Exam-Ready Answers (10 Marks Each)

1. Massive Blood Transfusion - Definition and Complications

Definition

• Transfusion of 3 units of PRBCs within 1 hour, or
• Use of 4 blood components within 30 minutes
• Replacement of >1 blood volume (approximately 70 mL/kg) within 24 hours

Complications of Massive Blood Transfusion

A. Metabolic Complications

• Stored blood is at 4°C; rapid infusion causes core temperature to fall
• Hypothermia reduces clotting factor activity, worsens coagulopathy, promotes arrhythmias
• Prevention: blood warmers, warming blankets, warmed IV fluids

• Citrate is the anticoagulant used in stored blood; it chelates ionized calcium
• In MBT, citrate accumulation causes hypocalcemia
• Manifestations: myocardial depression, prolonged QT, tetany, coagulopathy
• Treatment: IV calcium gluconate (10 mL of 10% solution per 4 units)

• Stored PRBCs leak potassium into plasma over time (plasma K+ in stored PRBCs = ~20.5 mmol/L at day 35)
• Rapid infusion can cause fatal cardiac arrhythmias, especially in neonates and those with renal failure
• Conversely, post-transfusion hypokalemia can occur as cells re-uptake K+

• Stored blood has a pH of ~6.79 and lactate of ~9.4 mmol/L
• Large transfusions deliver an acid load
• Worsened by tissue hypoperfusion from hemorrhagic shock (note: paradoxical metabolic alkalosis can develop later as citrate is metabolized to bicarbonate)

B. Hematologic / Coagulation Complications

• Stored PRBCs are depleted of clotting factors and platelets
• Massive transfusion with PRBCs alone dilutes functional factors below hemostatic threshold
• Target: PT/INR <1.5, fibrinogen >1.5 g/L
• Correction: FFP, cryoprecipitate, platelet transfusion

• Platelets are consumed and diluted; count may fall <50,000/µL
• Clinically manifested as diffuse microvascular oozing

• Triggered by massive hemorrhage, tissue injury, and release of procoagulants
• Consumption of clotting factors and platelets with secondary fibrinolysis
• Lab: raised PT/PTT, raised D-dimer, decreased fibrinogen

C. Cardiovascular Complications

• Rapid large-volume transfusion in patients with cardiac compromise
• Presents: dyspnea, hypertension, pulmonary edema, raised BNP
• Prevention: judicious rate of infusion, diuretics

• Stored blood develops microaggregates of platelets, leukocytes, fibrin
• Can cause pulmonary microvascular obstruction; use of microfilters (40 µm) helps

D. Infectious/Immunologic Complications

• Allogeneic transfusion suppresses immune function; associated with increased postoperative infections, tumor recurrence, and prolonged ICU stay

• Bacterial contamination (especially platelets), HIV (1:2.3 million), HCV (1:2.6 million), HBV (1:1.5 million)

Mnemonic for complications: "H3C2 DIM"

2. Mismatched Blood Transfusion - Management

Definition

Pathophysiology

• Recipient has preformed IgM antibodies against donor ABO antigens
• Antibody-antigen binding activates complement cascade → intravascular hemolysis within seconds to minutes
• Vasoactive mediators released → fever, hypotension, shock
• Hemoglobin released → renal tubular precipitation → acute renal failure
• Activation of coagulation → DIC

Clinical Features

• Fever, chills, rigors (early warning sign)
• Back pain / loin pain (due to renal involvement)
• Chest tightness, dyspnea
• Sensation of impending doom
• Burning at infusion site
• Headache, nausea, vomiting

• Hypotension, tachycardia, shock
• Hemoglobinuria (red/brown urine - "port-wine urine")
• Jaundice (later)

• Rise in temperature
• Unexplained tachycardia
• Hypotension
• Hemoglobinuria
• Diffuse oozing in surgical field (from DIC)

Laboratory Abnormalities

• Decreased hemoglobin/hematocrit
• Hemoglobinemia and hemoglobinuria
• Raised LDH, raised indirect bilirubin
• Decreased serum haptoglobin
• Positive direct antiglobulin (Coombs) test on post-transfusion specimen
• Evidence of DIC: prolonged PT/PTT, decreased fibrinogen, raised D-dimer
• Schistocytes/spherocytes on peripheral smear

Management (Stepwise)

• Disconnect at the earliest suspicion
• Do NOT restart the same unit

• Replace IV tubing completely
• Start aggressive IV crystalloid fluid therapy (Normal Saline)
• Target urine output: 1-2 mL/kg/hour to flush free hemoglobin from tubules and prevent renal tubular necrosis

