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Venous Thromboembolism - Comprehensive

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Venous Thromboembolism - Comprehensive

Comprehensive FRACS exam guide to VTE - Virchow's triad, risk stratification (Caprini, NICE), prophylaxis protocols (mechanical vs chemical), LMWH vs DOACs vs aspirin, PE diagnosis and management, post-thrombotic syndrome, and Australian guidelines

complete
Updated: 2025-01-08
High Yield Overview

VENOUS THROMBOEMBOLISM - COMPREHENSIVE

Virchow's Triad | Risk Stratification | Prophylaxis Protocols | Prevention & Treatment

40-60%DVT without prophylaxis (THA/TKA)
1-2%Fatal PE rate in major ortho
35 daysExtended prophylaxis duration (ACCP)
NNT 7Prophylaxis to prevent 1 DVT

VIRCHOW'S TRIAD

Stasis
PatternVenous pooling from immobility, bed rest, paralysis
TreatmentMechanical prophylaxis, early mobilization, IPC devices
Hypercoagulability
PatternTrauma-induced coagulopathy, malignancy, inherited thrombophilia
TreatmentChemical prophylaxis (LMWH, DOAC, aspirin)
Endothelial Injury
PatternSurgical trauma, fractures, tourniquet, cement reaction
TreatmentGentle surgical technique, cement gun venting

Critical Must-Knows

  • Virchow's triad is the pathophysiological foundation: Stasis + Hypercoagulability + Endothelial injury
  • Risk stratification is mandatory: Use Caprini score or NICE guidelines to determine prophylaxis intensity
  • Extended prophylaxis for 35 days is standard after THA, TKA, and hip fracture surgery (ACCP Grade 1B)
  • LMWH and DOACs are superior to aspirin alone for VTE prevention but aspirin is acceptable for lower-risk patients
  • DVT diagnosis: Compression ultrasound (sensitivity over 95% for proximal DVT)
  • PE diagnosis: CTPA is gold standard; V/Q scan if contrast contraindicated

Examiner's Pearls

  • "
    Virchow's triad explains why ALL orthopaedic surgery patients are at VTE risk
  • "
    Caprini score 5 or higher = high risk requiring chemical prophylaxis
  • "
    LMWH started 12h preop (European) or 12-24h postop (North American) - know both protocols
  • "
    DOACs (rivaroxaban, apixaban) are non-inferior to LMWH with better compliance
  • "
    Post-thrombotic syndrome affects 20-50% of DVT patients - compression reduces risk

Critical VTE Exam Concepts - High-Yield Alert

Virchow's Triad is Non-Negotiable

You MUST know the triad. Stasis (immobility), Hypercoagulability (trauma response, inherited disorders), Endothelial injury (surgery, fractures). Examiners expect you to explain how each component contributes to VTE risk in orthopaedic patients and how your prophylaxis strategy addresses each element.

Risk Stratification Determines Management

Know Caprini Score cutoffs: Score 0-1 = low risk (early ambulation), 2 = moderate (mechanical), 3-4 = high (mechanical + chemical), 5 or higher = highest (extended prophylaxis 35 days). NICE guidelines are alternative. Must individualize based on bleeding risk.

Timing of Chemical Prophylaxis

Critical timing knowledge: LMWH 12h before surgery (European) OR 12-24h after surgery (North American). DOACs started 6-12h postop (rivaroxaban 6-10h, apixaban 12-24h). Never give before spinal/epidural - risk of epidural hematoma. Know contraindications.

Extended Prophylaxis Duration

35 days is the standard for THA, TKA, hip fracture (ACCP Grade 1B). VTE risk persists 6-12 weeks postop. Stopping at hospital discharge is suboptimal. Aspirin alone may be used for extended phase if LMWH used perioperatively (AAOS).

VTE Prophylaxis Agents - Comparative Overview

AgentMechanismDosingAdvantagesDisadvantages
Enoxaparin (LMWH)Anti-Xa and anti-IIa inhibition40mg SC daily or 30mg BDGold standard, reversible with protamine, renal dosing availableInjection required, HIT risk (0.5%), monitoring if renal impairment
Rivaroxaban (DOAC)Direct Factor Xa inhibitor10mg PO dailyOral, fixed dose, no monitoring, non-inferior to LMWHNo reversal agent (andexanet expensive), avoid CrCl less than 15
Apixaban (DOAC)Direct Factor Xa inhibitor2.5mg PO BDOral, renal-safe (less than 25% renal), low bleedingTwice daily dosing, no reversal widely available
AspirinCOX-1 inhibition (antiplatelet)100-300mg PO dailyCheap, oral, low bleeding, patient familiarityInferior efficacy vs LMWH/DOAC, consider only for lower-risk or extended phase
WarfarinVitamin K antagonistTarget INR 2-3Oral, reversible with vitamin K/FFP, cheapRequires INR monitoring, interactions, slow onset, bridging needed
UFHAnti-IIa greater than anti-Xa5000 units SC BD-TDSFully reversible, short half-life, safe in renal failureHighest HIT risk (2-3%), requires more frequent dosing
Mnemonic

SHEVirchow's Triad

S
Stasis
Venous pooling from immobility, bed rest, paralysis, venous compression
H
Hypercoagulability
Trauma, surgery, malignancy, Factor V Leiden, prothrombin mutation, OCP, pregnancy
E
Endothelial injury
Surgical trauma, fractures, tourniquet ischemia, cement exothermic reaction

Memory Hook:SHE is at risk for VTE - Stasis, Hypercoagulability, Endothelial injury. All three present in major orthopaedic surgery!

Mnemonic

HIPSCaprini Risk Factors (5-point items)

H
Hip/Pelvis/Leg fracture
5 points - highest risk procedures
I
Immobilization more than 72h
Prolonged bed rest dramatically increases VTE risk
P
Prior VTE
5 points - strongest patient risk factor
S
Stroke or Spinal cord injury
5 points - paralysis causes profound stasis

Memory Hook:HIPS fractures and these factors score 5 points each on Caprini - automatic high-risk status!

