Transcript 5-Transfusion_Medicine.ppt

Transfusion Medicine
DR MOHAMED BILAL DELVI, MD
ASSOCIATE PROFESSOR
DEPT OF ANESTHESIA
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Many patients have died during early
years of transfusion medicine and it
was not until 1901 blood groups were
discovered.
Karl Landsteiner discovered that blood
clumping was an immunological
reaction which occurs when the
receiver of a blood transfusion has
antibodies against the donor blood
cells.
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Karl Landsteiner's work made it
possible to determine blood groups
and thus paved the way for blood
transfusions to be carried out safely.
For this discovery he was awarded the
Nobel Prize in Physiology (Medicine)
in 1930.
Overview
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Blood Components
– Collection
– Indications
– Modifications
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Pre-transfusion Testing
Transfusion Reactions
Collection of Blood
Products
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Whole blood donation
Whole Blood Separation
Collection of Blood
Products
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Apheresis
– Plateletpheresis
– Leukapheresis
– Erythrocytapheresis
– Plasmapheresis
– Stem Cell collection
Blood products
 Cellular Components:
–Red blood cells
- Leukocyte-reduced RBCs
- Washed RBCs
- Irradiated RBCs
–Platelets
- Whole blood derived platelets
- Single-donor platelets (Apheresis Platelets)
–Granulocytes
Blood products
 Acellular Components:
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Fresh-frozen plasma (FFP), Thawed plasma
Cryoprecipitate
Factor concentrates (VIII, IX)*
Albumin*
IVIG*
* Provided by pharmacy
Red Blood Cells
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Prepared from whole blood
or apheresis donation
250-300 mL
– 200-250 mL RBCs + < 50 mL plasma +
preservative/additive solution
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Stored 21-42 days at 1-6°C
Hct 55-65%
RBC Compatibility
Indications for RBC units
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Increase O2 carrying capacity
Symptomatic anemia
– Acute or chronic hemorrhage
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Acute loss of >30% of blood volume
– Hemolysis
– Marrow failure
– Hb < 8.0 gm/dL
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Don’t just look at hemoglobin level!
– Need to consider cardiac output, volume status, patient
history, etc.
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Exceptions
– Sickle cell anemia
– Cardiac or pulmonary disease
TRICC Trial
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Transfusion Requirements in Critical
Care
– Restrictive transfusion
Hemoglobin maintained at 7-9 gm/dL
 Averaged 2.6 units RBCs
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– Liberal transfusion
Hemoglobin maintained at 10-12 gm/dL
 Averaged 5.6 units RBCs
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– All outcomes evaluated favored restrictive
transfusion group
Contraindications for RBC
units
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Acute blood loss <20-30% blood
volume
– Crystalloids often adequate
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Nutritional anemias
Almost never indicated for Hb ≥ 10
gm/dL
Expected Results of RBC
Transfusion
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Dependent upon:
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Recipient blood volume
Pretransfusion Hb level
Clinical condition (hemolysis, fluid balance, active bleeding)
Hb content of unit
With one RBC unit for average adult:
– Hemoglobin -  1 gm/dL
– Hemotocrit -  3%
– May take 24 hours to see full effect
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RBC transfusion suppresses recipient red cell
production!
Ordering only one unit of RBCs is ok!
What is the difference
between a Type & Screen
and Type & Cross?
The difference is…
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Type & Screen
– ABO type and antibody screen/identification
– Valid for 3 months if no transfusion or pregnancy
history
– Valid for 3 days if transfused or pregnant
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Type & Cross (Crossmatch)
– ABO type and antibody screen/identification
– Requested number of units crossmatched for patient
and taken out of inventory
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Should only be ordered if you anticipate transfusion!
Pre-Transfusion Testing
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ABO/Rh type – 5 minutes
Antibody screen – 25 minutes
Antibody identification – 1 hour or
much more
Time required for units
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Uncrossmatched Group O-neg RBCs - < 5
minutes
Uncrossmatched type specific RBCs – ~ 15
minutes
Crossmatched RBCs – 30-45 minutes
Full ABO type, screen & crossmatch – 1
hour
Patient with multiple alloantibodies – may
take many hours!
FFP – 30-45 minutes for thawing
Cryo – 15 minutes for thawing
When to order RBC units
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When you are ready to transfuse!
– After units are out of refrigeration they must be
transfused within 4 hours!
