Bleeding Disorders

Hemostasis Essentials - Clotting Cascade Crew

Normal hemostasis:

1. Vascular Spasm: Rapid vessel constriction, limits initial blood loss.
2. Platelet Plug: Platelets adhere, activate, aggregate (Primary Hemostasis).
3. Coagulation Cascade: Sequential factor activation for fibrin clot (Secondary Hemostasis).
   • Intrinsic: Contact activation (collagen). Factors: XII, XI, IX, VIII. (Monitored by aPTT).
   • Extrinsic: Tissue Factor (TF III) release. Factor: VII. (Monitored by PT/INR).
   • Common: Convergence of pathways. Factors: X, V, II (Prothrombin), I (Fibrinogen), XIII (stabilizes clot).
4. Fibrinolysis: Plasmin-mediated breakdown of fibrin, restoring blood flow.

⭐ Vitamin K dependent factors are II, VII, IX, X, Protein C & S. (Mnemonic: 1972, C, S) 📌

Platelet Problems - Plug Pullers' Plight

• Thrombocytopenia (↓ Platelets):
  • ITP (Immune Thrombocytopenic Purpura): Autoantibodies vs GpIIb/IIIa. 📌 ITP: Idiots Trashing Platelets. Bleeding if < 10,000-20,000/μL.
  • TTP (Thrombotic Thrombocytopenic Purpura): ADAMTS13 deficiency (vWF cleaving protease).

    ⭐ TTP pentad: Fever, Anemia (microangiopathic hemolytic), Thrombocytopenia, Renal failure, Neurological symptoms (FAT RN).

  • HUS (Hemolytic Uremic Syndrome): E. coli O157:H7 (Shiga toxin). Triad: MAHA, thrombocytopenia, ARF.
  • DIC (Disseminated Intravascular Coagulation): Widespread clotting activation → consumption → bleeding. ↑PT/PTT/D-dimer, ↓Fibrinogen.
• Qualitative Platelet Defects:
  • Bernard-Soulier Syndrome: GpIb defect. Impaired adhesion to vWF. Large platelets.
  • Glanzmann Thrombasthenia: GpIIb/IIIa defect. Impaired aggregation.
• Von Willebrand Disease (vWD): Commonest inherited bleeding disorder; vWF defect. Mucocutaneous bleeding.
  • Types: 1 (partial quantitative ↓), 2 (qualitative defect), 3 (severe/total quantitative ↓).
  • Dx: ↓vWF:Ag, ↓Ristocetin cofactor activity, PTT may be ↑ (due to ↓FVIII).

Coagulation Chaos - Factor Fumbles

• Hemophilias: Inherited X-linked (A & B) or Autosomal (C) bleeding disorders due to specific factor deficiencies.

  Feature	Hemophilia A (Classic)	Hemophilia B (Christmas Dis.) 📌	Hemophilia C
  Deficiency	Factor VIII	Factor IX	Factor XI
  Inheritance	X-linked recessive	X-linked recessive	Autosomal Rec.
  Labs (PT/PTT/BT)	N PT, ↑PTT, N BT	N PT, ↑PTT, N BT	N PT, ↑PTT, N BT
  Severity (F.VIII/IX)	<1% severe, 1-5% mod., >5-40% mild	<1% severe, 1-5% mod., >5-40% mild	Variable bleeding

• Vitamin K Deficiency:
  • ↓ Factors II, VII, IX, X, Protein C & S (📌 2,7,9,10,C,S).
  • ↑PT (earliest), then ↑PTT. Normal BT.
  • Causes: Neonates, malabsorption, broad-spectrum antibiotics, warfarin.
• Liver Disease Coagulopathy:
  • ↓ Synthesis of most clotting factors (except FVIII, vWF) & anticoagulants.
  • ↑PT, ↑PTT. Dysfibrinogenemia. ↓Platelets (hypersplenism).
• Disseminated Intravascular Coagulation (DIC): Pathological systemic activation of coagulation. Widespread microthrombi consume platelets & factors, leading to bleeding.
  • Labs: ↑PT, ↑PTT, ↑BT, ↓Fibrinogen, ↑D-dimer (key), ↓Platelets, Schistocytes.

• Anticoagulant Effects:
  • Heparin: Potentiates Antithrombin III; ↑PTT.
  • Warfarin: Inhibits Vit K epoxide reductase; ↑PT/INR.

⭐ Mixing studies differentiate factor deficiency (correction with normal plasma) from an inhibitor (no correction).

Lab Lowdown - Bleed Sleuth

Key tests: Platelet Count (Plt Ct), BT/PFA-100, PT, aPTT. D-dimer for DIC. Fibrinogen levels. Thrombin Time (TT).

Lab Patterns:

High‑Yield Points - ⚡ Biggest Takeaways

• Hemophilia A (FVIII↓) & B (FIX↓): X-linked, ↑aPTT, normal PT/BT.
• Von Willebrand Disease (vWD): Most common inherited, ↑BT, often ↑aPTT (vWF stabilizes FVIII).
• ITP: Isolated thrombocytopenia (anti-GpIIb/IIIa Abs), ↑BT, normal PT/aPTT.
• DIC: Widespread clotting activation, ↑PT/aPTT/BT/D-dimer, ↓platelets, schistocytes.
• Vitamin K Deficiency: Affects II, VII, IX, X, C, S; ↑PT (early), then ↑aPTT.
• TTP: ADAMTS13 deficiency; Pentad: Fever, MAHA, Thrombocytopenia, Renal, Neurologic.