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TRALI vs TACO - Short Note (MD Anaesthesia)

Definition

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Incidence

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Pathophysiology

TRALI - Two mechanisms:

• Donor plasma contains anti-HLA (class I & II) or anti-HNA (human neutrophil antigen) antibodies
• These form from alloimmunization via pregnancy, prior transfusion, or transplantation - making multiparous female donors a high-risk source
• Antibodies complex with recipient leukocyte antigens on neutrophils, monocytes, and endothelial cells
• Neutrophil activation releases cytotoxic mediators - endothelial injury - capillary leak - non-cardiogenic pulmonary edema

• First hit: Underlying illness primes neutrophils on pulmonary microvasculature endothelium (critically ill, septic, surgical patients)
• Second hit: Stored blood products carry lipid degradation products (phosphatidylcholine derivatives) that activate already-primed neutrophils - capillary destruction
• Net result: Proteinaceous exudate floods interstitium and alveolar spaces

TACO:

• Volume/rate of transfusion overwhelms cardiac reserve
• Hydrostatic pressure rises in pulmonary capillaries - cardiogenic (transudative) edema
• Inflammation and endothelial activation also contribute beyond pure volume overload
• Risk amplified by pre-existing heart failure, renal insufficiency, hypoalbuminaemia, extremes of age

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Clinical Features - Comparison

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Diagnostic Criteria

TRALI (American-European Consensus / NHSN Hemovigilance):

1. Acute onset within 6 hours of transfusion
2. Hypoxemia: PaO2/FiO2 < 300, or SpO2 < 90% on room air
3. Bilateral pulmonary infiltrates on CXR
4. No evidence of left atrial hypertension (no circulatory overload)
5. No pre-existing ALI before transfusion

• TRALI Type I: No ARDS risk factors - classic definition
• TRALI Type II: Pre-existing mild ARDS or ARDS risk factors present (replaces "possible TRALI")

TACO (NHSN Hemovigilance):

• Acute respiratory distress
• Elevated BNP
• Elevated CVP
• Left heart failure on clinical/echo assessment
• Positive fluid balance
• Imaging evidence of pulmonary edema

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Key Differentiating Investigations

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Management

TRALI:

1. Stop transfusion immediately
2. Notify blood bank - quarantine all products from implicated donor
3. Supplemental O2; if severe: mechanical ventilation with lung-protective strategy (low tidal volume 6 mL/kg, PEEP optimisation - per ARDS protocol)
4. Caution with diuretics - hypotension may worsen; use fluid resuscitation to maintain end-organ perfusion if hypotensive
5. Vasopressors if required
6. Steroids: unclear benefit; avoid if > 14 days after lung injury onset (risk of increased damage per ARDS data)
7. ECMO: reserved for refractory severe TRALI (limited evidence)
8. Donor investigation: HLA/HNA antibody testing; defer donor if antibodies present

TACO:

1. Stop or slow transfusion immediately
2. Sit patient upright
3. Diuresis - furosemide IV (mainstay of treatment)
4. Supplemental O2; NIV/PPV if required
5. Vasodilators, nitrates if needed for afterload reduction
6. Monitor fluid balance, urine output, BNP trend

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Prevention

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Mnemonic: TRALI vs TACO

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Key Points for Exam

• TACO has overtaken TRALI as the leading cause of transfusion-related death in the USA
• Both occur within 6 hours of transfusion - timing alone cannot distinguish them
• BNP and CXR are the most practical differentiators at the bedside
• TRALI is managed with cautious fluids + lung-protective ventilation; TACO with aggressive diuresis
• They can co-exist - making clinical judgement essential
• Multiparous female donors are the most implicated donor type in TRALI
• TRALI is a clinical diagnosis - absence of donor antibodies does not exclude it
• For TRALI, the edema fluid protein-to-serum protein ratio > 0.75 confirms exudative (non-cardiogenic) nature

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TRALI vs TACO - Short Note (MD Anaesthesia)

