Download Transfusion reaction after cross-match

Transfusion reaction after cross-match
Dr.R.Muthukumaran M.D.,D.A., Professor Of Anaesthesiology., Thanjavur Medical College.,
Thanjavur.
Acute transfusion reactions range from bothersome yet clinically benign to life-threatening
reactions. The nature of the reaction may not be immediately apparent, because many reactions
begin with nonspecific symptoms such as fever or chills. In addition, patients receiving
transfusions often have complex underlying clinical conditions, the symptoms of which may
mimic a transfusion reaction. Thus, a patient experiencing symptoms or signs consistent with an
acute transfusion reaction must be evaluated promptly, with input from the transfusion service,
and treated as expeditiously as possible to minimize the impact of the reaction.
The causes of a suspected acute transfusion reaction of red blood cells, platelets, or plasma are,
●Volume overload – Transfusion Associated Circulatory Overload (TACO)
●Acute lung injury – Transfusion-Related Acute Lung Injury (TRALI)
●Febrile Non-Hemolytic Transfusion Reactions – Immunologic reactions (FNHTR)
●Sepsis – Transfusion-transmitted bacterial infection
●Urticaria – Immunologic blood transfusion reactions, Urticarial (allergic) reactions
●Anaphylaxis – Immunologic blood transfusion reactions, Anaphylactic reactions
●Acute hemolysis – Transfusion-associated immune and non immune-mediated hemolysis
Delayed transfusion reactions, which may occur in the days to weeks following a transfusion, are
●Delayed hemolysis – Immunologic blood transfusion reactions
●Thrombocytopenia – Immunologic blood transfusion reactions, Post-transfusion purpura
●Graft-versus-host disease – Transfusion-associated graft-versus-host disease
Reactions to other plasma-derived products, such as intravenous immune globulin (IVIG)
Frequency of Acute transfusion reactions (ATRs) is as follows
●Common reactions:
•Urticaria – 1 to 3%
•FNHTR – 0.1 to 1%. The frequency of FNHTR is higher with platelet transfusion than with red
blood cell (RBC) transfusion; and less with leuko reduced products.
●Relatively common reactions:
•TACO – <1 %
•TRALI – <0.01%
●Relatively rare reactions:
•Anaphylaxis – 1:20,000 to 1:50,000.
•Acute hemolytic transfusion reaction (AHTR) – 1:76,000, all occurring with RBC transfusion.
•Sepsis – 1:50,000 for platelets; 1:5,000,000 RBCs.
●Frequency too rare to calculate:
•Primary hypotensive reactions associated with angiotensin converting enzyme [ACE] inhibitors.
•Non-immune hemolysis.
•Air embolus.
The severity of ATRs also varies, although the discomfort of the patient may not always parallel
the risk of adverse outcomes. Potentially fatal acute reactions include TRALI, TACO, AHTR,
sepsis, and anaphylaxis. Relatively benign reactions include urticaria, hypothermia,
hypocalcemia, non-immune hemolysis, and FNHTR. Importantly, early signs and symptoms of
an ATR may not distinguish between benign and more serious transfusion reactions; so all ATRs
must be considered potentially serious and evaluated.
Mortality from acute transfusion reactions is a rare event, and mortality rates may differ
depending on the patient population and local transfusion practices. The reactions associated
with the greatest number of deaths were TRALI and AHTR. Limiting the use of FFP to male
donors and bacterial detection of apheresis platelets, have reduced the overall mortality rates.
The ATRs in decreasing order of fatality are TRALI, TACO, AHTR, sepsis, and anaphylaxis.
Transfusion-associated graft-versus-host disease (ta-GVHD) is mostly fatal.
An ATR should be considered when adverse signs and symptoms arise during or within 24 hours
after completion of a transfusion. Severe reactions occur mostly within the first 15 minutes of
transfusion.