Mnemonic

CLOTDVT Clinical Features

C
Calf pain/tenderness
Most common symptom - posterior calf, especially with dorsiflexion (Homans' sign)
L
Leg swelling unilateral
More than 3cm difference between calves is significant
O
Observable venous distension
Superficial collateral veins may be visible
T
Temperature increased/erythema
Warmth and redness over affected area

Memory Hook:Look for a CLOT - Calf pain, Leg swelling, Observable veins, Temperature change. But remember: 50% of DVTs are asymptomatic!

Overview and Epidemiology

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), represents one of the most significant preventable complications in orthopaedic surgery. Understanding VTE pathophysiology, risk stratification, and evidence-based prophylaxis is mandatory knowledge for fellowship examinations.

Definition:

  • DVT: Thrombus formation in the deep venous system, most commonly in lower extremity (iliac, femoral, popliteal, calf veins)
  • PE: Embolization of thrombus to pulmonary arterial circulation, causing ventilation-perfusion mismatch
  • VTE: Umbrella term encompassing the spectrum from asymptomatic calf DVT to fatal massive PE

Epidemiology in Orthopaedic Surgery:

VTE Incidence Without Prophylaxis

ProcedureDVT RateProximal DVTFatal PE
Total hip arthroplasty40-60%15-25%0.5-2%
Total knee arthroplasty40-84%10-20%0.5-1.5%
Hip fracture surgery40-60%15-30%2-7%
Knee arthroscopy5-15%1-2%Less than 0.1%
Spine surgery15-40%5-10%0.3-0.5%
Lower limb trauma40-80%10-20%1-2%

With Prophylaxis:

  • DVT rates reduced to 10-20% (mechanical only) or 1-5% (mechanical + chemical)
  • Fatal PE reduced to less than 0.5% with adequate prophylaxis
  • NNT (number needed to treat) approximately 7 to prevent one symptomatic VTE

Australian Context

VTE remains a leading cause of preventable hospital death in Australia. The Australian Commission on Safety and Quality in Health Care mandates VTE risk assessment for all hospital admissions. Compliance with prophylaxis protocols is a key hospital performance indicator.

Pathophysiology - Virchow's Triad

Rudolf Virchow described his famous triad in 1856, identifying three factors that predispose to venous thrombosis. All three are present in major orthopaedic surgery, explaining the extremely high VTE risk in this population.

Venous Stasis

Mechanism:

  • Normal venous return depends on calf muscle pump action and competent venous valves
  • Immobility eliminates calf muscle pump function
  • Venous pooling allows activated clotting factors to accumulate locally
  • Reduced clearance of activated factors overwhelms natural anticoagulant systems

Orthopaedic Causes:

  • Preoperative immobility (hip fracture, multiple trauma)
  • Intraoperative positioning (hip flexion, rotation)
  • Postoperative bed rest and reduced mobility
  • Cast immobilization
  • Lower limb paralysis (stroke, spinal cord injury)
  • Tourniquet application (distal stasis during inflation)

Prevention Strategies:

  • Early mobilization (day 0-1 post-surgery when safe)
  • Mechanical prophylaxis (IPC devices, GCS)
  • Ankle exercises and calf pump activation
  • Avoiding prolonged hip flexion
  • Physiotherapy protocols

Calf Muscle Pump

The calf muscle pump generates pressures of 200-300 mmHg during contraction, propelling blood centrally through competent valves. Loss of this pump (immobility) reduces venous velocity by 50% and allows thrombus formation in valve pockets.

Hypercoagulable State

Mechanism:

  • Tissue trauma activates the extrinsic coagulation pathway via tissue factor release
  • Surgical stress response increases fibrinogen, Factor VIII, and platelet reactivity
  • Systemic inflammatory response creates pro-thrombotic milieu
  • Natural anticoagulants (protein C, protein S, antithrombin III) may be consumed

Orthopaedic Causes:

  • Major tissue trauma and fractures
  • Surgical trauma and manipulation
  • Tourniquet use (reperfusion activates coagulation)
  • Cement exothermic reaction and fat embolism
  • Blood loss and transfusion (stored blood is procoagulant)

Patient Factors (Inherited):

  • Factor V Leiden (5% population, 20% of VTE patients)
  • Prothrombin G20210A mutation
  • Antithrombin III deficiency
  • Protein C or S deficiency
  • Hyperhomocysteinemia

Patient Factors (Acquired):

  • Malignancy (especially pelvic, lung, pancreatic)
  • Oral contraceptive pill and HRT
  • Pregnancy and postpartum state
  • Antiphospholipid syndrome
  • Myeloproliferative disorders
  • Nephrotic syndrome

Thrombophilia Testing

Do NOT routinely test for inherited thrombophilia preoperatively. Testing is indicated only if: (1) personal history of unprovoked VTE, (2) strong family history of VTE at young age, (3) VTE in unusual site. Testing does not change acute VTE management but may affect duration of anticoagulation.

Endothelial Injury

Mechanism:

  • Intact endothelium is anti-thrombotic (produces prostacyclin, nitric oxide, thrombomodulin)
  • Endothelial damage exposes subendothelial collagen and tissue factor
  • Platelet adhesion and activation initiates thrombosis
  • Surgical trauma directly damages venous endothelium

Orthopaedic Causes:

  • Direct vessel manipulation during surgery
  • Retractor placement against vessels
  • Tourniquet compression and ischemia-reperfusion
  • Bone cement exothermic reaction (heat injury)
  • Fracture fragments lacerating vessels
  • DVT catheter placement

Specific Procedural Risks:

  • THA: Femoral vein stretched and compressed during dislocation and leg positioning
  • TKA: Popliteal vein at risk during posterior capsule release
  • Hip fracture: Injury at time of fracture, manipulation during surgery
  • Acetabular fracture: Iliac vessels at risk during approach and fixation

Cement and VTE

Bone cement (PMMA) causes endothelial injury through: (1) exothermic reaction (temperatures of 60-80 degrees Celsius), (2) monomer toxicity, (3) fat and marrow embolization. This is why cemented procedures have higher VTE risk than uncemented, and why some advocate for a dose of LMWH before cementing.