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Definitions

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Epidemiology & Mortality Significance

TACO has overtaken TRALI as the leading transfusion-related killer in the USA, largely due to male-only plasma donor policies that reduced antibody-mediated TRALI, combined with improved TACO surveillance. (Tietz 7e)

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Pathophysiology

TRALI - Two Mechanisms

• Donor plasma contains anti-HLA (class I & II) or anti-HNA (human neutrophil antigen) antibodies, formed via alloimmunization from pregnancy, prior transfusion, or transplant
• Multiparous female donors are the highest-risk source
• Transfused antibodies bind recipient leukocyte antigens on neutrophils, monocytes, and endothelial cells
• Neutrophil activation releases oxidative and cytotoxic mediators
• Endothelial lining of pulmonary capillaries is destroyed - increased permeability - exudative, proteinaceous flood into interstitium and alveoli
• Anti-HNA3a antibodies carry the highest risk

• First hit: Underlying critical illness (sepsis, surgery, trauma, massive transfusion) primes and sequesters neutrophils on pulmonary microvasculature endothelium
• Second hit: Stored blood products deliver biologically active lipid degradation products (phosphatidylcholine derivatives) and cytokines that activate already-primed neutrophils
• Destruction of pulmonary capillary endothelium and non-cardiogenic edema follows
• Bioactive substance levels increase with prolonged blood storage
• Both mechanisms likely contribute in clinical practice (Barash Clinical Anesthesia 9e; Goldman-Cecil Medicine)

TACO

• Transfusion volume and/or rate exceeds the recipient's cardiac and renal capacity to handle the fluid load
• Hydrostatic pressure rises in pulmonary capillaries - transudative cardiogenic edema
• Inflammation and endothelial activation also contribute beyond pure volume overload
• Pre-existing ventricular dysfunction, renal insufficiency, hypoalbuminaemia, and positive fluid balance are predisposing factors (Tietz Laboratory Medicine 7e)

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Risk Factors

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Clinical Features - Side by Side

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Diagnostic Criteria

TRALI - NHSN Hemovigilance Criteria:

1. No pre-existing acute lung injury before transfusion
2. Acute lung injury (bilateral opacities on CXR)
3. Hypoxemia: PaO2/FiO2 <300 or SpO2 <90% on room air
4. Bilateral pulmonary infiltrates on imaging
5. No left atrial hypertension (i.e., no circulatory overload)
6. Onset within 6 hours of transfusion

• TRALI Type I: Classic - no ARDS risk factors; meets all above criteria
• TRALI Type II: Patient has pre-existing mild ARDS (PaO2/FiO2 200-300) or ARDS risk factors, but respiratory status was stable for 12 hours before transfusion and deteriorates post-transfusion (replaces old term "possible TRALI") (Murray & Nadel's; Tietz 7e)

TACO - NHSN Hemovigilance Criteria:

• Acute respiratory distress
• Elevated BNP
• Elevated CVP
• Evidence of left heart failure (clinical or echocardiographic)
• Positive fluid balance
• Imaging evidence of pulmonary edema (Tietz Laboratory Medicine 7e)

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Investigations - Key Differentiators

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Management

TRALI:

1. Stop transfusion immediately
2. Notify blood bank - quarantine all products from the implicated donor
3. Supplemental O2; if severe: intubation and mechanical ventilation
   • Lung-protective strategy (ARDS protocol): tidal volume 6 mL/kg IBW, optimise PEEP, avoid volume overload
4. Fluid resuscitation if hypotensive - diuretics are contraindicated if BP is low, as they will worsen haemodynamics
5. Vasopressors if hypotension persists despite fluid resuscitation
6. Steroids: no proven benefit; avoid if >14 days post-injury onset (risk of harm per ARDS data)
7. ECMO: reserved for severe refractory cases (limited evidence)
8. Donor investigation: Test for HLA and HNA antibodies; defer donor from future donations if antibodies confirmed
9. TRALI is a clinical diagnosis - absence of donor antibodies does not exclude it (Tietz 7e; Barash 9e; Miller's 10e)