The most common signs and symptoms are fever (a 1°C rise in temperature above baseline),
chills, pruritus, and urticaria. Often these resolve promptly without specific treatment. Other
findings indicating a more severe, potentially fatal reaction include respiratory distress,
hemoglobinuria, loss of consciousness, hypertension, hypotension, flank or back pain, jaundice,
abnormal bleeding, and mental status changes, including feelings of anxiety and/or dread or
oliguria/anuria. Disseminated bleeding or oozing from intravenous sites may be the only
indication that an anesthetized patient is experiencing an ATR.
The possibility of ATR in an anesthetized patient should be considered if the patient develops
fever, hypotension, wheezing, hypoxia, hives/angioedema, hemoglobinuria, oliguria/anuria, or
disseminated bleeding, including oozing from intravenous sites.
Steps to be taken without delay in a patient with a suspected ATR:
●Immediately stop the transfusion; save the remaining blood, bag and tubing for analysis.
●Maintaine a patent intravenous line with normal saline.
●Check the product labeling and patient identification to rule out swapping; also assess the
product for gross color changes or bubbles suggestive of bacterial contamination.
●Assess the patient, including symptoms of ATR; measure vital signs; perform a limited
physical examination guided by symptoms.
●Contact the transfusion service to discuss the appropriate evaluation and initial management.
If the check reveals that the patient received an incorrect product, the transfusion service must be
notified urgently because another patient may also be at risk of receiving an incorrect product.
The transfusion service needs the remaining (untransfused) component (bags and tubing) and
blood and urine samples of patient for testing.
Transfusion of the remaining product or another product is usually deferred until a preliminary
evaluation has been conducted. If the symptoms subside and the correct product is confirmed, a
decision regarding administration of further transfusions must be reached.
Reactions in which further transfusion of the same product include urticaria without other
allergic symptoms, fever due to an underlying illness rather than the transfusion, and TACO that
has resolved with diuresis or other measures. Transfusion of the original product should not be
continued in cases of suspected AHTR, anaphylaxis, sepsis, or TRALI.
Decisions regarding the need for additional transfusions of products other than the one associated
with the reaction depend on the original indication for the transfusion.
The clinical history and patient assessment are used to diagnose the type of reaction(s).
Subsequent laboratory testing and response to interventions help to confirm or refute the
suspected diagnosis.
Fever/chills — Fever (increase in temperature of >1°C), with or without a chill, is a critical sign
of an ATR. Fever/chills suggest an AHTR, a septic transfusion reaction, TRALI, or a FNHTR.
AHTR, sepsis, and TRALI are potentially fatal; FNHTR is less serious but is for the most part a
diagnosis of exclusion. Fever may be a component of the patient's underlying illness. ATRs not
accompanied by fever include: urticaria, anaphylaxis, primary hypotensive reactions caused by
ACE inhibitors, and TACO. Non-immune hemolysis, air embolus, hypocalcemia, and
hypothermia also generally are not associated with fever or chills.
●AHTR often presents with fever as the first sign of the reaction; therefore, hemolysis must be
excluded by a check for the appropriateness of transfused product for the patient and by
laboratory evaluation for hemolysis; this evaluation must go simultaneously with consideration
of other potential transfusion reactions also associated with fever (eg, TRALI, sepsis).
●Sepsis from a transfused product often presents initially with fever; sepsis occurs commonly
with platelet transfusion but can also be associated with RBCs or plasma. The product inspected
for signs of bacterial contamination including cloudiness, and microbiological testing done to
detect and identify organisms present.
●TRALI is often associated with fever and respiratory distress and a new infiltrate on chest
radiography.
●Fever with a chill is often a hallmark of a FNHTR.
Patients with a feeling of warmth or chills without a >1°C increase in temperature should be
observed for 15 to 30 minutes while the intravenous line is kept open with normal saline. If
symptoms subside, transfusion may be restarted slowly.
