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 TRANSFUSION REACTIONS AND  RANSFUSION REACTIONS AND  THEIR MANAGEMENT  THEIR MANAGEMENT By AIDA ALAUDIN

TRANSFUSION REACTIONS AND THEIR MANAGEMENT

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 TRANSFUSION REACTIONS AND TRANSFUSION REACTIONS AND THEIR MANAGEMENT THEIR MANAGEMENT

ByAIDA ALAUDIN

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Transfusion Reaction is any unfavorable transfusion-related

event occurring in a patient during or aftertransfusion of blood components

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Immediate and Delayed TransfusionReaction

ImmediateImmediate DelayedDelayed

  Immune EffectsImmune Effects

AHTRAHTR DHTRDHTR

FNHTRFNHTR AlloimmunizationAlloimmunization

Allergic reactionAllergic reaction PTPPTPAnaphylaxis & anaphylactoid reactionAnaphylaxis & anaphylactoid reaction TA-GVHDTA-GVHD

TRALITRALI

  Nonimmune EffectsNonimmune Effects

Bacterial contaminationBacterial contamination Iron overloadIron overload

TACOTACO TTVTTV

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IMMUNE HAEMOLYTIC TRANSFUSIONREACTION

Defined as the destruction of red cells in therecipient of a transfusion caused by immunealloantibodies of red cells.

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 Acute Hemolytic TransfusionReaction 

(Ab  in recipient serum) + (Ag  on RBC donor)

-  Neuroendocrine responses

-Complement Activation

-Coagulation Activation

- Cytokines Effects

 Acute hemolytic transfusion reaction

Pathophysiology

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Pathophysiology

Two mechanisms for RBCs destruction 1) Intravascular hemolysis

2) Extravascular hemolysis

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Signs and Symptoms of 

AHTRChills , feverHypotensionGeneralized bleeding

HemoglobinemiaHemoglobinuriaRenal failureDIC

Feelings of doom

Agitation

Facial flushing

Restlessness

Dyspnoea

Abdominal , chest orback pain

Pain along infusionvein

Nausea,vomiting

Diarrhoea

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Acute Hemolytic Transfusion

Reactions

v  -Acute onset within minutes or 1 2 hours

 after transfuse incompatible blood

v  -Most common cause is ABO incompatible

  transfusion

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Laboratory investigation for

AHTR10 ml of clotted blood labelled as post Tx sample 1 for 

- repeat ABO and Rhesus grouping

- repeat compatibility test

- Ab screening and Direct Coomb’s Test

Send another sample 24 hours later and label as post Tx sample 2

Send FBC in EDTA tube

Send blood sample for biochemistry lab for 

- serum electrolytes and renal profile

- serum bilirubin

Send blood for DIVC screening

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Laboratory investigation for

AHTRUrine output should be monitored and presence of hemoglobinuria noted

ECG should be done to check for evidence of hyperkalemia

Urine should be sent to confirm presence of hemoglobinuria

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Treatment of AHTRDepends on

Amount of incompatible blood transfused

Specificity of the offending antibody Clinical severity of the reaction

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TreatmentTreatment

u:Primary concerns  

- vigorous treatment of hypotension

- promotion of renal blood flow

 To prevent renal failure

 Acute Hemolytic TransfusionReaction

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Treatment of AHTR

Stop the transfusion immediately, inform bloodbank

IV line should be maintained with N/S infusion,initiall 20-30ml/kg to maintain SBP

Monitor vital signs and strict I/O chart(maintain urine output at 1-1.5ml/kg/hour

Maintain airway, give oxygen support if necessary

Administer IV Frusemide 1 mg/kg if urineoutput < 1ml/kg/hour

If patient is hypotensive, give inotrope IVdopamine 1 µg/kg/min

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PreventionPrevention

upreventing or detecting errors in every phase of the transfusionpreventing or detecting errors in every phase of the transfusion

process :process : 

usample acquisitionsample acquisition

uat all steps in laboratory testingat all steps in laboratory testinguat the time of issueat the time of issue

uat the time of transfusionat the time of transfusionuEnsuring that all clinical staff recognize signs and symptoms of Ensuring that all clinical staff recognize signs and symptoms of 

acute reactionacute reaction

AHTR

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Delayed Hemolytic TransfusionReaction

