Transfusion Medicine: Blood Products, Compatibility, and Reactions

Packed Red Blood Cells (PRBCs)

PRBCs are the most commonly transfused blood product, containing concentrated red blood cells with minimal plasma. Each unit contains approximately 200-250 mL and has a hematocrit of 55-80%. Primary indications include:

• Acute blood loss with hemodynamic instability
• Symptomatic anemia (Hb < 7-8 g/dL in stable patients)
• Chronic anemia refractory to medical therapy

PRBCs increase hemoglobin by approximately 1 g/dL per unit transfused in average-weight adults.

Fresh Frozen Plasma (FFP)

FFP contains all clotting factors and is indicated for coagulopathy correction when specific factor concentrates are unavailable. Key uses include:

• Warfarin reversal (when vitamin K is insufficient)
• Massive transfusion protocol
• Congenital factor deficiencies
• Liver disease with active bleeding

Typical dosing is 10-15 mL/kg, and FFP must be ABO-compatible but not Rh-matched.

Platelet Concentrates

Platelet products are available as pooled random donor platelets or single-donor apheresis units. Indications include:

• Thrombocytopenia with active bleeding (platelets < 50,000/μL)
• Prophylactic transfusion (platelets < 10,000/μL)
• Pre-operative preparation for high-risk procedures

One apheresis unit typically raises platelet count by 30,000-60,000/μL.

Cryoprecipitate

Cryoprecipitate is rich in fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Primary uses:

• Hypofibrinogenemia (fibrinogen < 100 mg/dL)
• von Willebrand disease (when DDAVP ineffective)
• Hemophilia A (when factor VIII concentrate unavailable)

Typical dosing is 1 unit per 10 kg body weight to achieve hemostatic fibrinogen levels.

ABO System Fundamentals

The ABO blood group system is determined by the presence or absence of A and B antigens on red blood cell surfaces. Key characteristics:

• Type A: A antigens present, anti-B antibodies in plasma
• Type B: B antigens present, anti-A antibodies in plasma
• Type AB: Both A and B antigens, no ABO antibodies (universal plasma donor)
• Type O: No A or B antigens, both anti-A and anti-B antibodies (universal RBC donor)

Naturally occurring ABO antibodies are primarily IgM, complement-activating, and capable of causing severe hemolytic reactions.

Rh System

The Rh system involves multiple antigens, with D being most clinically significant. Approximately 85% of the population is Rh-positive (D+). Critical considerations:

• Rh antibodies develop only after exposure (transfusion or pregnancy)
• Anti-D is typically IgG, crosses placenta, and causes delayed hemolytic reactions
• Rh-negative patients should receive Rh-negative blood when possible

Compatibility Rules

Emergency transfusion: Type O- blood can be used for any recipient when crossmatching is impossible, though type-specific blood should be used once available.

Type and Screen

The type and screen procedure includes:

1. ABO/Rh typing: Determines patient's blood group
2. Antibody screening: Detects unexpected red cell antibodies
3. Review of transfusion history: Identifies previous alloimmunization

Antibody screening uses commercially prepared red cells expressing common antigens (Duffy, Kidd, MNS, Kell systems). A positive screen requires antibody identification before transfusion.

Crossmatching Procedures

Major Crossmatch

The major crossmatch tests patient plasma against donor red cells to detect:

• ABO incompatibility
• Unexpected antibodies not detected in screening
• Low-titer antibodies

Electronic crossmatch may be performed when:

• Patient has negative antibody screen
• No history of clinically significant antibodies
• ABO/Rh typing performed twice with consistent results

Minor Crossmatch

Rarely performed in modern practice, tests donor plasma against patient red cells. Generally unnecessary due to dilution effect of transfused plasma.

