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

Delayed

Immune Haemolytic (AHTR) Allergic TRALI Anaphylactic FNHTR Bacterial contamination Non-immune Circulatory overload Massive transfusion effects

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 lifethreatening

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:

Prevention:

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

For patients on ACE inhibitors, use an alternative antihypertensive

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:

Clinical Presentation:

Estimated at 1 in 6715 units of RBC transfused

May be clinically silent, only detectable by tests Common features are:
Unexpected fall in post-transfusion hemoglobin Failure to obtain expected rise in hemoglobin posttransfusion 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 aplasiamortality 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
Irradiated for patients in all risk groups

Prevention:

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, Coombs Test

2-5mls EDTA tube for FBP/FBCretic 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 its transfusion set

ABO & Rh grouping, X-match, Coombs 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

For BB staff to fill in after Ix completed for pre and post transfusion samples and donor sample if available

Penyiasatan reaksi pemindahan darah

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