Coagulation Disorders

Hemostasis Basics - Cascade Craze

• Primary Hemostasis: Forms temporary platelet plug.
  • Vascular Spasm: Immediate vasoconstriction.
  • Platelet Phase:
    • Adhesion: vWF links platelets (GpIb) to subendothelial collagen.
    • Activation: Platelets release ADP, TXA₂, $Ca^{2+}$; GpIIb/IIIa activated.
    • Aggregation: Fibrinogen links platelets via GpIIb/IIIa.
• Secondary Hemostasis: Forms stable fibrin clot.
  • Coagulation Cascade: Sequential activation of zymogens.

-   📌 Vit K-dependent: Factors **II, VII, IX, X**; Proteins C & S. (Mnemonic: "2+7=9, then 10; C & S too!").
-   **Regulation:** Antithrombin (inhibits IIa, Xa, IXa, XIa), Protein C & S (degrade Va, VIIIa), TFPI (inhibits TF-VIIa, Xa).

⭐ Thrombin (IIa): key enzyme; converts fibrinogen to fibrin, activates V, VIII, XI, XIII, platelets; also activates Protein C (via thrombomodulin) for anticoagulation.

Primary Hemostasis Disorders - Platelet Predicaments

Disorders of platelet plug formation; present with mucocutaneous bleeding.

• Immune Thrombocytopenic Purpura (ITP): Autoimmune (anti-GpIIb/IIIa) vs platelets. ↓Plt, ↑megakaryocytes. Rx: Steroids, IVIG.
• Thrombotic Thrombocytopenic Purpura (TTP): ↓ADAMTS13 activity. Pentad. Schistocytes. Rx: Plasma exchange.
• Hemolytic Uremic Syndrome (HUS): Shiga toxin (E.coli O157:H7). Triad (MAHA, ↓Plt, AKI). Schistocytes. Rx: Supportive.
• Glanzmann Thrombasthenia: Defect GpIIb/IIIa. Impaired aggregation to all agonists except ristocetin.
• Bernard-Soulier Syndrome: Defect GpIb. Giant platelets. Impaired ristocetin-induced aggregation. 📌 Bernard-Soulier = Big Suckers (Giant Platelets, GpIb defect).
• von Willebrand Disease (vWD): Commonest inherited. ↓vWF quantity/quality. Types 1 (partial quant), 2 (qual), 3 (total). Dx: ↓Ristocetin cofactor activity, ↓vWF:Ag.

![Image placeholder: Blood smear findings in platelet disorders: schistocytes (TTP/HUS) and giant platelet (Bernard-Soulier)]

Secondary Hemostasis Disorders - Factor Fumbles

• Inherited Disorders:
  • Hemophilia A (FVIII↓), Hemophilia B (FIX↓): X-linked recessive. Clinical: Hemarthrosis, deep muscle hematomas, prolonged bleeding. Labs: ↑aPTT; Normal PT, BT, Platelet count. Tx: Factor concentrates; Desmopressin (DDAVP) for mild Hemophilia A.

    Feature	Hemophilia A	Hemophilia B (Christmas)
    Deficiency	Factor VIII	Factor IX
    Mnemonic 📌	A-Eight	B-Nine

• Acquired Disorders:
  • DIC (Disseminated Intravascular Coagulation): Common causes: Sepsis/Trauma. Patho: Systemic coagulation activation → consumption of factors/platelets & microthrombi formation. Labs: ↑PT, ↑aPTT, ↑TT, ↑D-dimer; ↓Platelets, ↓Fibrinogen; Schistocytes on smear.

-   **Liver Disease Coagulopathy:** ↓Synthesis of factors (II, VII, IX, X). Labs: ↑PT (most sensitive, earliest change), variable ↑aPTT.
-   **Vitamin K Deficiency:** ↓Factors II, VII, IX, X, Protein C & S. Causes: Malnutrition, malabsorption, antibiotics. Labs: ↑PT, then ↑aPTT. Tx: Vitamin K.
-   **Anticoagulant-induced:**
    -   Warfarin: ↓Vit K-dependent factors. Monitor INR (↑PT). Reverse: Vit K, PCC.
    -   Heparin (UFH): Potentiates Antithrombin III. Monitor aPTT. Reverse: Protamine sulfate.
    -   DOACs: Direct Factor Xa or thrombin inhibitors. Variable lab effects. Specific reversal agents available.

⭐ PT is the first test abnormal in early liver disease or Vit K deficiency due to Factor VII's short half-life.

Coagulation Lab Tests - Clot Clues

• PT/INR: Extrinsic (FVII) & common (FX, FV, FII, Fibrinogen) pathway. Monitors Warfarin.
• aPTT: Intrinsic (FXII, FXI, FIX, FVIII) & common pathway. Monitors Heparin.
• Thrombin Time (TT): Final fibrin formation. Sensitive to heparin, dysfibrinogenemia.
• Fibrinogen Assay: Quantitative. ↓ in DIC, liver disease.
• D-dimer: Fibrin degradation product. ↑ in DIC, VTE.
• Platelet Count: Quantitative. Bleeding Time (BT) for function (obsolete).
• Mixing Studies: Differentiate deficiency (corrects) vs. inhibitor (no correction).

  ⭐ Lupus anticoagulant: ↑aPTT, no correction with mixing, paradoxical thrombosis risk.

• Factor Assays: Pinpoint specific factor deficiencies (e.g., FVIII).

High‑Yield Points - ⚡ Biggest Takeaways

• Hemophilia A (FVIII def.) & B (FIX def.): X-linked recessive, hemarthrosis, ↑aPTT.
• vWD: Most common inherited bleeding disorder (AD), ↑BT, often ↑aPTT. Ristocetin test confirms.
• Vitamin K deficiency: Affects II, VII, IX, X, C, S. ↑PT & ↑aPTT.
• DIC: Clotting & bleeding. ↑PT/aPTT/BT, ↓platelets, ↑D-dimer, ↓fibrinogen.
• ITP: Isolated thrombocytopenia. Normal PT/aPTT. Often post-viral.
• TTP Pentad: Fever, thrombocytopenia, MAHA, renal, neuro. ADAMTS13 deficiency.