TACO:

1. Stop or slow transfusion immediately
2. Sit patient upright
3. Diuresis with IV furosemide - mainstay of treatment
4. Supplemental O2; NIV (CPAP/BiPAP) if required; intubation in severe cases
5. Vasodilators/nitrates for afterload reduction if needed
6. Monitor fluid balance, urine output, and serial BNP (Miller's Anesthesia 10e; Morgan & Mikhail 7e)

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Prevention

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Summary Comparison Table

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High-Yield Exam Points

• TACO is now the #1 cause of transfusion-related death in the USA (surpassed TRALI after male-donor plasma policy)
• Both occur within 6 hours - timing alone cannot distinguish them
• BNP and CXR are the most practical bedside differentiators
• TRALI has hypotension; TACO has hypertension - the single most useful clinical discriminator
• Leukopenia during/after transfusion = strongly suggests TRALI (neutrophil lung sequestration)
• TRALI is managed with cautious fluids if hypotensive + lung-protective ventilation
• TACO is managed with aggressive IV diuresis
• Both can co-exist, making clinical judgement and echo essential
• Multiparous female donors are most implicated in antibody-mediated TRALI
• TRALI is a clinical diagnosis; donor antibody testing confirms but absence does not exclude
• The 2019 Delphi Panel replaced "possible TRALI" with TRALI Type I (no ARDS risk factors) and TRALI Type II (pre-existing mild ARDS or ARDS risk factors)

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Activated Clotting Time (ACT) - Short Note (MD Anaesthesia)

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Definition

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Principle

• A whole-blood sample (typically 2 mL) is placed into a test tube or channel containing a contact-phase activator (celite/diatomaceous earth, kaolin, glass particles, or combinations)
• The activator accelerates clot formation via the intrinsic (contact) and common coagulation pathways (Factors XII, XI, IX, VIII, X, V, thrombin, fibrinogen)
• The sample is warmed to 37°C
• Clot formation is detected automatically by the device - various platforms use changes in:
  • Electromagnetic detection (magnet dislodgement by fibrin - Hemochron Response system)
  • Mechanical descent of a "plumb bob" / flag assembly slowing (Hepcon HMS Plus, Medtronic)
  • Velocity, pressure, oscillation, or optical changes (depending on platform)
• The time from blood addition to clot detection = ACT in seconds (Miller's Anesthesia 10e)

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Normal Values & Therapeutic Targets

The basis for the 400-480 second CPB target comes from Bull et al. (1975) and Doty et al. (1979). Evidence is largely anecdotal but universally adopted. (Miller's Anesthesia 10e)

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Heparin Dosing Protocol for CPB (ACT-Guided)

1. Measure baseline (pre-heparin) ACT - critical to exclude factor deficiencies (FXII, HMWK, prekallikrein) that may falsely elevate baseline ACT
2. Administer IV heparin 300-400 units/kg bolus
3. Check ACT 3-5 minutes after heparin administration
4. Target ACT >400 seconds before commencing CPB (most centres use 400-480 sec)
5. Monitor ACT every 20-30 minutes throughout CPB
6. Re-dose heparin if ACT falls below threshold
7. At CPB termination: reverse with protamine (1.0-1.3 mg per 100 units of heparin administered)
8. Recheck ACT after protamine - should return to baseline value (Fischer's Mastery of Surgery 8e; Miller's Anesthesia 10e)

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Activators Used and Their Significance

Key point: Results from different ACT platforms are NOT interchangeable - each device and activator produces different normal and therapeutic ranges. A device-specific protocol is essential. (Tietz 7e)

Aprotinin effect: If aprotinin is used, celite-ACT should be maintained at >750 seconds (nearly double normal CPB target), while kaolin-ACT remains unaffected and should be maintained at >400 seconds. This is because aprotinin prolongs celite-ACT in a dose-dependent manner independently of heparin. (Tietz 7e)

