von Willebrand Factor disease

Background

Deficiency in quantity or quality of von Willebrand Factor (vWF) increasing risk of bleeding

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

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

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

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

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

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