection Errors at BHC
Identified by the Blood Bank
Total Sample Errors Identified by
Bellevue Blood Bank
Number
400
200
0
2Q07 3Q07 4Q07 1Q08 2Q08 3Q08 4Q08 1Q09 2Q09 3Q09 4Q09
ABO Discrepancies
2
9
5
13
6
7
7
7
4
6
6
Specimen Not Signed
80
129
117 134 135 169
146 106
67
102
147
Total by Service
128 189
176 214 201 267
205 169 131 157
210
Where do the Errors occur?
SHOT Errors, 1996-2003, n=2340
Blood Center, 1.7%
Prescription, sampling, request, 19.7%
Unknown, >1%
Other, 1%
Collection, Administration, 48.4%
Hospital Blood Bank, 29%
Serious Hazards of Transfusion Study in UK
Transfusion Errors
• Transfusion errors in New York State*
–
Erroneous administration (1/19,000 units)
• ~50% of errors occurred outside the blood bank
–
Blood bank errors
• 29% of errors occurred in the blood bank (wrong test, issuance of
wrong unit etc.)
–
Multiple errors
• 20% involved errors at blood bank and on floor or lab
• Increased scrutiny of hospital reporting by regulatory
agencies
* JV Linden et al (2000) Transfusion, 40: 1207
Administration Errors
• What can be added to a line during a transfusion?
–
–
–
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Normal saline (0.9%)
ABO compatible plasma
5% Albumin
Plasma protein fraction
• What can never be added to a line during a transfusion?
– Lactated Ringer’s solution
• Contains 3 mEq/L ionized calcium
– 5% Dextrose
– Hypotonic sodium chloride solutions
– Almost all Medications
Running any of the above “never solutions” along with blood risks
hemolyzing the transfused cells.
Alloimmunization
• Chronically transfused patients can develop
antibodies to WBCs as well as RBCs
• Antibodies to WBCs
– Can cause febrile non-hemolytic transfusion reactions
• May avoid or reduce frequency and severity by
leukoreduction or pre-medication with antipyretics
• Antibodies to RBCs
– Can cause either acute (AHTR) or delayed hemolytic
reactions (DHTR)
– Can lead to hemolytic disease of the newborn
– May affect the availability of blood
Alloimmunization
• Incidence:
– RBC Antigens: 1:100 (1%)
– HLA Antigens: 1:10 (10%)
• Etiology: Immune response to foreign antigens
on RBC, WBCs, and platelets (HLA)
• Presentation: Positive blood group antibody
screening test, platelet refractoriness, delayed
hemolytic reaction, hemolytic disease of the
newborn
Impact of RBC Alloimmunization
• Hemolytic Transfusion Reactions
– Acute
– Delayed
• May make laboratory evaluation more
complicated
• Delay and Difficulty in providing
compatible blood for transfusion
• Hemolytic Disease of the Newborn
Recognition of Acute
Transfusion Reactions
• Signs and symptoms that may be associated
with any type of acute transfusion reaction
– Fever
• 1C (2F) increase in body temperature associated
with transfusion
– Shaking chills (rigors) with or without fever
– Pain at the infusion site or in the chest, abdomen, or
flanks
– BP changes
• Usually acute either hypertension
or hypotension
Types of Acute (<24 hours)
Transfusion Reactions (TXRs)
• Immunologic
– Hemolytic
– Fever/Chill
– Urticarial
– Anaphylactic
• Non-Immunologic
– Hypotension associated
with ACE inhibition
– TRALI
– Circulatory overload
(TACO)
– Non-immune hemolysis
– Air embolus
– Hypocalcemia
– Hypothermia
Hemolytic Transfusion Reactions
• Acute hemolytic transfusion reactions may be either
immune-mediated or nonimmune-mediated
• Immune-mediated
– Occur when a patient has an antibody directed against a RBC
antigen on the transfused RBCs or when the plasma in the
transfused blood product contains an antibody to an antigen
on the patient’s own RBCs
• Nonimmune-mediated
– Occur when RBCs are damaged prior to transfusion
– Generally results in hemoglobinemia and hemoglobinuria
without significant clinical symptoms.
