von Willebrand factor and its propeptide: the influence of secretion and clearance on protein levels and the risk of venous thrombosis
| Autor: | N H van Tilburg, V. Van Marion, F. R. Rosendaal, H. C. J. Eikenboom, R M Bertina, J. A. Van Mourik, Anne Yaël Nossent |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Enzyme-Linked Immunosorbent Assay Thrombophilia Risk Assessment ABO Blood-Group System Von Willebrand factor Antigen Reference Values hemic and lymphatic diseases Internal medicine ABO blood group system von Willebrand Factor Humans Medicine Secretion Antigens Protein Precursors Protein precursor Aged Venous Thrombosis Factor VIII biology business.industry Hematology Middle Aged medicine.disease Thrombosis Venous thrombosis Endocrinology Evaluation Studies as Topic Case-Control Studies cardiovascular system biology.protein Female business Biomarkers Half-Life circulatory and respiratory physiology |
| Zdroj: | Journal of Thrombosis and Haemostasis. 4:2556-2562 |
| ISSN: | 1538-7836 |
| DOI: | 10.1111/j.1538-7836.2006.02273.x |
| Popis: | Summary. Background and objectives: Elevated levels of factor (F)VIII are associated with an increased risk of thrombosis. FVIII levels are determined mainly by von Willebrand factor (VWF). We have investigated the contribution of secretion and clearance rates to the elevated VWF antigen (VWF:Ag) and to the risk of thrombosis. VWF is secreted in equimolar amounts with its propeptide, which has a shorter half-life. VWF propeptide can be used as a measure of VWF secretion and allows estimation of the VWF half-life. Methods and results: We have measured VWF propeptide, VWF:Ag, FVIII:Ag and FVIII activity (FVIII:C) in the Leiden Thrombophilia Study. In controls, high VWF propeptide was associated with high VWF:Ag, FVIII:Ag and FVIII:C. In contrast to mature VWF:Ag, VWF propeptide was not influenced by blood groups. Using an ELISA-based assay we have shown that VWF propeptide lacks ABO antigens. Levels were higher in men and increased with age. A long VWF half-life was also associated with high VWF:Ag, FVIII:Ag and FVIII:C. The VWF half-life was influenced by blood group (10 h in O vs. 12 h in non-O individuals), but not by sex, and only slightly by age. VWF propeptide was higher in thrombosis patients than in controls. The VWF half-life was similar in patients and controls (11.4 and 11.1 h, respectively). Conclusions: Both secretion and clearance rates are important determinants of VWF and FVIII levels. However, mainly high VWF and FVIII levels caused by increased secretion seem to be associated with thrombosis. ABO blood group influences the clearance rates of VWF rather than VWF secretion rates. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text