dr zalina- trafusion reaction and management.pdf
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TRANSFUSION SAFETY: NATIONAL TRAINING WORKSHOP
DR ZALINA MAHMOOD
PUSAT DARAH NEGARA
TRANSFUSION REACTION & MANAGEMENT
Introduction
BTS-supply blood as safe as possible
Some adverse effects cannot be completely predicted or avoided
Important to be aware of such risks
Aware of signs & symptoms of a possible reaction
Be prepared to take steps to mitigate the current episode & prevent future similar reactions
Many common clinical sign & symptom are associated with > 1 type of adverse reaction
Early recognition, prompt cessation of transfusion & further evaluation-keys to a successful outcome
Signs & symptoms that may indicate transfusion reaction
Fever Chills with or without rigors Respiratory distress Hyper or hypotension Abdomen /chest /flank or back pain Pain @ infusion site Skin manifestation Jaundice or haematuria Nausea/vomiting Oliguria/anuria
Classification 1 Acute
Immune
Haemolytic (AHTR)
Allergic
TRALI
Anaphylactic
FNHTR
Bacterial contamination
Non-immune
Circulatory overload
Massive transfusion effects
Delayed Immune
Delayed HTR
Alloimmunization
Transfusion GVHD
Post Transfusion Purpura
Non-immune
Transmissible Diseases (TTI)
Iron Overload
Classification 2
Adverse effects of transfusion may be grouped according to the main presenting features:
• Fever
• Dyspnea
• Urticaria and allergic reactions
• Hypotension
• Hemolysis
• Cytopenias
Reactions Commonly Presenting with Fever
• Bacterial contamination or sepsis
• Acute hemolytic transfusion reaction
• Febrile non-hemolytic transfusion reaction
Bacterial contamination 1
Rare:-
? use of sterile, disposable collection sets & clean phlebotomy
? first 30ml-diverted into a pouch & used to provide samples for laboratory testing
? unrecognized
? under reporting
BUT if occur, can rapidly be fatal
due to septicaemia, endotoxic shock
or both
Bacterial Contamination 2
Should be suspected when recipient develop
Fever > 38.5oC
Severe rigors
Hypotension
During or shortly after
transfusion
Severe cases-shock with renal
failure & DIC
Bacterial Contamination 3
Sources of organisms:
• Skin commensals from the donor
• Unrecognized bacteremia in the donor
• Contamination from the environment during collection/ or processing
Bacterial Contamination 4
Diagnosis:
Culture of the same organism from patient and component establishes the diagnosis of transfusion transmitted infection
Bacterial Contamination 5.
Management:
• STOP the transfusion
• Notify Blood Bank
• Clamp and return residual component to Blood Bank
• Send off blood & urine for culture
• Provide supportive treatment • START INTRAVENOUS ANTIBIOTICS
immediately without waiting
for blood culture results
Bacterial Contamination 6. Prevention:
Donor selection & pre donation interview
Collection Skin cleaning Divertion pouch Proper handling-blood bag on
floor Storage temperature
Processing Clean area Preserve sterility
Transfusion Inspect red cells for colour
changes prior to transfusion Transfuse within acceptable
duration
Reactions Commonly Presenting with Fever
• Bacterial contamination or sepsis
• Acute hemolytic transfusion reaction
• Febrile non-hemolytic transfusion reaction
AHTR 1 Due to incompatible blood being transfused
Effect: accelerated rbc destruction or haemolysis – intravascular and/or extravascular
Signs and Symptoms
Seen within few minutes of transfusion
First phase:
nausea
fever, chills
flushing
back/chest pain
uneasy feeling
Pain at infusion site
Second Phase
dyspnoea
flank pain
hypotension
renal failure, haemoglobinuria
bleeding – DIC
AHTR 2
Incidence ;
ABO/ Rh incompatibility : 1:6000 -1:20,000
Fatal HTRs : 1:100,000 – 1:600,000
AABB Technical Manual,16th Ed.
AHTR 3.
Management: • STOP the transfusion
• Notify the Blood Bank
• Send fresh blood sample and
residual blood product to BB
• Supportive care in ICU setting Blood pressure support
Inotropes
Hydration
Good urine output,
Avoiding fluid overload
AHTR 4.
