Update in VWD Laboratory Diagnosis

December 24, 2019 updated by: Aya omar mahmoud Aballah, Assiut University

Recent Modalities in Laboratory Diagnosis of Von Willebrand Disease

The present study will focus on the investigation of the global contribution and limitations of the multimeric analysis and mutation analysis in the VWD diagnostic process.

  1. To quantify the bleeding symptoms using bleeding assessment tools (BAT) which has developed by The International Society on Thrombosis and Haemostasis (ISTH) and correlate it to the diagnosis of different subtypes of VWD in Egyptian population.
  2. To assess the utility of (gain of function mutant GpIbα binding) as a recent functional assay that measures VWF activity in VWD patients.
  3. Clarify how the recent laboratory diagnostic modalities are required to streamline diagnosis , classification and improve treatment of VWD patients.
  4. Explore how the molecular analysis can resolve many of the drawbacks and limitations of phenotyping diagnosis (in Egyptian population which not studied before).

Study Overview

Status

Not yet recruiting

Detailed Description

von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by defects in amount, structure or function of von Willebrand factor (VWF) (1). The prevalence estimated on population studies ranges from 0.6% to 1.3%(2).VWD is classified into type 1 with partial deficiency of VWF , type 2 with qualitative defects of VWF and type 3 with complete deficiency of VWF (3) (4). In practice, distinctions between certain VWD types are not easy, difficulties may arise because patient phenotypes may vary over time, VWF mutations can have complex effects on phenotype, certain laboratory tests are inherently imprecise, and the boundary between normal and abnormal phenotypes may not be sharply defined(3) .Moreover, accurate diagnosis is difficult due to the variability of the disease, clinical expression and the difficulties in standardizing the panel of diagnostic tests(4) (5).The first level tests are the VWF antigen (VWF:Ag), VWF platelet binding (activity) and factor VIII activity (FVIII:C), whereas the second level tests include VWF collagen binding (VWF:CB), FVIII binding capacity (VWF:FVIIIB) and ristocetin-induced platelet aggregometry (RIPA) and multimeric analysis(6). The latest official classification of VWD refers to the VWF multimeric profile as an integral part of the diagnostic process (5, 7, 8). Pérez-Rodríguez et al., and his colleauges have classified the role of multimeric analysis into three different categories : 1) Great significance ; multimeric analysis was necessary to establish a clear diagnosis; 2) Concordant ; once established clear diagnosis with other tests, the multimeric analysis agreed with such diagnosis; 3) Not informative: the multimeric analysis did not provide information for the diagnosis(8). The multimer results in 54.6% of the patients of Pérez-Rodríguez A et al., showed great significance in diagnosis. The role of genetic analysis of VWF is tricky; It is not routinely indicated but it could be mandatory in some circumstances i.e., when test result would affect the patient's treatment choice and the suitable phenotypic assays are not available as in type 2N and 2B VWD (9). Nevertheless, there are several reasons for performing molecular analysis in patients phenotypically well characterized, e.g. confirm the patient's phenotypic diagnosis(9) , help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment and in counselling regarding inheritance(5). Inheritance counselling examples are: prenatal diagnosis of type 3 or severe type 1(9) and the identification of carrier status among family members which can be easily recognized once the proband's mutation(s) have been identified (10). The mutations identified in VWD type 3 are often clearly disease-causing mutations (nonsense, frame-shift and large deletions), whereas in VWD type 1, missense mutations often identified and can only be considered candidate mutations due to the lack of firm evidence of their causal effect. The approach of investigating gene mutations causing types 1 and 3 is similar and it is sophisticated as there is no particular area where mutations are identified, in contrast to VWD type 2, that requires only the evaluation of the exons encoding the specific functional domain(s) and the large majority of mutations are located in exon 28. This strategy can be applied to all type 2 VWD (2A, 2B, 2M and 2N)(table 1)(11).

VWD type 2A(IIA) 2A(IIE) 2A*(IIC) 2A(IID) 2B 2M 2M(CB) 2N* Domain A2 D3 D1-D2 CK A1 A1 A3 D'-D3 Exon 3' portion of 28 22, 25-27 and 5' portion of 28 2-17 51-52 5' portion of 28 5' portion of 28 29-32 17-25

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients referred for VWD diagnosis or previously diagnosed with VWD, in any age and any sex, in Upper Egypt

Description

Inclusion Criteria:

  • Patients referred for VWD diagnosis or previously diagnosed with VWD

Exclusion Criteria:

  • Patients with other bleeding disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of von willebrand factor multimers
Time Frame: one year
Von willebrand factor multimers detection by electrophoresis
one year
Von willebrand factor antigen
Time Frame: One year
Measurement of amount of von willebrand factor antigen by IU
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Azza M Mostafa, lecturar, Assiut University
  • Principal Investigator: Aya o Mahmoud, ass. lecturar, Assiut University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2020

Primary Completion (Anticipated)

March 2, 2022

Study Completion (Anticipated)

October 2, 2023

Study Registration Dates

First Submitted

March 27, 2019

First Submitted That Met QC Criteria

March 28, 2019

First Posted (Actual)

April 1, 2019

Study Record Updates

Last Update Posted (Actual)

December 27, 2019

Last Update Submitted That Met QC Criteria

December 24, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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