Blood Transfusion | Transfusion Therapy & Protocols

~118 Million

Units collected globally per year (WHO)

1 in 600

Risk of febrile non-hemolytic reaction

< 1:1,000,000

Fatal acute hemolytic reaction risk

Definition & Indications

Blood transfusion is the intravenous administration of whole blood or its components (red cells, platelets, plasma, cryoprecipitate) from a donor to a recipient to restore oxygen-carrying capacity, correct coagulopathy, or maintain circulating volume.

Common Indications

Acute Hemorrhage

Trauma, surgical bleeding, GI bleed, postpartum hemorrhage — Hb trigger depends on rate of loss

Symptomatic Anemia

Hb < 7 g/dL (general), < 8 g/dL (cardiac/elderly) — always assess symptoms

Coagulopathy / DIC

FFP, cryoprecipitate, platelets for active bleeding with abnormal coagulation

Thrombocytopenia

Platelets < 10,000/µL (prophylactic) or < 50,000/µL (pre-procedure/active bleed)

Exchange Transfusion

Sickle cell crisis, severe malaria (parasitemia >10%), neonatal hyperbilirubinemia

Massive Transfusion

≥10 units PRBC in 24h or ≥4 units in 1h with ongoing need — activate MTP

Restrictive vs. Liberal Strategy

The TRICC trial and subsequent evidence supports a restrictive transfusion threshold (Hb < 7 g/dL) for hemodynamically stable, non-cardiac ICU patients. Liberal thresholds (Hb < 9-10 g/dL) may be considered for acute coronary syndrome, symptomatic cardiac disease, and ongoing hemorrhage. Always transfuse for physiological need, not a number.

Blood Components

Each component has specific indications, storage requirements, and expected clinical effects.

🩸

Packed Red Blood Cells (PRBC)

Oxygen-carrying capacity restoration

Volume

~250-350 mL

Storage

1-6°C, up to 42 days

(CPDA-1: 35 days)

Infusion Time

1.5-4 hours

Must complete within 4h

Expected Rise

1 unit → Hb ↑ ~1 g/dL

Hct ↑ ~3%

Key Points:

Hematocrit 55-80%, minimal plasma
Leukoreduced units preferred (reduces febrile reactions, CMV transmission)
Irradiated units for immunocompromised patients (prevent TA-GVHD)
Washed PRBCs for patients with IgA deficiency or severe allergic reactions
Use 18-20G IV cannula; use blood warmer if rapid infusion or >2 units

🧪

Fresh Frozen Plasma (FFP)

Coagulation factor replacement

Volume

~200-250 mL

Storage

≤ -18°C, up to 1 year

Thaw at 37°C; use within 24h

Dose

10-15 mL/kg

Compatibility

ABO compatible

AB is universal donor

Indications:

Active bleeding with INR > 1.5 or PT/aPTT > 1.5× normal
DIC with active hemorrhage
Warfarin reversal (if PCC unavailable — PCC preferred)
Massive transfusion protocol (1:1:1 ratio with PRBC:FFP:Platelets)
TTP — therapeutic plasma exchange (NOT standard FFP transfusion)
NOT indicated for volume expansion or nutritional support

🔬

Platelet Concentrates

Hemostatic support

Storage

20-24°C with agitation

Shelf life: 5 days

Dose (Adult)

1 apheresis unit

or 4-6 random donor units

Expected Rise

↑ 30,000-50,000/µL

Infusion

Over 15-30 min

Never refrigerate

⚠ Contraindicated in: TTP/HUS (unless life-threatening bleed), Heparin-induced thrombocytopenia (HIT)

❄️

Cryoprecipitate

Fibrinogen & Factor VIII concentrate

Contains

Fibrinogen, Factor VIII, XIII, vWF, Fibronectin

Dose

1 unit/5 kg (typically 8-10 units adult)

Indication

Fibrinogen < 150 mg/dL with bleeding

Storage

≤ -18°C, 1 year; thawed: use within 6h

ABO & Rh Compatibility

ABO-incompatible transfusion is the leading cause of fatal transfusion reactions. Verification is the single most critical safety step.

RBC Compatibility Matrix

Recipient →	O−	O+	A−	A+	B−	B+	AB−	AB+

Compatible Incompatible

🩸 Universal Donor & Recipient

O Negative — Universal RBC Donor
Use in emergencies when blood type unknown. Limited supply (~7% population).

AB Positive — Universal RBC Recipient
Can receive RBCs from any ABO/Rh type.

AB Plasma — Universal Plasma Donor
Contains no anti-A or anti-B antibodies. Opposite logic to RBC.