Most often the result of an anamnesticresponse (transfusion, pregnancy,transplantation )

Mild clinical signs and symptomsUnexpected or unexplained decreased in Hb or

Hct after transfusion should be investigate aspossible DHTR

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Delayed Hemolytic Transfusion ReactionPathophysiology  - 2 types of DHTR

  1) secondary (anamnestic) response totransfused RBCs 3 – 7 day after Tx

  2) primary alloimmunization longer  - Extravascular hemolysis 

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Delayed Hemolytic Transfusion Reaction

Signs & Symptoms

mild fever or fever with chill

mild anemia

mild to moderate jaundice

Uncommon hemoglobinemia,

Hemoglobinuria, shock, renal failure

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Delayed Hemolytic Transfusion ReactionTherapy and Prevention - Goal of therapy is prevention - Treat severe complication if necessary - Alert to history of sensitization  (previous transfusion, Pregnancy,

transplantation)

  

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Febrile Nonhemolytic TransfusionReaction

( FNHTR)  Definition

Temperature increase of more or equal to1oC associated with transfusion, with nomedical explanation other than bloodtransfusion

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Pathophysiology of FNHTR - Patients

Leukocyte antibodies (HLA Ab)

- Blood donors leukocytes intransfused blood

 Activate complement system

 C 5a

-Pyrogen interleukin 1

( , )macrophage monocyte

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Febrile Nonhemolytic Transfusion

ReactionSigns & Symptoms

Fever with or without chills

most symptoms are mild

severe reaction :- headache,hypotension, cyanosis,tachycardia, tachypnea, dyspnea,

cough

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 Febrile Nonhemolytic Reaction Febrile Nonhemolytic Reaction

Diagnosis of FNHTR is by exclusion of other causes of transfusionDiagnosis of FNHTR is by exclusion of other causes of transfusionreactio as fever could be due to acute hemolytic transfusionreactio as fever could be due to acute hemolytic transfusionreaction or by bacterially contaminated blood.reaction or by bacterially contaminated blood.

TreatmentTreatmentu

discontinued blood transfusion if the patient has severe reactiondiscontinued blood transfusion if the patient has severe reactionuAntipyretic for feverAntipyretic for feveruIf patient has experienced 2 or more FNHTR, tryIf patient has experienced 2 or more FNHTR, try

- paracetamol orally I hour before transfusion- paracetamol orally I hour before transfusion

- slow transfusion and keep the patient warm- slow transfusion and keep the patient warmu

PreventionPreventionuusing leucocyte- depleted blood componentsusing leucocyte- depleted blood components

 

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Allergic Transfusion Reactions 

Probably the most frequent kind of reactionPathophysiology

Allergen – Reagin (IgE,IgG) Complex

attach mast cell (degranulation)

histamine/leukotrienes

Allergic reactions (urticaria)

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Allergic Transfusion Reactions

Signs & Symptoms - Urticaria (circumscribed areas of cutaneousedema and

itching) - severe reactions are rare

Therapy & Prevention - Stop transfusion temporarily while administering

antihistamine (Chlorpheniramine) by slow IV, transfusion can be continued if  urticariais the only symptom. But if patientdevelops

extensive

urticariaor a confluent total body rash, it would be necessaryto

stop the transfusion, even if symptoms have responded to treatment. - For patients who have had severe or frequent minor urticaria

following transfusion, administering oral antihistamine 30 mins before

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Anaphylactic and Anaphylactoid

reactions Anaphylaxis is a rare but life threatening

complication.

