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Coronary Circulation and Physiology

Notes for Anaesthesia (Miller's, Barash, Guyton)

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1. Coronary Anatomy

Left Coronary System

• The Left Main Coronary Artery (LMCA) arises from the left aortic sinus and divides into:
  • Left Anterior Descending (LAD): courses down the interventricular groove; gives rise to diagonal branches (anterolateral LV wall) and septal branches (interventricular septum, bundle branches, Purkinje system); terminates at the LV apex
  • Left Circumflex (LCx/LCCA): courses along the left AV groove; gives rise to obtuse marginal branches supplying the lateral LV wall

Right Coronary System

• Right Coronary Artery (RCA): traverses the right AV groove; gives off acute marginal branches to the RV anterior wall
• In 85% (right-dominant): RCA gives rise to the Posterior Descending Artery (PDA) supplying the posterior-inferior LV
• In 15% (left-dominant): LCx gives rise to the PDA

Territory Summary (Barash, p. 850-851)

Clinical pearl: Ischemia of the dominant artery territory can cause SA/AV nodal dysfunction and bradyarrhythmias. RCA or LAD occlusion can both cause RV dysfunction.

Papillary Muscle Blood Supply

• Posterior-medial papillary muscle: single supply from RCA or LCx (2:1 ratio) - highly vulnerable to ischemia; ~1/3 of people have dual supply (less susceptible)
• Anterolateral papillary muscle: dual supply from LAD + LCx - ischemia unusual

Coronary Venous Drainage

• ~75% of LV coronary venous blood returns via the coronary sinus to the right atrium
• RV venous blood returns via anterior cardiac veins directly to RA
• Small amount via Thebesian veins into all cardiac chambers (physiological right-to-left shunt)

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2. Coronary Physiology

2.1 Basic Flow Dynamics - Poiseuille's Law

Flow = Perfusion Pressure / Vascular Resistance

• Resistance varies with the 4th power of vessel radius - even tiny changes in caliber produce large changes in resistance
• Coronary blood flow is exquisitely sensitive to arteriolar vasomotor tone
• Blood viscosity (driven mainly by hemoglobin concentration) is a minor factor unless extreme polycythemia or haemodilution is present

• ~225-250 mL/min (~70 mL/min/100 g)
• Represents 4-5% of cardiac output
• With strenuous exercise: increases 3-4 fold (but cardiac workload increases 6-9 fold, so efficiency of oxygen utilisation must increase)

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2.2 Coronary Perfusion Pressure (CPP)

• Coronary venous pressure is negligible
• Elevated LVEDP impedes subendocardial blood flow - critical in aortic stenosis, LVH, heart failure
• After coronary stenosis, distal vessels dilate maximally - flow becomes pressure-dependent and manipulating CPP is the primary tool for managing ischaemia

CPP (LV) = Aortic DBP - LVEDP

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2.3 Phasic Nature of Coronary Flow - Systole vs Diastole

• ~70-80% occurs during diastole because extravascular compressive forces during systole markedly impede subendocardial intramural vessel flow
• During systole: intraventricular pressure and coronary vascular resistance both rise, compressing intramural vessels
• During diastole: metabolically mediated arteriolar dilation preferentially increases subendocardial flow

• Normal subepicardial : subendocardial flow = 1:1 (preserved by metabolic dilation during diastole)
• This ratio is compromised first by tachycardia, stenosis, or hypertrophy

• Intracavitary pressures remain below aortic pressure throughout the cardiac cycle
• Therefore, compressive forces do NOT significantly impede flow - RV/LA/RA flow is relatively continuous throughout the cardiac cycle

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2.4 Heart Rate and Coronary Flow

• Tachycardia shortens diastole disproportionately more than systole (non-linear relationship)
• Subendocardial flow is initially maintained by recruiting coronary flow reserve
• When flow reserve is exhausted (stenosis, LVH), tachycardia causes subendocardial ischaemia
• This is the mechanism behind beta-blockers as anti-ischaemic drugs - by slowing HR, they lengthen diastole and restore subendocardial perfusion time

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2.5 Myocardial Metabolism and Oxygen Requirements

• Heart weight = 0.5% of total body weight, yet accounts for 7% of total body oxygen consumption
• ~75% of haemoglobin-bound oxygen is extracted across the myocardial capillaries
• Coronary sinus PO₂ ≈ 20 mmHg (extremely low - near-maximal extraction at rest)