Combined Effect in Orthopaedic Surgery:

All three elements of Virchow's triad are present simultaneously in major orthopaedic procedures, creating a "perfect storm" for VTE:

  • Preoperative immobility (stasis)
  • Surgical trauma and tissue factor release (hypercoagulability)
  • Direct vessel injury and manipulation (endothelial injury)

This explains why THA and TKA have the highest VTE risk of any elective surgical procedures and why prophylaxis is mandatory.

Clinical Presentation

Deep Vein Thrombosis - Clinical Features

Important: Up to 50% of DVTs are asymptomatic, detected only on screening ultrasound. Clinical diagnosis is unreliable (sensitivity 50-60%, specificity 50%).

Symptoms:

  • Calf pain (most common) - often described as "cramping" or "tightness"
  • Leg swelling - may be acute or insidious onset
  • Warmth and redness over affected area
  • Heaviness or aching in leg
  • Pain worse with standing or walking

Signs:

  • Unilateral leg edema (more than 3cm difference significant)
  • Pitting edema
  • Calf tenderness on palpation
  • Increased warmth
  • Erythema (may be subtle)
  • Superficial venous distension
  • Homans' sign (calf pain on forced dorsiflexion) - unreliable, only 50% sensitive

Wells Score for DVT

Clinical FeaturePoints
Active cancer (treatment within 6 months or palliative)+1
Paralysis, paresis, or recent lower limb immobilization+1
Bedridden more than 3 days or major surgery within 12 weeks+1
Localized tenderness along deep venous system+1
Entire leg swollen+1
Calf swelling more than 3cm compared to other leg+1
Pitting edema confined to symptomatic leg+1
Collateral superficial veins (non-varicose)+1
Previously documented DVT+1
Alternative diagnosis at least as likely-2

Wells Score Interpretation:

  • 0 or less: Low probability (5% DVT prevalence)
  • 1-2: Moderate probability (17% DVT prevalence)
  • 3 or more: High probability (53% DVT prevalence)

Clinical Tip

In postoperative orthopaedic patients, the Wells score has limited utility because multiple risk factors are already present (recent surgery, immobility). Have a LOW threshold for imaging. If clinical suspicion exists, proceed directly to compression ultrasound regardless of Wells score.

Pulmonary Embolism - Clinical Features

Classic Triad (present in less than 20%):

  • Dyspnea
  • Pleuritic chest pain
  • Hemoptysis

Symptoms by Frequency:

  • Dyspnea (73%) - sudden onset, may be only at exertion initially
  • Pleuritic chest pain (66%) - sharp, worse on inspiration
  • Cough (37%)
  • Leg pain/swelling (26%)
  • Hemoptysis (13%)
  • Syncope (9%) - suggests massive PE
  • Anxiety or sense of impending doom

Signs:

  • Tachypnea (respiratory rate over 20) - most common sign
  • Tachycardia (heart rate over 100)
  • Hypoxia (SpO2 less than 95%)
  • Fever (low-grade, less than 38.5 degrees Celsius)
  • Elevated JVP
  • Loud P2 (pulmonary hypertension)
  • Right ventricular heave
  • Hypotension (massive PE only)
  • Cyanosis (late sign)

Massive PE Recognition

Massive PE is defined by hemodynamic instability: systolic BP less than 90 mmHg for 15 minutes or more, or requiring vasopressors, or cardiac arrest. This is a life-threatening emergency requiring immediate treatment (thrombolysis, embolectomy, ECMO consideration). Mortality without treatment exceeds 50%.

PE Severity Classification:

PE Severity and Management

SeverityHemodynamicsRV DysfunctionMortalityManagement
Low riskStableAbsentLess than 1%Anticoagulation, consider outpatient
Intermediate-lowStablePresent, troponin negative3-5%Anticoagulation, monitor closely
Intermediate-highStablePresent, troponin positive5-15%Anticoagulation, consider ICU, thrombolysis if deteriorates
High risk (massive)UnstablePresentMore than 15%Thrombolysis, surgical or catheter embolectomy, ECMO

Post-Thrombotic Syndrome (PTS)

Definition: Chronic complication of DVT characterized by venous hypertension due to valve incompetence and venous obstruction.

Epidemiology:

  • Affects 20-50% of patients following proximal DVT
  • Develops within 2 years of acute DVT in most cases
  • Risk factors: proximal DVT, recurrent ipsilateral DVT, obesity, poor anticoagulation, inadequate compression

Pathophysiology:

  • Acute thrombus damages venous valves
  • Valve incompetence leads to venous reflux
  • Residual thrombus causes venous obstruction
  • Venous hypertension causes edema, skin changes

Clinical Features:

  • Leg pain and heaviness (worse standing, better elevation)
  • Chronic swelling
  • Skin changes: hyperpigmentation, eczema, lipodermatosclerosis
  • Venous ulceration (severe cases, 5-10%)

Prevention:

  • Adequate anticoagulation for acute DVT (reduces recurrence)
  • Compression stockings for 2 years post-DVT
  • Early mobilization once anticoagulated
  • Catheter-directed thrombolysis for iliofemoral DVT (reduces PTS by 50%)

Compression Controversy

The SOX trial (NEJM 2014) challenged the benefit of compression stockings for PTS prevention, showing no difference vs placebo stockings. However, this trial had compliance issues, and most guidelines still recommend compression stockings for 2 years after proximal DVT. For the exam, know the controversy but recommend compression pending further evidence.

Investigations

DVT Diagnostic Pathway

D-dimer:

  • Highly sensitive (95%) but poorly specific (50%)
  • Elevated in: surgery, trauma, pregnancy, cancer, infection, inflammation
  • Negative D-dimer reliably excludes DVT in LOW pretest probability patients
  • In postoperative orthopaedic patients: D-dimer is almost always elevated - DO NOT use to rule out DVT

D-dimer Limitation

D-dimer has NO role in ruling out DVT in postoperative orthopaedic patients. It will be elevated from surgery and does not add diagnostic value. Proceed directly to imaging if DVT is suspected.