Prevention:
Meticulous attention to:
• Patient identification
• Sampling & labeling
• Identification during all phases of blood bank accession, testing, labeling & product issuing
• Identification of the recipient at initiation of transfusion including checking the wristband
Acute Hemolysis Not Due to Allo-antibodies
Other causes of hemolysis include:
• Overheating of RBC
• Freezing of RBC
• Medical device (e.g. blood warmer) malfunction
• Outdated RBC
• Transfusion under pressure with small bore needle
• Transfusion with hypotonic solution
Reactions Commonly Presenting with Fever
• Bacterial contamination or sepsis
• Acute hemolytic transfusion reaction
• Febrile non-hemolytic transfusion reaction
Febrile Non-hemolytic Transfusion Reactions (FNHTR) 1.
Def: Raised in body temp by
1oC associated with transfusion
without other explanation
Common adverse effect
Attributed to:
Soluble factors (cytokines) released by white cells and platelets during storage
Recipient antibodies against HLA determinants on transfused leucocytes /or platelet
FNHTR 2
Incidence : 5-10%
(ABC of Transfusion, 4th ed, 2009)
Reduced significantly to 0.1%-0.2% or less with introduction of leucodepletion of red cells & platelets
(AABB Technical Manual, 16th ed)
FNHTR 3
Clinical Presentation: Fever during or soon after
transfusion
May be associated with
Chills
Rigors
Nausea
Vomiting
Hypotension
Algorithm for Management of Transfusion Associated Fever 1.
Algorithm for Management of Transfusion Associated Fever 2.
Algorithm for Management of Transfusion Associated Fever 3.
Reactions Commonly Associated With Dyspnoea
Transfusion Related Acute Lung Injury (TRALI)
Transfusion Associated Circulatory Overload (TACO)
Anaphylaxis (urticaria and other allergic reactions will be included here)
Transfusion Related Acute Lung Injury 1.
TRALI:
Syndrome of acute respiratory distress with:
Dyspnoea, cyanosis
Hypoxia
Hypotension
Bilateral pulmonary edema
No evidence of congestive heart failure
Usually within 6 hours of transfusion
Plasma containing components
Transient-80% improves within 48-96 hours
Transfusion Related Acute Lung Injury 2.
Mechanism-associated with infusion of :
Antibodies to leukocyte (neutrophil) & HLA antigens
Biological response modifiers (BRMs)
2 event model
1st event:
Generation of BRM 20 to physiologic stress
(sepsis,surgery,massive transfusion)
Activates pulmonary vascular endothelial cells
Primes neutrophils
Sequestration of neutrophils in pulmonary microvasculature
2nd event:
Infusion of BRM & antibodies
Activate primed neutrophils in pulmonary microvasculature
Pulmonary endothelial damage, capillary leakage, & pulmonary oedema
Transfusion Related Acute Lung Injury 3.
Incidence: Unknown
Estimates : 1:1,300 to 1: 5,000 transfusions
Often unrecognized
Under-reported
Third commonest cause of
transfusion associated death
Transfusion Related Acute Lung Injury 4.
Management of TRALI
Supportive care
Mechanical ventilation required in about 75% of cases
Diuretics and steroids probably not useful
Prevention
Accurate diagnosis and reporting
Testing of donor(s) to identify the particular implicated donor
Deferral of implicated donors
Reactions Commonly Associated With Dyspnoea
Transfusion Related Acute Lung Injury (TRALI)
Transfusion Associated Circulatory Overload (TACO)
Anaphylaxis (urticaria and other allergic reactions will be included here)
Transfusion Associated Circulatory Overload 1.
Mechanism: TACO results when the
rate of transfusion is greater than cardiac function can accommodate, because of: Impaired cardiac function
AND/OR
Excessively rapid transfusion
Transfusion Associated Circulatory Overload 2.
Incidence:
About 1 in 700 transfusion episodes
Greater risk in elderly or infants
Presentation:
Dyspnoea
Orthopnoea
Engorged neck veins
Cyanosis
Tachycardia
Hypertension
Transfusion Associated Circulatory Overload 3.
Management:
STOP the transfusion
Administer diuretics e.g. lasix
Oxygen may be required
Restart the transfusion slowly if
Clinical status permits and
Blood is still within the permitted time out of storage
Prevention:
Assess cardiac status
Close monitoring of patients at risk
Use slower rate of transfusion (1mL/kg/H)
Premedicate with diuretics
Split the product into smaller aliquots
Monitor I/O
Reactions Commonly Associated With Dyspnoea
Transfusion Related Acute Lung Injury (TRALI)
Transfusion Associated Circulatory Overload (TACO)
Anaphylaxis (urticaria and other allergic reactions will be included here)
Allergic Reactions (Urticaria) 1.
