Transcript transfusion reactions

TRANSFUSION
Wei Mei
Department of Anesthesiology
Tongji Hospital
HISTORY OF BLOOD
TRANSFUSION
The first “modern” transfusion is attributed to
John Syng Physick in Philadelphia in 1795
 In 1900, Karl Landsteiner significantly advanced
the cause of blood compatibility with his
landmark discovery of the ABO blood groups

STORAGE OF BLOOD
 The
use of citrate to anticoagulate stored
blood by means of calcium chelation was a
landmark
 The first blood depots were established
during the First World War by the British
and were stocked prior to major
campaigns
 The Soviets established the first
permanent blood bank in a Leningrad
hospital in 1932
CLINICALLY AVAILABLE
BLOOD PRODUCTS
DIFFERENTIAL CENTRIFUGATION
FIRST CENTRIFUGATION
Closed System
Whole
Blood
Main Bag
RBC’s
Satellite
Bag
1
First
Platelet-rich
Plasma
Satellite
Bag
2
DIFFERENTIAL CENTRIFUGATION
SECOND CENTRIFUGATION
RBC’s
RBC’s
Plateletrich
PlasmaSecond
Platelet
Concentrate
Plasma
WHOLE BLOOD
A
unit of whole blood is collected in
citrate-phosphate-dextrose-adenine 1
(CPDA-1) anticoagulant, giving it a shelflife of 35 days and a volume of
approximately 510 mL (450 mL of blood
plus 63 mL of CPDA-1)
 Within 24 hours of collection, the platelets
are dysfunctional, and several plasma
coagulation factors are below optimal
levels, emphasizing the importance of the
component products despite the
disadvantage of increased donor exposure
COMPONENT PRODUCTS
Red cells for oxygen-carrying capacity
 Plasma for coagulation proteins
 Platelets for thrombocytopenia or platelet
dysfunction

RED CELL CONCENTRATES
Red cell concentrates, or packed red blood cells
(PRBCs), are obtained from CPDA-1anticoagulated whole blood after centrifugation of
most of the plasma and platelets
 The red cells are mixed with 100 mL of an
additive nutrient that extends the storage period
to 42 days and results in flow properties similar
to those of whole blood
 Current standards requiring 75% of transfused
cells to survive in the circulation for 24 hours

1
unit of packed RBCs will increase
hematocrit value by 3% to 5%
LEUKOCYTE-REDUCED RED CELLS
Leukocyte-reduced red cells (LRRCs) can be
prepared by a variety of methods, with varying
efficiency of white cell removal
 The minimum standard,established by the
American Association of Blood Banks (AABB), is
a leukocyte number in the final component of <5
× 10

WASHED RED CELLS
 Red
cells are washed using isotonic saline
solutions with some degree of red cell loss
with each wash cycle
 The primary aim of washing is to remove
plasma proteins to prevent severe allergic
transfusion reactions mediated by
recipient antibodies (most likely IgE) to
donor plasma proteins or preformed
antibodies to IgA in donor plasma, which
can cause anaphylaxis in IgA-deficient
patients
FROZEN RED CELLS
Red cells can be frozen (with glycerol used as a
cryoprotective agent) and stored in liquid
nitrogen or mechanical freezers
 Frozen red cells need to be transfused within 24
hours; posttransfusion survival rate is 85–90%

