von Willebrand Factor disease
From IDWiki
Background
- Deficiency in quantity or quality of von Willebrand Factor (vWF) increasing risk of bleeding
Classification
- Type 1 (80%): mild quantitative deficiency
- Type 2 (20%): qualitative deficiency (i.e. doesn't work properly)
- Type 2A: normal quantity, abnormal quality
- Type 2B: enhanced GP1b-binding, leading to platelet adhesion and clearance
- Type 2M, Type 2N
- Type 3 (<1%): autosomal-recessive absolute quantitative deficiency (i.e. none made)
- Acquired: vWF cleared by autoantibodies, sheared by aortic stenosis, or sequestered by thrombocytosis
Pathophysiology
- vWF is long multimer that helps platelet aggregation in response to endothelial damage
- vWF is released by endothelium in response to damage
- vWF binds Factor VIII as well as platelets
- It unravels, thereby exposing platelet binding sites
Epidemiology
- Most common inherited bleeding disorder, with a prevalence of 1 in 100
- Prevalence of significant bleeding is 1 in 10,000
- Most are inherited in autosomal dominant pattern (including types 1 and 2B and most 2A and 2M), though type 2N and 3, and some type 2A and 2M, are autosomal recessive
Clinical Manifestations
- Abnormal bleeding, usually mucocutaneous, and ranging from mild (common) to severe (rare)
- Easy bruising
- Heavy menstrual bleeding/menorrhagia
- Postpartum bleeding
- Types 2N and 3 can include joint, soft tissue, and GI bleeding
- Type 3 typically presents in infancy, such as prolonged bleeding after circumcision
Investigations
- CBC, PT/INR, PTT
- vWD screen: Factor VIII, vWF antigen, vWF activity (either ristocetin cofactor or collagen)
- Consider PFA-100 (in-vitro bleeding time) and blood type
- If suspecting Type 2:
- RIPA (ristocetin-induced platelet agglutination)
- Multimer studies for high molecular weight multimers (MHWM)
- vWF genetic testing
| vWF-Ag | vWF-RCo | FVIII | RIPA | Multimers | |
|---|---|---|---|---|---|
| Type 1 | ↓ | ↓ | ↓ | ↓ | N |
| Type 2A | ↓/N | ↓↓ | ↓/N | ↓↓ | Lack of HMWM |
| Type 2B | ↓/N | ↓ | ↓/N | ↑ | Lack of HMWM |
| Type 2M | N | ↓↓ | N | ↓↓ | N |
| Type 2N | N | N | ↓ | N | N |
| Type 3 | Absent | Absent | 0.05 u/mL | Absent | Absent |
Management
- For Type 1 and 2A
- Desmopressin (ddAVP) 0.3mg/kg (max 20mg) IV/SC can promote release of vWF from endothelium
- Lasts 8-12h, so can repeat q12-24h as long as needed
- Monitor for tachyphylaxis after 4 doses