Hypothermia is seen in recipients of large volumes of refrigerated blood products. Patients with
hypothermia feel cold but generally don’t have shaking chills. Warming the patient and/or the
blood product improves patient’s condition.
Respiratory distress — characterizes TACO, TRALI, and anaphylaxis. TACO and TRALI may
be difficult to differentiate because they both present with pulmonary edema. In addition, TACO
and TRALI can occur simultaneously. Distinguishing features between TRALI and TACO are,
●TACO is more often characterized by hypertension, while TRALI is often associated with
hypotension.
●The PAWP is usually elevated in TACO but not in TRALI.
●TRALI is more often accompanied by fever.
Anaphylaxis can be distinguished from TRALI and TACO by the rapidity of its onset, usually
within the first few moments of starting a transfusion. Anaphylaxis is characterized by
bronchospasm (with wheezing and respiratory distress), urticaria and angioedema, all of which
are absent in TRALI and TACO. Anaphylaxis may be associated with hypotension.
Respiratory distress may be due to an air embolism, a rare occurrence.
Hypotension (>20 mmHg) is characteristic of AHTR, TRALI, and sepsis. Hypotension may also
be due to blood loss. Intra-operative bleeding should be assessed. Each of these hypotensive
transfusion reactions has characteristic clinical and laboratory findings, making discrimination
among them relatively easy in most cases:
●AHTR may be accompanied by fever, chills, back pain, pain along the infusion vein, and
disseminated bleeding/oozing from intravenous catheters. Dark urine and/or oliguria may also
occur, but these are often seen later in the course of the reaction (eg, hours later). Laboratory
evaluation will show evidence of intravascular hemolysis.
●TRALI is accompanied by fever/chills, respiratory distress, rales on lung exam, and
hypoxemia; chest radiography shows bilateral pulmonary edema.
●Sepsis may be accompanied by fever/chills, and other findings of shock. Laboratory evaluation
will reveal the infectious organism, although this may take hours to days.
Additional, less-common causes of hypotensive reactions include air embolism and ACE
inhibitor medications. ACE inhibitor reactions are rare. (ACE inhibition in combination with
increased bradykinin levels in the transfused product). Withholding the ACE inhibitor for 24
hours prior to transfusion decreases this risk.
Laboratory testing — Individuals with urticaria alone, increase in temperature of <1°C, fever
related to the patient's underlying illness, and TACO may not require laboratory evaluation. In
contrast, all patients with suspected AHTR, anaphylaxis, sepsis, and TRALI will require
laboratory or other testing (eg, chest radiography).
Samples for evaluating a suspected transfusion reaction should be accompanied by information
regarding the patient and the reaction. Relevant information about the patient includes:
●Unique patient identifying information
●Underlying diagnosis and reason for the transfusion
●Recent febrile course
●Previous transfusion reactions
●Administration of any pre-transfusion medications (eg, acetaminophen, antihistamines,
glucocorticoids) or new medications (to which the patient might have an allergic reaction)
Important information about the reaction includes:
●Time of initiation of the transfusion
●Time of beginning of symptoms
●Time of stopping the transfusion
●Patient’s symptoms
●Patient’s vital signs
The blood/component container and associated tubings must be sent to the transfusion service
and/or hospital laboratory.
The hospital blood bank or laboratory will do the following within minutes:
●Check the component container, label, paperwork, and initial patient sample used for typing
and cross-matching
●Repeat ABO testing on the post-transfusion patient sample
●A visual check of both pre-and post-transfusion patient samples for evidence of hemolysis
●A direct antiglobulin (Coombs) test (DAT) on the post-transfusion patient sample
Exceptions include settings in which a specific type of non-hemolytic reaction is occurring (eg,
anaphylaxis, TACO or TRALI).
Additional testing and preliminary management will depend on the type of reaction suspected.