PERIOPERATIVE PERIOD
 With
gradual onset, the body’s
compensatory mechanisms for
maintaining oxygen delivery to the tissues
are effective
 The signs and symptoms of anemia
develop at a Hgb level of <7–8 g/dL
 National Institutes of Health suggest that
most surgical patients who are not
actively bleeding do not need transfusion
unless the Hgb level decreases to <7 g/dL
PERIOPERATIVE PERIOD
 Blood
losses of 5–10% of total blood
volume require minimal replacement
therapy
 Losses of up to 20% can be replaced
exclusively with volume expansion
 Losses of >25% generally require red cell
transfusion to restore oxygen-carrying
capacity, along with volume expansion to
restore intravascular volume and
maintain perfusion
AMERICAN SOCIETY OF
ANESTHESIOLOGISTS GUIDELINES
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1. Transfusion is rarely indicated when the hemoglobin
concentration is greater than 10 g/dL and is almost always
indicated when it is less than 6 g/dL, especially when the
anemia is acute
2. The determination of whether intermediate hemoglobin
concentrations (6 to 10 g/dL) justify or require RBC
transfusion should be based on the patient's risk for
complications of inadequate oxygenation
3. The use of a single hemoglobin “trigger” for all patients
and other approaches that fail to consider all important
physiologic and surgical factors affecting oxygenation is not
recommended
4. When appropriate, preoperative autologous blood
donation, intraoperative and postoperative blood recovery,
acute normovolemic hemodilution, and measures to decrease
blood loss (i.e., deliberate hypotension and pharmacologic
agents) may be beneficial
5. The indications for transfusion of autologous RBCs may
be more liberal than those for allogeneic RBCs because of less
frequent (but still significant) risks associated with the former
SAFETY OF BLOOD TRANSFUSION
Transfusion safety relies on the avoidance of
transfusion reactions
 The single most important contribution to
transfusion safety is uncompromising attention
to all details of patient, sample, and blood
product identification

RED BLOOD CELL COMPATIBILITY
Compatibility differs with components, as whole
blood contains all components, packed red cells
contain minimal plasma and antibodies
 Donor antibodies are present in FFP, which is a
component of platelet products; cryoprecipitate
does not contain donor antibodies
 ABO compatibility may increase the life span of
transfused platelets, and platelet units with high
plasma volume should be ABO matched like FFP
to avoid hemolysis of recipient native red cells
 Patients with blood group O express the H
antigen on the red cell surface but anti-H is very
rare

COMPATIBILITY TESTING
The ABO-Rh type, Crossmatch, and antibody
screen are frequently referred to as compatibility
tests
 These tests were designed to demonstrate
harmful antigen-antibody interactions in vitro so
that harmful in-vivo antigen-antibody
interactions could be prevented

ABO TYPING
Blood Group Red cells tested with
Serum tested with
Anti-A
Anti-B
A cells
B cells
A
+
-
-
+
B
-
+
+
-
AB
+
+
-
-
O
-
-
+
+
RH(D) ANTIGEN
 The
only additional required testing is
that for the Rh(D) antigen
 Sixty to 70 percent of Rh(D)-negative
recipients are immunized (produce anti-D)
if they are given blood transfusions with
Rh(D)-positive blood
 About 85% of individuals possess the D
antigen and are classified as Rh(D)
positive; the remaining 15%, who lack the
D antigen, are classified as Rh(D)
negative
CROSS-MATCHING
A
crossmatch is essentially a trial
transfusion within a test tube in which
donor RBCs are mixed with recipient
serum to detect a potential for serious
transfusion reaction
 The crossmatch can be completed in 45 to
60 minutes and is carried out in three
phrases: an immediate phase, an
incubation phase, and an antiglobulin
phase
ANTIBODY SCREENING
 The
screen is a trial transfusion between
the recipient's serum and commercially
supplied RBCs that are specifically
selected to contain optimal numbers of
RBC antigens or those antigens that will
react with antibodies that are commonly
implicated in hemolytic transfusion
reactions
 It is necessary to screen donor serum for
unexpected antibodies to prevent their
introduction into the recipient serum.
This screen is performed primarily to
prevent reactions between transfused
donor units
ABO COMPATIBILITY OF BLOOD
PRODUCTS
EMERGENCY TRANSFUSION
ABO-Rh typing alone results in a 99.8% chance of
a compatible transfusion, the addition of an
antibody screen increases the safety to 99.94%,
and a crossmatch increases this to 99.95%
 The preferred order for the selection of partially
crossmatched blood