Compression Ultrasound (Gold Standard):

  • Sensitivity: 95% for proximal DVT, 70-80% for calf DVT
  • Specificity: 98%
  • Technique: Inability to fully compress vein with probe pressure is diagnostic
  • Also visualizes thrombus echogenicity and venous flow patterns
  • Advantages: Non-invasive, no radiation, bedside available

When to Image:

  • Any clinical suspicion of DVT postoperatively
  • Unexplained leg swelling, pain, or warmth
  • Before anticoagulation cessation if DVT was diagnosed
  • PE diagnosed - evaluate for DVT source

Other Imaging:

  • CT venography: For pelvic and IVC extension, if US non-diagnostic
  • MR venography: Alternative for pelvic veins, no radiation
  • Contrast venography: Historical gold standard, rarely used now (invasive)

DVT Diagnostic Algorithm by Pretest Probability

ProbabilityD-dimerUltrasoundInterpretation
Low (Wells 0 or less)If negative: DVT excludedIf D-dimer positive: proceed to USSerial US if negative but high suspicion
Moderate (Wells 1-2)Not reliableProceed directlyConsider repeat US in 5-7 days if negative
High (Wells 3+)Do not useProceed directlyConsider venography if negative and high suspicion
Postoperative orthoDo not useProceed directlyLow threshold for imaging

PE Diagnostic Pathway

Initial Assessment:

  • ABG: Hypoxemia, hypocapnia, respiratory alkalosis (may be normal in small PE)
  • ECG: Sinus tachycardia (most common), S1Q3T3 (classic but rare), right heart strain, new RBBB
  • CXR: Often normal, Westermark sign (oligemia), Hampton hump (wedge infarct), pleural effusion

CTPA (CT Pulmonary Angiography) - Gold Standard:

  • Sensitivity: 95-98%
  • Specificity: 95-98%
  • Visualizes thrombus in pulmonary arteries
  • Also shows RV dilation (prognostic)
  • Requires IV contrast - contraindicated in severe renal impairment or contrast allergy

V/Q Scan:

  • Alternative when CTPA contraindicated
  • Reported as: Normal, Low probability, Intermediate probability, High probability
  • High probability V/Q with high clinical probability = 96% diagnostic
  • Many scans are "intermediate" - not helpful
  • Best in patients with normal CXR

Echocardiography:

  • Bedside assessment of RV function
  • Signs of RV strain: RV dilation, hypokinesis, McConnell's sign, septal bowing
  • Useful for risk stratification and guiding thrombolysis decision
  • NOT diagnostic for PE (cannot visualize pulmonary arteries)

Biomarkers:

  • Troponin: Elevated in RV strain, prognostic (higher mortality if positive)
  • BNP/NT-proBNP: Elevated in RV dysfunction, prognostic

When to Consider Thrombolysis

Thrombolysis (tPA) is indicated for massive PE with hemodynamic instability (systolic BP less than 90 mmHg). For intermediate-high risk PE (stable with RV dysfunction and positive troponin), thrombolysis is controversial - consider if clinical deterioration occurs. Bleeding risk is significant (2% intracranial hemorrhage).

VTE Screening Strategies

Routine Screening NOT Recommended:

  • ACCP and AAOS do NOT recommend routine ultrasound screening postoperatively
  • Most detected DVTs are asymptomatic calf DVTs with low clinical significance
  • Leads to overtreatment and prolonged anticoagulation
  • No proven mortality benefit from screening

When to Screen:

  • Symptomatic patients (clinical suspicion of DVT/PE)
  • Before major revision surgery (rule out residual DVT)
  • Before stopping anticoagulation (confirm resolution if indicated)
  • High-risk patients with contraindication to chemical prophylaxis

Surveillance Ultrasound:

  • Some centers perform screening at 2 weeks for high-risk patients
  • Evidence does not support routine surveillance
  • Focus should be on adequate prophylaxis, not screening

Exam Point

If asked about routine VTE screening after arthroplasty: "I do not recommend routine screening as per ACCP and AAOS guidelines. Screening detects asymptomatic DVTs that may not require treatment and leads to over-anticoagulation. I focus on adequate prophylaxis and investigate promptly if symptoms develop."

Management

Risk Stratification Systems

Caprini Score: The Caprini Risk Assessment Model is the most widely used tool for VTE risk stratification in surgical patients.

Caprini Score - Key Risk Factors

1 Point Each2 Points Each3 Points Each5 Points Each
Age 41-60Age 61-74Age 75 or moreHip, pelvis, leg fracture
Minor surgeryArthroscopic surgeryPrior VTEStroke (less than 1 month)
BMI over 25Major surgery over 45 minFamily history VTESpinal cord injury
Varicose veinsMalignancyPositive thrombophiliaElective arthroplasty
OCP/HRTBed rest over 72h

Caprini Score Interpretation:

  • 0: Very low risk (0.5% VTE) - Early ambulation only
  • 1-2: Low risk (1.5% VTE) - Mechanical prophylaxis
  • 3-4: Moderate risk (3% VTE) - Mechanical + chemical prophylaxis
  • 5 or more: High risk (6% VTE) - Mechanical + chemical + extended prophylaxis (35 days)

NICE Guidelines: UK National Institute for Health and Care Excellence provides alternative risk assessment.

Key Principles:

  • ALL orthopaedic inpatients require VTE risk assessment
  • ALL patients undergoing THA, TKA, hip fracture surgery are automatically HIGH RISK
  • Must also assess bleeding risk to balance prophylaxis

Bleeding Risk Assessment

Prophylaxis must balance VTE risk against bleeding risk. Consider bleeding risk factors: active bleeding, severe thrombocytopenia (platelets less than 50), coagulopathy, high-bleeding-risk surgery (spine, intracranial), recent major bleeding. If bleeding risk is high, use mechanical prophylaxis only until bleeding risk diminishes.

