Transfusion Reaction

Allied Guru

Introduction 

  • Blood transfusion ek life-saving therapeutic procedure hai jo medical aur surgical practice mein bahut widely use hoti hai, lekin yeh completely risk-free nahi hoti.

  • Transfusion reaction ka matlab hai koi bhi adverse clinical event jo whole blood ya blood components ke transfusion ke dauran ya baad occur kare, chahe uski severity mild ho ya severe.

  • Transfusion reactions mild, moderate ya life-threatening ho sakti hain — jisme simple febrile reaction ya allergic reaction se lekar severe complications jaise acute hemolytic reaction, sepsis, TRALI aur circulatory overload tak shamil hain.

  • Yeh reactions immune-mediated mechanisms ki wajah se ho sakti hain (jaise ABO incompatibility, alloantibody formation) ya non-immune causes ki wajah se (jaise bacterial contamination, volume overload, mechanical hemolysis).

  • Timing ke basis par, transfusion reactions ko classify kiya jata hai:

    • Acute reactions – jo transfusion ke dauran ya 24 hours ke andar hoti hain

    • Delayed reactions – jo transfusion ke kuch din ya weeks baad develop hoti hain

  • Acute hemolytic transfusion reaction, jo sabse zyada ABO mismatch ki wajah se hota hai, ek medical emergency hai aur agar isse jaldi identify aur manage na kiya jaye to high morbidity aur mortality ho sakti hai.

  • Transfusion reactions ke clinical manifestations aksar non-specific hote hain aur yeh sepsis, allergic reactions ya cardiac failure jaise acute conditions ko mimic kar sakte hain, is wajah se diagnosis challenging ho jata hai.

  • Isliye immediate clinical assessment ke saath-saath systematic laboratory investigation bahut zaroori hoti hai taaki diagnosis confirm ho sake, underlying cause identify ho aur appropriate management guide ki ja sake.

  • Laboratory evaluation ka role bahut important hota hai:

    • Blood group incompatibility detect karne mein

    • Immune ya non-immune hemolysis identify karne mein

    • Severity aur complications jaise DIC ya renal failure assess karne mein

    • Future transfusions mein reaction repeat hone se prevent karne mein

  • Ek well-defined transfusion reaction investigation protocol hemovigilance systems ko support karta hai, transfusion safety improve karta hai aur overall patient care ki quality enhance karta hai.

 

Etiology

I. Immune-Mediated Causes

Yeh reactions donor blood components ke antigens aur recipient ke antibodies ke beech antigen–antibody interaction ki wajah se hoti hain.

1. ABO Incompatibility

  • Acute hemolytic transfusion reaction ka sabse common aur sabse severe cause

  • Zyada tar clerical errors, mislabeling ya incorrect patient identification ki wajah se hota hai

  • Naturally occurring IgM antibodies complement system activate karti hain

  • Iske result mein hota hai:

    • Intravascular hemolysis

    • Shock

    • Disseminated intravascular coagulation (DIC)

    • Acute renal failure

2. Rh Incompatibility

  • Mainly Rh-negative recipients ko Rh-positive blood dene par hota hai

  • Usually delayed hemolytic transfusion reaction cause karta hai

  • IgG antibodies ke through mediated hota hai

  • ABO mismatch se kam severe hota hai, lekin clinically significant hota hai

3. Alloantibodies Against Minor Blood Group Antigens

  • Kell, Duffy, Kidd aur MNS systems ke against antibodies

  • Previous transfusions ya pregnancy ke baad develop hoti hain

  • Delayed hemolytic transfusion reactions (DHTR) ke liye responsible hoti hain

  • Routine compatibility testing ke dauran aksar miss ho jati hain

4. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

Is reaction ka cause hota hai:

  • Recipient ke antibodies jo donor leukocytes ke against hote hain

  • Blood storage ke dauran accumulate hue cytokines

  • Yeh reaction platelet aur whole blood transfusions ke saath zyada common hota hai