Pathophysiology- IgE antibody to IgA in donor plasma (anti-IgA antibodies)

- immediate generalized hypersensitivityreaction due to activity of IgE antibodies or thepresence of anti Ig-A in patients with congenitaldeficiency of IgA

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Anaphylactic and Anaphylactoid

reactionsSigns & Symptoms - Anaphylactic generalized flushing,

coughing, dyspnea, nausea, vomiting,

bronchospasm, chest pain, hypotension,abdominal cramps, diarrhea, arrythmias,hypotension, syncope, sndit can progress toloss of consciousness, shock, and rarely

death. - Anaphylactoid (less severe) urticaria,

periorbital swelling, dyspnea, orperilaryngeal edema

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Anaphylactic and Anaphylactoidreactions

Therapy and PreventionStop transfusion

Keep IV line open with 0.9% saline

Maintain airway and give oxygen, neb Salbutamol

can also be given

Medication :-

- IM epinephrine then repeat every 10 minsaccording to

blood pressure and pulse rate until improvementoccurs

- slow IV of antihistamine

Wash RBCs and blood components

Transfuse IgA deficiency blood

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Transfusion-related Acute Lung Injury (TRALI)

Acute and severe type of transfusion reaction that can be fatal

Pathophysiology  Leukocyte Ab in donor react with pt. leukocytes

Activate complements

Adherence of granulocytes to pulmonaryendothelium with release of proteolytic enzymes &

toxic O2

metabolites

Endothelial damage

Interstitial edema and fluid in alveoli

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Transfusion-related Acute Lung Injury

(TRALI)

Symptoms and signs

Fever

Non-productive coughHypotension

Tachypnea

Dyspnea

Diffuse pulmonary infiltration on X-rays

Clinical of noncardiogenic pumonary edema - within 4hours of transfusion

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Transfusion-related Acute Lung

Injury (TRALI)Therapy and Prevention

Manage in ICU setting as oxygen therapy andassissted ventilation are often required

Adequate respiratory and hemodynamic supportivetreatmentCorticosteroids might be helpfulIf antibodies are present, the blood center should

be notified so that the donor will be permanently

deferred from future donations.Patients who develop TRALI are unlikely to have

another reaction because it is most often donorspecific. 

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Transfusion-associated Circulatory

Overload (TACO)Patients at significant risk

Children

Elderly patientsChronic anemia

Cardiac disease

Thalassemia major or Sickle cell disease

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Pathophysiology

 Volume overload

 Congestive heart failure

 Pulmonary edema

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Symptoms and Signs

Dyspnea

CoughingCyanosis

Orthopnea

Chest discomfort

Headache

RestlessnessTachycardia

Systolic hypertensionincrease > 50

mm.Hg

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  Therapy & PreventionRapid reduction of hypervolemia

Respiratory and cardiac supportOxygen therapy

Diuretic

Therapeutic phlebotomy

  - Use appropiate transfusion rate - Use appropiate blood components

T h e ra p y

Pre v e n tioPre v e n tio

nn

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Metabolic ReactionCitrate toxicity

Hyperkalemia

Hypothermia

Coagulopathy in massive transfusion

Air embolism

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Transfusion-associated Graft-versus-Host Disease ( TA-GVHD)

Patient at risk q  Bone marrow

transplantationqChemotherapy

q  Radiation treatment

qNewborn

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Transfusion-associated Graft-versus-Host 

Disease ( TA-GVHD) Pathophysiology

Infusion of Immunocompetent Cells (Lymphocyte)

Patient at risk

proliferation of donor T lymphocytes

attack against patient tissue

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Graft-versus-Host ReactionSigns & Symptoms

§  ~Onset 3 to 30 days after transfusion§ –Clinical significant pancytopenia

§ ,Other effects include fever elevated

,liver enzymes

,copious watery diarrhea  erythematousskin erythroderma

 and desquamation

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Graft-versus-Host Reaction

Therapy :- , , ,Drugs corticosteroids methotrexate azathioprine:- , , ,Drugs corticosteroids methotrexate azathioprine

  antithymocyte globulin antithymocyte globulin

  But no adequate therapy But no adequate therapy

  PreventionPrevention

  ( - )Irradiation of Blood Components 25 30 Gy( - )Irradiation of Blood Components 25 30 Gy

 

avoid potential fatalities avoid potential fatalities

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Iron overload~1 unit of PRCs has 250 mg of Iron