Mechanical Prophylaxis

Rationale:

  • Addresses stasis component of Virchow's triad
  • No bleeding risk
  • Can be used when chemical prophylaxis contraindicated
  • Should be combined with chemical prophylaxis in high-risk patients

Modalities:

Mechanical Prophylaxis Options

ModalityMechanismEvidenceConsiderations
Intermittent Pneumatic Compression (IPC)Sequential compression mimics calf pump, releases nitric oxide30-50% DVT reduction vs noneMust be worn 18+ hours/day, remove for ambulation
Graduated Compression Stockings (GCS)Graduated pressure (18-23 mmHg at ankle)15-25% DVT reductionCorrect sizing essential, contraindicated in PAD
Venous Foot PumpCompression of plantar venous plexusSimilar to IPCAlternative if calf access limited
Early MobilizationActivates calf muscle pump naturallyFundamental to VTE preventionWithin 24-48h of surgery when safe

Contraindications to Compression:

  • Peripheral arterial disease (ABPI less than 0.8)
  • Severe peripheral neuropathy
  • Severe lower limb edema from cardiac failure
  • Skin conditions preventing application
  • Active DVT (compression may dislodge thrombus)

IPC Timing

IPC devices should be applied in the preoperative area and continue until patient is fully mobile. Compliance is critical - devices must be worn at least 18 hours/day to be effective. Remove only for ambulation, physiotherapy, and hygiene. Many studies showing limited IPC benefit had poor compliance.

Chemical Prophylaxis Agents

Low Molecular Weight Heparin (LMWH):

  • Enoxaparin (Clexane): Most common in Australia
  • Dosing: 40mg SC daily or 30mg SC BD (higher dose for very high risk)
  • Timing: 12h before surgery (European) OR 12-24h after surgery (North American)
  • Duration: Continue for 35 days after THA, TKA, hip fracture
  • Adjust for renal function: 30mg daily if CrCl 15-30 mL/min

Direct Oral Anticoagulants (DOACs):

  • Rivaroxaban (Xarelto): 10mg PO daily, start 6-10h postop
  • Apixaban (Eliquis): 2.5mg PO BD, start 12-24h postop
  • Dabigatran (Pradaxa): 110mg x 2 PO on day 1, then 220mg daily (not TGA-approved for prophylaxis in Australia)

Aspirin:

  • 100-300mg PO daily
  • AAOS considers aspirin acceptable for VTE prophylaxis
  • ACCP recommends LMWH or DOAC over aspirin (Grade 2B)
  • May be used for extended prophylaxis (days 10-35) after LMWH during hospital stay

Warfarin:

  • Target INR 2-3
  • Requires monitoring, interactions, slow onset
  • Less commonly used now due to DOAC availability
  • May be appropriate if patient already on warfarin for other indication

Chemical Prophylaxis Agent Selection

AgentAdvantagesDisadvantagesBest For
Enoxaparin (LMWH)Gold standard evidence, reversible, renal dosingInjection, HIT risk, monitoring if CKDAll high-risk patients, especially if bleeding concern
Rivaroxaban (DOAC)Oral, once daily, no monitoringNo reversal (andexanet costly), avoid severe CKDPatient preference, outpatient compliance
Apixaban (DOAC)Oral, renal-safe, lowest bleedingTwice dailyElderly, moderate CKD (CrCl 25-50)
AspirinCheap, oral, familiar, low bleedingInferior efficacyLower-risk or extended phase prophylaxis

Spinal and Epidural Anesthesia

Do NOT give LMWH within 12 hours before or 4 hours after spinal/epidural insertion or removal. DOACs require 24-48h washout before neuraxial procedures. Risk of spinal epidural hematoma (1:150,000 with proper timing, much higher if violated). This is a common exam question.

Timing and Duration of Prophylaxis

Timing of Initiation:

Prophylaxis Initiation Timing

AgentPreoperative TimingPostoperative TimingEvidence
LMWH (European protocol)12h before surgery-Slightly higher bleeding, possibly better efficacy
LMWH (North American protocol)-12-24h after surgeryLower bleeding, standard in Australia
Rivaroxaban-6-10h after surgeryRECORD trials protocol
Apixaban-12-24h after surgeryADVANCE trials protocol
Aspirin-24h after surgeryContinued from preop if already on

Duration of Prophylaxis:

Extended thromboprophylaxis for 35 days is standard for THA, TKA, and hip fracture surgery. VTE risk persists for 6-12 weeks postoperatively, with 25% of VTEs occurring after hospital discharge.

Prophylaxis Duration by Procedure

ProcedureDurationLevel of EvidenceComments
THA35 days (minimum 10-14 days)ACCP Grade 1BExtended prophylaxis reduces VTE by 50%
TKA35 days (minimum 10-14 days)ACCP Grade 1BSimilar benefit to THA
Hip fracture surgery35 daysACCP Grade 1BHighest risk, mandatory extended prophylaxis
Knee arthroscopyUntil mobile (few days)ACCP Grade 2BLow risk, early mobilization usually sufficient
Spine surgeryUntil mobile or longer if high riskVariableConsider patient factors, surgery extent
Lower limb fractureDuration of immobilization + 2 weeksACCP Grade 2CIndividualize based on mobility

Extended Prophylaxis

ACCP 2012 guidelines strongly recommend extended prophylaxis (35 days) for THA, TKA, and hip fracture surgery (Grade 1B). The EXCLAIM study showed 82% relative risk reduction in VTE with extended prophylaxis. Aspirin can be used for days 10-35 if LMWH used in hospital.

Surgical Management - IVC Filters

Inferior Vena Cava (IVC) Filter Indications

Absolute Indications:

  • Acute proximal DVT or PE with absolute contraindication to anticoagulation
  • Recurrent PE despite adequate anticoagulation
  • Complications of anticoagulation requiring cessation (major bleeding)

Relative Indications (Controversial):

  • Prophylactic filter in very high-risk trauma (controversial, not recommended routinely)
  • Free-floating iliofemoral thrombus (some advocate, others anticoagulate)
  • Massive PE with residual DVT where further embolization would be fatal
  • Poor cardiopulmonary reserve where any PE would be catastrophic

NOT Indicated:

  • Routine prophylaxis in trauma or orthopaedic surgery
  • As alternative to anticoagulation when anticoagulation is feasible
  • For calf DVT only

IVC Filters Are Not Routine Prophylaxis

Do NOT place IVC filters for VTE prophylaxis in trauma or orthopaedic patients who can receive anticoagulation. The PREPIC-2 trial showed no benefit of prophylactic filters in addition to anticoagulation, with increased DVT rates in filter group. Filters are for patients who CANNOT be anticoagulated.