1. Fatty acids (predominant substrate, ~60-70%)
2. Glucose
3. Lactate (taken up and oxidised under normal conditions; produced and released during ischaemia)

• Anaerobic glycolysis is activated but ATP yield is severely limited
• Contraction ceases within 10-15 seconds of acute coronary occlusion (unless collateral flow is present)
• Lactate is released (rather than consumed) - lactate production is a marker of myocardial ischaemia

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3. Regulation of Coronary Blood Flow

3.1 Metabolic (Local) Regulation - DOMINANT MECHANISM

• Most important regulator of coronary flow
• Coronary flow is tightly coupled to myocardial oxygen demand ("flow-metabolism coupling")
• When O₂ demand rises, the myocardium releases vasodilator mediators that dilate coronary arterioles
• Key mediators of metabolic vasodilation:
  • Adenosine (most important) - produced from AMP breakdown during increased ATP turnover; potent arteriolar dilator
  • Nitric oxide (NO) - produced by endothelial NOS; causes SMC relaxation
  • Hypoxia - direct relaxation of vascular smooth muscle
  • CO₂ / H⁺ (local acidosis) - vasodilation
  • K⁺ released during repolarisation
  • Prostaglandins (prostacyclin, PGI₂)

3.2 Autoregulation

• Coronary flow is maintained constant over a CPP range of approximately 60-140 mmHg
• Below this range (CPP < 60 mmHg): flow falls (pressure-dependent zone) → ischaemia
• Above this range (CPP > 140 mmHg): flow rises (pressure breakthrough)
• Autoregulation is mediated by myogenic response of arteriolar smooth muscle + metabolic feedback
• In stenotic vessels: distal vessels are already maximally dilated to maintain resting flow; autoregulation is abolished and flow becomes entirely pressure-dependent - hence the importance of CPP in CAD patients
• Autoregulation is impaired by: volatile anaesthetics (dose-dependent), extreme tachycardia, severe hypoxia, marked acidosis

3.3 Neural (Autonomic) Regulation

• The coronary vasculature receives both sympathetic and parasympathetic innervation
• Sympathetic (α₁-adrenergic): direct vasoconstriction of coronary vessels
• Sympathetic (β₂-adrenergic): vasodilation (less prominent)
• Net effect of sympathetic stimulation: vasodilation predominates because metabolic effects (increased HR, contractility → increased O₂ demand → metabolic vasodilation) override the direct α₁ constrictive effect
• Parasympathetic (vagal): mild coronary vasodilation; acetylcholine acts via endothelial muscarinic receptors to produce NO
• Coronary conductance is regulated by arterial baroreflex: vasodilator response is induced by a rise in aortic pressure
• At low plasma fentanyl concentrations (1-2 ng/mL), baroreflex coronary control is enhanced; at higher concentrations, it is depressed (Miller's, p. 2769)

3.4 Endothelial Regulation

• Nitric oxide (NO) - synthesised by eNOS; released in response to shear stress, acetylcholine, bradykinin, substance P
• Prostacyclin (PGI₂) - via endothelial COX pathway
• Endothelium-derived hyperpolarising factor (EDHF)

• Endothelin-1 (ET-1) - potent vasoconstrictor; upregulated in atherosclerosis, heart failure
• Thromboxane A₂ (TXA₂)

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4. Determinants of Myocardial Oxygen Supply and Demand

4.1 Oxygen Supply Determinants

4.2 Oxygen Demand Determinants

Wall Stress = (Pressure × Radius) / (2 × Wall Thickness)

• LV dilatation (increased radius) → increased wall stress → increased O₂ demand
• LV hypertrophy (increased wall thickness) → reduced wall stress per unit - but capillary density may not increase proportionately, reducing O₂ supply to the hypertrophied myocardium

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5. Coronary Flow Reserve (CFR)

• CFR = Maximum coronary blood flow (after maximal vasodilation) / Resting coronary blood flow
• Normal CFR ≈ 4-5 (flow can increase 4-5 fold from baseline)
• CFR is the physiological "buffer" that allows increased demand (exercise, tachycardia) to be met
• A stenosis of >50% diameter begins to limit maximum flow; >70-80% impairs resting flow

• Coronary artery stenosis (most common)
• LV hypertrophy (increased resting flow + reduced maximum flow due to reduced capillary density)
• Microvascular disease (diabetes, hypertension)
• Tachycardia (exhausts reserve)
• Anaemia, hypotension

