Pharmacotherapeutics III · PharmD Year 4
Venous Thromboembolism
Deep Vein Thrombosis (DVT) & Pulmonary Embolism (PE) — Complete Exam Guide
01 Definition & Overview
Venous Thromboembolism (VTE) is a spectrum of disease encompassing:
• Deep Vein Thrombosis (DVT) — formation of a blood clot (thrombus) within the deep veins, most commonly the proximal leg veins (femoral, popliteal, iliac).
• Pulmonary Embolism (PE) — migration of a DVT clot to the pulmonary vasculature, causing obstruction. Can be life-threatening.
VTE is the 3rd most common cardiovascular disorder after MI and stroke, with ~1–2 cases per 1,000 person-years.
• Deep Vein Thrombosis (DVT) — formation of a blood clot (thrombus) within the deep veins, most commonly the proximal leg veins (femoral, popliteal, iliac).
• Pulmonary Embolism (PE) — migration of a DVT clot to the pulmonary vasculature, causing obstruction. Can be life-threatening.
VTE is the 3rd most common cardiovascular disorder after MI and stroke, with ~1–2 cases per 1,000 person-years.
02 Pathophysiology — Virchow's Triad
🩸
Hypercoagulability
Factor V Leiden, Protein C/S deficiency, antiphospholipid syndrome, OCP use, malignancy
🫀
Venous Stasis
Immobility, prolonged bed rest, obesity, CHF, long flights, varicose veins
🔬
Endothelial Injury
Surgery, trauma, IV catheter, indwelling devices, inflammation
Clot Formation Mechanism
Venous thrombi are predominantly red clots (fibrin + RBCs), unlike arterial thrombi (platelet-rich "white clots"). The coagulation cascade (intrinsic/extrinsic pathways) converges on thrombin (Factor IIa), which converts fibrinogen → fibrin, forming the clot mesh. This is the primary target for anticoagulants.
03 Risk Factors
🔴 Major Risk Factors
- Major surgery (orthopedic, abdominal)
- Active malignancy
- Prior VTE history
- Inherited thrombophilia (Factor V Leiden)
- Trauma / fractures
- Antiphospholipid syndrome
🟡 Moderate / Minor Risk Factors
- Oral contraceptives / HRT
- Pregnancy & postpartum
- Immobility / long-haul travel
- Obesity (BMI >30)
- Inflammatory bowel disease
- Nephrotic syndrome
- Age >60 years
04 Clinical Presentation
DVT Signs & Symptoms
- Unilateral leg swelling, pain, warmth
- Erythema / discoloration of the limb
- Homans' sign (calf pain on dorsiflexion — low sensitivity)
- Pitting edema
- May be completely asymptomatic (~50%)
PE Signs & Symptoms
- Sudden onset dyspnea (most common)
- Pleuritic chest pain
- Tachycardia, tachypnea
- Hypoxia (↓ SpO₂)
- Hemoptysis (rare but classic)
- Syncope / hemodynamic collapse (massive PE)
- S1Q3T3 pattern on ECG (right heart strain)
05 Diagnosis
Wells Score for DVT (Pre-test Probability)
+1
Active cancer+1
Paralysis / plaster immobilization+1
Bedridden >3 days / surgery within 12 wks+1
Localized tenderness along deep veins+1
Entire leg swollen+1
Calf swelling >3 cm vs. other leg+1
Pitting edema (symptomatic leg)+1
Collateral superficial veins−2
Alternative diagnosis more likelyScore ≤1: Low probability → D-dimer. If negative, VTE excluded.
Score 2+: Moderate/High → proceed to Compression Ultrasonography (CUS).