• Send: recipient blood (DAT, repeat type & crossmatch, plasma-free Hb, CBC, chemistry, haptoglobin, LDH, bilirubin, PT/PTT, D-dimer, fibrinogen)
• Send: residual donor blood + tubing back to blood bank for re-crossmatch and culture
• Send: urine for hemoglobinuria

• Vigorous IV fluids remain the cornerstone
• Furosemide: may be used as a diuretic to maintain urine flow if fluid-loaded
• Mannitol (20%, 100 mL): osmotic diuretic to prevent tubular precipitation
• Vasopressors (dopamine/noradrenaline) if hypotension persists despite fluids

• Fresh Frozen Plasma (FFP) for coagulation factor replacement
• Cryoprecipitate if fibrinogen <1 g/L
• Platelet transfusion if count <50,000/µL with active bleeding

• If oliguric/anuric despite above measures: renal replacement therapy (hemodialysis)
• Monitor urea, creatinine, electrolytes

• High-dose IV hydrocortisone to reduce immune-mediated inflammatory response

• Formal incident reporting
• Identify source of error (clerical/laboratory)

3. Complications of Blood Transfusion - Immune-Mediated

A. HEMOLYTIC REACTIONS

1. Acute Hemolytic Transfusion Reaction (AHTR)

• Cause: ABO incompatibility (preformed IgM antibodies) - almost always a clerical error
• Mechanism: Intravascular complement-mediated hemolysis within minutes
• Clinical: Fever, chills, back pain, hemoglobinuria, hypotension, shock, DIC, renal failure
• Onset: During or within hours of transfusion
• Management: Stop transfusion, IV fluids, maintain urine output (see above)
• Incidence: 1:100,000 units; mortality 1:100,000 units

2. Delayed Hemolytic Transfusion Reaction (DHTR)

• Cause: Non-ABO antibodies (Kidd, Duffy, Rh, Kell antigens) - anamnestic (secondary) antibody response in previously sensitized patient
• Mechanism: Extravascular hemolysis by IgG antibodies; initially below detection on crossmatch
• Onset: 3-10 days post-transfusion
• Clinical: Falling Hb/Hct, mild fever, jaundice, hemoglobinuria (less severe than AHTR)
• Lab: Positive DAT, new alloantibody on repeat screen, raised bilirubin/LDH
• Management: Usually self-limiting; supportive care; future crossmatch must identify new antibody

B. NON-HEMOLYTIC IMMUNE REACTIONS

3. Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

• Most common immune-mediated reaction (incidence: 0.1-1% per unit)
• Cause: Two mechanisms:
  • Recipient anti-leukocyte antibodies reacting with donor WBC antigens
  • Cytokines (IL-1, IL-6, TNF-alpha) accumulated in stored blood during "storage lesion"
• Clinical: Temperature rise ≥1°C (1.8°F) during or within 4 hours of transfusion, with rigors and chills - no other explanation
• Diagnosis of exclusion - must rule out AHTR first, especially in first-time transfusion or with T >2°C rise
• Treatment: Stop transfusion, acetaminophen (paracetamol); rigors treated with meperidine (0.5-0.75 mg/kg) or fentanyl; leukocyte-reduced blood reduces risk by ~50% for RBCs, ~93% for platelets

4. Allergic / Anaphylactic Reactions

• Mild (urticarial): Caused by recipient antibodies against donor plasma proteins; presents as hives, pruritus, flushing; incidence ~1%
  • Management: Slow/stop transfusion, antihistamines; may restart slowly if symptoms resolve
• Severe (anaphylaxis): Rare but life-threatening; often in IgA-deficient patients who have anti-IgA antibodies; presents with bronchospasm, laryngospasm, hypotension, cardiovascular collapse within seconds to minutes
  • Management: Stop transfusion immediately - do NOT restart same unit; treat as anaphylaxis (epinephrine, steroids, antihistamines); future transfusions require IgA-deficient or washed blood products

5. Transfusion-Related Acute Lung Injury (TRALI)

• Leading cause of transfusion-related mortality in many countries
• Mechanism: Donor anti-HLA or anti-HNA (human neutrophil antigen) antibodies react with recipient leukocytes in pulmonary microvessels, causing neutrophil activation and capillary leak (non-cardiogenic pulmonary edema)
• Diagnostic Criteria (CDC/NHSN):
  • No acute lung injury before transfusion
  • Acute onset during or within 6 hours of transfusion cessation
  • Hypoxemia: PaO2/FiO2 ≤300 mmHg OR SpO2 <90% on room air
  • Bilateral infiltrates on CXR
  • No evidence of left atrial hypertension (distinguishes from TACO)
• Clinical: Acute respiratory distress, non-productive cough, fever, hypotension
• Management: Supportive; supplemental O2, mechanical ventilation if needed; no diuretics (unlike TACO); usually resolves in 48-96 hours
• Prevention: Use of male-donor plasma (female donors more likely to have HLA antibodies from pregnancy); leukocyte reduction