IVC Filter Types and Placement

Retrievable Filters:

  • Designed for temporary placement (less than 3-6 months)
  • Should be removed once anticoagulation can be safely resumed
  • Examples: Celect, Denali, Gunther Tulip, OptEase
  • Retrieval rate disappointingly low (20-40% in practice)

Permanent Filters:

  • For permanent anticoagulation contraindication
  • Examples: Greenfield, Bird's Nest, Simon Nitinol
  • Rarely placed now (most contraindications are temporary)

Placement:

  • Percutaneous via femoral or jugular vein approach
  • Fluoroscopic or intravascular ultrasound guidance
  • Position below renal veins (protect renal venous drainage)
  • Suprarenal placement if infrarenal IVC thrombosis or pelvic DVT

Complications:

  • Filter thrombosis (5-10%)
  • Filter migration (3-5%)
  • IVC perforation (rare)
  • Filter fracture and embolization
  • Increased DVT risk distal to filter
  • Retrieval complications (stuck filters)

Retrieval Strategy

For the exam: "Retrievable IVC filters should be removed once anticoagulation can be safely initiated, typically within 3-6 months. I would coordinate with interventional radiology for elective retrieval. Leaving filters in situ long-term increases DVT risk and filter-related complications."

Complications

VTE Complications and Management

ComplicationIncidencePresentationManagement
Post-thrombotic syndrome20-50% after proximal DVTChronic leg swelling, pain, skin changes, ulcerationPrevention: compression stockings for 2 years. Treatment: compression, elevation, wound care for ulcers
Recurrent VTE5-10% at 1 year on anticoagulationNew DVT or PE symptomsEnsure therapeutic anticoagulation, consider extended/indefinite therapy
Chronic thromboembolic pulmonary hypertension (CTEPH)2-4% after PEPersistent dyspnea 6+ months post-PEReferral to pulmonary hypertension centre, pulmonary endarterectomy
Phlegmasia cerulea dolensRareMassive iliofemoral DVT, cyanotic limb, compartment syndrome riskUrgent surgical thrombectomy or catheter-directed thrombolysis, fasciotomy if compartment syndrome
Anticoagulation bleeding3-5% major bleeding on therapeutic anticoagulationGI bleed, intracranial hemorrhage, surgical site bleedingHold anticoagulation, reversal agents, transfusion, surgical hemostasis if needed
Heparin-induced thrombocytopenia (HIT)0.5% with LMWH, 2-3% with UFHPlatelet drop more than 50% at 5-14 days, paradoxical thrombosisStop all heparin, switch to non-heparin anticoagulant (argatroban, fondaparinux)

HIT Recognition

Heparin-Induced Thrombocytopenia is a prothrombotic emergency despite low platelets. 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher causes) helps assess probability. If HIT suspected: (1) Stop ALL heparin immediately, (2) Start alternative anticoagulant (argatroban, fondaparinux - NOT warfarin alone), (3) Send HIT antibody testing. HIT can cause limb loss, stroke, PE, and death.

Evidence Base

RECORD Trials (2008-2009)

1
Eriksson BI, Borris LC, Friedman RJ, et al. • N Engl J Med (2008-2009)
Key Findings:
  • Rivaroxaban 10mg daily superior to enoxaparin for VTE prevention after THA and TKA
  • RECORD1 (THA): Total VTE 1.1% vs 3.7% (rivaroxaban vs enoxaparin)
  • RECORD3 (TKA): Total VTE 9.6% vs 18.9%
  • No significant difference in major bleeding
Clinical Implication: DOACs are non-inferior to LMWH for VTE prophylaxis after arthroplasty and offer oral administration advantage. This changed practice toward DOACs as acceptable alternative to LMWH.

ADVANCE Trials (2009-2011)

1
Lassen MR, Raskob GE, Gallus A, et al. • N Engl J Med (2009-2011)
Key Findings:
  • Apixaban 2.5mg BD non-inferior to enoxaparin 40mg for VTE prevention
  • ADVANCE-2 (TKA): Total VTE 15% apixaban vs 24% enoxaparin
  • ADVANCE-3 (THA): Total VTE 1.4% vs 3.9%
  • Lower major bleeding with apixaban vs enoxaparin
Clinical Implication: Apixaban is effective for VTE prophylaxis with potentially lower bleeding risk than enoxaparin. Twice-daily dosing is a practical consideration.

EPCAT II Trial (2018)

1
Anderson DR, Dunbar M, Murnaghan J, et al. • N Engl J Med (2018)
Key Findings:
  • Aspirin 81mg daily non-inferior to rivaroxaban 10mg for extended prophylaxis after THA/TKA
  • VTE rates: 0.64% aspirin vs 0.70% rivaroxaban at 90 days
  • All patients received rivaroxaban for first 5 days postoperatively
  • Similar bleeding rates between groups
Clinical Implication: Aspirin may be used for extended prophylaxis (days 5-35) after initial LMWH or DOAC. This is cost-effective and convenient but requires initial potent anticoagulation perioperatively.

PREPIC-2 Trial (2015)

1
Mismetti P, Laporte S, Pellerin O, et al. • JAMA (2015)
Key Findings:
  • Retrievable IVC filter + anticoagulation vs anticoagulation alone in PE patients
  • No reduction in recurrent PE at 3 months (3.0% vs 1.5%, p=0.5)
  • Higher DVT rate in filter group at 3 months (5.9% vs 2.6%)
  • Filters showed no mortality benefit
Clinical Implication: Prophylactic IVC filters do not reduce PE when anticoagulation is given. Filters are reserved for patients who cannot receive anticoagulation. Do not place filters routinely in high-risk patients.

Exam Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

Scenario 1: VTE Prophylaxis Protocol for THA

EXAMINER

"A 68-year-old woman is scheduled for elective total hip arthroplasty for osteoarthritis. She has well-controlled hypertension and type 2 diabetes. What is your VTE prophylaxis strategy?"