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Clinical Variables Affecting ACT

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Limitations of ACT

1. Poor sensitivity at low heparin concentrations - aPTT or anti-Xa better for therapeutic heparin monitoring
2. Poor reproducibility between platforms and operators (duplicate measurements recommended; electrochemical analysers like i-STAT improve reproducibility)
3. Poor correlation with actual heparin concentration - due to variability in heparin-binding proteins and AT levels
4. Results >600 seconds exceed the linear response range - non-linear at extreme heparin concentrations
5. Artificially prolonged by hypothermia, hemodilution, thrombocytopenia, aprotinin - may overestimate anticoagulation
6. Artificially shortened by platelet lysis, surgical stress - may underestimate anticoagulation
7. Cannot detect heparin resistance (see below) - a "therapeutic" ACT does not guarantee adequate anticoagulation in all patients
8. Platform non-interchangeability - different devices give different values for same sample
9. Factor deficiency interference - congenital contact factor deficiencies render the test unusable (Miller's Anesthesia 10e; Tietz 7e)

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Heparin Resistance

• Antithrombin (AT) deficiency - most important mechanism
  • Congenital: rare
  • Acquired: preoperative heparin therapy (most common - found in ~40% of patients pre-treated with heparin), sepsis, DIC, liver disease, nephrotic syndrome
• Elevated heparin-binding proteins (acute phase reactants)
• Activated platelets (thrombocytosis, platelet count >300,000/μL)
• Sepsis / inflammatory states

1. Administer additional heparin (incremental doses)
2. If AT-mediated: give Fresh Frozen Plasma (FFP) (contains AT) or AT concentrate to restore AT to >60% of normal - restores heparin responsiveness
3. Consider alternative anticoagulants if HIT is suspected (argatroban, bivalirudin) (Miller's Anesthesia 10e)

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ACT vs Other Heparin Monitoring Tests

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ACT in Specific Clinical Settings

1. Cardiopulmonary Bypass (CPB)

• Primary monitoring tool during CPB
• Target: >400-480 seconds throughout bypass
• Guidelines (STS/SCA/AmSECT 2018): ACT monitoring with routine heparin supplementation at fixed intervals is a safe alternative to heparin concentration monitoring (Class IIb, Level C)
• Adding heparin concentration monitoring to ACT may reduce thrombin generation and fibrinolysis (Class IIb, Level B), though effects on transfusion are inconsistent

2. ECMO

• Most widely used POC test for ECMO anticoagulation
• Target: 180-220 seconds (1.5× normal)
• Limitations: affected by anaemia, hypofibrinogenaemia, thrombocytopenia, coagulation factor deficiencies, hypothermia, hemodilution
• aPTT and anti-Xa assays increasingly preferred in adult ECMO for better accuracy

3. Percutaneous Coronary Intervention (PCI)

• Target: 250-350 seconds
• Shorter target than CPB as full systemic anticoagulation not required

4. Off-Pump CABG / Minimally Invasive Cardiac Surgery

• Target: >300 seconds
• Lower target than on-pump CPB

5. Endovascular Procedures / Vascular Surgery

• Target: 250-300 seconds

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Protamine Reversal and ACT

• After CPB, heparin is reversed with protamine (1 mg neutralises ~100 units heparin)
• Standard dose: 1.0-1.3 mg protamine per 100 units of heparin
• ACT should return to baseline (pre-heparin) value after adequate protamine
• Guidelines: limit protamine/heparin ratio to <2.6 mg/100 units to avoid anticoagulant effect of excess protamine
• Persistent ACT prolongation post-protamine suggests:
  • Inadequate protamine dose (heparin rebound)
  • Residual anticoagulation from hypothermia/hemodilution
  • Coagulopathy (dilutional, consumptive) - consider viscoelastic testing (TEG/ROTEM) (Miller's Anesthesia 10e)