6. Transfusion-Associated Circulatory Overload (TACO)

• Mechanism: Volume overload in patients with poor cardiac/renal reserve
• Clinical: Hypertension (vs hypotension in TRALI), dyspnea, pulmonary edema, raised BNP
• Management: Upright posture, diuretics (furosemide), oxygen; slower transfusion rate in at-risk patients (elderly, CHF)
• Distinguishing from TRALI: TACO - raised BNP, elevated PCWP, cardiomegaly; TRALI - normal/low PCWP, leukocyte antibodies in donor blood

7. Post-Transfusion Purpura (PTP)

• Rare; occurs 5-10 days post-transfusion in previously sensitized patients
• Mechanism: Alloantibodies (usually anti-HPA-1a) destroy both donor AND recipient platelets
• Clinical: Sudden severe thrombocytopenia (platelet count <10,000/µL), purpura, bleeding
• Management: IV immunoglobulin (IVIG) - first line; plasmapheresis; avoid platelet transfusion (paradoxically worsens)

8. Transfusion-Related Immunomodulation (TRIM)

• Allogeneic blood suppresses immune function (downregulation of NK cells, T-helper cells)
• Clinically associated with: increased postoperative infections, cancer recurrence after curative surgery, increased ICU length of stay
• Leukoreduction reduces (but does not eliminate) TRIM

9. Graft-versus-Host Disease (TA-GvHD)

• Transfusion-associated; occurs in immunocompromised patients (premature neonates, organ transplant recipients, cancer patients on chemotherapy)
• Donor T-lymphocytes engraft and attack host tissues
• Clinical: Fever, erythroderma, diarrhea, hepatitis, pancytopenia; mortality >90%
• Prevention: Irradiation of cellular blood components (25 Gy gamma irradiation)

Summary Table - Immune-Mediated Reactions

4. Autologous Transfusion + Current Status

Definition

Types of Autologous Transfusion

1. Preoperative Autologous Donation (PAD)

• Collection starts 4-5 weeks before surgery (ideally no later than 28 days before)
• Each session collects 1-2 units of whole blood, repeated weekly
• Minimum interval between donations: 72 hours (to allow plasma volume restoration)
• Eligibility: Hematocrit ≥34% or Hb ≥11 g/dL before each donation
• Usually 3-4 units can be collected; combined with iron supplementation + erythropoietin to boost erythropoiesis
• Stored for up to 35-42 days in CPD anticoagulant

• Eliminates risk of transfusion-transmitted infections (HIV, HCV, HBV)
• Eliminates risk of alloimmunization
• Reduces (but does not eliminate) risk of TRALI
• Provides compatible blood for patients with multiple alloantibodies or rare blood types
• Acceptable to some patients who refuse allogeneic blood (e.g., Jehovah's Witnesses - debated)

• Not risk-free: clerical errors can still cause ABO incompatibility
• Bacterial contamination possible
• Metabolic derangements from stored blood (same as allogeneic stored blood)
• TACO and TRIM can still occur
• High wastage rate (~45% of PAD units are never transfused)
• Creates preoperative anemia - postdonation anemia is a significant concern
• Not cost-effective for routine low-risk procedures
• Donated units cannot be used by general blood bank if unused

2. Acute Normovolemic Hemodilution (ANH)

• 1-2 units withdrawn via large-bore IV catheter just before surgical incision
• Volume replaced with crystalloid (3:1 ratio) and/or colloid (1:1 ratio) to maintain normovolemia
• Target hematocrit: 21-25% (hemodiluted)
• Blood stored in CPD bags at room temperature for up to 6 hours (preserves platelet function)
• Reinfused after major blood loss (or end of surgery)

• Fresh autologous blood returned (with viable platelets and clotting factors)
• Simple and inexpensive
• No storage lesion concerns

• Use now rare due to improving safety of allogeneic transfusion
• Requires significant anticipated blood loss (>1000 mL) to be worthwhile
• Not suitable for patients with cardiovascular compromise (cannot tolerate hemodilution)

