Which of the following is the PRIMARY defect in von Willebrand disease type 1?

Explanation

## Von Willebrand Disease Type 1: Quantitative Deficiency **Key Point:** Type 1 vWD is the most common form (75% of cases) and is characterized by a **proportionate reduction in both quantity and function** of von Willebrand factor (vWF). ### Classification of vWD Types | Type | Defect | Frequency | vWF Antigen | vWF Activity | FVIII | Inheritance | |------|--------|-----------|-------------|--------------|-------|-------------| | **Type 1** | Quantitative deficiency | 75% | ↓ Mild–moderate | ↓ Proportionate | ↓ Mild | Autosomal dominant | | **Type 2** | Qualitative defect (multiple subtypes) | 20% | ↓ Variable | ↓ Disproportionate | ↓ Variable | Autosomal dominant | | **Type 3** | Complete deficiency | 5% | Absent | Absent | ↓↓ Severe | Autosomal recessive | **High-Yield:** In type 1 vWD, the ratio of vWF activity to vWF antigen is **normal (>0.6)**, distinguishing it from type 2 (where activity is disproportionately reduced). **Clinical Pearl:** Type 1 vWD typically presents with mild mucocutaneous bleeding (epistaxis, menorrhagia, easy bruising) and is often diagnosed incidentally or after a bleeding challenge (surgery, trauma). ### Why Type 1 is Quantitative 1. All vWF molecules present are **structurally normal** but **reduced in number** 2. Both vWF antigen and vWF activity are reduced **proportionately** 3. Factor VIII levels are mildly reduced (vWF carries and stabilizes FVIII) 4. Inheritance is autosomal dominant with variable penetrance **Mnemonic:** **"Type 1 = Quantity down, Quality OK"** — the vWF that is present works normally; there is simply less of it.