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High-Yield Summary

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Exam Points

• ACT monitors intrinsic and common pathways - heparin, factor deficiencies, thrombocytopenia, hypothermia all affect it
• Celite vs kaolin - aprotinin prolongs only celite-ACT; when using aprotinin, switch to kaolin or target celite-ACT >750 sec
• Baseline ACT mandatory before heparin - factor XII/HMWK deficiency grossly prolongs baseline and renders the test unreliable
• ACT does not directly measure heparin concentration - a normal ACT can exist with AT deficiency despite adequate heparin levels (and vice versa)
• Anti-Xa is superior in ECMO, LMWH monitoring, and where coagulopathy/thrombocytopenia exists
• High-dose thrombin time (HiTT) correlates better with heparin concentration and is unaffected by hemodilution/hypothermia - a newer alternative to ACT

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Prothrombin Time (PT), INR & aPTT — Short Note (MD Anaesthesia)

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THE COAGULATION CASCADE — Conceptual Framework

Important caveat: The classic cascade is an oversimplification. Individuals with Factor XII, prekallikrein, or HMWK deficiencies have a prolonged aPTT but do not bleed clinically, because in vivo haemostasis is primarily initiated by the TF-VIIa complex. (Miller's Anesthesia 10e)

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PART 1: PROTHROMBIN TIME (PT)

Definition and Principle

1. Tissue factor (thromboplastin) - derived from animal brain/lung or recombinant sources
2. Phospholipid
3. Calcium (to overcome specimen chelation)

• PT assesses the extrinsic and common pathways
• Sensitive to deficiencies of: Fibrinogen (I), II (prothrombin), V, VII, X
• Three of these (II, VII, X) are vitamin K-dependent - hence PT monitors warfarin (Miller's Anesthesia 10e; Quick Compendium of Clinical Pathology 5e)

Normal Values

Sensitivity of PT

• Most sensitive to Factor VII deficiency (shortest half-life of all factors: ~4-6 hours) - first to fall in liver disease, warfarin initiation, vitamin K deficiency
• Factor levels as low as 40-50% of normal may NOT prolong PT with some reagents (reagent-dependent)
• PT is less sensitive to fibrinogen and factors II and V deficiencies (Miller's Anesthesia 10e)

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PART 2: INTERNATIONAL NORMALIZED RATIO (INR)

Background and Problem it Solves

• Different laboratories use different thromboplastin reagents (from different animal/recombinant sources) with varying sensitivity to factor VII and warfarin
• This caused significant interlaboratory variation in PT results - a patient's PT at one hospital could not be compared with results from another
• INR was introduced by the WHO and International Committee on Thrombosis and Hemostasis to standardize PT reporting globally

Formula

• Patient PT = measured PT in seconds
• Mean Normal PT = geometric mean of multiple normal samples from that laboratory's own reference range
• ISI (International Sensitivity Index) = a numerical index assigned to each lot of thromboplastin reagent by testing it against an international recombinant standard. It describes how sensitive that reagent is relative to the international standard (ISI = 1.0 = identical to standard; higher ISI = less sensitive reagent) (Harrison's Principles 22e; Miller's Anesthesia 10e; Schwartz's Surgery 11e)

Key Points about INR

• The INR was specifically designed for monitoring warfarin (VKA) therapy - its standardization is validated for anticoagulated patients only
• INR is NOT valid in patients NOT on warfarin (e.g., liver disease, coagulopathy of critical illness) - using INR to guide FFP transfusion in liver disease is unreliable because the ISI calibration applies only to the VKA-treated population
• Chromogenic factor X assay is preferred for monitoring warfarin when lupus anticoagulant or other inhibitors are present (these interfere with the INR) (Quick Compendium 5e)

Clinical Uses of PT/INR

1. Monitor warfarin (VKA) therapy - primary use
2. Assess liver synthetic function - PT/INR rises early in acute hepatic failure (factor VII has the shortest half-life of liver-synthesised factors: 4-6 hrs)
3. Screen for coagulopathy before invasive procedures / surgery
4. Vitamin K deficiency diagnosis and monitoring of treatment
5. DIC - PT is prolonged (usually PT > aPTT in DIC)

