8.3 Pulmonary Vascular Disease & Thromboembolism

8.3 Pulmonary Vascular Disease & Thromboembolism

Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) represent manifestations of venous thromboembolism (VTE). On USMLE Step 2 CK, key testing points include calculating the Wells score, applying the PERC rule and age-adjusted D-dimer thresholds, initiating pre-imaging anticoagulation in high-probability patients, identifying acute right heart strain, managing massive PE with thrombolysis, and classifying pulmonary hypertension.

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Pathophysiology & Virchow's Triad

Venous thromboembolism formation is governed by Virchow's Triad:

1. Venous Stasis: Prolonged immobilization (>3 days), major surgery, long-distance flights (>6-8 hours), stroke, heart failure.
2. Endothelial Injury: Trauma, orthopedic surgery (total hip/knee replacement), central venous catheters, previous DVT.
3. Hypercoagulability: Active malignancy, oral contraceptives / HRT, Factor V Leiden mutation (most common inherited hypercoagulable state), Antiphospholipid Syndrome (lupus anticoagulant, anti-beta-2 glycoprotein I), Protein C/S deficiency, Prothrombin G20210A mutation.

Anatomic Origin: Greater than 90% of pulmonary emboli originate from deep proximal veins of the lower extremities (iliac, femoral, popliteal veins). Thrombi in distal calf veins rarely cause hemodynamically significant PE.

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Clinical Presentation & Diagnostic Clues

• Symptoms: Acute-onset dyspnea (most common symptom overall), pleuritic chest pain, cough, hemoptysis, and syncope (indicates massive PE causing sudden drop in cardiac output).
• Physical Examination: Tachypnea (RR >20/min), tachycardia (HR >100/min), low-grade fever, prominent pulmonic component of S2 (loud P2), jugular venous distension (JVD), and unilateral lower extremity swelling/tenderness.
• Chest Radiograph (CXR): Frequently normal (the most classic USMLE vignette clue). Rare findings include Westermark sign (focal oligemia distal to embolus) and Hampton hump (wedge-shaped, pleural-based consolidation indicating pulmonary infarction).
• Electrocardiogram (EKG):
  • Most Common Finding: Sinus tachycardia.
  • Signs of Acute Right Ventricular (RV) Strain: S1Q3T3 pattern (deep S wave in lead I, Q wave in lead III, inverted T wave in lead III), right axis deviation, right bundle branch block (RBBB), and T-wave inversions in leads V1–V4.
• Echocardiogram (TTE): RV dilation, hypokinesis of the RV free wall with sparing of the apex (McConnell sign), interventricular septum flattening ("D-shaped" left ventricle), and elevated RV systolic pressure.

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Diagnostic Algorithms: Wells Score, PERC Rule & Age-Adjusted D-Dimer

Wells Criteria Scoring System

• Interpretation:
  • Wells Score > 4: PE Likely (High Probability) -> Proceed directly to CT Pulmonary Angiography (CTPA).
  • Wells Score ≤ 4: PE Unlikely (Low/Moderate Probability) -> Proceed to High-Sensitivity D-Dimer.

PERC Rule (Pulmonary Embolism Rule-out Criteria)

Applied ONLY in patients with a LOW pre-test probability (Wells ≤ 4 or low clinical gestalt). If ALL 8 criteria are met, PE is excluded without ordering a D-dimer or imaging:

1. Age < 50 years
2. Heart rate < 100 beats/min
3. Pulse oximetry SpO2 ≥ 95% on room air
4. No prior DVT or PE
5. No recent surgery or trauma within 4 weeks
6. No hemoptysis
7. No estrogen use (OCPs or HRT)
8. No unilateral leg swelling

Age-Adjusted D-Dimer Threshold

In patients > 50 years old with low/moderate PE probability, standard D-dimer (cut-off 500 ng/mL) yields high false-positive rates. Use the Age-Adjusted D-Dimer Formula:

• Age-Adjusted Cut-off = Age × 10 ng/mL FEU (e.g., for a 72-year-old patient, normal cut-off is 720 ng/mL).
• A D-dimer below the age-adjusted threshold safely rules out PE without CT scan.