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To be returned to stock units must be out of refrigeration
< 30 minutes
Temperature must not be >10°C
– Many units are wasted because they are not
transfused in time
– If not ready just order a type & screen or type &
cross
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Cannot be re-issued if sterility compromised
How do you give an RBC
unit?
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23 gauge needle or larger (18 gauge
preferred)
Run at 2-5 mL/min
– Maximum time to transfuse 4 hours
– Vital signs within 15 minutes of start
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Compatible solutions
– 0.9% normal saline
Modified RBC units
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Leukocyte-reduced RBCs
– Pre-storage
– Post-storage (using issued filter)
– Indications:
Prevention of HLA alloimmunization
 Prevention of febrile non-hemolytic
transfusion reactions
 Prevention of CMV transmission
 Prevention of transfusion associated
immunosuppression
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Modified RBC units
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CMV negative RBCs
– Donor is seronegative for CMV
– Indications:
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Protect patient from severe CMV infection
Premature infants (<1200 gms) born to CMV seronegative
mothers
CMV-seronegative pregnant women
CMV-seronegative bone marrow and hematopoietic
progenitor cell or solid organ transplant recipients
CMV-seronegative patients who are severely
immunosuppressed
– **Leukocyte-reduced PRBCs are considered
equivalent to CMV seronegative units with regard to
risk of CMV transmission
Modified RBC units
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Washed RBCs
– 99% of plasma is removed
– Shelf life of 24 h after washing
– 180 ml and Hct 75%
– Indications:
History of severe or frequent allergic transfusion
reactions
 IgA deficiency
 Hyperkalemia, especially in a child or infant
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Modified RBC units
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Irradiated RBCs
– RBCs exposed to cesium
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Crosslinks T-lymphocyte DNA
– Prevents proliferation
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Changes expiration date to 28 days after
irradiation
– Indication:
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Prevention of transfusion-associated GVHD
Transfusion Associated
GVHD
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Partial match between recipient and
donor HLA type
– Donor lymphocytes aren’t recognized as
foreign, proliferate and attack the recipient
tissues
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Or due to severe immunosuppression in
recipient
Signs appear within 3-50 days
– fever, skin rash, diarrhea, marrow
aplasia
– mortality rate ~90%
Patients at risk for TAGVHD
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Congenital immunodeficiencies
Intrauterine transfusion
Recipients of blood from 1st degree
relatives or HLA “matched” units
Bone marrow or stem cell transplant
recipients
Hodgkin’s disease recipients
NOT indicated for HIV patients
Modified RBC units
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Frozen RBCs
– RBCs frozen in glycerol & stored up to 10
years
– Used to preserve rare blood types
– RBCs must be washed multiple times
prior to transfusion
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Expire 24 hours after thawing and washing
– VERY expensive
Platelets
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Whole blood derived platelets
– “Random donor platelets”
– 50 mL
– Dose
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10-15 mL/kg
4-6 units for an average adult
– Stored 5 days at room temperature with agitation
– Must transfuse within 4 hours after pooling
– Expected increment of 5-10K/μL/unit (or 20-60K/
μL/dose)
– $50/unit (max of $300/dose)
Platelets
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Apheresis platelets
– “Single donor platelets”
– Also referred to as
“Jumbo platelets”
– 100 mL
– Dose
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1 apheresis unit
Stored 5 days at room temperature with agitation
Expected increment of 30-40K/μL/dose (unit)
$500/unit!