5. Allergic Reactions

  • Donor plasma proteins ke against hypersensitivity reaction

  • Mild urticaria se lekar severe anaphylaxis tak ho sakta hai

  • Plasma-rich blood products ke saath zyada common

6. Anaphylactic Reaction

  • IgA deficiency wale patients mein dekha jata hai

  • Recipient ke anti-IgA antibodies donor IgA ke saath react karte hain

  • Rapid onset hota hai jisme:

    • Bronchospasm

    • Hypotension

    • Shock

7. Transfusion-Related Acute Lung Injury (TRALI)

  • Donor ke anti-leukocyte ya anti-HLA antibodies ki wajah se hota hai

  • Immune-mediated pulmonary capillary damage hota hai

  • Result mein non-cardiogenic pulmonary edema develop hota hai

II. Non-Immune-Mediated Causes

Yeh reactions antigen–antibody mechanism ke bina, physical, chemical ya biological factors ki wajah se hoti hain.

1. Bacterial Contamination of Blood Products

  • Zyada tar platelet transfusions ke saath associated hota hai (kyunki platelets room temperature par store hote hain)

  • Improper collection ya storage ki wajah se hota hai

  • Septic transfusion reaction develop hota hai

  • Symptoms:

    • High fever

    • Hypotension

    • Shock

2. Mechanical Hemolysis

Iska cause hota hai:

  • Small-gauge needles ka use

  • Faulty transfusion pumps

  • Transfusion ke dauran excessive pressure

➡ Result: Non-immune intravascular hemolysis

3. Thermal Injury

  • Overheated ya improperly warmed blood transfuse karne par

  • RBC membrane damage hota hai

  • Hemolysis develop hoti hai

4. Chemical Hemolysis

  • Hypotonic solutions ya drugs/IV fluids se contamination

  • RBC destruction (lysis) hota hai

5. Transfusion-Associated Circulatory Overload (TACO)

  • Rapid ya excessive transfusion volume ki wajah se hota hai

  • Zyada common in:

    • Elderly patients

    • Pediatric patients

    • Cardiac ya renal failure patients

  • Result mein cardiogenic pulmonary edema develop hota hai

III. Metabolic & Storage-Related Causes

Stored blood mein biochemical changes ki wajah se yeh reactions hote hain.

1. Citrate Toxicity

  • Citrate calcium ko bind karta hai

  • Hypocalcemia hota hai (especially massive transfusion mein)

  • Symptoms: paresthesia, tetany, arrhythmias

2. Hyperkalemia

  • Stored RBCs se potassium leak hota hai

  • Massive ya rapid transfusion mein risk zyada hota hai

  • Neonates aur renal failure patients ke liye zyada dangerous

3. Hypothermia

  • Cold blood products ka infusion

  • Cardiac arrhythmias aur coagulopathy cause karta hai

IV. Procedural & Clerical Errors

  • Galat patient identification

  • Samples ka wrong labeling

  • Blood grouping ya crossmatching errors

  • Galat blood component transfuse karna

  • Transfusion protocols follow na karna

➡ Serious transfusion reactions ka sabse preventable cause

V. Patient-Related Risk Factors

  • Previous transfusions

  • History of transfusion reactions

  • Pregnancy (alloimmunization)

  • IgA deficiency

  • Cardiac ya renal disease

 

Epidemiology

Distribution by Type of Transfusion Reaction

1. Febrile Non-Hemolytic Transfusion Reactions (FNHTR)

  • FNHTR sabse common transfusion reaction hai

  • Red cell transfusions ke 0.1–1% cases mein dekha jata hai

  • Platelet transfusions ke saath incidence zyada hoti hai

  • Leukoreduction use karne se FNHTR ki frequency significantly kam ho jati hai

2. Allergic Reactions

  • 1–3% plasma-containing transfusions mein hoti hain

  • Zyada tar reactions mild hoti hain, jaise:

    • Urticaria

    • Itching

  • Severe anaphylactic reactions bahut rare hoti hain

3. Acute Hemolytic Transfusion Reactions (AHTR)

  • Incidence: lagbhag 1 in 38,000–70,000 transfusions

  • Sabse common cause: ABO incompatibility

  • Majority cases clerical errors ya patient identification errors ki wajah se hote hain

  • Yeh reactions laboratory testing failure ki wajah se kam hoti hain

4. Delayed Hemolytic Transfusion Reactions (DHTR)

  • Delayed onset ki wajah se aksar under-reported hoti hain

  • Incidence zyada hoti hai:

    • Multiply transfused patients mein

  • Hematologic disorders (jaise thalassemia, sickle cell disease) wale patients mein common

5. Transfusion-Related Acute Lung Injury (TRALI)

  • TRALI transfusion-related mortality ke leading causes mein se ek hai

  • Incidence: 1 in 5,000–10,000 transfusions

  • Risk zyada hota hai plasma-rich components ke saath

  • Male-only plasma donors use karne se TRALI ka risk kaafi kam ho gaya hai

6. Transfusion-Associated Circulatory Overload (TACO)

  • Incidence: 1–8% high-risk populations mein

  • Kai hemovigilance systems ke according, TACO sabse common cause of transfusion-related death ban chuka hai

  • Yeh reaction frequently underdiagnosed hota hai

7. Septic (Bacterial) Transfusion Reactions

  • Rare but highly fatal hote hain

  • Zyada tar platelet transfusions ke saath hote hain kyunki platelets room temperature par store kiye jate hain

  • Estimated incidence:

    • 1 in 100,000–250,000 transfusions

Population-Based Risk Distribution

High-Risk Groups

In patients mein transfusion reactions ka risk zyada hota hai:

  • Elderly patients

  • Neonates aur pediatric patients

  • Cardiac ya renal disease wale patients

  • Immunocompromised individuals

  • Massive ya repeated transfusions lene wale patients

Gender Differences

  • Historically, TRALI zyada common tha jab plasma multiparous female donors se liya jata tha

  • Donor selection policies change karne se yeh risk significantly reduce ho gaya hai

Component-Specific Epidemiology

Platelets

  • Sabse highest rate of transfusion reactions

  • Zyada tar febrile aur septic reactions

Plasma

  • Allergic reactions aur TRALI ka risk zyada hota hai

Packed Red Cells

  • Sabse zyada hemolytic reactions ke saath associated

Geographical & System-Based Factors

  • Transfusion reaction ki incidence depend karti hai:

    • Transfusion practices par

    • Hemovigilance reporting systems par

    • Quality control measures par

  • Developed countries mein incidence zyada report hoti hai kyunki:

    • Surveillance systems better hote hain

    • Actual reaction rate zaroori nahi ki zyada ho

 

Pathophysiology 

I. Immune-Mediated Transfusion Reactions

Yeh reactions donor blood components aur recipient immune system ke beech antigen–antibody interaction ki wajah se hoti hain.

1. Acute Hemolytic Transfusion Reaction (AHTR)

Mechanism

  • Sabse commonly ABO incompatibility ki wajah se hota hai

  • Recipient ke paas pre-formed IgM antibodies hoti hain jo donor RBC antigens ke against hoti hain

  • IgM antibodies complement system ko rapidly activate karti hain

Pathophysiological Events

  • Complement activation → Intravascular hemolysis

  • Donor RBCs ka rapid destruction

  • Is process mein release hota hai:

    • Free hemoglobin

    • LDH

    • Potassium

  • Free hemoglobin haptoglobin se bind karta hai → haptoglobin depletion

  • Free hemoglobin kidneys se filter hota hai → hemoglobinuria

  • Nitric oxide scavenging → vasoconstriction

  • Cytokine release → fever aur hypotension

  • Severe cases mein:

    • DIC

    • Acute renal failure

    • Shock

2. Delayed Hemolytic Transfusion Reaction (DHTR)

Mechanism

  • Transfusion ke days ya weeks baad occur hota hai

  • IgG alloantibodies minor blood group antigens ke against banti hain

  • Common antigens: Kell, Kidd, Duffy

Pathophysiology

  • Antibody-coated RBCs ko macrophages remove karte hain

  • Extravascular hemolysis (spleen aur liver mein)