TYPE-SPECIFIC, PARTIALLY
CROSSMATCHED BLOOD
 When
using uncrossmatched blood, it is
best to obtain at least an ABO-Rh typing
and an immediate-phase crossmatch
 This incomplete crossmatch is
accomplished by adding the patient's
serum to donor RBCs at room
temperature, centrifuging it, and then
reading it for macroscopic agglutination.
 This takes 1 to 5 minutes and eliminates
serious hemolytic reactions resulting from
errors that may occur in ABO typing
TYPE-SPECIFIC, UNCROSSMATCHED
BLOOD
For those who have never been exposed to foreign
RBCs, most ABO type-specific transfusions are
successful
 Caution should be used for patients who have
previously received transfusions or have had
pregnancies

TYPE O RH-NEGATIVE (UNIVERSAL
DONOR), UNCROSSMATCHED
BLOOD
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People with type O blood have been called universal
donors and their blood can be used in emergency
transfusions when typing or crossmatching is not
available
Some type O donors produce high titers of hemolytic
IgG, IgM, anti-A, and anti-B antibodies
Type O Rh-negative, uncrossmatched packed RBCs
should be used in preference to type O Rh-negative
whole blood because packed erythrocytes have
smaller volumes of plasma and are almost free of
hemolytic anti-A and anti-B antibodies
During emergency transfusion of more than two units
of type O Rh-negative, uncrossmatched whole blood,
the patient probably cannot be switched to his or her
blood type (A, B, or AB) as soon as the blood bank
determines the correct blood type
SPECIFIC RECOMMENDED
PROTOCOL
 Infuse
crystalloids or colloids.
 Draw a blood sample for typing and
crossmatching.
 If crossmatched blood is not ready to give,
use type-specific or type O Rh-negative
cells or type O Rh-positive cells for males
or postmenopausal females without a
history of transfusions; type-specific,
partially crossmatched blood; or typespecific, uncrossmatched blood
COMPLICATIONS
 Changes
in Oxygen Transport
 Coagulation
 Dilutional Thrombocytopenia
 Low Levels of Factors V and VIII
 Disseminated Intravascular Coagulationlike Syndrome (DIC)
 Citrate Intoxication and Hyperkalemia
 Temperature
 Acid-Base Abnormalities
TRANSFUSION REACTIONS
Hemolytic Transfusion Reaction
 Delayed Hemolytic Transfusion Reaction
(Immune Extravascular Reaction)
 Nonhemolytic Transfusion Reactions

HEMOLYTIC TRANSFUSION REACTION
The classic signs and symptoms of a hemolytic
transfusion reaction—chills, fever, chest and
flank pain, and nausea—are masked by
anesthesia
 Under general anesthesia, the only signs may be
hemoglobinuria, bleeding diathesis, or
hypotension

FREQUENCY AND SIGNS AND SYMPTOMS OF
HEMOLYTIC TRANSFUSION REACTIONS IN 40
PATIENTS
HAPTOGLOBIN
RENAL SYSTEM

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Although there are several consequences of intravascular
hemolysis, mainly the renal and coagulation systems are
affected
The exact cause of acute renal failure from intravascular
hemolysis is controversial, but the most common
hypothesis is that hemoglobin in the form of acid hematin
precipitates in the distal tubule and causes mechanical
tubular blockage.
The magnitude of the precipitation probably is inversely
related to the volume of urine flow and its pH
The primary emphasis of therapy should be directed
toward maintaining urinary output in excess of 75 mL/hr
by generous administration of intravenous fluids and
diuretics
Alkalinization of the urine to prevent precipitation of acid
hematin in the distal tubules is of questionable value but is
easy and therefore recommended
COAGULATION SYSTEM
DIC commonly occurs with hemolytic transfusion
reactions, probably because RBC stroma is
severed, releasing erythrocytin, which activates
the intrinsic system of coagulation
 This activated coagulation leads to fibrin
formation
 Subsequently, platelets and factors I, II, V, and
VII are consumed
 Hypotension during a hemolytic transfusion
reaction may result from activation of the
kallikrein system.[69] After a series of reactions,
plasma kininogen is converted to bradykinin, a
potent vasodilator that can cause hypotension.

