title: Defective von willebrand factor activity detected by the filterometer in three clinical conditions.
abstract: When exposed to high levels of shear in a filterometer, platelets bind to von Willebrand factor (vWF) via receptors Ib and IIb/IIIa, forming aggregates that block the filteromer. In this study we used the filterometer to explore the mechanisms by which abnormal vWF-platelet interaction might occur. In the first phase of the study, the global vWF-platelet interaction in native blood was investigated. In the second phase, to eliminate the difference that platelets might contribute, samples of platelet-poor plasma from test individuals were added to normal control blood and the mixtures were investigated by the filterometer. The filterometer results were adjusted for the antigen concentrations to obtain vWF potency ratios. Sodium dodecyl sulphate (SDS) agarose gel electrophoresis and SDS-Polyacylamide gel electrophoresis (PAGE) were used to analyze multimeric size and proteolytic profiles of vWF. Pregnancy was associated with high platelet retention, high vWF antigen concentration, normal multimeric size distribution, but decreased vWF potency ratios. The plasma samples of pregnancy contained one 183-kDa fragment not detected in normal plasma. These results suggested that in pregnancy, platelets were highly active. However, presumably due to abnormal proteolytic cleavage, vWF potency was decreased. This decrease in vWF potency might minimize the risk of thrombosis in association with highly active platelets. Renal transplant patients had normal platelet retention but high vWF levels. The plasma vWF contained normal multimers. A decrease in vWF potency, presumably caused by toxic inhibitors in the plasma, was detected. Aortic valve stenosis patients had decreased platelet retention, normal or slightly increased vWF antigen concentration and a decrease in large multimers. As a result, the vWF potency was markedly decreased. However, the results obtained with the filterometer became normal when the studies were repeated 3 months postpartum, when renal function had improved after transplantation, and when the aortic valves were corrected by surgery. These results indicate that the filterometer is a useful tool for elucidating the mechanisms by which vWF-platelet interaction might be impaired in various clinical conditions.
authors.affiliation: Haematology Research, St. Marys Hospital Portsmouth, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: O'Brien
authors.forename: H M
authors.initials: HM
authors.lastname: Tsai
authors.forename: M D
authors.initials: MD
authors.lastname: Etherington
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000503:physiopathology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D003251:Constriction, Pathologic / Q000097:blood; D019281:Dimerization; D005260:Female; D005374:Filtration / Q000379:methods; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry; D010974:Platelet Aggregation; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods*; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000097:blood; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D014841:von Willebrand Factor