🔬 Pre-Transfusion Testing

1. ABO & Rh typing — Forward & reverse grouping

2. Antibody Screen — Indirect Coombs test (IAT) for irregular antibodies

3. Crossmatch — Full crossmatch (30-45 min) or electronic crossmatch if no antibodies detected

4. Bedside Check — Two-person verification: patient ID ↔ blood unit label ↔ compatibility report

⚠ CRITICAL: Most fatal transfusion errors are clerical — wrong blood to wrong patient. Bedside verification prevents this.

Transfusion Protocols

Step-by-Step Administration Protocol

Step 1 — Consent & Order

Obtain informed consent. Document indication, number of units, any special requirements (irradiated, CMV-negative, leukoreduced). Verify no religious/personal objections.

Step 2 — Sample Collection

Collect Type & Screen sample. Label at bedside with patient name, DOB, MRN, date/time, phlebotomist initials. Never pre-label tubes.

Step 3 — IV Access

Ensure patent IV access: 18-20G cannula preferred (20G minimum for adults). Dedicated line or Y-set with 0.9% Normal Saline only. Never add medications to blood. Do not use Ringer's Lactate (calcium causes clotting).

Step 4 — Pre-Medication (if indicated)

For patients with history of febrile/allergic reactions: Acetaminophen 650mg PO + Diphenhydramine 25-50mg IV/PO, 30 min prior. Steroids (hydrocortisone 100mg IV) for severe allergic history.

Step 5 — Bedside Verification (CRITICAL)

Two qualified staff independently verify: (1) Patient identity (name + DOB/MRN + wristband), (2) Blood unit label ABO/Rh matches compatibility report, (3) Unit number matches, (4) Expiry date valid, (5) Visual inspection — no clots, discoloration, leaks.

Step 6 — Baseline Vitals

Record temperature, pulse, BP, respiratory rate, SpO₂ before starting transfusion. These serve as comparison for detecting reactions.

Step 7 — Initiation

Start slowly: 2 mL/min for first 15 minutes. Stay with patient. Most severe reactions occur within the first 50 mL. Then increase rate to complete within 4 hours maximum.

Step 8 — Monitoring

Vitals at: 15 min, 30 min, hourly, and on completion. Monitor for fever (↑>1°C), chills, urticaria, dyspnea, chest/back pain, hypotension, dark urine.

Step 9 — Completion & Documentation

Record final vitals, total volume infused, duration, any adverse events. Document in patient chart. Return blood bank slip if required by protocol.

🚨 Massive Transfusion Protocol (MTP)

Activated when ≥10 units PRBC anticipated in 24h, or ≥4 units in 1h with ongoing hemorrhage, or hemodynamic instability despite crystalloid resuscitation.

1 : 1 : 1

PRBC : FFP : Platelets

(PROPPR Trial ratio)

6 units

Per MTP cycle (cooler)

6 PRBC + 6 FFP + 1 apheresis plt

TXA

1g IV within 3h of injury

(CRASH-2 Trial evidence)

Also monitor: Calcium (citrate toxicity → give CaCl₂ 1g per 4 units), Temperature (use warmers), Potassium (hyperkalemia risk), pH (acidosis).

Transfusion Reactions

Classification by timing, severity, and pathophysiology.

Acute Hemolytic Transfusion Reaction (AHTR)

LIFE-THREATENING Immune

Cause

ABO incompatibility → intravascular hemolysis. Usually clerical error.

Timing

Minutes to hours. Often within first 50 mL.

Signs & Symptoms

Fever, chills, flank/chest pain, hypotension, tachycardia, hemoglobinuria (red/dark urine), DIC, renal failure, anxiety/doom feeling.

Lab Findings

↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, + DAT (Coombs), hemoglobinemia, pink serum.

Febrile Non-Hemolytic Reaction (FNHTR)

MOST COMMON

Cause: Cytokines released from WBCs during storage, or recipient antibodies against donor WBC antigens.

Features: Temperature ↑ ≥1°C, rigors, chills. No hemolysis. Onset during or 1-6h post-transfusion.

Management: Stop transfusion → rule out hemolytic reaction → Acetaminophen, Meperidine 25-50mg IV for severe rigors. Use leukoreduced products in future.

Allergic / Anaphylactic Reactions

Severity Spectrum

Mild Urticarial (1-3%)
Localized hives/itching. Can slow rate, give diphenhydramine 25-50mg IV, resume if resolves. No need to stop permanently.

Anaphylaxis (1:20,000-50,000)
Bronchospasm, stridor, hypotension, angioedema. STOP transfusion. Epinephrine 0.3-0.5mg IM stat. IgA deficiency is classic cause. Future: washed or IgA-deficient products.

TRALI (Transfusion-Related Acute Lung Injury)

LEADING CAUSE OF DEATH

Definition: Non-cardiogenic pulmonary edema within 6h of transfusion. Bilateral infiltrates on CXR, hypoxemia (PaO₂/FiO₂ < 300), no evidence of volume overload.