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6. Coronary Steal Phenomenon

• Occurs when a vasodilator (e.g., adenosine, dipyridamole, isoflurane) dilates normal vessels but cannot further dilate vessels distal to a stenosis (already maximally dilated)
• Blood is "stolen" from the ischaemic territory through collateral vessels to the dilated normal territory
• Isoflurane: most implicated volatile agent; causes coronary vasodilation and can produce steal in patients with "steal-prone" anatomy (parallel coronary stenoses with collaterals)
• Opioids: do NOT produce steal phenomena and do not diminish coronary vasomotor response (Miller's, p. 2769)
• Steal-prone anatomy: requires two stenoses and a collateral vessel connecting the territories; relatively uncommon (~23% of patients with CAD have steal-prone anatomy)

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7. Anaesthetic Effects on Coronary Circulation

Volatile Anaesthetics

• All volatile agents decrease MVO₂ by reducing HR, contractility, and wall tension (decrease in SVR reduces afterload)
• Isoflurane, desflurane, sevoflurane: all produce coronary vasodilation via K-ATP channel opening
• Ischaemic preconditioning by volatile agents: clinically significant myoprotective mechanism mediated through K-ATP channel opening, adenosine receptors, and PKC activation

Opioids (Miller's, p. 2769)

• No significant effect on coronary vasomotion or myocardial metabolism at clinical doses
• Do NOT produce steal phenomena
• Do not diminish large coronary arteriole response to vasoactive agents
• Baroreflex coronary control: enhanced at low fentanyl concentrations (1-2 ng/mL), depressed at high concentrations
• Opioids can mimic ischaemic preconditioning - opioid receptor stimulation (especially κ and δ receptors) reduces infarct size in animal models
• Remote preconditioning (ischaemia of intestine, kidney, limb) is mediated through myocardial κ-opioid receptors
• Postconditioning: δ-opioid receptor activation during early reperfusion protects against infarction; can be enhanced by morphine + isoflurane combination
• Late preconditioning (24 hours after morphine) has also been demonstrated in animal models

Perioperative Ischaemia Management

• Vigilant monitoring needed for supply-demand imbalance: ECG with ST-segment analysis + TEE for regional wall motion abnormalities
• Causes of reduced supply: hypotension, tachycardia, anaemia, coronary vasoconstriction
• Causes of increased demand: tachycardia, increased afterload (hypertension), increased contractility
• Beta-blockers: cornerstone - reduce HR (lengthen diastole, reduce demand), and prevent even small perioperative HR increases

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8. Myocardial Ischaemia and Infarction

Ischaemia Cascade (in order of appearance):

1. Metabolic changes (lactate production, reduced ATP)
2. Diastolic dysfunction (relaxation impaired)
3. Systolic dysfunction (regional wall motion abnormality - detected by TEE)
4. ECG changes (ST changes)
5. Symptoms (chest pain) - last to appear

Consequences of Acute Myocardial Infarction (Guyton, p. 271-272):

1. Decreased cardiac output - systolic stretch: ischaemic muscle passively bulges outward during systole, wasting contractile energy; cardiogenic shock if >40% LV infarcted (mortality 40-50%)
2. Pulmonary oedema - reduced CO → reduced renal flow → fluid retention → elevated pulmonary venous pressure
3. Ventricular fibrillation - most common cause of sudden death; two high-risk windows: within 10 minutes of infarction, and 1-several hours later

Ischaemic Preconditioning

• Brief episodes of ischaemia-reperfusion make the myocardium more resistant to subsequent prolonged ischaemia
• Mediated by: adenosine A₁ receptors, K-ATP channels, PKC, mitochondrial permeability transition pore
• Early preconditioning: within minutes, lasts 1-2 hours
• Late preconditioning: 24-72 hours after stimulus (mediated by protein synthesis, iNOS)
• Opioids and volatile anaesthetics can both pharmacologically precondition the heart

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9. Quick Reference - Key Numbers

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• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e - Chapter 12 (Coronary Anatomy, pp. 850-858; Coronary Physiology, pp. 857-869)
• Miller's Anesthesia, 10e - Coronary Anatomy & Determinants of MVO₂ (pp. 7584-7586); Opioids & Coronary Circulation (pp. 2769-2770)
• Guyton & Hall Textbook of Medical Physiology - Coronary Circulation (pp. 270-272)

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Blood Transfusion - Concise Chapter Notes

Miller's Anesthesia, 10th Edition - Chapter 45

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PART 1: COMPREHENSIVE NOTES

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1. Historical Evolution of Transfusion Practice

"The timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss to improve patient outcome."