EXCEPTIONAL ANSWER
This patient is high-risk for VTE as all THA patients are automatically in the highest risk category. My prophylaxis strategy addresses all three elements of Virchow's triad. For stasis, I would use mechanical prophylaxis with intermittent pneumatic compression devices applied preoperatively and continued until fully mobile, combined with early mobilization from day 1 post-surgery with physiotherapy. For hypercoagulability, I would use chemical prophylaxis with either enoxaparin 40mg subcutaneously daily starting 12-24 hours postoperatively, or a DOAC such as rivaroxaban 10mg daily starting 6-10 hours postoperatively. I would continue chemical prophylaxis for 35 days as per ACCP guidelines, as VTE risk persists 6-12 weeks after surgery. For endothelial injury, my surgical technique minimizes excessive manipulation, and I ensure adequate hydration perioperatively. I would also provide patient education about VTE symptoms and advise seeking medical attention if leg swelling, pain, or shortness of breath develops. Before initiating prophylaxis, I would confirm no contraindications such as active bleeding, severe thrombocytopenia, or planned neuraxial anesthesia within the appropriate time window.
KEY POINTS TO SCORE
THA patients are automatically high-risk for VTE
Combine mechanical and chemical prophylaxis
Extended prophylaxis for 35 days is standard (ACCP Grade 1B)
LMWH or DOAC are first-line agents
Early mobilization from day 1 post-surgery
COMMON TRAPS
✗Forgetting to mention Virchow's triad as pathophysiological basis
✗Recommending only 10-14 days of prophylaxis instead of 35 days
✗Not addressing timing of chemical prophylaxis relative to surgery
✗Recommending aspirin alone as first-line (inferior efficacy)
LIKELY FOLLOW-UPS
"What are the components of Virchow's triad?"
"What is the timing for LMWH before epidural removal?"
"How would you manage this patient if she had a history of HIT?"
VIVA SCENARIOCritical

Scenario 2: Suspected PE Postoperatively

EXAMINER

"A 72-year-old man is 5 days post total knee arthroplasty. He develops sudden onset dyspnea, pleuritic chest pain, and is tachycardic at 110 bpm. SpO2 is 88% on room air. What is your management?"

EXCEPTIONAL ANSWER
This presentation is highly concerning for pulmonary embolism, which is a medical emergency. I would immediately stabilize the patient by applying supplemental oxygen to maintain SpO2 above 94%, establishing IV access, and placing on continuous monitoring. I would perform a rapid clinical assessment including vital signs, ECG for right heart strain patterns, and arterial blood gas. If hemodynamically stable, I would immediately arrange CTPA as the gold standard investigation for PE diagnosis. While awaiting imaging, I would initiate therapeutic anticoagulation with enoxaparin 1mg/kg subcutaneously or unfractionated heparin if urgent reversal may be needed. If hemodynamically unstable with systolic BP less than 90 mmHg, this represents massive PE requiring immediate involvement of ICU, consideration of thrombolysis with tPA, and potentially ECMO or surgical embolectomy. I would also arrange echocardiography to assess right ventricular function and biomarkers including troponin and BNP for risk stratification. If PE is confirmed, I would continue therapeutic anticoagulation for minimum 3 months, investigate for DVT source with lower limb ultrasound, and consider thrombophilia testing after acute episode if this were an unprovoked event.
KEY POINTS TO SCORE
Immediate oxygen and stabilization
CTPA is gold standard for PE diagnosis
Start therapeutic anticoagulation while awaiting imaging if high suspicion
Assess hemodynamic stability to determine if massive PE requiring thrombolysis
Risk stratify with echo and biomarkers
COMMON TRAPS
✗Delaying anticoagulation while waiting for imaging
✗Not recognizing hemodynamic instability indicating massive PE
✗Failing to escalate to ICU and thrombolysis discussion for massive PE
✗Ordering D-dimer in postoperative patient (will be elevated from surgery)
LIKELY FOLLOW-UPS
"What are the indications for thrombolysis in PE?"
"How would you manage if patient had contraindication to anticoagulation?"
"What is the duration of anticoagulation after PE?"
VIVA SCENARIOCritical

Scenario 3: Contraindication to Anticoagulation

EXAMINER

"A 58-year-old man with hip fracture also has active GI bleeding from a peptic ulcer. He requires surgery within 24-48 hours. How do you manage VTE prophylaxis?"

EXCEPTIONAL ANSWER
This patient presents the challenging situation of very high VTE risk from hip fracture in the context of an absolute contraindication to chemical prophylaxis due to active bleeding. My approach would be multimodal. First, I would optimize management of the GI bleeding by involving gastroenterology for urgent endoscopy and hemostasis, ensuring adequate resuscitation, and considering proton pump inhibitor infusion. Second, I would maximize mechanical prophylaxis with intermittent pneumatic compression devices applied immediately and continued throughout hospital admission, graduated compression stockings if no lower limb issues, and early mobilization as permitted by the fracture and surgery. Third, I would consider IVC filter placement before surgery if the GI bleeding is unlikely to be controlled quickly and anticoagulation will be contraindicated for more than 72 hours. The indication would be for temporary protection against PE in a very high-risk patient who cannot receive anticoagulation. I would use a retrievable filter with plan for removal once anticoagulation can be started. Fourth, I would reassess daily and initiate chemical prophylaxis as soon as bleeding is controlled and it is safe to do so, typically once endoscopic hemostasis is achieved and patient is stable for 24-48 hours. The key principle is that mechanical prophylaxis alone is insufficient for hip fracture, and we must work toward initiating chemical prophylaxis as soon as safely possible.
KEY POINTS TO SCORE
Active bleeding is absolute contraindication to anticoagulation
Maximize mechanical prophylaxis immediately
IVC filter consideration for prolonged anticoagulation contraindication
Involve gastroenterology for bleeding source control
Reassess daily and start chemical prophylaxis as soon as safe
COMMON TRAPS
✗Starting anticoagulation despite active bleeding
✗Relying on mechanical prophylaxis alone long-term for hip fracture
✗Not considering IVC filter for prolonged contraindication
✗Failing to recognize this as a multidisciplinary problem
LIKELY FOLLOW-UPS
"What are the indications for IVC filter placement?"
"When would you remove the IVC filter?"
"What are the complications of IVC filters?"