DIAGNOSIS
If a hemolytic reaction is suspected, blood and
urine samples should be sent to the laboratory for
examination. The blood bank should check all
paperwork to ensure that the correct blood
component was transfused to the patient
 Laboratory tests should be performed to
determine the presence of hemoglobinemia: a
direct antiglobulin test, repeat compatibility
testing, repeat other serologic tests (i.e., ABO and
Rh), and analysis of urine for hemoglobinuria
 As soon as a hemolytic transfusion reaction is
recognized, platelet count, prothrombin time, and
partial thromboplastin time should be
determined to provide baseline values with which
subsequent laboratory values can be compared

STEPS IN THE TREATMENT OF A
HEMOLYTIC TRANSFUSION
REACTION
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1. STOP THE TRANSFUSION.
2. Maintain the urine output at a minimum of 75 to 100 mL/hr by
the following methods:
a. Generously administer fluids intravenously and possibly
mannitol (12.5 to 50 g, given over 5 to 15 minutes).
b. If intravenously administered fluids and mannitol are
ineffective, administer furosemide (20 to 40 mg) intravenously.
3. Alkalinize the urine; because bicarbonate is preferentially
excreted in the urine, only 40 to 70 mEq of sodium bicarbonate
per 70 kg of body weight is usually required to raise the urine pH
to 8, whereupon repeat urine pH determinations indicate the
need for additional bicarbonate.
4. Assay urine and plasma hemoglobin concentrations.
5. Determine platelet count, partial thromboplastin time, and
serum fibrinogen level.
6. Return unused blood to blood bank for repeat crossmatch.
7. Send patient's blood and urine sample to blood bank for
examination.
8. Prevent hypotension to ensure adequate renal blood flow.
DELAYED HEMOLYTIC
TRANSFUSION REACTION
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Immune Extravascular Reaction
Donor cells may survive well initially, but after a
variable delay (2 to 21 days) they are hemolyzed
Occurs mainly in recipients sensitized to RBC
antigens by previous blood transfusions or pregnancy
level of antibody at the time of transfusion is too low
to be detected or too low to cause RBC destruction
RBC destruction occurs only when the level of
antibody is increased after a secondary stimulus (i.e.,
anamnestic response)
Antibodies most commonly involved in delayed
hemolytic reactions are those in the Rh and Kidd
systems rather than the ABO system
Delayed hemolytic reaction may not be preventable
NONHEMOLYTIC TRANSFUSION
REACTIONS
Usually are not serious and are febrile or allergic
in nature
 Febrile reactions
 Allergic reactions

FEBRILE REACTIONS
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The symptoms consist of chills, fever, headache, myalgia,
nausea, and nonproductive cough occurring shortly after
blood transfusion
Less frequently, the patient may have hypotension, chest
pain, vomiting, and dyspnea
Even pulmonary infiltrations with x-ray evidence of
prehilar nodule formation and lower lung infiltrates along
with overt pulmonary edema have been reported
Caused by pyrogenic cytokines and intracellular contents
released by donor leukocytes
Use of leukoreduced blood will reduce the incidence of
febrile reactions
A direct antiglobulin test readily differentiates a hemolytic
reaction from a febrile reaction because this test rules out
the attachment of an RBC antibody to transfused donor
RBCs
There is no clear consensus on whether the transfusion
should be terminated when a febrile reaction occurs
ALLERGIC REACTIONS
Can be minor, anaphylactoid, or anaphylactic
 Anaphylactoid is similar to anaphylaxis clinically
but are not mediated by IgE
 Most allergic transfusion reactions are minor and
are thought to be caused by the presence of
foreign protein in the transfused blood
 The most common symptom is urticaria
associated with itching
 When these reactions are clearly not a serious
hemolytic reaction, the transfusion does not need
to be discontinued
 Antihistamines are used to relieve the symptoms
of the allergic reaction

ANAPHYLAXIS
A more severe form of allergic reaction involving
anaphylaxis occurs in which the patient has
dyspnea, hypotension, laryngeal edema, chest
pain, and shock
 These are anaphylactic reactions caused by the
transfusion of IgA to patients who are IgA
deficient and have formed anti-IgA
 This type of reaction does not involve red cell
destruction and it occurs very rapidly, usually
after the transfusion of only a few milliliters of
blood or plasma
 The patients who experience these anaphylactic
reactions can be given transfusions with washed
RBCs from which all traces of donor IgA have
been removed or with blood lacking the IgA
protein

ACUTE TRANSFUSION REACTIONS

1.
2.
3.
4.
5.