Diagnostic Workup Summary
| Test | Use | Notes |
|---|---|---|
| D-Dimer | Rule out VTE (low probability) | High sensitivity, low specificity. Elevated in infection, pregnancy, surgery — not specific. |
| Compression Ultrasonography (CUS) | Diagnose DVT | Non-compressible vein = DVT. First-line imaging. |
| CT Pulmonary Angiography (CTPA) | Gold standard for PE | Preferred over V/Q scan in most settings |
| V/Q Scan | PE when CTPA contraindicated | Use in pregnancy, CKD, contrast allergy |
| Echocardiography | Assess RV strain (massive PE) | RV dilation = poor prognosis marker |
| Troponin / BNP | Risk stratify PE | Elevated = myocardial stress → worse outcomes |
06 Pharmacological Treatment
Treatment Goals
- Prevent clot extension and PE
- Promote clot resolution
- Prevent recurrence
- Prevent post-thrombotic syndrome (PTS)
- Prevent chronic thromboembolic pulmonary hypertension (CTEPH)
| Drug | Class / MOA | Dose (VTE Treatment) | Key Notes |
|---|---|---|---|
| Rivaroxaban | Direct Xa inhibitor (DOAC) | 15 mg BID × 21 days → 20 mg OD with food | ✅ Preferred 1st-line. No INR monitoring. Avoid in CrCl <15. |
| Apixaban | Direct Xa inhibitor (DOAC) | 10 mg BID × 7 days → 5 mg BID | ✅ Preferred 1st-line. Safest in renal impairment. No food restriction. |
| Dabigatran | Direct Thrombin Inhibitor (DOAC) | 150 mg BID (after 5–10 days parenteral) | Requires initial parenteral anticoagulation. Avoid CrCl <30. |
| Edoxaban | Direct Xa inhibitor (DOAC) | 60 mg OD (after 5–10 days parenteral) | Requires initial heparin bridge. Avoid if CrCl >95 (↓ efficacy). |
| Warfarin | Vit K antagonist — inhibits II, VII, IX, X | Individualized; target INR 2–3 | Requires heparin bridge (5–7 days overlap). Many interactions. Monitor INR. |
| UFH (Unfractionated Heparin) | Antithrombin activator → inhibits IIa, Xa | 80 units/kg bolus → 18 units/kg/hr IV infusion (weight-based) | Monitor aPTT (target 60–100 sec). Reversible with protamine. Use in renal failure, high bleeding risk surgery. |
| Enoxaparin (LMWH) | Antithrombin activator → mainly anti-Xa | 1 mg/kg SC BID or 1.5 mg/kg OD | ✅ Preferred in pregnancy & cancer-associated VTE. Monitor anti-Xa if CrCl <30 or obesity. Partial reversal with protamine. |
| Fondaparinux | Indirect selective Xa inhibitor | 5–10 mg SC OD (weight-based) | No HIT risk. Avoid CrCl <30. No antidote available. |
| Alteplase (tPA) | Thrombolytic — plasminogen activator | 100 mg IV over 2 hrs | ⚠️ Reserved for massive PE (hemodynamic instability). High bleeding risk. |
07 Duration of Anticoagulation
| Clinical Scenario | Duration |
|---|---|
| Provoked DVT/PE (reversible risk factor — surgery, trauma) | 3 months |
| First unprovoked DVT/PE (low bleed risk) | ≥3 months → consider extended / indefinite |
| Recurrent VTE | Indefinite (long-term) |
| Active malignancy (cancer-associated VTE) | Indefinite or until cancer resolved (LMWH or rivaroxaban/apixaban preferred) |
| Antiphospholipid Syndrome | Indefinite — warfarin preferred (INR 2–3) |
| Distal DVT (asymptomatic, low risk) | Surveillance vs. 3 months |
08 Special Populations
🤰 Pregnancy
- LMWH (Enoxaparin) is drug of choice — does NOT cross placenta
- Warfarin contraindicated (teratogenic in 1st trimester; fetal hemorrhage)
- DOACs contraindicated (no safety data)
- Continue anticoagulation for 6 weeks postpartum (min 3 months total)
🎗️ Cancer-Associated VTE (CAT)
- Preferred: Apixaban, Rivaroxaban (DOAC) — non-inferior to LMWH
- Avoid DOACs in GI/GU malignancy (higher bleeding risk) → use LMWH
- Indefinite duration while cancer is active
- Warfarin less preferred (unstable INR with chemo)
🫘 Renal Impairment
- CrCl 15–29: Apixaban preferred DOAC
- CrCl <15 / HD: UFH preferred (monitor aPTT)
- Avoid dabigatran (80% renal excretion)
- Warfarin acceptable (not renally cleared)
⚠️ Heparin-Induced Thrombocytopenia (HIT)
- Platelet drop >50% after 5–14 days heparin
- Paradoxically prothrombotic!
- Tx: Stop ALL heparin (UFH & LMWH)
- Use: Argatroban (DTI) or Fondaparinux
- 4T score used for diagnosis
09 VTE Prophylaxis
Pharmacological Prophylaxis Agents
| Agent | Dose | Indication |
|---|---|---|
| Enoxaparin
|
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