Hemophilia and Von Willebrand Disease

Overview & Genetics - Bleeding Blueprint

• Hemophilia: X-linked recessive disorders affecting clotting factors.
  • Hemophilia A: Factor VIII (FVIII) deficiency. More prevalent.
  • Hemophilia B (Christmas Disease): Factor IX (FIX) deficiency.
• Von Willebrand Disease (vWD): Most common inherited bleeding disorder; typically Autosomal Dominant.
  • Quantitative or qualitative defect in von Willebrand Factor (vWF).
  • vWF roles: Essential for platelet adhesion to injury sites; carrier and stabilizer for FVIII.

⭐ vWD is the most common inherited bleeding disorder, impacting primary hemostasis (platelet function) and often FVIII levels (secondary hemostasis component).

Hemophilia (A & B) - Royal Pains

• X-linked recessive:
  • Hemophilia A: Factor VIII (FVIII) deficiency. 📌 "Aight" for Eight.
  • Hemophilia B (Christmas Disease): Factor IX (FIX) deficiency. 📌 "Be-Nign" for B-Nine.
• Clinical: Hemarthrosis (knees, elbows), muscle hematomas, prolonged bleeding post-trauma/surgery. ICH is critical.
• Labs: ↑aPTT; normal PT, BT, platelets. Factor assays confirm.
• Severity (Factor levels):
  • Severe: <1 IU/dL (<1%) - spontaneous bleeds.
  • Moderate: 1-5 IU/dL (1-5%) - bleeds post mild trauma.
  • Mild: >5-40 IU/dL (5-40%) - bleeds post surgery/major trauma.

⭐ Hemarthrosis is the hallmark of severe hemophilia, often starting when toddlers begin to walk.

Von Willebrand Disease - Sticky Platelets

• Most common inherited bleeding disorder; primarily autosomal dominant.
• Pathophysiology: Deficiency or dysfunction of von Willebrand Factor (vWF).
  • vWF functions: Mediates platelet adhesion to subendothelium (vWF ↔ GpIb), carrier for Factor VIII (protects FVIII from degradation).
• Clinical: Predominantly mucocutaneous bleeding (epistaxis, gingival bleeding, menorrhagia, easy bruising). Hemarthrosis is rare (unlike hemophilia).
• Types:
  • Type 1: Partial quantitative vWF deficiency (most common, ~75%).
  • Type 2: Qualitative vWF defect (2A, 2B, 2M, 2N).
  • Type 3: Near-complete or total vWF deficiency (severe, autosomal recessive).
• Labs: ↑ Bleeding Time (BT), Normal or ↑ aPTT (due to ↓FVIII), Normal PT.

  ⭐ The Ristocetin cofactor assay (vWF:RCo) is the most specific test for vWF functional activity.

Diagnosis & Differentiation - Lab Clues

• Core Panel: PT (normal), Platelet count (normal).
• Hemophilia A/B: Hallmark is isolated ↑ aPTT. Bleeding Time (BT) is normal. Definitive: Specific ↓ Factor VIII (A) or ↓ Factor IX (B) assays.
• Von Willebrand Disease (VWD): BT typically prolonged (↑). aPTT can be normal or ↑ (if FVIII significantly low). Key tests: ↓ vWF antigen (vWF:Ag), ↓ vWF activity (e.g., Ristocetin Cofactor - vWF:RCo), multimer analysis.

  ⭐ Mixing study: Patient plasma + Normal plasma corrects aPTT in factor deficiency (Hemophilia), not with inhibitors.

Management & Complications - Stop the Bleed!

• Acute Bleed Management:
  • RICE (Rest, Ice, Compression, Elevation).
  • Antifibrinolytics (Tranexamic acid, EACA).
  • Hemophilia A: Factor VIII. Goal: 30-50% (minor), 80-100% (major). DDAVP (0.3 mcg/kg) for mild cases.
  • Hemophilia B: Factor IX. Goal: 30-50% (minor), 80-100% (major).
  • VWD: DDAVP (Type 1), vWF-FVIII concentrates (Type 2/3, or DDAVP ineffective).
• Prophylaxis: Regular factor infusions for severe Hemophilia prevents spontaneous bleeds.
• Key Complications:
  • Hemophilia: Inhibitor development, arthropathy (recurrent hemarthrosis).
  • VWD: Menorrhagia, post-op/dental bleeds.

  ⭐ DDAVP is contraindicated in VWD Type 2B (risk of thrombocytopenia) and Type 3 (ineffective).

High‑Yield Points - ⚡ Biggest Takeaways

• Hemophilia A (↓Factor VIII) & B (↓Factor IX): X-linked recessive; cause hemarthrosis.
• Von Willebrand Disease (vWD): most common inherited bleeding disorder (autosomal dominant); mucocutaneous bleeding.
• Labs: PTT prolonged in both. Bleeding time prolonged in vWD (normal in hemophilia). PT normal.
• Desmopressin (DDAVP) for mild Hemophilia A & Type 1 vWD.
• Treatment: Hemophilia with factor concentrates. vWD with DDAVP, cryoprecipitate, or vWF concentrates.
• Mixing study corrects PTT in factor deficiency.