Von Willebrand Factor, Deficiency
Conditions
Brief summary
The Low Von Willebrand in Ireland Cohort (LoVIC) study focuses on the bleeding phenotype and biological mechanisms underlying low Von Willebrand Factor (VWF) levels.
Detailed description
All patients with bleeding disorders in Ireland are registered on a national bleeding disorder database and attend the National Coagulation Centre in St. James's Hospital, Dublin, Ireland or the paediatric centre, Our Lady's Children's Hospital Crumlin for annual review. At review eligible patients will be invited to participate in the Low Von Willebrand in Ireland Cohort (LOVIC) study. Following consent, an extensive bleeding assessment tool will be administered by a coagulation haematologist to all participants from which the International Society of Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH BAT) and the Condensed Molecular and Clinical Markers for the Diagnosis and Management of Type 1 Von Willebrands Disease (MCMDM-1 VWD) scores can be derived. In addition, blood will be drawn for von Willebrand factor (VWF) measurements, VWF propeptide, platelet VWF. Citrated plasma and DNA will be stored for each patient. The relationship between laboratory parameters, (including von Willebrand factor, platelet VWF, FVIII and concomitant coagulation disorders) and the clinical phenotype in patients with low VWF will be studied. We will assess the effect of the laboratory parameters on the severity of bleeding tendency. In the future mutation analysis of the VWF gene will be performed in all participants in the LOVIC study. Historical patient records and laboratory results will be reviewed and DDAVP (1-desamino-8-D-arginine vasopressin) fall off studies documented where available. If no previous DDAVP fall off study has been performed patients will be invited to attend.
Interventions
None listed
Sponsors
St. James's Hospital, Ireland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) \>30 IU/dL \<50 IU/dL.
Exclusion criteria
* Pregnant patients * Hospitalised patients/acutely unwell patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores | at enrolment | The ISTH-BAT and Condensed MCMDM-1 VWD score of all participants will be determined at enrollment using a physician directed questionnaire using only symptoms prior to their diagnosis with Low VWF. This will help elucidate the bleeding phenotype, if any, associated with Low VWF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of patients with Low VWF with abnormal plasma VWF clearance | 2 years | For each individual enrolled the Von Willebrand factor propeptide (VWF:pp, U/dL), Von Willebrand factor antigen (VWF:Ag IU/dL) and Factor VIII:C (FVIII:C IU/dL) levels at enrolment will be determined. From this data the plasma VWF clearance will be ascertained using the plasma VWF:pp/VWF:Ag ratio. In addition, the FVIII:C/VWF:Ag ratio will be calculated to determine the contribution of altered VWF synthesis to Low VWF. |
| The rate of response to DDAVP in Irish patients with low Von Willebrand factor levels | 3 years | For each individual with no contraindication a DDAVP trial will be performed with plasma VWF levels taken pre and at 1 and 4 hours post DDAVP. The rate of plasma VWF level fall off for each trial will be determined and the area under the curve (AUC) calculated. Complete response will be defined as a three fold increase from baseline. |
| The number of patients with Low VWF with reduced plasma VWF synthesis | 3 years | For each individual enrolled the Von Willebrand factor antigen (VWF:Ag IU/dL) and Factor VIII:C (FVIII:C IU/dL) levels at enrolment will be determined. From this data the plasma FVIII:C/VWF:Ag ratio will be calculated to determine the contribution of altered VWF synthesis to Low VWF. |
Countries
Ireland
Contacts
Primary ContactMichelle Lavin, FRCPath
Outcome results
None listed