A 32-year-old woman with a lifelong history of easy bruising and recurrent epistaxis is found to have a prolonged bleeding time and normal PT/aPTT. Platelet count is 150,000/µL. Which of the following is NOT a feature of von Willebrand disease?

## Distinguishing von Willebrand Disease from Other Coagulation Disorders **Key Point:** von Willebrand disease (vWD) presents with a characteristic pattern of bleeding time abnormality, but aPTT is typically NORMAL or only mildly prolonged — and critically, it does NOT correct with normal plasma mixing in the acute setting because the defect is in vWF synthesis, not a circulating inhibitor. ### Pathophysiology of vWD **High-Yield:** vWD is characterized by: - Quantitative or qualitative deficiency of von Willebrand factor (vWF) - Secondary reduction in factor VIII (which is stabilized and transported by vWF) - Platelet dysfunction due to impaired vWF–platelet glycoprotein Ib interaction - Defective primary hemostasis (bleeding time prolonged) with variable secondary hemostasis involvement ### Laboratory Pattern in vWD | Parameter | Finding | Reason | |-----------|---------|--------| | **Bleeding time** | Prolonged | Platelet dysfunction from vWF deficiency | | **PT** | Normal | Extrinsic pathway intact | | **aPTT** | Normal or mildly prolonged | Factor VIII only moderately reduced; not a factor deficiency | | **Platelet count** | Normal (except Type 2B) | No thrombocytopenia in classic vWD | | **vWF:Ag** | Reduced | Quantitative deficiency | | **Factor VIII activity** | Reduced proportionally | Stabilized by vWF | | **Mixing study** | Does NOT correct aPTT | vWF is synthesized endogenously; not a circulating inhibitor | **Clinical Pearl:** The mixing study (incubating patient plasma 1:1 with normal plasma) corrects factor deficiencies (e.g., factor VIII deficiency from hemophilia A) but NOT vWD, because the problem is synthesis, not inhibition. This is a key differentiator from hemophilia A, which also presents with low factor VIII but has normal bleeding time. ### Inheritance Pattern **Mnemonic: vWD-AD** — von Willebrand Disease is Autosomal Dominant in ~75% of cases (Type 1), with Type 2 (partial/qualitative) and Type 3 (complete deficiency, autosomal recessive) accounting for the remainder. ### Why Option 3 Is Wrong aPTT in vWD does NOT correct with normal plasma mixing. This is the key trap. In hemophilia A (factor VIII deficiency), aPTT DOES correct because the patient is missing a circulating factor that normal plasma supplies. In vWD, the patient's endothelial cells and megakaryocytes cannot synthesize adequate vWF, so adding normal plasma transiently supplies vWF, but the underlying defect persists. Moreover, vWD aPTT is often normal or only mildly prolonged because factor VIII is not severely reduced — it is merely reduced proportionally to vWF levels. **Warning:** Do not confuse vWD with hemophilia A. Both have low factor VIII, but hemophilia A has normal bleeding time and normal vWF, while vWD has prolonged bleeding time and low vWF. ## Summary Table: vWD vs. Hemophilia A | Feature | vWD | Hemophilia A | |---------|-----|-------------| | **Bleeding time** | Prolonged | Normal | | **vWF level** | Low | Normal | | **Factor VIII** | Low (proportional to vWF) | Very low | | **aPTT** | Normal or mildly ↑ | Prolonged | | **Mixing study** | Does NOT correct | DOES correct | | **Inheritance** | Autosomal dominant (75%) | X-linked recessive | [cite:Robbins 10e Ch 13]