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2. Blood Procurement and Transfusion-Transmitted Infections

Donor Sources

• Allogeneic (homologous): From another person
• Autologous: Patient's own blood (preoperative donation, ANH, cell salvage)
• Directed donation: From a specific designated donor (e.g., family member)

Infectious Disease Testing (All units in the US, 2021)

• HIV-1/2 antibody (ELISA + NAT)
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV + NAT)
• HTLV-I/II antibody
• West Nile Virus (NAT)
• Treponema pallidum (syphilis)
• Trypanosoma cruzi (Chagas disease) - first donation only
• Babesia (endemic areas)
• Zika virus (NAT)

Risk of Transfusion-Transmitted Infection (per unit, screened blood, USA)

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3. Biochemical Changes in Stored Blood (Storage Lesion)

Anticoagulant-Preservative Solutions

• Hct of CPDA-1 PRBCs ≈ 65%, volume ~250 mL
• Hct of AS-1 PRBCs ≈ 55-60%, volume ~310 mL (100 mL additive solution added)
• Storage regulation: At least 70% of transfused RBCs must remain in circulation for 24 hours post-transfusion

Progressive Storage Lesion Changes (RBC)

• Hct: 57%, pH 6.79, pCO₂ 79 mmHg, HCO₃ 11 mmol/L, Na⁺ 126 mmol/L, K⁺ 20.5 mmol/L, Glucose 24 mmol/L, Lactate 9.4 mmol/L

2,3-DPG Restoration

• 2,3-DPG is depleted within 1-2 weeks of storage
• After transfusion: 50% restored within 24 hours, complete restoration in 48-72 hours in most patients
• Clinical significance: Stored blood transfused acutely may initially deliver less O₂ at tissue level (though at normal physiologic pH, the oxyhemoglobin curve returns toward normal fairly quickly)

Duration of Storage - Clinical Evidence

• Multiple RCTs (RECESS, INFORM, TRANSFUSE, ABLE trials) have largely shown no significant difference in outcomes between fresh and older stored blood in most clinical settings
• Current evidence does not support a specific preference for fresh blood in most patients

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4. Blood Components - Characteristics and Indications

4.1 Packed Red Blood Cells (PRBCs)

• Same Hb content as whole blood but plasma removed; Hct ~57-60%
• Indication: Symptomatic anaemia OR Hb below the transfusion trigger

• ✅ Normal saline (0.9% NaCl) - most common
• ✅ 5% Dextrose in 0.9% or 0.45% NaCl
• ✅ Normosol-R (pH 7.4)
• ❌ Lactated Ringer - contains Ca²⁺ → can activate clotting cascade, NOT recommended
• ❌ Hypotonic solutions → RBC swelling → haemolysis

• 1 unit PRBCs raises Hb by ~1 g/dL (Hct by ~3%) in a 70 kg adult
• Formula: Units needed = (Target Hb - Current Hb) × Body weight (kg) × 0.3

4.2 Preoperative Anaemia and Transfusion Triggers

• Restrictive: Transfuse when Hb ≤ 7-8 g/dL
• Liberal: Transfuse when Hb ≤ 9-10 g/dL
• 2022 Cochrane Review (48 trials, >21,000 patients): Restrictive strategy reduced transfusion exposure by 41% with NO increase in mortality, MI, stroke, pneumonia, or thromboembolism

• Cardiac surgery / active CAD: Consider transfusion at Hb 8-9 g/dL
• Hip fracture repair (FOCUS trial): Restrictive (Hb 8 g/dL) equivalent to liberal
• ICU patients (TRICC trial): Restrictive (7 g/dL) equivalent or superior to liberal (10 g/dL) except in acute MI/unstable angina

1. Iron (oral or IV) - treat iron-deficiency anaemia ≥4 weeks preoperatively ideally
2. Erythropoiesis-stimulating agents (ESAs) - epoetin alfa, darbepoetin - for renal anaemia, chemotherapy anaemia; risk: hypertension, thrombotic events
3. Vitamin B12/folate if deficient
4. Avoid preoperative transfusion in stable anaemia - recent data show no benefit and may increase complications

