Diagnostic Differentiation of von Willebrand Disease Types 1 and 2 by von Willebrand Factor Multimer Analysis and DDAVP Challenge Test
Autor: | Jan Jacques Michiels, Petr Smejkal, Ulrich Budde, Alain Gadisseur, Tatiana Pricangova, Inge Vangenechten, Angelika Batorova, Miroslav Penka |
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Rok vydání: | 2016 |
Předmět: |
Von Willebrand factor type C domain
congenital hereditary and neonatal diseases and abnormalities von Willebrand Disease Type 2 030204 cardiovascular system & hematology Gene mutation von Willebrand Disease Type 1 Diagnosis Differential 03 medical and health sciences 0302 clinical medicine Von Willebrand factor hemic and lymphatic diseases von Willebrand Factor medicine Von Willebrand disease Humans Deamino Arginine Vasopressin Desmopressin biology business.industry Hematology General Medicine medicine.disease Penetrance Molecular biology ADAMTS13 Glycoprotein Ib 030220 oncology & carcinogenesis Mutation biology.protein Human medicine Protein Multimerization business circulatory and respiratory physiology medicine.drug |
Zdroj: | Clinical and applied thrombosis/hemostasis |
ISSN: | 1938-2723 1076-0296 |
Popis: | The European Clinical Laboratory and Molecular (ECLM) classification of von Willebrand disease (vWD) is based on the splitting approach which uses sensitive and specific von Willebrand factor (vWF) assays with regard to the updated molecular data on structure and function of vWF gene and protein defects. A complete set of FVIII:C and vWF ristocetine cofactor, collagen binding, and antigen, vWF multimeric analysis in low- and medium-resolution gels, and responses to desmopressin (DDAVP) of FVIII:C and vWF parameters are mandatory. The ECLM classification distinguishes recessive types 1 and 3 vWD from recessive vWD 2C due to mutations in the D1 and D2 domains and vWD 2N due to mutations in the D′-FVIII-binding domain of vWF. The ECLM classification differentiates between mild vWD type 1 with variable penetrance of bleedings from symptomatic dominant type 1 vWD secretion defect and/or clearance defect with normal vWF multimers versus vWD 1M and 2M with normal or smeary vWF multimers in low- and medium-resolution gels. High-quality multimeric analysis of vWF in medium-resolution gels based on a DDAVP challenge test clearly delineates and distinguishes each of the dominant type 2 vWDs 1/2E, 2M, 2B, 2A, and 2D caused by vWF gene mutations in the D3 multimerization domain, loss or gain-of-function mutations in the glycoprotein Ib receptor A1 domain, gene mutations in the A2 proteolytic domain, and the C-terminal dimerization domain, respectively. |
Databáze: | OpenAIRE |
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