1.
2.
3.
4.
5.
Immune mediated
Acute hemolytic transfusion reaction (AHTR)
Transfusion-related acute lung injury
Febrile nonhemolytic transfusion reaction
Urticarial reaction
Anaphylactic
Nonimmune mediated
Nonimmune hemolysis
Bacterial contamination
Volume overload
Metabolic
Embolic
DELAYED TRANSFUSION REACTIONS

1.
2.
3.

1.
2.
Immune mediated
Delayed hemolytic transfusion reaction (DHTR)
Posttransfusion purpura
Graft-versus-host disease
Nonimmune mediated
Transfusion-transmitted infection
Iron overload
INFECTIVITY OF BLOOD
Hepatitis B
 Hepatitis C
 Acquired Immunodeficiency Syndrome
 Human T-Cell Lymphotropic Virus Type 1
 Cytomegalovirus
 Other Transfusion-Associated Infectious Diseases

OTHER ADVERSE EFFECTS OF
BLOOD TRANSFUSION
Transfusion-Associated Graft-versus-Host
Disease
 Transfusion-Related Acute Lung Injury
 Adverse Ocular Reaction
 Transfusion-Related Immunomodulation

TRANSFUSION-ASSOCIATED
GRAFT-VERSUS-HOST DISEASE
Transfusion-associated graft-versus-host disease
is caused by engraftment of donor lymphocytes
from transfused blood products, initiating an
immune reaction against recipient tissues
 Severely immunocompromised patients are at
risk
 Directed donations from first- or second-degree
relatives are at risk because transfused
lymphocytes with shared HLA haplotypes cannot
be recognized and eliminated
 A generalized rash, leukopenia, and
thrombocytopenia occur
 Sepsis and death usually result
 Irradiation of blood can prevent transfusionassociated graft-versus-host disease from
occurring

TRANSFUSION-RELATED ACUTE
LUNG INJURY
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TRALI is now the leading cause of transfusion-related
mortality
Manifests as noncardiogenic pulmonary edema
Clinically, symptoms and signs appear 1 to 2 hours after
transfusion and are in force within 6 hours
Fever, dyspnea, fluid in the endotracheal tube, and severe
hypoxia are typical
During anesthesia, a persistent decrease in blood oxygen
saturation can be the presenting sign
Chest radiograph is characteristic of pulmonary edema,
circulatory overload (i.e., left atrial hypertension) is not
present
All blood components, especially FFP, are implicated as
caustic factors
There is no specific therapy other than stopping the
transfusion and instituting critical care supportive
measures
Most patients recover in 96 hours, although TRALI
remains the leading cause of transfusion-related death
BLOOD COMPONENT THERAPY
Packed Red Blood Cells
 Platelet Concentrates
 Fresh Frozen Plasma
 Cryoprecipitate
 Prothrombin Complex

PACKED RED BLOOD CELLS
PLATELET CONCENTRATES
If platelets are stored at room temperature, they
are satisfactory to use 7 days after collection with
constant and gentle agitation
 Bacterial contamination, mainly from platelet
concentrates, is the third leading cause of
transfusion-related deaths
 The estimated incidence of bacterial
contamination of platelets was about 1 case in
2,000
 For any patient who develops a fever within 6
hours after receiving platelets, sepsis from
platelets should be considered
 Presently, platelet concentrates are routinely
tested for bacteria and are the only blood product
that is stored at room temperature