  • Hemoglobin gradually kam hota hai

  • Mild jaundice aur anemia develop hota hai

  • Usually less severe hota hai, lekin clinically important hota hai

3. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

Mechanism

  • Recipient ke antibodies donor leukocytes ke against

  • Blood storage ke dauran cytokines accumulate ho jate hain

    • IL-1

    • IL-6

    • TNF-α

Pathophysiology

  • Cytokine release ki wajah se hota hai:

    • Fever

    • Chills

    • Rigors

  • RBC destruction nahi hota

  • Platelet transfusions ke saath common

4. Allergic Transfusion Reaction

Mechanism

  • IgE-mediated hypersensitivity donor plasma proteins ke against

Pathophysiology

  • Mast cell degranulation

  • Histamine release

  • Symptoms:

    • Urticaria

    • Pruritus

    • Flushing

5. Anaphylactic Transfusion Reaction

Mechanism

  • IgA-deficient recipients mein hota hai

  • Recipient ke anti-IgA antibodies donor IgA se react karte hain

Pathophysiology

  • Massive mediator release

  • Vasodilation aur bronchoconstriction

  • Rapid onset:

    • Hypotension

    • Bronchospasm

    • Shock

6. TRALI

Mechanism (Two-Hit Hypothesis)

  • First hit: Patient ki clinical condition pulmonary neutrophils ko prime karti hai

  • Second hit: Donor ke anti-HLA ya anti-neutrophil antibodies neutrophils ko activate karte hain

Pathophysiology

  • Pulmonary capillaries mein neutrophil activation

  • Endothelial damage

  • Capillary leak

  • Non-cardiogenic pulmonary edema

  • 6 hours ke andar acute hypoxemia

 

Evaluation of Transfusion Reaction 

I. Immediate Clinical Evaluation

  • Reaction suspect hote hi transfusion turant stop karo

  • IV access normal saline se maintain karo

  • Record karo:

    • Symptoms ka time of onset

    • Blood component ka type aur volume

    • Vital signs: temperature, BP, pulse, respiratory rate, oxygen saturation

  • Life-threatening features assess karo:

    • Hypotension ya shock

    • Respiratory distress

    • Chest / back pain

    • Hemoglobinuria

    • Altered mental status

    • Anaphylaxis ke signs

II. Bedside & Clerical Evaluation

  • Patient identity re-check karo:

    • Wristband

    • Blood bag label

    • Compatibility tag

  • Verify karo:

    • Patient name & ID

    • Blood group & Rh type

    • Unit number & expiry date

➡ Clerical error fatal transfusion reactions ka sabse common cause hai, especially ABO mismatch mein.

III. Sample Collection for Lab Evaluation

Immediately laboratory bhejo:

  • Patient ka post-transfusion blood sample (EDTA + plain)

  • Remaining donor blood unit with tubing

  • Patient ka urine sample (agar hemolysis suspected ho)

  • Pre-transfusion sample (agar available ho)

IV. Basic Laboratory Evaluation

1. Repeat ABO & Rh Typing

  • Patient sample aur donor unit dono par

  • ABO/Rh mismatch confirm ya exclude karta hai

Interpretation:

  • Koi bhi discrepancy → acute hemolytic transfusion reaction strongly suggestive

2. Repeat Crossmatch

  • Major crossmatch (recipient serum vs donor RBCs)

Interpretation:

  • Incompatible → immune incompatibility

  • Compatible → minor antigen mismatch ya non-immune cause socho

3. Direct Antiglobulin Test (DAT)

  • RBCs par antibodies/complement detect karta hai

Interpretation:

  • Positive DAT → immune-mediated hemolysis

  • Negative DAT → non-immune hemolysis ya non-hemolytic reaction

4. Visual Inspection for Hemolysis

  • Centrifuged plasma ka color dekha jata hai

Findings:

  • Pink / red plasma → hemoglobinemia

  • Clear plasma → hemolysis unlikely

Urine:

  • Red/brown urine without RBCs → hemoglobinuria

V. Hemolysis Workup

  • Hemoglobin & Hematocrit

    • Unexpected fall → hemolysis

  • Serum bilirubin

    • Indirect bilirubin ↑ → hemolysis

  • LDH

    • RBC destruction ki wajah se ↑

  • Serum haptoglobin

    • Intravascular hemolysis mein low/absent

  • Reticulocyte count

    • Delayed hemolytic reactions mein ↑

VI. Evaluation for Complications

Renal Function Tests

  • Serum creatinine

  • Blood urea

  • Urine output monitoring

Purpose: Hemoglobinuria-induced AKI detect karna

Coagulation Profile

  • PT, aPTT, D-dimer, fibrinogen

Purpose: Severe hemolysis mein DIC detect karna

VII. Infectious (Septic) Reaction Evaluation

  • Blood cultures:

    • Patient se

    • Donor blood unit se

  • Gram stain (agar available ho)

➡ Positive culture = medical emergency

VIII. Pulmonary Reaction Evaluation

TRALI

  • 6 hours ke andar respiratory distress

  • Chest X-ray: bilateral infiltrates

  • Normal cardiac function

  • Fluid overload absent

TACO

  • Volume overload signs

  • Raised BP, JVP

  • Pulmonary edema on X-ray

  • Diuretics se improvement

IX. Immunohematological Evaluation

  • Antibody screening & identification

  • Minor blood group alloantibodies detect karna

  • Previous transfusion history se comparison

X. Documentation & Reporting

  • Sabhi clinical & lab findings document karo

  • Report karo:

    • Blood bank

    • Transfusion committee

    • Hemovigilance system

  • Patient record par clearly mention karo:
    “History of transfusion reaction”

 

Diagnosis 

I. Basis of Diagnosis

Diagnosis in cheezon par based hota hai:

  • Transfusion aur symptom onset ka timing

  • Clinical manifestations

  • Laboratory evidence (hemolysis / infection / overload)

  • Other causes ka exclusion

II. Clinical Diagnostic Criteria

Transfusion ke dauran ya baad agar ho:

  • Fever (≥1°C rise)

  • Chills / rigors

  • Hypotension / shock

  • Chest, back, flank pain

  • Dyspnea / hypoxia

  • Dark urine

  • Rash / urticaria / bronchospasm

  • Sudden respiratory distress

  • Unexplained bleeding

➡ Early recognition bahut critical hai, especially AHTR mein.

III. Laboratory Diagnosis

  • Repeat ABO/Rh typing

  • DAT

  • Hemolysis panel

  • Crossmatch re-testing

➡ Positive DAT + hemolysis signs = hemolytic transfusion reaction

IV. Specific Reaction Diagnosis

  • AHTR: Early onset + positive DAT + intravascular hemolysis

  • DHTR: Late onset + alloantibodies

  • FNHTR: Fever only, labs normal

  • Allergic: Urticaria, itching

  • Anaphylaxis: Sudden shock, bronchospasm

  • Septic: Positive blood cultures

  • TRALI: Non-cardiogenic pulmonary edema

  • TACO: Volume overload, cardiac signs

 

Complications

Hematological

  • Acute intravascular hemolysis

  • Delayed hemolytic anemia

  • DIC

Renal

  • Acute kidney injury

  • Dialysis requirement

Cardiovascular

  • Shock

  • TACO → heart failure

Pulmonary

  • TRALI

  • Acute respiratory failure / ARDS

Infectious

  • Septic shock

  • Secondary infections

Metabolic

  • Hyperkalemia

  • Hypocalcemia

  • Hypothermia

Immunological

  • Alloimmunization

  • Anaphylaxis

Mortality

  • Severe reactions fatal ho sakte hain

  • Leading causes: TRALI, TACO, AHTR, sepsis