4.3 Platelet Concentrates

• Prophylactic: < 50,000/μL for most invasive procedures; < 100,000/μL for CNS/ocular surgery
• Therapeutic (active bleeding): < 50,000/μL + microvascular bleeding
• Massive transfusion: Platelet count < 50,000/μL (massive transfusion dilutes platelets)

4.4 Fresh Frozen Plasma (FFP)

• Contains all plasma proteins including labile factors V and VIII
• Processed soon after donation, frozen within 8 hours (FFP) or 24 hours (PF24)
• Thawed plasma: stored 1-6°C for up to 5 days - logistically useful for trauma centres
• PF24 is comparable to FFP except ~25% less factor VIII and slight reduction in factor V
• Dose: 10-15 mL/kg typically; 1 unit (~250 mL) raises all factors by ~3%

1. Obtain coagulation studies first (when feasible)
2. INR > 2.0 in absence of heparin with active/anticipated bleeding
3. Coagulopathy during massive transfusion > 1 blood volume (~70 mL/kg) when coagulation tests unavailable
4. Known factor deficiency with bleeding when specific concentrates unavailable
5. Warfarin reversal with severe bleeding when prothrombin complex concentrates (PCCs) unavailable

4.5 Cryoprecipitate

• Produced by slow thawing of FFP at 4°C - precipitate re-suspended in ~10-15 mL plasma
• Contents per unit: Fibrinogen (~250 mg), Factor VIII (~80 IU), vWF, Factor XIII, Fibronectin
• Stored at -18°C; once thawed, used within 4-6 hours
• 1 unit per 7-10 kg raises fibrinogen by ~50 mg/dL

• Hypofibrinogenaemia (fibrinogen < 100 mg/dL with bleeding; < 150 mg/dL in obstetric haemorrhage)
• Haemophilia A (factor VIII deficiency) - if specific concentrate unavailable
• von Willebrand disease - if specific concentrate/DDAVP unavailable
• Factor XIII deficiency
• DIC with bleeding

4.6 Freeze-Dried (Lyophilised) Plasma

• Dehydrated plasma that reconstitutes with sterile water
• Advantage: Room temperature storage, long shelf life, instant availability
• Being re-evaluated for prehospital/military use

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5. Massive Transfusion

Lethal Triad of Trauma

Hypothermia + Acidosis + Coagulopathy - mutually reinforce each other

Massive Transfusion Protocol (MTP) - Damage Control Resuscitation

• Reconstituted whole blood concept: PRBC : FFP : Platelets in a ratio approaching 1:1:1
• This ratio mimics whole blood and prevents dilutional coagulopathy
• Evidence: Military experience, prospective studies (PROPPR trial - 1:1:1 vs 1:1:2 ratio showed improved haemostasis and 24-hour survival with 1:1:1)

• Factor V: falls to 50% at 21 days, 20% at 35 days
• Factor VIII: falls to 30% at 21 days, 20% at 35 days
• However: only 5-20% of Factor V and 30% of Factor VIII are needed for surgical haemostasis - levels rarely fall below these thresholds during massive transfusion alone

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6. Compatibility Testing

ABO-Rh System

• Serum contains naturally occurring antibodies (anti-A, anti-B) against absent antigens
• Anti-A and anti-B are IgM antibodies - activate complement → acute intravascular haemolysis
• 15% of all transfusion-related deaths are from ABO-incompatibility haemolytic reactions

• 85% of people are Rh(D) positive; 15% Rh(D) negative
• Anti-D antibodies are IgG - do NOT fix complement readily → primarily extravascular haemolysis
• 60-70% of Rh(D)-negative recipients given Rh(D)-positive blood will form anti-D antibodies

Types of Compatibility Tests

1. Uncrossmatched O− PRBCs: Immediate availability; for life-threatening haemorrhage
2. ABO-specific uncrossmatched: After blood group identified (~5-10 min)
3. Electronic crossmatch: After 2 separate ABO typings - equivalent safety to full crossmatch
4. Full serologic crossmatch: Full compatibility assured

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7. Autologous Blood Strategies

7.1 Preoperative Autologous Donation (PAD)

• Patient donates their own blood 3-5 weeks before elective surgery
• Usually 1-3 units collected weekly, last donation ≥72 hours pre-op
• Advantages: Eliminates allogeneic transfusion risks; no cross-matching needed
• Disadvantages:
  • Risk of same collection/labelling errors
  • Blood cannot always be used (wastage)
  • Donation itself causes anaemia → may paradoxically increase transfusion rate
  • Not cost-effective for low-risk surgeries