Emergency Transfusion Protocols

Type O Emergency Release:

• Use O- blood for females of childbearing age
• O+ acceptable for males and post-menopausal females
• Maximum 4 units before type-specific blood required

Abbreviated Crossmatch:

• Immediate-spin saline crossmatch (5 minutes)
• Detects ABO incompatibility only
• Used when clinical urgency prevents full crossmatch

Sample Requirements:

• Two separate blood samples for initial typing
• Fresh sample (< 72 hours) if transfused within 3 months
• Patient identification critical to prevent errors

Acute Hemolytic Transfusion Reactions (AHTR)

Most dangerous transfusion reaction, typically caused by ABO incompatibility. Pathophysiology:

• Complement activation by IgM antibodies
• Intravascular hemolysis with hemoglobinuria
• Release of vasoactive mediators causing shock
• Activation of coagulation cascade (DIC)

Clinical presentation:

• Fever, chills, back/flank pain
• Hemoglobinuria (red/brown urine)
• Hypotension, tachycardia
• Dyspnea, chest tightness

Management:

1. Immediately stop transfusion
2. Maintain IV access, send samples to blood bank
3. Support blood pressure, ensure adequate urine output
4. Monitor for DIC, acute kidney injury

Febrile Non-Hemolytic Transfusion Reactions (FNHTR)

Most common transfusion reaction, caused by:

• Anti-HLA antibodies (previous pregnancy/transfusion)
• Anti-granulocyte antibodies
• Cytokine accumulation in stored blood products

Clinical features:

• Temperature rise ≥ 1°C or ≥ 38.3°C
• Chills, rigors (without hemolysis)
• Usually occurs within 1-6 hours

Prevention and management:

• Leukoreduced blood products
• Acetaminophen premedication
• Rule out hemolytic reaction first

Allergic Reactions

Mild allergic reactions (urticaria, pruritus):

• Caused by plasma protein sensitivity
• Treat with antihistamines, may continue transfusion
• Consider washed RBCs for recurrent reactions

Severe anaphylactic reactions:

• IgA deficiency with anti-IgA antibodies (rare)
• Bronchospasm, hypotension, angioedema
• Requires immediate epinephrine, IV steroids
• Future transfusions require IgA-deficient donors

Pathophysiology and Risk Factors

TRALI represents acute lung injury occurring within 6 hours of transfusion. Two-hit hypothesis:

First hit: Patient factors creating neutrophil priming

• Critical illness, surgery, infection
• Underlying inflammatory conditions

Second hit: Transfusion-related factors

• Antibody-mediated: Donor anti-HLA or anti-neutrophil antibodies
• Non-antibody mediated: Bioactive lipids, cytokines in stored blood

High-risk donors:

• Multiparous women (higher HLA antibody prevalence)
• Previously transfused donors
• Male donors have lower TRALI risk

Clinical Presentation

Acute respiratory distress developing during or within 6 hours of transfusion:

• Dyspnea, tachypnea, hypoxemia
• Bilateral pulmonary infiltrates on chest imaging
• Normal or low pulmonary capillary wedge pressure (distinguishes from TACO)
• Fever, hypotension may be present

Laboratory findings:

• Arterial blood gas: hypoxemia, respiratory alkalosis
• Leukopenia followed by leukocytosis
• Normal BNP/pro-BNP (helps exclude TACO)

Diagnosis and Management

Diagnostic criteria (must have all):

1. Acute onset within 6 hours of transfusion
2. PaO2/FiO2 ≤ 300 mmHg or SpO2 < 90% on room air
3. Bilateral infiltrates on chest radiograph
4. No evidence of left atrial hypertension

Management is supportive:

• Immediate cessation of transfusion
• Supplemental oxygen, mechanical ventilation if needed
• Conservative fluid management (avoid overload)
• No specific pharmacologic therapy proven effective

Prevention strategies:

• Use plasma from male donors when possible
• Screen female donors for HLA antibodies
• Leukoreduction may reduce but not eliminate risk

Prognosis: Most patients recover within 48-96 hours with appropriate supportive care. Mortality rate approximately 10-15%.