Acute Immune-Mediated
Hemolytic Transfusion Reactions
• Incidence: 1:38,000 to 1:70,000
– Some reports as high as 1:25,000 transfusions
• Occur during or within 24 hours after transfusion
• Can be fatal
• Most often due to clerical and sample identification
errors
• Hemolysis can be intravascular or extravascular
• Intravascular
– Most often due to ABO blood group mismatch
Acute Immune-Mediated
Hemolytic Transfusion Reactions
• Signs and Symptoms
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Chills
Fever
Hypotension
Renal failure with
oliguria
DIC
Back pain
Pain along infusion vein
Anxiety
Pain at infusion site
– Hemoglobinurea
– Hemoglobinemia
• Can detect 2.5 to 5 ml
RBC hemolysis
Acute Immune-Mediated
Hemolytic Transfusion Reactions
• Treatment
–
–
–
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Immediately discontinue the transfusion
Maintain venous access for emergency management.
Anticipate hypotension, renal failure, and DIC.
Prophylactic measures to reduce the risk of renal failure may
include
• Low-dose dopamine (1-5 mcg/kg/min)
• Vigorous hydration with crystalloid solutions (3000 mL/m2/24 h)
• Osmotic diuresis with 20% mannitol (100 mL/m2/bolus followed by 30
mL/m2/h for 12 h).
– If DIC is documented and bleeding requires treatment,
transfusions of frozen plasma, pooled cryoprecipitate for
fibrinogen, and/or platelets may be indicated.
Febrile Non-Hemolytic
Transfusion Reactions (FNHTRs)
• Most frequently reported of all reactions
– About 1% of all transfusions
• Incidence:
– RBCs: 1:200 to 1:17 (0.5-0.6%)
– Platelets: 1:100 to 1:3 (1-38%)
• Increase in temperature of 1C or 2F with no other
explanation
• Presentation: Chills/rigors, rise in temperature (>1C),
headache, vomiting
• Most FNHTRs can be prevented
Febrile Non-Hemolytic Transfusion
Reactions (FNHTRs)
• Etiology: Due to antibodies to WBCs and/or
accumulated cytokines especially in platelets
– Current theory is that FNHTRs are caused by
cytokines, such as interleukin (IL)-1, IL-6, IL-8, and
tumor necrosis factor-alpha (TNFa), which are
generated and accumulate during the storage of
blood components
• Prevention:
– Antipyretic pre-medication with acetaminophen
– Leukoreduced blood products
Urticarial TXRs
•
•
•
•
Incidence: 1:100 to 1:33 (1-3%)
Second most frequently reported reaction
Presentation: Urticaria, pruritis, rash, flushing
Etiology: Antibody to donor plasma proteins
– Due to Type 1 hypersensitivity to donor plasma proteins
– Urticarial transfusion reactions (UTRs) occur when soluble
allergenic substances in the plasma of the donated blood
product react with preexisting IgE antibodies in the
recipient. This causes mast cells and basophils to release
histamine, leading to hives or urticaria
Urticarial TXRs
• Lab Testing: Rule out
hemolysis
• Prevention:
– Antihistamines,
treatment or premedication (PO or IV)
– May restart transfusion
of unit slowly after
antihistamine if
symptoms resolve
Anaphylactic TXRs
• Incidence: 1:20,000 to 1:50,000
• 1:800 to 1:900 people have no detectable
IgA
• Etiology: Antibody to donor plasma proteins
(includes IgA, C4)
• Presentation: Hypotension without fever,
urticaria, bronchospasm (respiratory
distress, wheezing), local edema, anxiety
Anaphylactic TXRs
• Treatment:
– Immediate cessation of the
transfusion
– Epinephrine, 0.3 mL of a
1:1000 solution
intramuscularly
– Preparation, for possible
administration, of an
intravenous epinephrine drip
– Airway maintenance,
oxygenation
– Volume maintenance with
saline
– Vasopressors (eg,
dopamine), if necessary
• Prevention:
– Antihistamines,
corticosteroids, beta-2
agonists
– IgA-deficient blood
components if IgA-deficient
patient
– Washed blood products
Transfusion Associated
Acute Lung Injury (TRALI)
• Incidence: 1:1,300 to 1:5,000
• Etiology: Most likely caused by antibodies in donated
blood products that react with patient white cells or
visa-versa
– Antigen-Antibody reaction results in increasing the permeability of
the pulmonary micro-circulation so that high-protein fluid enters the
interstitium and the alveolar air spaces
• Presentation: Noncardiogenic pulmonary edema,
hypoxemia, respiratory failure, hypotension, fever,
dypsnea, chills
– Develops within 1-2 hours of transfusion. Usually present within 4-6
hours
– Can be difficult to distinguish from ARDS
TRALI
• Leading cause of transfusion deaths
in US for the last two reporting years
• Pulmonary edema arises from
capillary injury not volume overload
• Can occur after the transfusion of
any type of blood product
• Most patients (>80%) recover
adequate pulmonary function within
2 to 4 days
• Observed mortality rate is less than
10%
• Patients are treated with supportive
care and may require ventalitory
assistance
• Diuretics are contraindicated
Normal Chest X-Ray
TRALI Chest X-Ray
TRALI Edema Fluid
Transfusion Associated
Circulatory Overload (TACO)
• Incidence: <1%
– Mayo Clinic estimated that incidence to be 1:708
• Etiology: Volume overload Pulmonary edema secondary to
congestive failure can occur with transfusion-associated
volume/circulatory overload (TACO)
• At risk patients include elderly patients, small children,
and/or those with compromised cardiac function.
