Details:

Alternative Title:
J Thromb Haemost
Publisher's site:
http://dx.doi.org/10.1111/jth.12902
Personal Author:
Boylan, Brian ; Rice, Anne S. ; De Staercke, Christine ; Eyster, M. Elaine ; Yaish, Hassan M. ; ... More +
Boylan, Brian ; Rice, Anne S. ; De Staercke, Christine ; Eyster, M. Elaine ; Yaish, Hassan M. ; Knoll, Christine M. ; Bean, Christopher J. ; Miller, Connie H. Less -
Corporate Authors:
Hemophilia Inhibitor Research Study Investigators
Description:
Background

Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis.

Objectives

Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes.

Patients/Methods

Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence.

Results

Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB.

Conclusions

These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy.


Subject:
[+]
Adolescent
Adult
Biomarkers
Blood Coagulation
Blood Coagulation Tests
Case-Control Studies
Child
DNA Mutational Analysis
Factor VIII
Genetic Predisposition To Disease
Hemophilia A
Hemorrhage
Heterozygote
Homozygote
Humans
Male
Mutation
Phenotype
Predictive Value Of Tests
Protein Binding
Von Willebrand Factor
Young Adult

Source:
J Thromb Haemost. 13(6):1036-1042.
Pubmed ID:
25780857
Pubmed Central ID:
PMC4512234
Document Type:
Journal Article
Funding:
CC999999/Intramural CDC HHS/United States
Place as Subject:
United States
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:3dbd534c74d745c6ddcee8e50ed344aa509efefb47e2de255216839b43e8d3fa
File Type:

Supporting Files

• nihms698860.nxml

  bin

More +