View source for Von Willebrand Factor disease

==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 (&lt;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

{| class="wikitable"
!
! 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]]