Typically present with local rash, urticaria, or pruritus
Mostly mild, non life-threatening and not accompanied by fever or other severe symptoms
Aetiology:
Exposure to soluble substance or protein in donor plasma, which the recipient has been sensitized to
Increased risk in pt with history of allergy
Incidence : 1-3% (AABB Technical Manual, 16th ed)
Allergic Reactions (Urticaria) 2.
Management:
STOP the transfusion temporarily
Anti-histamine-slow IV
Restart transfusion slowly if urticaria involves less than two thirds of body AND there are no other signs of a more severe reaction
Prevention:
Premedication with anti-histamine 30 mins prior to transfusion
Allergic Reactions (Anaphylaxis) 1.
Anaphylactic reactions are rare but may be life-threatening
Incidence 1 in 40,000 transfusion episodes
Etiology:
usually (80%) unexplained
Anti IgA in an IgA deficient patient
Antibodies to polymorphic (genetic variable) donor proteins (e.g. IgG)
Transfusion of an allergen in the donor to sensitized patient
Passive transfer of IgE
Allergic Reactions (Anaphylaxis) 2.
Clinical Presentation:
Begins 1-45 minutes after start
Cutaneous reaction (hives, flushing)
Airway obstruction, dyspnoea, wheezing, stridor
Acute anxiety
Hypotension
Nausea and vomiting
Allergic Reactions (Anaphylaxis) 3.
Management:
STOP the transfusion immediately
Maintain IV line with normal saline
Maintain airway & give oxygen
Prompt administration of adrenaline 0-5-1.0 mg i.m every 10 mins (according to BP & HR) until improvement occurs
Chlorpheniramine 10-20mg (slow IV)
Algorithm for Management of Dyspnea
Algorithm for Management of Allergic Reactions 1.
Algorithm for Management of Allergic Reactions 2.
Algorithm for Management of Allergic Reactions 3.
Transfusion Associated Hypotension 1.
Incidence unknown
Mechanism: Not clearly defined
Kinin activation involved?
Genetic variation in capacity to degrade kinin by ACE
Use of ACE inhibitors (antihypertensive agents)
Transfusion Associated Hypotension 2.
Clinical Presentation: Drop in systolic or diastolic
BP >/= 30mmHg
Most with platelet transfusion
May also have nausea, vomiting, dyspnoea or urticaria
Serious morbidity rare
May resemble TRALI but no pulmonary edema
Lasts up to 3 hours
Transfusion Associated Hypotension 3.
Management: Usually detectable
within 15 minutes
STOP the transfusion, do not restart
Supportive care including IV fluids
Consider TRALI and allergic reactions in the differential diagnosis
Prevention: For patients on ACE
inhibitors, use an alternative anti-hypertensive
Algorithm for Management of Transfusion Associated
Hypotension
Delayed Adverse Effects of Transfusion
Some adverse events occur days to years following transfusion Delayed hemolytic transfusion reactions
Cytopenias Transfusion associated graft vs. host disease
Post transfusion purpura
Transfusion transmitted infections Viral
Prion
Parasitic
(Bacterial infection discussed under “fever”)
Delayed Hemolytic Transfusion Reactions 1.
Immune destruction of transfused RBC 2 days or more post-transfusion
Recipient sensitization by prior transfusion or pregnancy
Recipient antibody level below threshold of detectability
Antibodies usually in the Rhesus (E,c), Kidd, Kell and Duffy systems
Delayed Hemolytic Transfusion Reaction 2.
Incidence: Estimated at 1 in 6715 units of RBC transfused
Clinical Presentation: May be clinically “silent”, only detectable by tests Common features are:
Unexpected fall in post-transfusion hemoglobin Failure to obtain expected rise in hemoglobin post-
transfusion Post-transfusion jaundice Post-transfusion spherocytosis on blood film
Rarely life-threatening, resembling acute HTR; Kidd system antibodies especially
Delayed Hemolytic Transfusion Reactions 3.
Prevention:
Routine check of past transfusion/blood bank records
Personal record card for sensitized patient
Flag medical record of sensitized patient
Transfusion Associated Graft vs. Host Disease (TAGvHD)1.