Stabilize the patient simultaneously. None of the urgent interventions needed to stabilize the
patient will interfere with the evaluation and in some cases, response to these interventions may
help in diagnosis by improving patient symptoms (eg, diuresis for presumed TACO; epinephrine
for presumed anaphylactic reaction). Symptomatic treatment is initiated while awaiting results
of laboratory testing. The aggressiveness of interventions depends on the severity of the reaction
and the suspected diagnosis.
Suspected AHTR — initiate aggressive hydration. Aggressive hydration is used to minimize
complications of free hemoglobin in the circulation, which may include acute kidney injury;
disseminated intravascular coagulation; and symptoms of vasospasm (eg, chest pain). Hydration
with normal saline should be used to maintain renal output of >1 mL/kg/hour; use an intravenous
diuretic such as furosemide. If DIC is suspected, additional blood component transfusion may be
necessary, including platelets, plasma, and/or cryoprecipitate, depending on the degree of
bleeding and laboratory findings.
If the diagnosis of AHTR is less clear, obtain laboratory testing first and begin vigorous
hydration only if laboratory testing is positive.
Laboratory testing for AHTR includes the following, which is done in consultation with the
transfusion service:
●Repeat ABO compatibility testing
●Additional antibody studies if ABO incompatibility is excluded
●Repeat cross-match with pre-and post-transfusion specimens using an indirect antiglobulin
(IAT) method
●Direct antiglobulin (Coombs) testing (DAT)
●Observation of the serum for pink color and analysis for free hemoglobin
●Serum haptoglobin, lactate dehydrogenase (LDH) and unconjugated bilirubin levels to
document hemolysis
●Coagulation testing for DIC if the patient has increased bleeding
●Observation of the urine for pink color and analysis for free hemoglobin
●Serial hemoglobin levels to determine the severity of hemolytic anemia and possible need for
additional RBC transfusions
A nephrologist consulted for prophylactic measures to prevent or reduce renal damage; a
hematologist consulted if the patient has evidence of DIC.
RBCs may be damaged or hemolyzed prior to transfusion, resulting in transfusion of free
hemoglobin rather than hemolysis of transfused cells within the patient. Due to thermal injury to
the cells from inappropriate warming or from rapid thawing of frozen products. This is less
severe than AHTR because the amount of free hemoglobin is limited, and hemolysis is not
ongoing; however, if large amounts of free hemoglobin are transfused, symptoms can be
significant. Findings include pink serum, pink urine, negative DAT, negative IAT, and a
compatible cross-match. Analysis of the remaining (untransfused) product will also reveal a pink
supernatant, after centrifugation. Brisk diuresis induced by infusion of 500 mL normal saline per
hour or as tolerated is usually adequate. Hydration is continued until hemoglobinuria resolves.
Anaphylaxis — a patient with an apparent anaphylactic reaction (eg, hypotension, wheezing,
angioedema) should receive epinephrine (0.2 to 0.5 mL of a 1:1000 solution) subcutaneously or
intramuscularly. In severe cases, 0.5 mL of a 1:10,000 aqueous solution may be administered
intravenously. Antihistamines are also administered. Inhaled bronchodilators may be needed in
some patients. In addition to managing the reaction, the response to these interventions further
supports the diagnosis of anaphylaxis.
Laboratory testing for an anaphylactic reaction should include quantitative immunoglobulin A
(IgA) levels as well as the presence of antibodies to immunoglobulin A (anti-IgA). This testing is
not indicated in patients with isolated urticaria.
Suspected sepsis — is based on an abnormal appearance of the transfused product (purple or
brown discoloration of RBC components; bubbles in a platelet component) or severe
fever/chills/hypotension without evidence of hemolysis on initial laboratory testing. Gram stain
should be performed on the returned component, and cultures should be performed on both the
remaining component and a post-transfusion blood sample from the patient. A complete blood
count (CBC) with white blood cell count (WBC) is also obtained.