Advantage = single donor
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Less infectious risk
Less risk of HLA alloimmunization
Platelets
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Express ABO antigens
– Will get best increment with ABO
compatible platelets
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DO NOT express Rh antigens
– Can give regardless of Rh type
– However, platelets contain a small
amount of RBCs
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Rh-negative woman of child-bearing age
should receive Rh negative platelets
Indications for Platelets
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Thrombocytopenia
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<10,000 in uncomplicated patients
<20,000 if febrile or septic
<50,000 if bleeding or undergoing major surgery
<100,000 for neurosurgery or ophthalmologic
procedures
Thrombocytopathy
– Congenital defects
– Drugs (ASA, Plavix)
– External agents (cardiac bypass or ECMO)
Failure of expected
platelet increment
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Consumption (after 24 hours)
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Fever
Infection
Drugs (Amphotericin)
Bleeding
Hepatosplenomegaly
DIC
Anti-HLA or platelet-antigen antibodies
(after 10-60 minutes)
Modified Platelet Units
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Washed platelets
Leukocyte-reduced platelets
Irradiated
Contraindications for
Platelets
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TTP/HUS
Heparin-induced thrombocytopenia
(HIT)
ITP (relative contraindication)
Uremia-related platelet dysfunction
– DDAVP
– Cryoprecipitate
– RBC transfusion (keep HCT > 30%)
Granulocytes
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Collected via apheresis
– Donor stimulated with dexamethasone & G-CSF
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250-300 mL
Should be given once daily for at least 5 days
Indications
– Persistent fever or infection not responding to antimicrobial
therapy
– Severe neutropenia (<500/μL)
– Reversible bone marrow hypoplasia
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Must have CMV-negative donor to prevent CMV
transmission
Must be given within 24 hours of collection
Fresh Frozen Plasma
(FFP)
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Whole blood plasma
– 200 -250 ml
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Also collected by apheresis = Jumbo FFP
– 400-600 mL
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All coagulation factors and other proteins
Stored frozen for 1 year
Dose
– 10-15 mL/kg
– 2-4 whole blood units OR 1-2 Jumbo FFP
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Expect 20-30% increase in all factor levels
Plasma Compatibility
Indications for FFP
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Coagulopathy due to multiple factor
deficiencies
– Liver disease
– Reversal of nutritional Vit K deficiency or
Warfarin overdose
– Massive transfusion
– TTP/HUS
– PT/PTT > 1.5 x normal
Cryoprecipitate
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Made from 1 unit partially thawed FFP
15 mL
Fibrinogen, factor VIII, VWF, factor XIII
Stored 1 year frozen, 6 hours thawed
If pooled must be given in 4 hours
Dose
– 1 unit/10 kg
– 10-20 units in average adult
Indications for cryo
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Fibrinogen deficiency
Von Willebrand's disease
Uremic thrombocytopathy
Factor XIII deficiency
Topical fibrin glue
**Not for replacement of Factor VIII!
Other products
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Albumin
Factor concentrates
– Factor VIII
– Factor IX
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IVIG
The number one risk of
transfusion is…
A.
B.
C.
D.
Hemolytic reaction
Infectious disease
TRALI
Circulatory Overload
The #1 infectious risk of
transfusion is…
A.
B.
C.
D.
E.
F.
Hepatitis B
Hepatitis C
HIV
Bacterial Contamination/Sepsis
HTLV 1/2
Malaria
Risks of Transfusion
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Infectious disease
– Units tested for HIV, Hep B, Hep C, syphilis,
WNV, HTLV, Chagas disease
HIV 1 : 2 million
 Hep C 1 : 2 million
 Hep B 1 : 250,000
 Bacterial infection of clinical importance
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– 1:25,000 for platelets
– 1:250,000 for RBCs
Transfusion Reactions
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STOP the transfusion
Send all tubing and a patient sample to the blood
bank
Labs
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Bilirubin
LDH
Haptoglobin
Urine hemoglobin
Blood Bank Work-up
– Clerical check & visual inspection
– Pre & Post transfusion ABO re-type (patient & unit)
– Pre & Post transfusion Direct Antiglobulin Test (Direct
Coomb’s)
Hemolytic Transfusion
Reaction
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Acute (within 24 hours) or delayed (within
several days)
Incompatible RBCs
– Due to ABO incompatibility (IgM) 
Intravascular hemolysis
– Due to alloimmunization from prior transfusion
and/or pregnancy (usually IgG) Extravascular
hemolysis
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Most common cause = clerical error
– Also low titer antibodies not detected on initial
screen (Rh and Kidd)
Pathophysiology
Hypotension
Vasoconstriction, renal
ischemia
Platelet activation
Hemolytic Transfusion
Reactions
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Signs and Symptoms:
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Fever, Chills/rigors
Anxiety
Flushing/Pallor
Chest/ abdominal/ back pain
N/V/D
Dyspnea
Hypotension
Hemoglobinuria
Jaundice
Oliguria/anuria
Pain or oozing at transfusion site
Hemolytic Transfusion
Reactions
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Treatment = supportive
– IV fluids for hypotension
– Diuretics - maintain urine output at 30100 mL/h
– Low dose dopamine (severe cases)
– Heparin
Hemolytic Transfusion
Reactions
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Prevention
– Blood type & antibody screen every 3 days
– Minimum of 2 identifiers used to ID patient (NOT
room number), initials of phlebotomist
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Labeling of specimen at bedside
– Maintain patient blood type & antibody history
records
– Barcoded bracelets, transfusion safety officers,
