# Clinical Cases: Venous Thromboembolism

## Case 1: Deep Vein Thrombosis

### Patient Presentation
A 45-year-old woman presents with 3 days of progressive left leg swelling and pain. She returned from a 12-hour flight from Europe 5 days ago. She has a history of obesity and recently started oral contraceptive pills for menorrhagia. She denies shortness of breath, chest pain, or hemoptysis.

### Vital Signs
- Blood Pressure: 132/78 mmHg
- Heart Rate: 82 bpm
- Respiratory Rate: 16/min
- Oxygen Saturation: 98% on room air
- Temperature: 37.2°C

### Physical Examination
- General: Well-appearing, mild discomfort
- Cardiovascular: Regular rhythm, no murmurs
- Pulmonary: Clear
- Left lower extremity: Swelling from ankle to mid-thigh, 4 cm circumference difference at calf, warmth, erythema, tenderness along medial thigh
- Right lower extremity: Normal

### Initial Workup
- **D-dimer**: 2,450 ng/mL (normal <500)
- **CBC**: Normal
- **Creatinine**: 0.8 mg/dL
- **Compression ultrasound**: Non-compressible left common femoral and popliteal veins

### Clinical Image
![DVT Ultrasound](image_01.png)
*Figure 1: Compression ultrasound demonstrating non-compressibility of the femoral vein (arrow), diagnostic of deep vein thrombosis. Normal veins completely compress with probe pressure.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What is this patient's Wells score for DVT and pretest probability?**
   - A) Low probability
   - B) Moderate probability (Wells 1-2)
   - C) High probability (Wells ≥3)
   - D) Cannot calculate

2. **What is the role of D-dimer in DVT diagnosis?**
   - A) Confirms DVT when positive
   - B) Rules out DVT when negative in low/moderate pretest probability patients
   - C) Should be obtained in all patients
   - D) Not useful in DVT evaluation

3. **What is the appropriate initial anticoagulation for this patient?**
   - A) Warfarin alone
   - B) DOAC (rivaroxaban, apixaban) or LMWH followed by warfarin
   - C) Aspirin only
   - D) IVC filter placement

4. **What is the recommended duration of anticoagulation for this patient?**

5. **What are this patient's risk factors for VTE?**

### Answers

1. **C) High probability (Wells ≥3)** - Wells criteria for DVT:
   - Active cancer: 0
   - Paralysis/immobilization: 0
   - Bedridden >3 days or surgery <12 weeks: 0
   - Tenderness along deep veins: 1
   - Entire leg swollen: 1
   - Calf swelling >3 cm: 1
   - Pitting edema: 1
   - Collateral superficial veins: 0
   - Alternative diagnosis as likely: 0
   - **Total: 4** (≥3 = high probability)

2. **B) Rules out DVT when negative in low/moderate pretest probability patients** - D-dimer has high negative predictive value. A negative D-dimer in low/moderate probability patients effectively excludes DVT. High pretest probability patients should proceed directly to imaging.

3. **B) DOAC (rivaroxaban, apixaban) or LMWH followed by warfarin** - Options include:
   - DOACs (rivaroxaban, apixaban) as monotherapy - preferred for most patients
   - LMWH bridge to warfarin (target INR 2-3)
   - LMWH alone (preferred in cancer-associated thrombosis)
   - DOACs are contraindicated with estrogen-containing contraceptives should be discontinued

4. **Recommended duration of anticoagulation**:
   - This is a provoked DVT (long-haul flight + OCPs)
   - Standard treatment: **3 months**
   - After 3 months, reassess: if provoking factors removed (stopped OCPs, no further immobilization), can discontinue
   - If unprovoked or ongoing risk factors, consider extended anticoagulation
   - Proximal DVT has higher recurrence risk than distal DVT

5. **Risk factors for VTE in this patient**:
   - Prolonged immobilization (12-hour flight)
   - Oral contraceptive pills (estrogen increases clotting factors)
   - Obesity (inflammatory state, venous stasis)
   - These are transient/reversible risk factors
   - Counsel on VTE prevention for future travel (hydration, mobilization, compression stockings, consider prophylactic LMWH for high-risk patients)

---

## Case 2: Pulmonary Embolism

### Patient Presentation
A 58-year-old man with recently diagnosed prostate cancer (2 weeks post-biopsy) presents with sudden-onset shortness of breath and right-sided pleuritic chest pain that started 6 hours ago. He also reports mild hemoptysis. He has been relatively sedentary since his diagnosis while awaiting treatment planning.

