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Thrombotic Disorders

Thrombotic Disorders

Thrombotic Disorders

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Basics & Virchow's Triad - Clot Chaos Crew

Thrombosis (pathological clot) arises from Virchow's Triad (📌 SHE):

  • Stasis (Abnormal Blood Flow): Slowed circulation.
    • E.g., Immobility, atrial fibrillation (AF), DVT history.
  • Hypercoagulability: ↑ blood's clotting tendency.
    • E.g., Factor V Leiden, OCPs, malignancy, pregnancy, antiphospholipid syndrome.
  • Endothelial Injury: Vessel wall damage.
    • E.g., Trauma, surgery, hypertension, smoking, catheters.

⭐ Factor V Leiden is the most common inherited thrombophilia, predisposing to venous thromboembolism.

Inherited Thrombophilias - Bad Blood Genes

These genetic defects predispose to venous thromboembolism (VTE). Most are autosomal dominant (AD).

ConditionDefectInheritanceKey Risks/Associations
Factor V Leiden (FVL)APC resistance ($Arg506Gln$)AD📌 Most common; DVT, PE, RPL.
Prothrombin G20210A↑ Prothrombin levelsAD2nd common; DVT, PE.
Protein C Deficiency↓ Protein CADDVT, PE, warfarin-induced skin necrosis, neonatal purpura.
Protein S Deficiency↓ Protein SADDVT, PE, warfarin-induced skin necrosis.
Antithrombin Deficiency↓ AntithrombinADDVT, PE, heparin resistance; most severe.

Acquired Thrombophilias - Lifestyle Clot Culprits

  • Antiphospholipid Syndrome (APLS):
    • Criteria: Clinical (thrombosis, pregnancy morbidity) & Lab (📌 LAC: Lupus Anticoagulant, aCL, anti-β2GPI).
    • Antiphospholipid syndrome antibody mechanism
  • Heparin-Induced Thrombocytopenia (HIT):
    • Type 1 (mild, early). Type 2 (immune, 5-10 days, thrombotic).
    • 4Ts Score (Thrombocytopenia, Timing, Thrombosis, oTher causes):
  • Malignancy: Trousseau's (migratory thrombophlebitis).
  • PNH: GPI defect (CD55/59↓), venous thrombosis.
  • Nephrotic Syndrome: ATIII, Protein C/S loss; ↑ procoagulants.

⭐ HIT Type 2: Abs vs PF4-heparin complex.

DVT/PE - Deep Trouble Clots

  • DVT: Unilateral leg swelling, pain, warmth, erythema.
  • PE: Dyspnea, pleuritic chest pain, tachypnea, tachycardia. Massive PE: hypotension.
  • Wells Score (DVT): Factors: cancer, immobilization, surgery, tenderness, leg/calf swelling (>3cm), edema. Score ≥2: DVT likely.
  • Wells Score (PE): Factors: DVT signs, PE #1 Dx, HR >100bpm, immobilization/surgery, prior DVT/PE, hemoptysis, cancer. Score >4: PE likely.
  • Initial Management: Anticoagulation (LMWH, DOACs). Thrombolysis/embolectomy for massive PE/extensive DVT.

⭐ Westermark sign (oligemia), Hampton's hump (wedge infarct), Palla's sign (enlarged right descending PA) are classic (but rare) CXR findings in PE.

Anticoagulant Arsenal - Clot Busters Guide

ClassMOAOnsetMonitoringReversal Agent(s)Key Side Effect(s)
UFHPotentiates Antithrombin; inactivates Xa, IIaRapid IVaPTTProtamine SulfateBleeding, HIT
LMWHPotentiates Antithrombin; mainly Xa inactivationRapid SCAnti-Xa (renal)Protamine Sulfate (partial)Bleeding, ↓HIT risk
WarfarinInhibits Vit K epoxide reductase (↓ II,VII,IX,X,C,S)Slow (days)PT/INR (2-3)Vit K, PCC/FFPBleeding, Skin necrosis
DOACsDirect Thrombin (Dabigatran) or Xa inhibitorsRapidNone routineIdarucizumab (Dabi), Andexanet alfa (Xa-i)Bleeding, GI upset

High‑Yield Points - ⚡ Biggest Takeaways

  • Virchow's triad (stasis, hypercoagulability, endothelial injury) is fundamental to thrombosis.
  • Factor V Leiden is the most common inherited thrombophilia.
  • Antiphospholipid syndrome (APS) features arterial/venous thrombosis and recurrent fetal loss; linked to lupus anticoagulant & anticardiolipin antibodies.
  • Heparin-Induced Thrombocytopenia (HIT) causes paradoxical thrombosis with low platelets after heparin; suspect with platelet drop >50%.
  • Disseminated Intravascular Coagulation (DIC) involves widespread microthrombi and factor consumption, leading to bleeding and thrombosis.
  • Thrombotic Thrombocytopenic Purpura (TTP) presents with a pentad (fever, thrombocytopenia, MAHA, renal, neuro); due to ADAMTS13 deficiency.
  • Warfarin-induced skin necrosis is a risk in Protein C or S deficiency if heparin bridging is inadequate.

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