transfusion team
RBC Autoantibodies
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Antibodies that react with all RBCs,
including the patient’s own
– Causes: medications, autoimmune
disease, idiopathic
– May or may not be clinically significant
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Ordering RBCs
– Crossmatch will be positive
– Monitor closely for signs of hemolysis
Febrile Non-hemolytic
Transfusion Reactions
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Majority of transfusion reactions
Increase in temperature
– 1° C
– 2° F
– No other cause for fever
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All labs unchanged from pretransfusion
Febrile Non-hemolytic
Transfusion Reactions
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Pathophysiology
– Pyrogenic cytokines in cellular units
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Pre-transfusion
– WBCs in unit make cytokines during storage
– Platelets
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Post-transfusion
– Recipient anti-WBC antibody stimulates donor WBCs
– RBCs
Febrile Non-hemolytic
Transfusion Reactions
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Treatment
– Anti-pyretics
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Prevention
– Leukoreduced units
– Acetaminophen premedication*
Bacterial Contamination
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#1 infectious risk of transfusion
Mostly a problem with platelet units
– Gram positive cocci
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Rarely a problem with RBC units
– Yersinia enterocolitica most common
Bacterial Contamination
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Symptoms
– High fever/rigors (>2° F increase)
– Abdominal cramping/nausea/vomiting
– Shock
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Blood product may be discolored
Bacterial Contamination
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Treatment
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Stop transfusion
Culture patient and product bag
IV antibiotics
Pressor support
Prevention
– Proper phlebotomy technique at donation
– Careful donor history
– pH testing and/or culture of platelet units
Allergic Transfusion
Reactions
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45% of all transfusion reactions
More common with FFP
Symptoms
– Pruritus
– Urticaria
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Pathophysiology
– IgE in the patient reacts with donor plasma
proteins
– Donor plasma has IgE which reacts with patient
plasma proteins
Allergic Transfusion
Reactions
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Treatment
– Benadryl
– Corticosteroids
– The only reaction in which the transfusion
can be resumed
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Prevention
– Benadryl premedication*
– Washed RBCs/platelets
Anaphylactic Transfusion
Reactions
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More severe allergic reaction
Pathophysiology
– IgA deficient patients with anti-IgA
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Almost immediate reaction
– Clinical symptoms range from urticaria to shock
& cardiac arrest
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Treatment
– Epinephrine, corticosteroids
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Prevention
– Washed products
– IgA deficient products
Transfusion Associated
Circulatory Overload (TACO)
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1 in 100 transfusions
High volume or rate of transfusion exceeds ability of
patient’s cardiovascular system to handle additional
workload
– Underlying cardiovascular of pulmonary pathology
– Elderly
– Normovolemic anemia (thalassemia)
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Symptoms:
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Dyspnea, Orthopnea
Hypoxemia
Pulmonary edema
Hypertension (>50 mmHg increase in SBP)
Increased central venous pressure
Increased BNP
TACO
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Treatment
– Stop or slow rate of infusion
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Split unit into aliquots
Washed RBCs – less volume
– Diuretics
– Oxygen
– Supportive care
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Prevention
– Vigilant assessment of pt’s ins/outs
– Slow rates of infusion/aliquots
– Diuretics
Transfusion Related Acute
Lung Injury (TRALI)
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All components implicated
– FFP most commonly
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1 in 1000 transfusions
– Extremely underreported
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Pathophysiology
– Anti-HLA in donor plasma activates PMNs in
pulmonary capillaries of recipient 
capillary leakage
– Anti-HLA antibodies form after prior
transfusion or pregnancy
TRALI
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Symptoms
– Sudden new onset hypoxemia (O2 sat
<90%) or increased FiO2 requirement
– CXR with bilateral infiltrates (like ARDS)
– Absent signs of circulatory overload
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Pre/Post transfusion BNP ratio <2
– No preexisting lung injury or ARDS
– Onset within 6 hours of transfusion
TRALI
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Treatment
– Supportive measures
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Prevention
– Use of male plasma
– Defer implicated donors
Test donor for anti-HLA antibodies
 Compare to HLA type of patient
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Other complications of
transfusion
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Alloimmunization
– 18-47% in sickle cell patients
– 5-11% in thalassemia patients
– 20% without underlying hematologic/oncologic disease
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Iron overload
Metabolic abnormalities
– Hypocalcemia
– Hyperkalemia
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Coagulopathy
Hypothermia
GVHD
Take Home Points…
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While extremely safe when used
appropriately, transfusion is still not
without risk.
Know what you are ordering and the
implications of your orders.
Blood is not a limitless resource!
Don’t make assumptions…call the
blood bank!