Intravenous broad-spectrum antibiotic therapy should be administered based on the severity of
clinical symptoms or obvious abnormal appearance of the transfused product. Antibiotics may be
adjusted based on the results of the gram stain or culture of the product, but should not be
withheld while awaiting these results.
Respiratory distress patients may be having TACO or TRALI. In some cases the distinction
between these reactions is obvious; in others it may be difficult, or TACO and TRALI may both
occur concurrently.
The chest radiography, pulse oximetry and arterial blood gas measurement to be done. Hypoxia
should be corrected with supplemental oxygen. Severe respiratory compromise may require
transfer to an ICU for possible intubation and mechanical ventilation.
TACO is more likely in patients who have received a large volume of fluid over a short period of
time, extremes of ages, or those with cardiac disease and in patients with findings of
hypertension, heart failure, or elevated PAWP. Hypoxemia and pulmonary edema on chest
radiography may be seen in TACO. If TACO is suspected, sitting/ headup position and diuresis
should be initiated. Patients with TACO who do not respond to diuresis can be treated with
phlebotomy. An elevated NT-Pro BNP measurement is supportive of TACO.
TRALI is more likely in patients who have respiratory distress out of proportion to the volume of
fluid received or early on during the transfusion. Other findings in TRALI include respiratory
distress of sudden onset; fever; hypotension; and pink frothy airway secretions. Unlike TACO, a
diagnosis of TRALI requires hypoxemia and an abnormal chest radiograph. Individuals with
underlying acute lung injury or an alternative risk factor for acute lung injury are referred to as
having "possible TRALI." Patients with suspected TRALI should have samples sent for HLA
typing and possible testing for HLA and/or neutrophil antibodies. The blood bank must be
informed of a suspected TRALI case so that appropriate specimens may be obtained from the
donor (or donors) involved. Analysis of the pulmonary edema fluid may be helpful in
distinguishing TACO (cardiogenic/ transudate) from TRALI (non-cardiogenic/ exudates) in rare
cases.
Importantly, if TACO and/or TRALI do not appear to explain the clinical picture, assessment for
other causes of respiratory distress should be pursued, including transfusion reactions such as
sepsis and other coincident medical conditions such as pulmonary embolism or myocardial
ischemia .
When the patient has a mild reaction, the ultimate course of the reaction is initially unknown.
Thus, it is important to monitor the patient until the reaction has subsided.
Isolated fever with or without a chill is most often caused by a FNHTR; however, the diagnosis
of FNHTR cannot be established until it is clear that the patient is not having an AHTR, sepsis,
or TRALI. Thus, many cases of isolated fever must initially be managed as an AHTR.
●For patients with unresolving/ uncomfortable fever, oral acetaminophen may be administered.
Aspirin should be avoided because it inhibits platelet function. Severe rigors can be treated with
meperidine. These medications will not interfere with subsequent laboratory testing (eg, it is not
necessary to withhold acetaminophen until cultures are obtained).
●Patients who develop additional symptoms should be managed as if they are having an AHTR,
and appropriate laboratory testing should be obtained.
Isolated hives/itching — Patients with isolated hives or itching do not require laboratory testing,
as long as there are no other allergic symptoms such as angioedema, wheezing, or hypotension.
The transfusion should be paused for 15 to 30 minutes until it is clear that additional allergic
symptoms are not developing.
Diphenhydramine can be used to relieve pruritus; however, not all patients will require
pharmacologic intervention. The patient should be queried about driving home before
diphenhydramine is administered because this may cause drowsiness. Diphenhydramine can be
administered orally or intravenously, at a dose of 25 to 100 mg, depending on the severity of
symptoms and the size of the patient. In mild cases of isolated hives or itching that resolve
promptly, the transfusion may be restarted with the original unit.
If the patient develops more severe allergic symptoms, such as wheezing, angioedema, or
hypotension, the transfusion should be discontinued immediately and additional interventions to
treat anaphylaxis should be employed.