Australian Context

Australian Guidelines and Resources:

VTE prophylaxis in Australia is guided by multiple authoritative sources that should inform clinical practice and are relevant to FRACS examinations.

Therapeutic Guidelines (eTG): The Antibiotic (eTG) and Cardiovascular (eTG) guidelines provide evidence-based recommendations for VTE prophylaxis and treatment in the Australian context. Key recommendations align with international guidelines including ACCP, with emphasis on:

  • Risk stratification for all surgical patients
  • Mechanical and chemical prophylaxis for high-risk orthopaedic procedures
  • Extended prophylaxis (35 days) for THA, TKA, and hip fracture surgery
  • LMWH or DOAC as first-line agents

NHMRC Patient Blood Management Guidelines: Module 2 (Perioperative) includes recommendations on VTE prophylaxis as part of comprehensive perioperative care. The guidelines emphasize individualized risk assessment and multimodal prophylaxis.

Australian Commission on Safety and Quality in Health Care: VTE prevention is a national clinical care standard. All hospitals must:

  • Perform VTE risk assessment on admission
  • Document prophylaxis plan
  • Monitor compliance with prophylaxis protocols
  • Report VTE as a hospital-acquired complication

PBS-Listed Agents (Pharmaceutical Benefits Scheme): The following agents are PBS-listed for VTE prophylaxis after orthopaedic surgery in Australia:

  • Enoxaparin (Clexane) - first-line LMWH
  • Rivaroxaban (Xarelto) - PBS streamlined for THA, TKA prophylaxis
  • Apixaban (Eliquis) - PBS listed for THA, TKA prophylaxis
  • Aspirin - available OTC, used for extended prophylaxis

Quitline (13 7848) and Smoking Cessation: Smoking is an independent risk factor for VTE. Preoperative smoking cessation counseling should be provided, and patients can be referred to Quitline for support. Smoking cessation for 4 or more weeks preoperatively reduces complications including VTE.

Australian VTE Prevention

The Australian Commission on Safety and Quality in Health Care includes VTE as a key hospital-acquired complication for reporting. This means hospitals track VTE rates and compliance with prophylaxis protocols. Understanding the medicolegal and quality improvement aspects of VTE prevention is important for FRACS candidates.

VENOUS THROMBOEMBOLISM - COMPREHENSIVE

High-Yield Exam Summary

Virchow's Triad (SHE)

  • •Stasis: Immobility, venous pooling - treat with mechanical prophylaxis, early mobilization
  • •Hypercoagulability: Trauma, surgery, inherited thrombophilia - treat with chemical prophylaxis
  • •Endothelial injury: Surgery, fractures, cement - minimize with gentle technique
  • •All three present in major orthopaedic surgery - explains high VTE risk

Risk Stratification (Caprini)

  • •Score 0: Very low risk (0.5%) - early ambulation only
  • •Score 1-2: Low risk (1.5%) - mechanical prophylaxis
  • •Score 3-4: Moderate risk (3%) - mechanical + chemical prophylaxis
  • •Score 5+: High risk (6%) - mechanical + chemical + extended prophylaxis (35 days)
  • •5-point factors: Hip/pelvis/leg fracture, prior VTE, stroke, spinal cord injury, arthroplasty

Chemical Prophylaxis Agents

  • •Enoxaparin: 40mg SC daily, start 12-24h postop, gold standard LMWH
  • •Rivaroxaban: 10mg PO daily, start 6-10h postop, Factor Xa inhibitor
  • •Apixaban: 2.5mg PO BD, start 12-24h postop, renal-safe DOAC
  • •Aspirin: 100-300mg daily, acceptable for extended phase or lower-risk patients
  • •All THA/TKA/hip fracture: 35 days extended prophylaxis (ACCP Grade 1B)

DVT Diagnosis

  • •Wells Score: 3+ = high probability (53% prevalence)
  • •D-dimer: DO NOT use postoperatively (always elevated)
  • •Compression ultrasound: Gold standard, 95% sensitive for proximal DVT
  • •Clinical features: Calf pain, unilateral leg swelling, warmth (CLOT mnemonic)
  • •50% of DVTs are asymptomatic

PE Diagnosis and Severity

  • •CTPA: Gold standard (95% sensitivity and specificity)
  • •Low risk PE: Stable, no RV dysfunction - anticoagulation, consider outpatient
  • •Intermediate PE: Stable, RV dysfunction - anticoagulation, close monitoring
  • •Massive PE: Hemodynamic instability (SBP less than 90) - thrombolysis, embolectomy, ECMO
  • •Biomarkers: Troponin and BNP for risk stratification

Key Timing Points

  • •LMWH: 12h before (European) or 12-24h after surgery (North American)
  • •Rivaroxaban: 6-10 hours postoperatively
  • •Apixaban: 12-24 hours postoperatively
  • •Neuraxial: LMWH 12h before and 4h after epidural manipulation
  • •DOACs: 24-48h washout before neuraxial procedures

Key Trials

  • •RECORD trials: Rivaroxaban superior to enoxaparin for THA/TKA prophylaxis
  • •ADVANCE trials: Apixaban non-inferior to enoxaparin with lower bleeding
  • •EPCAT II: Aspirin non-inferior to rivaroxaban for extended prophylaxis (after initial DOAC)
  • •PREPIC-2: IVC filters do not reduce PE when anticoagulation given
  • •SOX trial: Compression stockings showed no PTS benefit (controversial)

Contraindications to Chemical Prophylaxis

  • •Active bleeding or high bleeding risk
  • •Severe thrombocytopenia (platelets less than 50)
  • •Recent intracranial hemorrhage or neurosurgery
  • •Epidural/spinal within timing window
  • •HIT (for heparin products)
  • •If contraindicated: maximize mechanical prophylaxis, consider IVC filter
Quick Stats
Reading Time115 min
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