Thrombotic Disorders

Intro & Virchow's - Clotting 101

• Thrombosis: Pathological intravascular clot (thrombus). Hemostasis: Physiological process (platelets, factors, endothelium) stopping blood loss.
• Virchow's Triad (critical for thrombosis):
  • Endothelial Injury: Procoagulant switch (e.g., inflammation, trauma).
  • Abnormal Blood Flow: Stasis (e.g., DVT) or turbulence (e.g., aneurysms).
  • Hypercoagulability: ↑ procoagulants / ↓ anticoagulants (inherited/acquired).

    ⭐ Factor V Leiden: most common inherited thrombophilia (Activated Protein C resistance).

• Coagulation Cascade:
  • Intrinsic (PTT) & Extrinsic (PT/INR) pathways converge.
  • Common pathway: Factor Xa → Thrombin (IIa) → Fibrin clot.
  • 📌 Vit. K-dependent factors: II, VII, IX, X; Proteins C & S.

Inherited Causes - Risky Genes

• Key inherited hypercoagulable states predisposing to Venous Thromboembolism (VTE).
• Most are autosomal dominant (AD) with variable penetrance.
• Screening considered in VTE < 50 yrs, recurrent VTE, or strong family history.

Acquired Causes - Attack of Clots

• Antiphospholipid Syndrome (APS):
  • Autoantibodies: Lupus anticoagulant, Anti-cardiolipin, Anti-β2 GPI.
  • Clinical: Venous/arterial thrombosis, recurrent fetal loss.
  • Lab: Paradoxical ↑aPTT (Lupus Anticoagulant).
• Heparin-Induced Thrombocytopenia (HIT Type II):
  • IgG to PF4-heparin complex → platelet activation → thrombosis & thrombocytopenia (↓platelets >50%).
  • Onset 5-10 days post-heparin. 📌 Heparin Induces Thrombosis & Thrombocytopenia.

• Disseminated Intravascular Coagulation (DIC):
  • Systemic coagulation activation & consumptive coagulopathy. Causes: Sepsis, trauma, malignancy.
• Malignancy:
  • Trousseau's syndrome (migratory thrombophlebitis). Tumor procoagulants.
• Other Risk Factors:
  • Immobilization, surgery, OCPs/HRT, nephrotic syndrome, Myeloproliferative Neoplasms (MPNs), PNH.

⭐ Lupus anticoagulant (APS) paradoxically prolongs aPTT in vitro but causes in vivo thrombosis.

DVT/PE & Diagnosis - Clot Detectives

• DVT (Deep Vein Thrombosis):
  • Signs: Unilateral leg swelling, pain, warmth, erythema.
  • Risk: Virchow's Triad (📌 SHE: Stasis, Hypercoagulability, Endothelial injury).
  • Dx: Wells Score (PTP) → D-dimer (if low PTP) → Compression US (Gold Std).
• PE (Pulmonary Embolism):
  • Signs: Sudden dyspnea, pleuritic chest pain, cough, hemoptysis, tachycardia.
  • Dx: Wells/Geneva Score (PTP) → D-dimer (if low PTP) → CTPA (Gold Std). V/Q if CTPA C/I.
  • ECG: S1Q3T3 (classic, rare), sinus tachycardia. ABG: ↓PaO₂, ↓PaCO₂ (resp. alkalosis).

⭐ For suspected PE, if Wells score ≤ 4 (PE unlikely) AND D-dimer is negative, PE can be safely excluded (often guided by PERC rule).

High‑Yield Points - ⚡ Biggest Takeaways

• Virchow's triad (endothelial injury, stasis, hypercoagulability) is fundamental to thrombosis.
• Factor V Leiden (APC resistance) is the most common inherited thrombophilia.
• Antiphospholipid Syndrome (APS) causes thrombosis and pregnancy morbidity with characteristic autoantibodies.
• TTP presents with a pentad (MAHA, thrombocytopenia) due to ADAMTS13 deficiency.
• DIC: widespread microthrombi, consumption coagulopathy, bleeding; ↑D-dimer, ↓fibrinogen.
• Heparin-Induced Thrombocytopenia (HIT) paradoxically causes thrombosis via anti-PF4 antibodies.
• Protein C or S deficiency increases risk of warfarin-induced skin necrosis.