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PART 3: ACTIVATED PARTIAL THROMBOPLASTIN TIME (aPTT)

Definition and Principle

1. Phospholipid (partial thromboplastin - substitutes for platelet surface)
2. Contact activator - negatively charged surface: celite (diatomite), kaolin, silica, or ellagic acid
3. After a fixed incubation period, calcium is added in excess to overcome chelation

• Contact activator initiates the intrinsic (contact) pathway (Factors XII → XI → IX → VIII)
• Progresses through the common pathway (X, V, II, I)
• Clot time is recorded in seconds (Miller's Anesthesia 10e; Barash's Clinical Anesthesia 9e; Quick Compendium 5e)

Normal Values

Critical: There is no universal normal range for aPTT analogous to INR. Each laboratory must establish its own therapeutic aPTT range for its specific reagent-instrument combination by correlation with anti-Xa heparin levels. (Tietz 7e; Miller's Anesthesia 10e)

Sensitivity of aPTT

• Most sensitive to Factors VIII and IX deficiency (detects haemophilia A and B)
• A factor level must fall to <30-40% of normal to prolong the aPTT (some factors not prolonged until <15%)
• Not prolonged by isolated Factor VII deficiency (extrinsic only)
• Not prolonged by Factor XIII deficiency (cross-linking, not clot formation) (Miller's Anesthesia 10e; Quick Compendium 5e)

Clinical Uses of aPTT

1. Monitor unfractionated heparin (UFH) therapy - primary clinical use
2. Screen for intrinsic pathway factor deficiencies (Haemophilia A: FVIII, Haemophilia B: FIX, Factor XI deficiency)
3. Detect lupus anticoagulant (antiphospholipid syndrome)
4. Monitor direct thrombin inhibitors (argatroban, bivalirudin) at moderate doses
5. Detect contact factor deficiencies (FXII, prekallikrein, HMWK) - causes prolonged aPTT without bleeding risk

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PART 4: SPECIMEN COLLECTION REQUIREMENTS

• 3.2% trisodium citrate (blue-top tube) - chelates calcium to prevent ex vivo clotting
• Blood:anticoagulant ratio = 9:1 (critical - deviation prolongs results)
• Full fill of tube essential - underfilling overanticoagulates the specimen and artificially prolongs results
• Tests performed at 37°C (hypothermia in the patient impairs enzymatic reactions; lab testing at 37°C does NOT reflect in vivo coagulopathy from patient hypothermia)
• Sample stable for: test within 4 hours of collection; if delayed, centrifuge and freeze
• Samples for heparin monitoring must be tested within 1 hour (platelet activation releases PF4 which neutralizes heparin, shortening aPTT over time) (Tietz 7e; Quick Compendium 5e)

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PART 5: CAUSES OF PROLONGATION

PT Prolonged, aPTT Normal

aPTT Prolonged, PT Normal

Both PT and aPTT Prolonged

PT and aPTT Both Normal, Bleeding Present

• Factor XIII deficiency (cross-links fibrin; not measured by PT/aPTT)
• Platelet dysfunction (Bernard-Soulier, Glanzmann thrombasthenia)
• von Willebrand Disease (mild Type 1)
• Fibrinolysis (alpha-2 antiplasmin deficiency) (Quick Compendium 5e; Barash 9e)

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PART 6: MIXING STUDY (50:50 Mix)

• Mix equal volumes of patient plasma + normal donor plasma (1:1)
• Repeat the PT or aPTT

Even in severe factor deficiency, substantial correction occurs - normal plasma at 50% mix provides ~50% factor levels which is usually above the threshold for clot formation. (Barash's Clinical Anesthesia 9e; Miller's Anesthesia 10e)

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PART 7: aPTT for UFH MONITORING — Perioperative Context