• Severe aortic stenosis, unstable angina, bacteraemia/septicaemia, severe anaemia, seizure disorders, acute illness, inability to donate (very young, morbidly obese)

7.2 Acute Normovolemic Haemodilution (ANH)

• Expected major blood loss > 20% blood volume
• Hb ≥ 12 g/dL preoperatively
• No significant CAD, renal/hepatic impairment, hypovolaemia

7.3 Intraoperative Cell Salvage (ICS)

• Provides leukocyte-reduced, washed, plasma-free blood
• No risk of allogeneic transfusion complications
• Cost-effective in procedures with >1 L expected blood loss

• Malignancy (risk of tumour cell reinfusion) - can use leukocyte depletion filter
• Bacterial contamination of surgical field (intestinal perforation) - relative contraindication
• Sickle cell disease - may return sickled cells (though debated)
• Amniotic fluid contamination in obstetric surgery - relative; leukodepletion filters reduce risk

• Air embolism, haemolysis, microaggregates, coagulopathy (washing removes coagulation factors), hypovolaemia from inadequate re-infusion

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8. Transfusion Reactions

8.1 Acute Haemolytic Transfusion Reaction (AHTR)

• In awake patient: Fever, chills, back/flank pain, chest pain, nausea/vomiting, anxiety, sense of doom, flushing, haematuria
• Under general anaesthesia (masked): Haemoglobinuria (first sign), unexplained hypotension, microvascular bleeding (oozing), DIC
• As little as 10 mL of incompatible blood can trigger a reaction
• As little as 50 mL can exceed haptoglobin binding capacity (Hb > 100 mg/100 mL plasma) → free Hb in plasma

1. Stop the transfusion immediately
2. Keep IV access open with normal saline
3. Notify blood bank and return blood bag + tubing
4. Maintain urine output ≥ 1 mL/kg/hr (goal 75-100 mL/hr)
5. Administer furosemide or mannitol to force diuresis
6. Treat hypotension with IV fluids ± vasopressors
7. Send blood and urine to blood bank for examination (DAT, repeat crossmatch)
8. Monitor for DIC (PT, aPTT, fibrinogen, D-dimer, platelet count)
9. Prevent/treat acute renal failure (avoid nephrotoxins, maintain BP)

8.2 Delayed Haemolytic Transfusion Reaction (DHTR)

• Occurs 2-21 days post-transfusion
• Mechanism: Prior sensitisation to minor RBC antigens (Rh, Kidd system most common) → anamnestic IgG response after re-exposure → extravascular haemolysis (reticuloendothelial system)
• More common in: females, multiply-transfused patients
• Signs: Unexplained fall in Hb, jaundice, haemoglobinuria (mild), rarely renal failure
• NOT preventable by pre-transfusion testing (antibody level too low to detect at time of transfusion)
• Clinical pearl: Consider DHTR in any patient with unexplained Hb drop 2-21 days post-transfusion before returning to OR for "bleeding"

8.3 Transfusion-Related Acute Lung Injury (TRALI)

• Leading cause of transfusion-related mortality (2012-2016, FDA data)
• Definition: New acute lung injury (ALI/ARDS) within 6 hours of transfusion in absence of other ALI risk factor; bilateral infiltrates on CXR, PaO₂/FiO₂ < 300, no left atrial hypertension

1. First hit: Patient risk factors (surgery, critical illness, inflammation)
2. Second hit: Donor antibodies (anti-HLA class I/II or anti-neutrophil antibodies) or biologically active lipids in stored blood → neutrophil activation → pulmonary capillary leak

• All blood components implicated; FFP highest risk (large plasma volume, female multiparous donors have higher anti-HLA antibody prevalence)
• Mitigation strategy: Male or never-transfused female donors for plasma/platelets

• Stop transfusion immediately
• Supportive care (O₂, ventilatory support - ARDS protocol)
• Notify blood bank; quarantine all units from same donor
• No specific therapy; most recover within 96 hours