3. Perioperative Blood Salvage (Cell Salvage / Intraoperative Blood Salvage - IOBS)

• Shed blood is aspirated into reservoir mixed with heparin
• After sufficient collection, RBCs are washed to remove debris, anticoagulant, activated clotting factors, and fat
• Concentrated RBCs (Hct 50-60%) are reinfused

• Septic contamination of surgical field
• Malignancy (relative - concern for tumor cell reinfusion; newer systems with leukocyte depletion filters may reduce this risk)
• Bowel contamination

Current Status of Autologous Transfusion

1. Dramatically reduced risk of transfusion-transmitted infections (HIV risk now 1:2.3 million)
2. High wastage rate (~45% of PAD units wasted) - costly and inefficient
3. Adoption of restrictive transfusion strategies (transfuse only when Hb <7-8 g/dL) means fewer patients actually need the donated units
4. IOBS (cell salvage) is now preferred - clinically efficacious, no storage concerns, less wasteful
5. Erythropoiesis-stimulating agents (ESAs) + iron are recommended for anemic patients before surgery as an alternative blood conservation strategy

• Patients with multiple alloantibodies or rare blood types where compatible blood is difficult to source
• Patients who refuse allogeneic blood (e.g., certain religious groups)
• PAD remains in use but is NOT recommended routinely due to cost and high wastage

• Optimize preoperative hemoglobin (iron, ESA, B12, folate)
• Minimize surgical blood loss (cell salvage, tranexamic acid, deliberate hypotension)
• Use restrictive transfusion triggers (Hb 7-8 g/dL)
• IOBS (cell salvage) is the cornerstone for major operations

5. Blood Component Therapy

Introduction

Blood Components and Their Uses

1. Packed Red Blood Cells (PRBCs)

• pH: 6.79; pCO2: 79 mmHg; plasma K+: 20.5 mmol/L; lactate: 9.4 mmol/L

• Symptomatic anemia
• Acute blood loss with hemodynamic compromise
• Transfuse when Hb <7 g/dL in critically ill patients (restrictive strategy)
• Hb <8 g/dL in patients with cardiovascular disease or undergoing cardiac surgery
• Never transfuse solely to augment volume when no significant anemia exists

2. Fresh Frozen Plasma (FFP)

• Active bleeding with documented coagulation factor deficiency (PT/INR >1.5 or APTT >1.5x normal)
• Reversal of warfarin in emergency (before PCC availability)
• Massive transfusion (1:1 with PRBCs)
• TTP (therapeutic plasma exchange)
• DIC with active bleeding

3. Platelet Concentrates

• Active bleeding with platelets <50,000/µL
• Prophylactic transfusion when platelets <10,000/µL (risk of spontaneous hemorrhage)
• Pre-procedure threshold: <50,000/µL for minor procedures, <100,000/µL for neurosurgery/ophthalmic surgery
• Massive transfusion (1:1:1 protocol with PRBCs and FFP)

4. Cryoprecipitate

• Factor VIII (80-120 IU/bag)
• von Willebrand Factor (vWF)
• Fibrinogen (150-250 mg/bag)
• Factor XIII
• Fibronectin

• Hypofibrinogenemia (fibrinogen <1 g/L) - most common indication
• Hemophilia A (when Factor VIII concentrate unavailable)
• von Willebrand disease (when vWF concentrate unavailable)
• Massive transfusion / DIC with fibrinogen deficiency
• Uremic bleeding (desmopressin preferred but cryoprecipitate second line)

5. Factor Concentrates

• Factor VIII concentrate: Hemophilia A
• Factor IX concentrate: Hemophilia B
• Prothrombin Complex Concentrate (PCC): Emergency reversal of warfarin; contains factors II, VII, IX, X (4-factor PCC); faster and more reliable than FFP for anticoagulation reversal
• Recombinant Factor VIIa (rFVIIa): Life-threatening hemorrhage unresponsive to conventional therapy; very expensive

6. Granulocyte Transfusions (Rarely Used)

• Indications: Severe neutropenia (<500/µL) with life-threatening bacterial/fungal infection unresponsive to antibiotics; neonatal sepsis
• Short shelf life (24 hours); must be ABO and Rh compatible; irradiated to prevent TA-GvHD

7. Human Albumin

• 4.5% solution: volume expansion in hypoalbuminemia, liver cirrhosis, spontaneous bacterial peritonitis, large-volume paracentesis
• 20-25% (hyperoncotic): hypoalbuminemia, hepatorenal syndrome

Transfusion Thresholds (ASA 2015 Guidelines)

Special Modifications to Blood Components