• UFH therapy monitored by aPTT for therapeutic (moderate-dose) anticoagulation
• Therapeutic target: aPTT 1.5-2.5× mean normal of the laboratory's own reference
• Each laboratory must calibrate its aPTT therapeutic range against anti-Xa heparin concentrations (0.3-0.7 IU/mL) using patient samples - NOT in vitro spiked samples
• If baseline aPTT is already prolonged (lupus anticoagulant, factor inhibitors): aPTT cannot be used - use anti-Xa assay instead
• aPTT is NOT suitable for high-dose heparin monitoring during CPB (values become unmeasurable) - use ACT instead
• LMWH does not require aPTT monitoring routinely - use anti-Xa if needed (obese, renal impairment, paediatrics, pregnancy) (Tietz 7e; Miller's Anesthesia 10e)

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PART 8: PERIOPERATIVE RELEVANCE

Preoperative Assessment

• PT/INR + aPTT are routine preoperative coagulation screens before major surgery
• INR >1.5 is a threshold widely used before invasive procedures (neuraxial, central line, major surgery), though this is institution-specific
• They are poor predictors of surgical bleeding in patients without known coagulopathy - routine preoperative screening in low-risk patients is not recommended
• Must review in: liver disease, anticoagulation therapy, malnutrition, haematological disorders, massively transfused patients, bone marrow suppression

Intraoperative

• PT/INR guides FFP transfusion in coagulopathic bleeding (INR >1.5 with active bleeding)
• aPTT monitors UFH in vascular surgery, ECMO, cardiac catheterisation (ACT preferred in cardiac surgery/CPB)
• Critical limitation: PT and aPTT are performed on plasma at 37°C - they do NOT account for:
  • Hypothermia (coagulation enzyme activity reduced in vivo)
  • Acidaemia (impairs clotting factor function)
  • Thrombocytopenia or platelet dysfunction
  • Hypofibrinogenaemia (PT/aPTT may be normal with fibrinogen 100-150 mg/dL)
  • Hypocalcaemia (calcium is added to the assay)
• Viscoelastic tests (TEG/ROTEM) provide a more comprehensive assessment in the bleeding patient (Barash's Clinical Anesthesia 9e; Morgan & Mikhail 7e)

Postoperative

• Monitor coagulopathy in ICU, massive transfusion, post-hepatic surgery, post-cardiac surgery
• Serial PT/INR to guide FFP, vitamin K, PCC dosing

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PART 9: LIMITATIONS SUMMARY

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PART 10: COMPARATIVE SUMMARY TABLE

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High-Yield Exam Points

• PT tests extrinsic + common pathway; aPTT tests intrinsic + common pathway
• INR = (Patient PT / Mean Normal PT)^ISI - standardises PT for warfarin monitoring only
• ISI = International Sensitivity Index assigned to each thromboplastin lot
• Factor VII has the shortest half-life (~4-6 h) - PT/INR rises earliest in liver failure and warfarin initiation
• aPTT has no universal standard - each lab must set its own therapeutic range for UFH by anti-Xa correlation
• Prolonged aPTT + normal PT + no bleeding = contact factor deficiency (FXII, prekallikrein, HMWK) or lupus anticoagulant
• Mixing study corrects = factor deficiency; does not correct = inhibitor; corrects then prolongs on incubation = acquired FVIII inhibitor
• Both PT and aPTT normal with bleeding = think FXIII deficiency, platelet dysfunction, mild vWD, fibrinolysis
• Lab PT/aPTT tested at 37°C - does NOT reflect the coagulopathy of hypothermia and acidaemia in the patient
• INR is NOT validated for guiding FFP in liver disease - INR liver calibration (INRliver) is a research tool; routine INR overestimates coagulopathy as liver disease also reduces anticoagulants (protein C, S)
• aPTT cannot be used for CPB heparin monitoring (too high to measure) - use ACT; cannot be used if baseline is elevated (lupus anticoagulant) - use anti-Xa
• TEG/ROTEM provide superior guidance in massive haemorrhage over static plasma PT/aPTT tests

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