/Removed by body 1 mg day

  accumulate iron Hemosiderosis

  iron accumulate in tissue 

Hemochromatosis

 

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Posttransfusion HemosiderosisAffected organ :- heart, liver, endocrine glands

Signs & Symptoms - muscle weakness, fatigue, weight loss, mild

jaundice, anemia, mild diabetes, and cardiacarrhythmia

Therapy Iron – chelating agentPrevention transfuse with young RBCs 

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AlloimmunizationResult from prior exposure to donor bloodcomponents

Significant complication even small amount

of bloodAdverse effects may include

difficulty in finding compatible blood

transfusion reactionplatelet refractoriness

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AlloimmunizationPathophysiology

1st exposure moderate

production IgM and IgGantibody by foreign antigens

2nd exposure rapid

production of large amount of IgG 

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AlloimmunizationSigns & Symptoms

mild slight fever and Hb

severe platelet refractorinesswith bleeding

Therapy & Prevention

depends on type and severity

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Posttransfusion PurpuraRare complication

Rapid onset of thrombocytopenia as a result of anamnestic production of platelet

alloantibodyUsually occurs in multiparous woman

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Posttransfusion PurpuraPathophysiology

  Platelet Ab (anti-PLA1

) attach platelet

surface destruction by RES

Signs & Symptoms

Purpura and thrombocytopenia

occur 

~ 1 – 2 weeks after transfusion

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Posttransfusion PurpuraTherapy and Prevention

Get expert advise from the

Transfusion MedicineDepartment

Corticosteroids combined withhigh dose of IVIg

Exchange transfusion

Plasmapheresis

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Bacterial contamination

reactionCause gram –ve, gram +ve bacteria  most frequent – Yersinia enterocolitica

Pathophysiology

Bacteria growing in cold temperature

Produced endotoxin

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Symptoms & SignsAcute onset within ~ 30 min after

transfusion

Dryness and flushing skin

Fever, hypotension, shaking chills, muscle

pain, vomitting, abdominal cramps, bloody

diarrhea, hemoglobinuria, shock, renalfailure, and DIC.

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Therapy & PreventionBroad – spectrum antibiotics

Symptomatic treatmentPrevention 

ØPhlebotomy and blood components preparation &processing , thawing by sterile technique.

Therapy

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Transfusion – Transmitted DiseasesViral Infections

Hepatitis Viruses :- HBV, HCV

Retroviruses :- HIVHerpesviruses :- CMV, EBV

Parvovirus :- Human B19 parvovirus

Prion :- infectious particle of CJD

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Transfusion – Transmitted DiseasesBacterial Infection

Gram negative and positive

SyphilisLyme disease (Borrellosis)

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Transfusion – Transmitted DiseasesParasitic Infections

Malaria

Chagas disease

Toxoplasmosis

Leishmaniasis

S l i l T ti

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Serological Testingfor Infectious markers

HIV – Ag

Anti – HIV

HBsAgAnti – HCV

Test for syphilis 

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Steps to take when a transfusion

reaction occursStop the transfusion immediately

Leave the needle in the vein and begin infusingnormal saline

Obtain vital signs

Begin O2

if pulmonary symptoms are

prominent

Carry out PE : lung, heart, skin, signs of abnormal bleeding

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Steps to take when a transfusion

reaction occursObtain a new blood sample for repeat RBCcompatibility test and inspection forhemolysis

Obtain a urine sample if the patient canvoid

Obtain a chest x-ray if pulmonary symptomare prominent

Make a preliminary assesment of thesituation

Begin definitive treatment

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- -Non Immune Mediated Hemolysis- -Non Immune Mediated Hemolysis

CausesCausesuPhysical or chemical destruction of Physical or chemical destruction of 

blood: freezing, heating, hemolyticblood: freezing, heating, hemolytic

drugdrugusolution added to bloodsolution added to bloodu

Bacterial contaminationBacterial contaminationTreatmentTreatment

–depends on the causesdepends on the causesumild reaction supportive treatmentmild reaction supportive treatmentusevere reaction intensive treatmentsevere reaction intensive treatment  

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 Thank you