8.4 Transfusion-Associated Circulatory Overload (TACO)

• Hydrostatic pulmonary oedema from volume overload
• Presentation: Dyspnoea, hypertension, elevated JVP, bilateral crackles, pulmonary oedema
• Distinguishes from TRALI by: Evidence of fluid overload (raised BNP/NT-proBNP, elevated LAP), hypertension, responds to diuretics
• Management: Slow or stop transfusion; diuretics; upright positioning; O₂
• Risk factors: Elderly, small body weight, cardiac dysfunction, renal failure, rapid infusion rate

8.5 Comparison: TRALI vs TACO

8.6 Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

• Most common transfusion reaction
• Cause: Recipient antibodies against donor leukocyte antigens; cytokines accumulated in stored components
• Temperature rise ≥ 1°C during or within 4 hours of transfusion
• Management: Stop transfusion, rule out haemolytic reaction; antipyretics (paracetamol)
• Prevention: Leukoreduction of blood products (filtration to remove >99.9% WBCs)

8.7 Allergic and Anaphylactic Reactions

• Mild allergic: Urticaria, pruritus - caused by donor plasma proteins
  • Management: Antihistamines; can restart transfusion slowly if symptoms resolve
• Anaphylaxis: IgA-deficient patients with anti-IgA antibodies
  • Management: Stop transfusion; epinephrine; standard anaphylaxis treatment
  • Prevention: Use IgA-deficient donor blood or washed RBCs

8.8 Other Adverse Effects

• Transfusion-associated graft-versus-host disease (TA-GvHD): Donor T-lymphocytes attack immunocompromised recipient; near 100% fatal; prevented by irradiation of cellular blood products for at-risk patients
• Post-transfusion purpura: Sudden severe thrombocytopenia 5-10 days post-transfusion; anti-HPA-1a antibodies; treated with IVIG
• Immunomodulation (TRIM): Transfusion-related immunomodulation - transfusion may suppress immunity; associated with increased infections, cancer recurrence, and possibly worse outcomes in some settings (data mixed)
• Iron overload: In chronically transfused patients (e.g., sickle cell, thalassaemia); treated with chelation therapy

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9. Citrate, Hyperkalaemia, Hypothermia, Acid-Base

Citrate Intoxication

• Citrate chelates ionised Ca²⁺ → hypocalcaemia → myocardial depression, hypotension, dysrhythmias, coagulopathy
• Risk: Infusion > 1 unit every 10 minutes, liver disease, liver transplantation, hypothermia, hyperventilation (increases citrate binding), neonates
• Even at these rates, ionised Ca²⁺ may not fall enough to cause bleeding in healthy adults
• Treatment: IV Calcium chloride (preferred in cardiac surgery - faster onset) or calcium gluconate

Hyperkalaemia

• Stored blood K⁺: ~20 mEq/L at 21 days; up to 60 mEq/L at 42 days and in irradiated units
• Net K⁺ gain per unit is modest (~10 mEq when accounting for blood lost)
• Clinically significant: Transfusion rate > 120 mL/min
• High risk: Neonates, renal failure, massive transfusion of irradiated blood
• Use the freshest available blood for at-risk patients

Hypothermia

• Stored blood at 4°C can rapidly drop patient's core temperature
• Hypothermia impairs coagulation factors and platelet function even at small decreases
• < 30°C: Ventricular irritability, cardiac arrest
• Prevention: Blood warmers (37-38°C water bath or plate warmers); never microwave blood; upper temperature limit ~43°C to prevent haemolysis

Acid-Base

• CPD preservation pH 5.5; immediately drops blood pH from 7.4 → 7.1
• After 21 days: pH ~6.9, pCO₂ ~150-220 mmHg, lactate elevated
• With adequate ventilation: The respiratory component (high pCO₂) has little consequence
• Post-transfusion: Often a metabolic alkalosis develops (citrate metabolised to bicarbonate by liver) rather than expected acidosis

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10. Measurement of Blood Loss

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PART 2: OSCE QUESTIONS ON BLOOD TRANSFUSION

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OSCE Station 1: Emergency Transfusion Scenario

A: Uncrossmatched O Rhesus-negative PRBCs (universal donor; immediately available; no crossmatching needed)

A: 1:1:1 ratio (PRBCs : FFP : Platelets) - "damage control resuscitation" to reconstitute whole blood and prevent coagulopathy

A: Hypothermia + Acidosis + Coagulopathy - mutually reinforcing; hypothermia impairs coagulation factor function, acidosis impairs enzyme activity, coagulopathy causes further bleeding and worsening perfusion. Recognising and breaking this cycle is the cornerstone of massive haemorrhage management.