### Vital Signs
- Blood Pressure: 108/72 mmHg
- Heart Rate: 112 bpm
- Respiratory Rate: 26/min
- Oxygen Saturation: 89% on room air
- Temperature: 37.4°C

### Physical Examination
- General: Anxious, mild respiratory distress
- Cardiovascular: Tachycardic, prominent P2, RV heave
- Pulmonary: Decreased breath sounds at right base, no wheezes
- Extremities: Right calf tenderness with mild swelling

### Laboratory and Imaging
- **D-dimer**: 4,200 ng/mL
- **Troponin I**: 0.18 ng/mL (mildly elevated)
- **BNP**: 580 pg/mL
- **ABG (room air)**: pH 7.48, PaCO2 28 mmHg, PaO2 62 mmHg
- **ECG**: Sinus tachycardia, S1Q3T3 pattern, right heart strain
- **CT pulmonary angiography**: Large saddle pulmonary embolus with bilateral segmental involvement

### Clinical Image
![Saddle PE CT](image_02.png)
*Figure 2: CT pulmonary angiography demonstrating a saddle pulmonary embolus at the bifurcation of the main pulmonary artery with extension into both right and left pulmonary arteries.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What is this patient's Pulmonary Embolism Severity Index (PESI) class and risk stratification?**
   - A) Low risk - outpatient treatment possible
   - B) Intermediate risk - consider admission
   - C) High risk (massive PE) - requires hemodynamic support
   - D) Not applicable

2. **What findings indicate right ventricular dysfunction in PE?**
   - A) Elevated BNP and troponin, RV dilation on CT, ECG changes (S1Q3T3)
   - B) Elevated D-dimer only
   - C) Hypoxemia only
   - D) Pleuritic chest pain

3. **What is the appropriate treatment approach for this intermediate-high risk PE?**
   - A) Thrombolysis
   - B) Anticoagulation with close monitoring; consider thrombolysis if hemodynamic deterioration
   - C) Surgical embolectomy
   - D) Anticoagulation and early discharge

4. **What is the role of thrombolysis in PE?**

5. **What are the long-term anticoagulation considerations for cancer-associated thrombosis?**

### Answers

1. **B) Intermediate risk - consider admission** - This patient has:
   - Submassive/intermediate-risk PE: Hemodynamically stable but with RV dysfunction
   - Risk factors: Cancer, elevated troponin and BNP, RV strain on ECG/CT
   - Requires hospital admission for monitoring and anticoagulation
   - Not massive PE (would require shock/hypotension)

2. **A) Elevated BNP and troponin, RV dilation on CT, ECG changes (S1Q3T3)** - RV dysfunction markers:
   - Elevated troponin (myocardial injury)
   - Elevated BNP (RV strain)
   - RV/LV ratio >0.9 on CT
   - RV dilation on echocardiography
   - ECG: S1Q3T3, T-wave inversions V1-V4, right bundle branch block
   - These indicate intermediate-high risk requiring close monitoring

3. **B) Anticoagulation with close monitoring; consider thrombolysis if hemodynamic deterioration** - Management:
   - Start anticoagulation immediately (LMWH, fondaparinux, or UFH for cancer)
   - ICU or step-down monitoring
   - If hemodynamic deterioration (shock, persistent hypotension), escalate to thrombolysis
   - Catheter-directed therapy is an alternative to systemic thrombolysis

4. **Role of thrombolysis in PE**:
   - **Massive/high-risk PE** (with hemodynamic instability): Thrombolysis indicated if no contraindications
   - **Intermediate-risk PE**: Consider if clinical deterioration; routine use not recommended
   - **Low-risk PE**: Not indicated
   - Systemic thrombolysis: Alteplase 100 mg over 2 hours
   - Catheter-directed thrombolysis: Lower dose, may reduce bleeding risk
   - Contraindications: Recent surgery, active bleeding, stroke history, intracranial disease

5. **Anticoagulation for cancer-associated thrombosis**:
   - LMWH was traditional standard of care (CLOT trial)
   - DOACs (edoxaban, rivaroxaban) are now preferred for most cancer-associated VTE (non-GI cancers)
   - Avoid DOACs in GI/GU malignancies (increased bleeding risk)
   - Duration: Extended/indefinite while cancer is active or during treatment
   - Reassess periodically for bleeding risk vs. thrombotic risk

---

## Case 3: Unprovoked VTE and Thrombophilia Evaluation

### Patient Presentation
A 32-year-old woman presents with acute left leg swelling and is diagnosed with extensive iliofemoral DVT. She has no recent travel, surgery, immobilization, or hormone use. She is otherwise healthy with no medical history. Her mother had a DVT at age 40, and her maternal grandmother died of a "blood clot in the lungs" at age 55.