PLATELET CONCENTRATES
 Platelets
chosen for transfusion probably
will continue to be chosen without regard
to antigen systems
 Under ideal circumstances, one platelet
concentrate usually produces an increase
of about 7000 to 10,000 platelets/mm3 at 1
hour after transfusion to the 70-kg adult
 Many factors, including splenomegaly,
previous sensitization, fever, sepsis, and
active bleeding, may lead to decreased
survivals and decreased recovery of
transfused platelets
ASA
RECOMMENDATIONS
 Prophylactic platelet transfusion is ineffective and rarely
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indicated when thrombocytopenia is due to increased platelet
destruction (e.g., idiopathic thrombocytic purpura)
Prophylactic platelet transfusion is rarely indicated in surgical
patients with thrombocytopenia due to decreased platelet
production when the platelet count is greater than 100 × 109/L
and is usually indicated when the platelet count is less than 50
× 109/L. The determination of whether patients with
intermediate platelet counts (50 to 100 × 109/L) require therapy
should be based on the patient's risk of bleeding
Surgical and obstetric patients with microvascular bleeding
usually require platelet transfusion if the platelet count is less
than 50 × 109/L and rarely require therapy if it is greater than
100 × 109/L. With intermediate platelet counts (50 to 100 ×
109/L), the determination should be based on the patient's risk
for more significant bleeding
Vaginal deliveries or operative procedures ordinarily associated
with insignificant blood loss may be undertaken in patients with
platelet counts less than 50 × 109/L
Platelet transfusion may be indicated despite an apparently
adequate platelet count if there is known platelet dysfunction
and microvascular bleeding
FRESH FROZEN PLASMA
It contains all the plasma proteins, particularly
factors V and VIII, which gradually decline
during the storage of blood
 The major risk is transmission of infectious
diseases, such as hepatitis B, hepatitis C, and
AIDS
 Other risks include sensitization to foreign
proteins

ASA GUIDELINES
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1. For urgent reversal of warfarin therapy
2. For correction of known coagulation factor deficiencies for
which specific correlates are unavailable
3. For correction of microvascular bleeding in the presence of
increased (>1.5 times normal) prothrombin time(PT) or partial
thromboplastin time(PTT)
4. For correction of microvascular bleeding secondary to
coagulation factor deficiency in patients transfused with more
than 1 blood volume and when PT and PTT cannot be obtained in
a timely fashion
5. FFP should be given in doses calculated to achieve a
minimum of 30% of plasma factor concentration (usually achieved
with administration of 10 to 15 mL/kg of FFP), except for urgent
reversal of warfarin anticoagulation, for which 5 to 8 mL/kg of
FFP usually suffice. Four to five platelet concentrates, 1 unit of
single-donor apheresis platelets, or 1 unit of whole blood provides
a quantity of coagulation factors similar to that contained on 1
unit of FFP (except for decreased, but still hemostatic,
concentrations of factors V and VIII in whole blood)
6. FFP is contraindicated for augmentation of plasma volume or
albumin concentration
THE ONLY INDICATIONS FOR FFP
ADMINISTRATION (ASA)
1. Replacement of isolated factor deficiencies
(as documented by laboratory evidence)
 2.
Reversal of warfarin effect
 3.
In cases of antithrombin III deficiency
 4.
Treatment of immunodeficiencies
 5.
Treatment of thrombotic thrombocytopenia
purpura
 6.
Massive blood transfusion (rarely and only
when factors V and VIII are less than 25% of
normal)
 7.
Requirements for indications 1 and 6 are
prothrombin and partial thromboplastin times at
least 1.5 times longer than normal.

CRYOPRECIPITATE
Contains significant levels of factor VIII and
fibrinogen
 Also contains von Willebrand factor and
fibronectin
 All other plasma proteins are present in only
trace amounts
 Cryoprecipitate is frequently administered as
ABO compatible
 Cryoprecipitate should be administered through
a filter and as rapidly as possible (at least
200 mL/hr )
 The use of cryoprecipitate in the treatment of
factor VIII deficiency or hemophilia A

INFORMED CONSENT
Before any transfusion is given, informed consent
should be obtained from the patient or guardian
 A dramatic example was the passage of the Paul
Gann Blood Safety Act in California. This law
mandates that patients be informed of the risks
of blood transfusions and of any alternatives