– This often occurs in association with surgery, where large
fluid volumes and some blood are administered.
• Presentation: Dyspnea, orthopnea, tachycardia and a
wide pulse pressure, often with hypertension, and may
begin near the end of the transfusion, or within six hours.
Headache is common, and seizures have been reported.
Transfusion Associated
Circulatory Overload (TACO)
• In order to avoid TACO for routine transfusions of blood
components, a transfusion rate of approximately 2.0 to
2.5 mL/kg per hour is acceptable.
– Thus, for an average-sized adult, one unit of packed red
cells should be transfused over a 1.5 to 2 hour period.
• Patients deemed to be at risk of TACO (eg, small stature
or low body weight, elderly, known or suspected poor
cardiac function) can generally be safely transfused at a
rate of 1 mL/kg per hour.
– Such patients should also be monitored more closely
during the transfusion for signs and symptoms of TACO.
Transfusion Associated
Circulatory Overload (TACO)
• Treatment consists of fluid mobilization
(diuretics) and supplementary oxygen.
– Noninvasive positive pressure ventilation may be
helpful in the acute management of patients with
severe respiratory compromise.
• Phlebotomy in 250 mL increments, with or
without reinfusion of the removed red cells, may
be necessary if symptoms persist or diuresis
cannot be promoted.
Other Rare Complications
•
Hypothermia
– Incidence: Dependent on
clinical setting
– Etiology: Rapid infusion
of cold blood
– Presentation: Cardiac
arrhythmia
– Therapeutic/ Prophylactic
approach: Employ blood
warmers
•
Non-Immune Hemolysis
– Incidence: Rare
– Etiology: Physical or chemical
destruction of blood (heating,
freezing, hemolytic drug or solution
added to blood or line)
– Presentation: Hemoglobinuria
– Lab testing:
•
•
•
•
Plasma-free Hb
DAT (should be negative)
Test unit for hemolysis
Look at segments verses unit
– Therapeutic/Prophylactic approach:
Identify and eliminate cause
Other Rare Complications
•
Air
–
–
–
Embolus
Incidence: Rare
Etiology: Air infusion via line
Presentation: Sudden SOB,
acute cyanosis, pain, cough,
hypotension, cardiac
arrhythmia
– Therapeutic approach: Lay
patient on left side with legs
elevated above chest and
head
•
Hypocalcemia (Ionized Ca2+)
– Incidence: Dependent on
clinical setting
– Etiology: Rapid citrate
infusion. Can occur with
massive transfusion of citrated
blood, delayed metabolism of
citrate, or during apheresis
procedures
– Presentation: Paresthesia,
tetany, arrhythmia
Delayed (>24 hours) TXRs
• Immunologic
– Alloimmunization
• RBC antigens
• HLA antigens
• WBC antigens
– Hemolytic
– Graft-vs-Host Disease
(TA-GVHD)
– Post-transfusion
Purpura
• Non-Immunologic
– Iron overload
Delayed Hemolytic TXRs
• Incidence: 1:11,000 to 1:5000
• Etiology: Anamnestic immune response to RBC
antigens
• Occur 5-20 days after transfusion
• Hemolysis:
– Classically extravascular
– Can be intravascular
• Kidd antibodies are able to fix complement and thus
can cause intravascular hemolysis
Delayed Hemolytic TXRs
• Caused by antibodies that were undetectable at
the time of compatibility testing
– Patients frequently “shop around” for their health care
and are thus treated at different hospitals
– Without an accurate transfusion history &/or prior test
results it is possible to miss clinically significant
antibodies
– >30% of antibodies disappear (become undetectable)
with time, but recipients can mount an anamnestic
response to further stimulation by transfusion
Delayed Hemolytic TXRs
• Presentation: Fever, decreasing hemoglobin,
new positive antibody screening test, mild
jaundice, often no signs or symptoms
• Lab testing:
–
–
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Positive antibody screen
Spherocytes on peripheral screen
DAT (Classically “mixed field”)
