View source for Von Willebrand Factor disease

== Definition ==

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

== Type ==

* 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 (&lt;1%): autosomal-recessive absolute quantitative deficiency (i.e. none made)
* Acquired: vWF cleared by autoantibodies, sheared by aortic stenosis, or sequestered by thrombocytosis

== Physiology ==

* 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 bleeding disorder with a prevalence of 1 in 100
* Prevalence of significant bleeding is 1 in 10,000

== Clinical Presentation ==

== Investigations ==

* CBC, PT/INR, PTT
* vWD screen: Factor VIII, vWF antigen, vWF activity (either ristocetin 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

{|
!
!align="center"| '''vWF-Ag'''
!align="center"| '''vWF-RCo'''
!align="center"| '''FVIII'''
!align="center"| '''RIPA'''
!align="center"| '''Multimers'''
|-
| '''Type 1'''
|align="center"| ↓
|align="center"| ↓
|align="center"| ↓
|align="center"| ↓
|align="center"| N
|-
| '''Type 2A'''
|align="center"| ↓/N
|align="center"| ↓↓
|align="center"| ↓/N
|align="center"| ↓↓
|align="center"| Lack of HMWM
|-
| '''Type 2B'''
|align="center"| ↓/N
|align="center"| ↓
|align="center"| ↓/N
|align="center"| ↑
|align="center"| Lack of HMWM
|-
| '''Type 2M'''
|align="center"| N
|align="center"| ↓↓
|align="center"| N
|align="center"| ↓↓
|align="center"| N
|-
| '''Type 2N'''
|align="center"| N
|align="center"| N
|align="center"| ↓
|align="center"| N
|align="center"| N
|-
| '''Type 3'''
|align="center"| Absent
|align="center"| Absent
|align="center"| 0.05 u/mL
|align="center"| Absent
|align="center"| 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

{{DISPLAYTITLE:von Willebrand Factor disease}}
[[Category:Hematology]]