### Vital Signs
- Blood Pressure: 118/72 mmHg
- Heart Rate: 78 bpm
- Respiratory Rate: 14/min
- Oxygen Saturation: 99% on room air

### Physical Examination
- General: Well-appearing
- Left lower extremity: Swelling, erythema from ankle to groin
- Otherwise normal examination

### Imaging
- **Duplex ultrasound**: Extensive thrombus in left external iliac, common femoral, and femoral veins

### Clinical Image
![Iliofemoral DVT](image_03.png)
*Figure 3: Doppler ultrasound showing extensive iliofemoral deep vein thrombosis with absent flow in the common femoral vein and visualized echogenic thrombus.*

**Image Source**: Educational illustration for teaching purposes.

### Questions

1. **What features of this case suggest inherited thrombophilia?**
   - A) Age >65
   - B) Young age (<50), unprovoked VTE, strong family history of VTE
   - C) Recent surgery
   - D) Presence of cancer

2. **When should thrombophilia testing be performed?**
   - A) During acute thrombosis on anticoagulation
   - B) After completing anticoagulation therapy, typically 2-4 weeks after stopping
   - C) Before starting anticoagulation
   - D) Testing is never indicated

3. **What inherited thrombophilias should be tested for?**
   - A) Factor V Leiden only
   - B) Factor V Leiden, prothrombin G20210A mutation, antithrombin deficiency, protein C and S deficiency
   - C) All clotting factors
   - D) Only acquired conditions

4. **How does diagnosis of thrombophilia affect management?**

5. **What is the recommended duration of anticoagulation for unprovoked proximal DVT?**

### Answers

1. **B) Young age (<50), unprovoked VTE, strong family history of VTE** - Features suggesting inherited thrombophilia:
   - Age <50 years at first VTE
   - Unprovoked (idiopathic) VTE
   - Strong family history (first-degree relatives with VTE)
   - Recurrent VTE
   - VTE at unusual sites (cerebral, splanchnic, upper extremity)
   - Warfarin-induced skin necrosis (protein C/S deficiency)

2. **B) After completing anticoagulation therapy, typically 2-4 weeks after stopping** - Testing timing:
   - Acute thrombosis and anticoagulation affect results
   - Warfarin decreases protein C and S
   - Heparin decreases antithrombin
   - DOACs can affect lupus anticoagulant testing
   - Wait 2-4 weeks after stopping anticoagulation for accurate results
   - Testing rarely changes acute management

3. **B) Factor V Leiden, prothrombin G20210A mutation, antithrombin deficiency, protein C and S deficiency** - Standard thrombophilia panel:
   - Factor V Leiden mutation (most common)
   - Prothrombin G20210A mutation
   - Antithrombin deficiency
   - Protein C deficiency
   - Protein S deficiency
   - Also consider: Antiphospholipid antibodies (acquired), homocysteine

4. **How thrombophilia diagnosis affects management**:
   - Does NOT change acute treatment (still anticoagulate)
   - May influence duration of anticoagulation (extended/indefinite for high-risk thrombophilias)
   - Informs family screening and counseling
   - Guides risk assessment for future events (surgery, pregnancy, estrogen use)
   - Antithrombin deficiency and antiphospholipid syndrome have highest recurrence risk
   - Heterozygous Factor V Leiden has relatively low recurrence risk

5. **Duration of anticoagulation for unprovoked proximal DVT**:
   - Minimum 3 months
   - After 3 months, assess for extended therapy
   - Extended anticoagulation (indefinite) generally recommended for unprovoked proximal DVT if bleeding risk acceptable
   - Use risk assessment tools (HERDOO2, DASH score) to guide decision
   - If extended therapy chosen, consider reduced-dose DOAC (apixaban 2.5 mg BID, rivaroxaban 10 mg daily) after initial 6 months
   - Annual reassessment of risk-benefit

---

## Learning Points

1. **Wells criteria** help stratify pretest probability for DVT and PE; guide appropriate use of D-dimer and imaging.

2. **D-dimer** has high negative predictive value; negative D-dimer in low/moderate probability effectively excludes VTE.

3. **DOACs** are preferred for most VTE; LMWH remains important for cancer-associated thrombosis (especially GI cancers).

4. **PE risk stratification** (massive, submassive, low-risk) guides treatment intensity; thrombolysis reserved for hemodynamic instability.

5. **Unprovoked VTE** warrants consideration of extended anticoagulation and, in select cases, thrombophilia testing.