Clinical manifestation typically begin 8-10 days after transfusion (3-30 days)
S & S :maculopapular rash,fever, enterocolitis with watery diarrhea, elevated LFT, pancytopenia
Leads to profound marrow aplasia-mortality rate> 90%
Aetiology: 3 requirements for GVHD:
Differences in HLA Immunocompetent cells in
graft Host incapable to reject
immunocompetent cells
TAGvHD 2.
Situations giving rise to risk include:
Congenital immunodeficiency states
Intra-uterine and neonatal exchange transfusions
Pre-term infants
Directed donations from family members
Hematological malignancy, especially of B-cell origin
Post-transplant (bone marrow, stem cell, solid organ)
Aggressive therapy for solid tumors
Treatment with purine analogues
TAGvHD 3.
Incidence: Unknown 13 reported deaths in
UK over 5 years, mostly B-cell malignancies
Diagnosis by: Biopsy (skin, liver,
bone marrow)HLA typing of donor and recipient
TAGvHD 4.
Management: Supportive care
Antibiotics
Largely ineffective
Survival usually associated with immunosuppressive therapy
Prevention: Irradiated for patients in all
risk groups
Post-Transfusion Purpura (PTP)
Relatively uncommon
Purpura & thrombocytopenia (platelet < 10,000) within 9 days after transfusion (1-24 days)
Aetiology: platelet specific alloantibodies in patients
Mx:
test for plt specific antibodies
IVIG 1g/kg daily for 2 days-expected increase in plt count within 4 days after therapy
High dose corticosteroids
Transfusions Transmitted Infection (TTI)
Various methods put in place including NAT testing
Risk is still there
Patients involved should be informed & counseled
BB should be informed to identify the donors & their status determined
Recommended to trace back all the blood that has been transfused to the patients within 6 months period from last negative results
Iron overload
A unit of RBCs contains app 250mg iron
Average rate of excretion app 1mg per day
Stored as hemosiderin & ferritin-accumulates in liver, heart, spleen, endocrine organs
Greater risk in chronically transfused patients
Mx: iron chelation
Samples??
Blood sample
8-10ml of blood in EDTA
Repeat ABO/Rh grouping, repeat crossmatch
for A/b screening + id, Coomb’s Test
2-5mls EDTA tube for FBP/FBC-
retic count , Hb and platelet count
features suggestive of haemolysis in FBP
Biochemistry – if suspected haemolysis
Serum Bilirubin and LDH
Culture and Sensitivity
presence of microorganism if we suspect bacterial contamination
Blood bag/s and it’s transfusion set ABO & Rh grouping, X-match, Coomb’s
C&S
Urine sample – inspection, Hb or RBC (dipstick) and urobilinogen (if
available)
Repeat blood samples and urine after 24H
Other tests
Chest X-Ray – must exclude TRALI and TACO
Presence of bilateral pulmonary infiltrate
Features of ARDS (clinically must tally)
Delayed rxn FBC – Hb, Platelet count
TTI screening
Iron overload – serum ferritin
Skin biopsy – TA-GVHD
Forms to be completed
Laporan reaksi kepada darah atau plasma
For ward doctors to fill in with the post-transfusion samples to BB
Penyiasatan reaksi pemindahan darah
For BB staff to fill in after Ix completed for pre and post transfusion samples and donor sample if available
Reporting format for adverse transfusion event
For HO/MO to fill in and submitted to BB/PDN after all the investigations was done
Take home messages
Some adverse effects cannot be completely predicted or avoided
Aware of signs & symptoms of a possible reaction
If not sure- STOP the transfusion & call for help
Proper documentation needed in reporting adverse transfusion reaction
Patient identification & diagnosis
S & S involved
Blood/blood product
Relevant blood test results
Take home messages
Some adverse effects cannot be completely predicted or avoided
Aware of signs & symptoms of a possible reaction
If not sure- STOP the transfusion & call for help
Proper documentation needed in reporting adverse transfusion reaction
Patient identification & diagnosis
S & S involved
Blood/blood product
Relevant blood test results
Early recognition of adverse reactions;
reactions from different causes can exhibit similar manifestations
every symptoms should be considered potentially serious
transfusion should be discontinued until the cause is determined
References
1. American Association of Blood Banking (AABB),16th Edition.
2. Transfusion Practice Guidelines for Clinical and Laboratory Personnel, 3rd Edition March 2008.
3. Strategies for Safe Blood Transfusion, World Health Organization (WHO) Publication, 1998.
4. ABC of Transfusion, 4th edition, 2009