Prevention of Venous Thrombosis (VTE)

Introduction

Venous Thromboembolism (VTE), comprising Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), is a leading cause of preventable hospital death. For the MCCQE1, demonstrating competence in VTE prophylaxis is crucial, reflecting the Medical Expert and Health Advocate CanMEDS roles. You must be able to stratify risk, identify contraindications to anticoagulation, and select appropriate prophylactic measures based on Canadian guidelines.

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Canadian Context: VTE affects approximately 1 in 1000 Canadians annually. Thrombosis Canada provides the gold-standard clinical guides often referenced in Canadian medical practice and exams.

Pathophysiology and Risk Stratification

Understanding the mechanism of thrombosis is essential for selecting the right preventive strategy.

Virchow’s Triad

The classic triad describing the three broad categories of factors that contribute to thrombosis:

Stasis: Immobility, paralysis, atrial fibrillation, venous obstruction.
Endothelial Injury: Surgery, trauma, indwelling catheters.
Hypercoagulability: Malignancy, pregnancy, inherited thrombophilias (Factor V Leiden), estrogen therapy.

Risk Assessment Models (RAMs)

While clinical judgment is paramount, specific scores help quantify risk.

Padua Prediction Score: Used for medical inpatients. A score ≥ 4 indicates high risk.
Caprini Risk Assessment Model: Used for surgical patients to determine the duration and type of prophylaxis.

MCCQE1 High-Yield Risk Factors

Strong Risk Factors: Fracture of hip or leg, hip or knee replacement, major general surgery, major trauma, spinal cord injury.
Moderate Risk Factors: Arthroscopic knee surgery, central venous lines, chemotherapy, CHF or respiratory failure, malignancy, oral contraceptive therapy, stroke, pregnancy/postpartum.
Weak Risk Factors: Bed rest >3 days, immobility due to sitting (travel), increasing age, obesity, varicose veins.

Methods of Thromboprophylaxis

Prophylaxis is broadly categorized into mechanical and pharmacological methods.

1. Mechanical Prophylaxis

Used primarily when anticoagulation is contraindicated (e.g., active bleeding, high risk of bleeding, platelets <50 x 10⁹/L).

Graduated Compression Stockings (GCS): Less effective than IPC; caution in peripheral arterial disease.
Intermittent Pneumatic Compression (IPC): Preferred mechanical method for high-risk surgical patients.

2. Pharmacological Prophylaxis

The standard of care for most hospitalized patients at risk.

Agent	Mechanism	Canadian Clinical Use Notes
LMWH (e.g., Dalteparin, Enoxaparin)	Inhibits Factor Xa > IIa	First-line for most medical/surgical patients. Renal clearance required (caution if CrCl <30 mL/min).
Unfractionated Heparin (UFH)	Potentiates Antithrombin III	Preferred in severe renal failure (CrCl <30 mL/min). Short half-life. Risk of HIT.
Fondaparinux	Selective Factor Xa inhibitor	Alternative in patients with history of HIT. Contraindicated in severe renal impairment.
DOACs (e.g., Rivaroxaban, Apixaban)	Direct Xa or Thrombin inhibitor	Widely used in orthopedic surgery (hip/knee arthroplasty). Oral administration is convenient.
Warfarin	Vit K Antagonist	Rarely used for initial prophylaxis in acute hospital settings due to delayed onset and monitoring needs.

Clinical Approach to Prophylaxis

Step 1: Assess VTE Risk

Determine if the patient is surgical, medical, or obstetric. Apply appropriate risk factors (e.g., “Is this a 40-year-old with pneumonia or an 80-year-old post-hip fracture?”).

Step 2: Assess Bleeding Risk

Check for absolute contraindications:

Active hemorrhage
Severe trauma to head or spinal cord (with hemorrhage)
Platelet count <50 x 10⁹/L (variable threshold, but <50 is a red flag)
Coagulopathy (INR >1.5-2.0 not due to reversible causes)

Step 3: Select Modality

High Bleeding Risk: Mechanical prophylaxis (IPC).
Low Bleeding Risk: Pharmacological prophylaxis (LMWH is usually preferred over UFH due to once-daily dosing and lower HIT risk).

Step 4: Re-evaluate

Daily assessment of bleeding risk and renal function is required.