Pathophysiology and Risk Factors

TACO results from volume overload leading to cardiac decompensation and pulmonary edema. Key risk factors:

Patient factors:

• Advanced age (> 60 years)
• Cardiac dysfunction (CHF, valvular disease)
• Chronic kidney disease
• Small body habitus
• Positive fluid balance

Transfusion factors:

• Rapid infusion rate (> 2 mL/kg/hour)
• Large transfusion volume
• Multiple blood products

Clinical Features and Diagnosis

Presentation typically within 2-6 hours of transfusion:

• Dyspnea, orthopnea, tachypnea
• Elevated blood pressure, tachycardia
• Jugular venous distension
• Pulmonary crackles, S3 gallop
• Peripheral edema

Diagnostic workup:

• Chest radiograph: Cardiomegaly, pulmonary vascular congestion
• BNP/pro-BNP: Significantly elevated (> 1.5× baseline)
• Echocardiogram: May show systolic/diastolic dysfunction
• Central venous pressure: Elevated if measured

TACO vs. TRALI Differentiation

Management and Prevention

Acute management:

1. Stop or slow transfusion
2. Upright positioning, oxygen therapy
3. Loop diuretics (furosemide 20-80 mg IV)
4. Consider ACE inhibitors if hypertensive
5. Non-invasive ventilation if severe

Prevention strategies:

• Pre-transfusion diuretics in high-risk patients
• Slow infusion rates (< 2 mL/kg/hour)
• Split large volume transfusions
• Monitor fluid balance carefully
• Consider single-unit transfusions when appropriate

Definition and Activation Criteria

Massive transfusion is classically defined as replacement of one blood volume (approximately 70 mL/kg) within 24 hours. Modern activation criteria:

Clinical triggers:

• Ongoing blood loss requiring ≥ 4 units PRBCs in 1 hour
• Anticipated need for ≥ 10 units PRBCs
• Hemodynamic instability with active bleeding

Scoring systems (Assessment of Blood Consumption - ABC score):

• Penetrating mechanism: 1 point
• SBP ≤ 90 mmHg: 1 point
• Heart rate ≥ 120 bpm: 1 point
• Positive FAST exam: 1 point

ABC score ≥ 2 predicts massive transfusion need with 75% sensitivity.

Balanced Resuscitation Strategy

1:1:1 Protocol (PRBCs:FFP:Platelets):

• Based on military experience and civilian trauma data
• Prevents dilutional coagulopathy
• Improves survival in trauma patients

Product ratios:

• 6 units PRBCs : 6 units FFP : 1 apheresis platelet unit
• Alternatively: 6 PRBCs : 6 FFP : 1 pooled platelet unit

Monitoring parameters:

• CBC, PT/PTT, fibrinogen every 30 minutes
• ABG, lactate, calcium levels
• Viscoelastic testing (ROTEM/TEG) if available

Hemostatic Goals and Adjuncts

Target laboratory values:

• Hemoglobin: 7-9 g/dL
• Platelet count: > 50,000/μL
• PT/PTT: < 1.5× control
• Fibrinogen: > 150 mg/dL
• Ionized calcium: 1.1-1.3 mmol/L

Adjunctive therapies:

Tranexamic acid (TXA):

• Antifibrinolytic agent reducing mortality
• Dose: 1 g IV loading, then 1 g over 8 hours
• Most effective within 3 hours of injury

Cryoprecipitate:

• Used when fibrinogen < 100-150 mg/dL
• Dose: 10 units (2 pools) raises fibrinogen ~75 mg/dL

Calcium supplementation:

• Citrate in blood products chelates calcium
• Give 1 g calcium chloride per 4-6 units transfused

Complications and Management

Metabolic complications:

• Hypocalcemia: Monitor ionized calcium, supplement as needed
• Hyperkalemia: From cell lysis in stored blood
• Acid-base imbalance: Metabolic acidosis from hypoperfusion
• Hypothermia: Use blood warmers, maintain normothermia

Coagulation complications:

• Dilutional coagulopathy prevented by balanced protocols
• Monitor with point-of-care testing when available
• Consider recombinant factor VIIa in refractory bleeding