Which laboratory finding best distinguishes Hemophilia A from von Willebrand disease in a patient presenting with mucosal bleeding and a prolonged activated partial thromboplastin time (aPTT)?

## Distinguishing Hemophilia A from von Willebrand Disease ### Key Laboratory Differentiator **Key Point:** The hallmark distinction lies in **von Willebrand factor (vWF) antigen levels** — normal in Hemophilia A, reduced in vWD. ### Comparative Laboratory Profile | Feature | Hemophilia A | von Willebrand Disease | |---------|--------------|------------------------| | **vWF Antigen (vWF:Ag)** | Normal | Reduced/Absent | | **Factor VIII Activity** | Reduced/Absent | Reduced (proportional to vWF) | | **aPTT** | Prolonged | Prolonged | | **Bleeding Time** | Normal | Prolonged (Type 1 & 3) | | **Platelet Function** | Normal | Abnormal (impaired adhesion) | | **Inheritance Pattern** | X-linked recessive | Autosomal dominant (Type 1) | ### Pathophysiologic Basis 1. **Hemophilia A**: Deficiency or dysfunction of coagulation **Factor VIII** alone; vWF (which carries and stabilizes Factor VIII) is structurally and quantitatively normal. 2. **von Willebrand Disease**: Primary defect is in the **vWF gene**; Factor VIII is secondarily reduced because vWF is its carrier protein. vWF also mediates platelet adhesion, explaining the prolonged bleeding time. **High-Yield:** In vWD, Factor VIII activity correlates with vWF levels (both reduced proportionally). In Hemophilia A, vWF is normal but Factor VIII is isolated low. ### Clinical Pearl **Clinical Pearl:** Bleeding time (now rarely used but still tested) is **normal in Hemophilia A** (platelet function intact) but **prolonged in vWD** (defective platelet adhesion due to vWF deficiency). This was historically the quickest bedside discriminator. ### Why This Matters - **Hemophilia A** → treat with Factor VIII concentrates or desmopressin (if mild) - **vWD** → treat with desmopressin (increases both vWF and Factor VIII) or vWF concentrates The correct answer identifies the **single most specific laboratory discriminator**: normal vWF antigen with reduced Factor VIII activity is pathognomonic for Hemophilia A. [cite:Harrison 21e Ch 139]