Scenario-Specific Management (Canadian Guidelines)

Medical Inpatients

Medical Inpatients (e.g., HF, Pneumonia, Sepsis)

Indication: Acutely ill medical patients admitted to hospital with reduced mobility.
First Line: LMWH (e.g., Enoxaparin 40 mg SC daily or Dalteparin 5000 units SC daily).
Renal Failure (CrCl <30 mL/min): UFH 5000 units SC BID or TID.
Duration: Until discharge or full mobility is restored.

Complications of Prophylaxis

Heparin-Induced Thrombocytopenia (HIT)

A life-threatening immune-mediated reaction.

Suspect if: Platelet count drops by >50% or thrombosis occurs 5–10 days after starting heparin.
4Ts Score: Thrombocytopenia, Timing, Thrombosis, oTher causes ruled out.
Management:
1. STOP all heparin (including flushes).
2. Send HIT antibodies (ELISA) and functional assay (Serotonin Release Assay - Gold Standard).
3. Start non-heparin anticoagulant (e.g., Fondaparinux, Argatroban, Danaparoid).
4. Do NOT give platelet transfusions (can precipitate thrombosis).

Key Points to Remember for MCCQE1

Exam High-Yield Checklist

Renal Function Matters: Always look at Creatinine/GFR before prescribing LMWH. If GFR <30, switch to UFH.
Pregnancy: LMWH is safe; Warfarin causes embryopathy.
Epidurals: Remember the “12-hour rule” for prophylactic LMWH to prevent spinal epidural hematoma.
Cancer: LMWH has historically been preferred over Warfarin for VTE treatment in cancer (“CLOT trial”), though DOACs are now increasingly used.
Superficial Thrombophlebitis: Generally does not require full anticoagulation unless near the saphenofemoral junction (risk of DVT).

Sample Question

Clinical Scenario

A 72-year-old female is admitted to the orthopedic ward following a right total hip arthroplasty performed earlier today. She has a history of hypertension and Type 2 diabetes controlled with metformin. Her preoperative creatinine clearance was 25 mL/min. There is no history of bleeding disorders. The surgical team requests VTE prophylaxis orders.

Which one of the following is the most appropriate pharmacological prophylaxis for this patient?

Options

A. Enoxaparin (LMWH) 30 mg SC every 12 hours
B. Unfractionated Heparin (UFH) 5000 units SC every 12 hours
C. Warfarin with a target INR of 2.5
D. Dabigatran 110 mg PO daily
E. Aspirin 81 mg PO daily

Explanation

The correct answer is:

B. Unfractionated Heparin (UFH) 5000 units SC every 12 hours

Detailed Breakdown:

Analysis of the Patient: Post-operative total hip arthroplasty (High Risk for VTE). Key finding: Creatinine clearance is 25 mL/min (Severe renal impairment).
Option A (Enoxaparin): Low Molecular Weight Heparins (LMWH) are renally cleared. While dose adjustments can be made, in severe renal failure (CrCl <30 mL/min), accumulation increases bleeding risk significantly. Standard dosing is contraindicated.
Option B (UFH): Unfractionated Heparin is minimally cleared by the kidneys and is the preferred agent for VTE prophylaxis in patients with severe renal failure.
Option C (Warfarin): While used in orthopedics, it takes days to reach therapeutic levels and is rarely used as the immediate post-op initiation agent without a bridge, and maintaining stable INR is difficult. It is not the most appropriate immediate choice compared to heparin options in the hospital setting.
Option D (Dabigatran): This is a DOAC (Direct Thrombin Inhibitor). It is approximately 80% renally excreted and is contraindicated or requires extreme caution/dose reduction (which is not specified here) in severe renal impairment.
Option E (Aspirin): While recent guidelines suggest aspirin can be used in selected low-risk orthopedic patients, this patient has significant comorbidities and renal risks. Furthermore, compared to UFH in a high-risk renal patient, UFH is the standard guideline-based answer for safety and efficacy in the acute phase.

References

Thrombosis Canada. Clinical Guides: Thromboprophylaxis: Non-Orthopedic Surgery & Medical Patients. Available at: https://thrombosiscanada.ca
Kahn SR, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012.
Falck-Ytter Y, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012.
Medical Council of Canada. Objectives for the Qualifying Examination (MCCQE) Part I.