Clinical trial NCT03167320: Low Von Willebrand in Ireland Cohort Study
Official title: Low Von Willebrand in Ireland Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Von Willebrand Factor, Deficiency
Lead sponsor: St. James's Hospital, Ireland
Sponsor class: OTHER
First posted: 2017-05-25
Enrollment: 400
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals (adults/children \>3 years) with low Von Willebrand Factor (VWF) levels; defined as two lowest VWF levels (VWF Antigen and/or VWF Ristocetin cofactor activity and/or VWF Collagen Binding) \>30 IU/dL \<50 IU/dL.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Irish patients with Low Von Willebrand Factor with abnormal bleeding scores
timeFrame: at enrolment
Secondary outcomes:
measure: The number of patients with Low VWF with abnormal plasma VWF clearance
timeFrame: 2 years
measure: The rate of response to DDAVP in Irish patients with low Von Willebrand factor levels
timeFrame: 3 years
measure: The number of patients with Low VWF with reduced plasma VWF synthesis
timeFrame: 3 years
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St. James's Hospital
Study officials:
affiliation: St. James's Hospital, Dublin Ireland
name: James S O'Donnell, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Doherty D, Michelle Lavin, Byrne M, Nolan M, O'Sullivan JM, Ryan K, O'Connell NM, Haberichter SL, Christopherson PA, Di Paola J, James PD, O'Donnell JS. Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance. Blood Adv. 2023 Feb 14;7(3):302-308. doi: 10.1182/bloodadvances.2022007340.
citation: Aguila S, Lavin M, Dalton N, Patmore S, Chion A, Trahan GD, Jones KL, Keenan C, Brophy TM, O'Connell NM, Ryan K, Byrne M, Nolan M, Patel A, Preston RJS, James P, Di Paola J, O'Sullivan JM, O'Donnell JS. Increased galactose expression and enhanced clearance in patients with low von Willebrand factor. Blood. 2019 Apr 4;133(14):1585-1596. doi: 10.1182/blood-2018-09-874636. Epub 2019 Feb 15.
citation: Lavin M, Aguila S, Dalton N, Nolan M, Byrne M, Ryan K, White B, O'Connell NM, O'Sullivan JM, Di Paola J, James PD, O'Donnell JS. Significant gynecological bleeding in women with low von Willebrand factor levels. Blood Adv. 2018 Jul 24;2(14):1784-1791. doi: 10.1182/bloodadvances.2018017418.
citation: Lavin M, Aguila S, Schneppenheim S, Dalton N, Jones KL, O'Sullivan JM, O'Connell NM, Ryan K, White B, Byrne M, Rafferty M, Doyle MM, Nolan M, Preston RJS, Budde U, James P, Di Paola J, O'Donnell JS. Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels. Blood. 2017 Nov 23;130(21):2344-2353. doi: 10.1182/blood-2017-05-786699. Epub 2017 Sep 15.