Ignite Creation Date:
2024-05-06 @ 12:57 PM
Last Modification Date:
2024-10-26 @ 1:07 PM
Study NCT ID:
NCT03896997
Status:
UNKNOWN
Last Update Posted:
2019-12-27
First Post:
2019-03-27
Brief Title:
Update in VWD Laboratory Diagnosis
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Recent Modalities in Laboratory Diagnosis of Von Willebrand Disease
Status:
UNKNOWN
Status Verified Date:
2019-12
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
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 06 to 132VWD 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 defined3 Moreover accurate diagnosis is difficult due to the variability of the disease clinical expression and the difficulties in standardizing the panel of diagnostic tests4 5The first level tests are the VWF antigen VWFAg VWF platelet binding activity and factor VIII activity FVIIIC whereas the second level tests include VWF collagen binding VWFCB FVIII binding capacity VWFFVIIIB and ristocetin-induced platelet aggregometry RIPA and multimeric analysis6 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 diagnosis8 The multimer results in 546 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 ie when test result would affect the patients 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 eg confirm the patients phenotypic diagnosis9 help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment and in counselling regarding inheritance5 Inheritance counselling examples are prenatal diagnosis of type 3 or severe type 19 and the identification of carrier status among family members which can be easily recognized once the probands mutations 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 domains 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 2Ntable 111
VWD type 2AIIA 2AIIE 2AIIC 2AIID 2B 2M 2MCB 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
VWD type 2AIIA 2AIIE 2AIIC 2AIID 2B 2M 2MCB 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None