Choice of Imaging Modality

• CT Pulmonary Angiography (CTPA): First-line imaging (gold standard) for acute PE.
• Ventilation/Perfusion (V/Q) Scan: Preferred when CTPA is contraindicated due to severe renal insufficiency (eGFR < 30 mL/min), severe iodinated contrast allergy, or pregnancy (to reduce maternal breast radiation).

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Acute PE Management Algorithm

1. Pre-Imaging Anticoagulation (High-Yield Step 2 CK Rule)

If clinical pre-test probability is HIGH (Wells > 4) and the patient is hemodynamically stable with no contraindications, START THERAPEUTIC ANTICOAGULATION IMMEDIATELY PRIOR TO CTPA IMAGING!

2. Hemodynamically Stable PE (SBP ≥ 90 mmHg)

• Initial Pharmacotherapy: Low-Molecular-Weight Heparin (LMWH, e.g., Enoxaparin 1 mg/kg SC q12h), Subcutaneous Fondaparinux, or Direct Oral Anticoagulants (DOACs, e.g., Apixaban, Rivaroxaban).
• Unfractionated Heparin (UFH) IV infusion is preferred over LMWH in:
  1. Severe renal impairment (CrCl < 30 mL/min).
  2. Patients at high risk of bleeding where rapid reversal (protamine sulfate) may be required.
  3. Hemodynamically unstable patients or those who may imminently undergo thrombolysis or embolectomy.
• Long-Term Anticoagulation: DOACs (Apixaban, Rivaroxaban, Dabigatran, Edoxaban) are first-line over Warfarin. Warfarin requires bridging with heparin for ≥5 days AND until INR is ≥ 2.0 for ≥24 hours. Duration: 3 months for provoked PE; indefinite for unprovoked PE or active malignancy.

3. Hemodynamically Unstable / Massive PE (SBP < 90 mmHg or Drop ≥ 40 mmHg for >15 min)

• Medical Emergency: Causes right ventricular failure and obstructive shock.
• First-Line Treatment: Emergency Systemic Thrombolytic Therapy (e.g., IV Recombinant Tissue Plasminogen Activator - tPA / Alteplase 100 mg over 2 hours).
• Contraindications to Thrombolysis: Recent intracranial hemorrhage, ischemic stroke within 6 months, CNS neoplasm, major trauma/surgery within 3 weeks, active internal bleeding.
• Alternatives: If thrombolysis is contraindicated or fails: Catheter-Directed Thrombolysis / Embolectomy or Surgical Pulmonary Embolectomy.

4. Indications for Inferior Vena Cava (IVC) Filter

1. Absolute contraindication to anticoagulation (e.g., active major GI bleeding, recent intracranial hemorrhage).
2. Recurrent PE despite proven therapeutic anticoagulation.
3. Severe bleeding complications secondary to anticoagulation therapy.

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Pulmonary Hypertension (PH) & CTEPH

Definition & Diagnosis

Defined as mean pulmonary arterial pressure (mPAP > 20 mmHg) at rest measured via Right Heart Catheterization (gold standard).

WHO Classification Groups & Targeted Therapies

• Group 1: Pulmonary Arterial Hypertension (PAH): Idiopathic, hereditary (BMPR2 mutation), Systemic Sclerosis. Treated with endothelin receptor antagonists (Bosentan), PDE-5 inhibitors (Sildenafil), or prostacyclins (Epoprostenol).
• Group 2: PH due to Left Heart Disease: HFrEF, HFpEF, valvular disease. Treated by managing underlying heart failure (diuretics, ACEi). PAH-specific vasodilators are contraindicated.
• Group 3: PH due to Lung Disease / Hypoxia: COPD, ILD, OSA. Treated with supplemental oxygen and lung disease management.
• Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Follows unresolved acute PE resulting in organized fibrotic clot obstruction. Diagnosed via V/Q scan (shows mismatched perfusion defects). Curative Treatment: Surgical Pulmonary Thromboendarterectomy (PTE); medical therapy includes Riociguat.
• Group 5: Multifactorial / Systemic: Hematologic or systemic conditions (sarcoidosis).