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OSCE Station 2: Transfusion Reaction Under Anaesthesia

A: Acute haemolytic transfusion reaction (AHTR), most likely due to ABO incompatibility from a clerical/identification error. Intravascular haemolysis caused by complement activation from recipient anti-A or anti-B IgM antibodies against donor RBC antigens.

A: 1. Stop the transfusion immediately 2. Maintain IV access with normal saline 3. Return blood bag + tubing to blood bank 4. Maintain urine output ≥ 1 mL/kg/hr (furosemide/mannitol + IV fluids) 5. Treat hypotension (fluids ± vasopressors) 6. Send blood and urine samples to blood bank 7. Monitor for DIC (coagulation screen) 8. Recheck patient identity and blood product labelling

A: In an awake patient: fever, chills, back/flank pain, chest pain, nausea, anxiety, "sense of doom". Under GA, all symptoms are masked except: haemoglobinuria, unexplained hypotension, and microvascular bleeding/oozing (signs of DIC).

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OSCE Station 3: TRALI vs TACO

A: Stop transfusion; notify blood bank; quarantine donor units; supportive care (O₂, ARDS ventilation strategy - low tidal volume); most recover within 96 hours; no specific therapy.

A: FFP - highest plasma volume; female multiparous donors have higher rates of anti-HLA antibodies. Mitigation: Use male or never-transfused female donors for plasma products.

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OSCE Station 4: Blood Storage and Compatibility

A: No. CPDA-1 extends shelf life to only 35 days. It would need to have been collected in an additive solution (AS-1/3/5) which extends shelf life to 42 days.

A: Lactated Ringer solution - contains calcium which can chelate the citrate anticoagulant and re-activate the coagulation cascade, causing clot formation in the tubing/blood bag.

A: O Rhesus-negative PRBCs - universal donor; O group lacks A and B antigens so no ABO reaction; Rh-negative to prevent alloimmunisation (especially in females of childbearing age).

A: T&S = ABO-Rh typing + antibody screen; blood held but NOT formally crossmatched. Used for elective procedures with a low probability of transfusion (e.g., elective cholecystectomy). If screen is negative and emergency arises, blood can be released quickly (<10 min). Saves resources vs crossmatching blood that is unlikely to be needed.

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OSCE Station 5: Blood Components and Indications

A: Contents: Fibrinogen (~250 mg), Factor VIII, vWF, Factor XIII, fibronectin. Indications: Hypofibrinogenaemia (< 100-150 mg/dL with bleeding), DIC, Haemophilia A (if concentrate unavailable), vWD, Factor XIII deficiency.

A: Transfuse platelets preoperatively. The threshold for neuraxial procedures (spinal, lumbar puncture) is generally ≥ 50,000/μL (CNS/eye surgery requires ≥ 100,000/μL). After 1 adult therapeutic dose (pool) of platelets, expect an increment of ~20,000-30,000/μL.

A: (1) INR > 2.0 with active/anticipated bleeding; (2) Coagulopathy during massive transfusion > 1 blood volume when coag tests unavailable; (3) Known factor deficiency with bleeding when specific concentrate unavailable; (4) Warfarin reversal with severe bleeding when PCC unavailable.

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OSCE Station 6: Autologous Blood / Patient Blood Management

A: Pre-operatively, whole blood is withdrawn and volume replaced with crystalloid (3:1) or colloid (1:1). During surgery, surgical bleeding has a lower Hct, so less RBC mass is lost per unit volume. Blood is re-infused in reverse order of collection (last unit drawn is given back first); the first unit collected (highest Hb, most factors, best platelets) is saved and given last.

A: (1) Malignancy - risk of tumour cell reinfusion (mitigated by leukodepletion filter); (2) Bacterial contamination of field (bowel perforation); (3) Amniotic fluid contamination in obstetrics - relative contraindication; leukodepletion filters now used to allow use in obstetric haemorrhage.

A: PBM = evidence-based, multidisciplinary approach to preserve and optimise the patient's own blood. Three pillars: (1) Optimise red cell mass preoperatively (treat anaemia with iron, ESAs, vitamins); (2) Minimise blood loss (meticulous haemostasis, antifibrinolytics - TXA, surgical techniques); (3) Optimise/harness anaemia tolerance (restrictive transfusion thresholds, optimise O₂ delivery and consumption).

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