Mechanism: Donor anti-HLA or anti-neutrophil antibodies → neutrophil activation → pulmonary capillary leak.

Management: Supportive — O₂, intubation/ventilation if needed. Diuretics NOT helpful (not cardiogenic). Resolves in 48-96h typically. Mortality ~5-10%.

Prevention: Male-only plasma donors (reduces risk).

TACO (Transfusion-Associated Circulatory Overload)

Underdiagnosed

Features: Dyspnea, orthopnea, ↑ JVP, peripheral edema, hypertension, ↑ BNP, pulmonary edema on CXR. Onset during or within 6-12h.

Risk Factors: Elderly, CHF, renal failure, small body habitus, rapid infusion.

Management: Stop/slow transfusion, upright positioning, IV furosemide 20-40mg, O₂.

TRALI vs TACO: BNP (↑ in TACO), fluid balance (positive in TACO), BP (↑ TACO, ↓ TRALI), response to diuretics (TACO responds).

Delayed Reactions

Delayed Hemolytic (1-28 days): Anamnestic antibody response. Falling Hb, mild jaundice, + DAT. Usually self-limiting.

TA-GVHD (1-6 weeks): Donor T-cells attack recipient. Pancytopenia, rash, liver failure. >90% mortality. Prevention: irradiate products for at-risk patients.

Iron Overload: After >20 units (each unit = ~250mg Fe). Monitor ferritin. Chelation with deferasirox/deferoxamine.

Infectious Risks

Bacterial Contamination: Highest with platelets (room temp storage). Fever, rigors, shock. Blood cultures + broad-spectrum antibiotics.

Viral (per unit risk with NAT):

HIV: ~1 in 1.5 million
HCV: ~1 in 1.2 million
HBV: ~1 in 280,000

Parasitic: Malaria, Chagas, Babesia — screen in endemic regions.

🚨

Emergency Management

Immediate actions when a transfusion reaction is suspected.

🛑 Universal First Response — ANY Suspected Reaction

1

STOP the Transfusion

Immediately clamp the line. Do NOT flush. Keep IV access open with NS via separate line.

2

Maintain Airway & Vitals

A-B-C assessment. O₂ supplementation. Full vitals: HR, BP, RR, SpO₂, Temp.

3

Verify Identity

Re-check patient ID against blood unit label and compatibility form. Clerical error is the #1 cause of fatal AHTR.

4

Notify Blood Bank & Team

Call blood bank immediately. Notify attending physician. Return blood unit + tubing to blood bank.

5

Send Investigations

Repeat Type & Screen (new sample, opposite arm). DAT, LDH, haptoglobin, bilirubin, free Hb, UA for hemoglobinuria, blood cultures (×2).

6

Monitor & Document

Monitor urine output (target >1 mL/kg/h), strict I/O. Document everything: time, signs, actions, labs sent.

Specific Emergency Protocols

Acute Hemolytic Reaction — Emergency Protocol

1. Universal first response (above)

2. Aggressive IV NS resuscitation (target UOP > 100 mL/h in adults)

3. IV Furosemide 40-80mg to maintain diuresis and prevent renal failure

4. Manage DIC: Platelets, FFP, cryoprecipitate as needed

5. Vasopressors for refractory hypotension

6. Renal replacement therapy (dialysis) if oliguric renal failure develops

7. ICU admission for close monitoring

Anaphylaxis — Emergency Protocol

1. STOP transfusion. Call for help.

2. Epinephrine 0.3-0.5 mg IM (1:1000) anterolateral thigh. Repeat q5-15 min.

3. High-flow O₂ (15L/min via NRB mask)

4. IV NS 1-2L bolus for hypotension

5. Nebulized salbutamol for bronchospasm

6. Hydrocortisone 200mg IV (prevents biphasic reaction)

7. Diphenhydramine 50mg IV

8. If refractory: Epinephrine drip 1-10 µg/min IV. Consider intubation.

9. Check IgA levels. Future: washed or IgA-deficient products only.

TRALI — Emergency Protocol

1. Stop transfusion. Supportive care.

2. Aggressive O₂ supplementation. Intubate if PaO₂/FiO₂ < 200.

3. Lung-protective ventilation (Vt 6 mL/kg IBW, Pplat < 30 cmH₂O)

4. Do NOT give diuretics (non-cardiogenic edema — diuretics worsen hypovolemia)

5. Differentiate from TACO: BNP, echo, fluid balance, response to diuretics (TACO responds, TRALI doesn't)

6. Notify blood bank — donor investigation for anti-HLA antibodies

7. ICU admission. Most resolve within 48-96h.

Bacterial Sepsis — Emergency Protocol

1. Stop transfusion. Return unit for Gram stain + culture.

2. Blood cultures ×2 from patient (separate sites)

3. Broad-spectrum antibiotics STAT: Piperacillin-tazobactam 4.5g IV + Vancomycin 25-30 mg/kg IV

4. Aggressive fluid resuscitation (30 mL/kg crystalloid)

5. Vasopressors if septic shock (Norepinephrine first-line)

6. ICU for sepsis bundle management

Special Clinical Scenarios

🤰 Obstetric Transfusion

• Rh-negative mothers: Anti-D immunoglobulin (RhoGAM) within 72h of delivery/miscarriage/procedure if baby is Rh-positive

