dr zalina- trafusion reaction and management.pdf

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


Sources of organisms:

• Skin commensals from the donor

• Unrecognized bacteremia in the donor

• Contamination from the environment during collection/ or processing


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

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

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.

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


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


Incidence: Unknown

Estimates : 1:1,300 to 1: 5,000 transfusions

Often unrecognized

Under-reported

Third commonest cause of

transfusion associated death


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

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


Incidence:

About 1 in 700 transfusion episodes

Greater risk in elderly or infants

Presentation:

Dyspnoea

Orthopnoea

Engorged neck veins

Cyanosis

Tachycardia

Hypertension


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

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


Clinical Presentation:

Begins 1-45 minutes after start

Cutaneous reaction (hives, flushing)

Airway obstruction, dyspnoea, wheezing, stridor

Acute anxiety

Hypotension

Nausea and vomiting


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.

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)


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


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

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

dr zalina- trafusion reaction and management.pdf

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