Test for hemolysis (visual inspection for
hemoglobinemia, LDH, bilirubin, urinary
hemosiderin as clinically indicated)
Delayed Hemolytic TXRs
• Prevention: Excellent patient histories
and historical blood bank/blood center
testing records
– Enables the correct RBCs lacking the
patient’s antibody to be selected
Delayed Hemolytic TXRs
• 50% of patients who become
alloimmunized will develop multiple
antibodies
• 50% are anti-Rh blood group system
– E most common
• 20% are anti-Kell and anti-Kidd (Jka &
Jkb)
Hemolytic Disease of the
Newborn
• Maternal IgG antibodies
made following a
previous RBC exposure
cross the placenta
• IgG antibodies bind to
the fetal RBCs
• The antigen-antibody
complexes result in fetal
RBC hemolysis and
anemia
Hemolytic Disease of the
Newborn



Prolonged anemia leads to
increased erythropoiesis in fetal
liver
This causes disruption of portal
circulation, impaired albumin
synthesis, decreased plasma
colloid osmotic pressure
The decreased osmotic pressure
of severe anemia causes
cardiovascular failure, tissue
hypoxia, and death in utero
Transfusion Associated Graftvs-Host Disease (TA-GVHD)
• Incidence: Rare
• Etiology: Donor lymphocytes engraft in
recipient and mount an attack on the
host tissues
• Presentation: Rash, erythroderma,
maculopapular rash, anorexia, nausea,
vomiting, diarrhea, hepatitis,
pancytopenia, fever, bone marrow
fibrosis and failure
• Lab testing:
– Skin biopsy
– Bone marrow biopsy and HLA typing
TA-GVHD
• Can develop in patients whose immune system fails
to recognize transfused WBC as foreign
• Transfused WBCs (CD4 & CD8 cells) attack and kill
host’s immune system
• Prevention: Irradiation of blood components for
patients at risk of developing TA-GVHD
– Including:
•
•
•
•
Low infant birth weight neonates
Congenital immunodeficiencies
Certain malignancies including Hodgkin’s Disease
Fludarabine chemotherapy
• Hematopoietic stem cell transplants
• HLA matched products
• Blood products from blood related donors
Irradiation of Blood Products
• Since TA-GVHD depends upon:
– Number of viable, immunologically
competent lymphocytes transfused
Degree of HLA similarity between donor and
recipient
Immunocompetence of recipient


• Gamma irradiation reduces/eliminates
lymphocyte proliferative capacity
(2500cGy)
• It is necessary to irradiate all cellular
blood components including RBC,
platelets, and granulocytes
Post-Transfusion Purpura (PTP)
• Incidence: Rare (>250 cases in
literature)
– Female-to-male ratio is 26:1
• Etiology: Recipient platelet antibodies
destroys autologous and transfused
platelets
• Presentation: Thrombocytopenic
purpura, bleeding, 8-10 days following
transfusion
• The typical patient is a multiparous
woman or a patient with history of
previous transfusions
• Thrombocytopenia is usually severe
with platelet counts below 10,000
• Can be associated with significant
hemorrhage
Post-Transfusion Purpura
• Treatment
– Consists of prompt initiation of IVIG at a dose of 2
g/kg over 2 or 5 days, in split fractions
– Steroids can be used in conjunction
– Plasma exchange (TPE)
– Transfusion of HPA-1a negative platelets (if patient
is HPA-1b) can be used in life threatening
hemorrhagic circumstances
• Course
– PTP is generally self-limited with full recovery within
21 days
– 10-15% of patients have been reported to die from
PTP
Iron Overload
• Major problem for chronically transfused patients
– Sickle Cell Anemia
– Thalassemia
• Incidence: Invariable after >100 units of RBCs, risk
occurs after >50 units
• Etiology: Multiple transfusions with obligate iron
load in transfusion-dependent patient
• 1 mg of iron per 1 ml of RBCs transfused (every
unit of RBC contains approximately 200mg iron)
• Presentation: Diabetes, cirrhosis, cardiomyopathy
• THE BEST TX IS NO TRANSFUSION