• Postpartum hemorrhage: Activate MTP early. Consider cell salvage during C-section.

• Kleihauer-Betke test to quantify fetomaternal hemorrhage and guide anti-D dose

• Always use Rh-negative PRBC for Rh-negative women of childbearing age

👶 Neonatal / Pediatric

• Volume: 10-15 mL/kg PRBC over 3-4 hours

• Use CMV-negative, irradiated, leukoreduced components

• Exchange transfusion for severe neonatal jaundice (bilirubin > 25 mg/dL term / lower for preterm)

• Syringe technique for small volumes; dedicated blood warmer

• Risk of hyperkalemia higher with stored units — use fresh (<7 day) for neonates

❤️ Cardiac Surgery & ACS

• Transfuse at Hb < 8 g/dL in ACS/perioperative cardiac patients

• TRICS III trial: restrictive (Hb <7.5) non-inferior to liberal in cardiac surgery

• Cell salvage during cardiac surgery reduces allogeneic transfusion

• Monitor for TACO — cardiac patients at highest risk

• Slow infusion rates (1 mL/kg/h) to avoid volume overload

🧬 Sickle Cell Disease

• Simple transfusion: target Hb 10 g/dL (do NOT exceed — hyperviscosity risk)

• Exchange transfusion for: acute chest syndrome, stroke, severe crisis. Target HbS <30%

• Extended phenotype matching (C, E, Kell minimum) — reduces alloimmunization

• Sickle-negative donor units only

• Chronic transfusion program: iron chelation mandatory

🛐 Jehovah's Witnesses

• Respect autonomy. Document informed refusal clearly.

• Alternatives: EPO, IV iron, cell salvage (some accept), TXA, controlled hypotension

• Acute normovolemic hemodilution (ANH) — acceptable to some

• Minimize blood draws. Pediatric tubes. Point-of-care testing.

• Minors: Court order may be required for life-saving transfusion

🧪 Autoimmune Hemolytic Anemia

• Crossmatch will be incompatible — transfuse "least incompatible" units when life-threatening

• Warm AIHA: IgG antibodies. DAT positive. First-line: steroids + transfuse if critical Hb.

• Cold AIHA: IgM + complement. Use blood warmer. Avoid cold exposure.

• Extended phenotyping before first transfusion is ideal

Monitoring & Quality

Vital Signs Monitoring Schedule

Time Point	Parameters	Action if Abnormal
Pre-transfusion	T, HR, BP, RR, SpO₂	Establish baseline. Document.
15 minutes	T, HR, BP, RR, SpO₂	STOP if T↑>1°C, new symptoms
30 minutes	T, HR, BP, RR, SpO₂	Reassess. Increase rate if stable.
Hourly	T, HR, BP, RR, SpO₂	Ongoing surveillance
Completion	T, HR, BP, RR, SpO₂	Final set. Document total time/volume.
1h Post-completion	T, HR, BP	Detect delayed febrile reactions

📊 Post-Transfusion Labs

Hemoglobin / Hematocrit15-60 min post

Platelet Count1h post (10-60 min)

PT/INR, aPTT, FibrinogenAfter FFP/cryo

Electrolytes (K⁺, Ca²⁺)After massive transfusion

ABG / LactateIf hemorrhagic shock

🔒 Safety Checklist

Informed consent obtained & documented Type & Screen sample collected & verified Two-person bedside verification completed Baseline vitals recorded Blood warmer connected (if indicated) Slow start (2 mL/min × 15 min) observed 15-minute vitals checked & documented Completed within 4 hours

⚡ Quick Reference — Transfusion Triggers

Stable ICU / Medical

Hb < 7 g/dL

TRICC, TRISS trials

Cardiac / ACS

Hb < 8 g/dL

MINT, REALITY trials

Active Hemorrhage

Clinical judgment

Don't wait for lab Hb

Platelets (Prophylactic)

< 10,000/µL

Without bleeding

Platelets (Pre-procedure)

< 50,000/µL

Invasive procedures

FFP

INR > 1.5 + bleeding

Not for INR correction alone