The impact of blood shear rate on arterial thrombus formation.

The shear rate and corresponding shear stress have impacts on arterial thrombus formation. In particular, the effects of increasing concentration of platelets at the vessel wall and activation of platelets at this site increase the growth and stability of the thrombi which may result in a fatal narrowing of the arterial lumen. The efficacy of many antithrombotic agents is shear dependent as well.

Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer.

Background: Conventional tests for vitamin B(12) deficiency measure total serum vitamin B12, whereas only that portion of vitamin B12 carried by transcobalamin (holotranscobalamin) is metabolically active. Measurement of holotranscobalamin (holoTC) may be more diagnostically accurate for detecting B(12) deficiency that requires therapy. We developed an automated assay for holoTC that can be used on the Abbott AxSYM immunoassay analyzer.

Validation of the human tissue factor/FVIIa complex as an antithrombotic target and the discovery of a synthetic peptide.

This review focuses on the validation of the principal initiator of human coagulation, the tissue factor (TF)/coagulation factor (F)VIIa complex, as an antithrombotic target, as well as on the discovery of a cyclic pentapeptide (PN7051), which dose-dependently inhibits TF/FVIIa-induced coagulation and thrombus formation. Target validation and studies of antithrombotic efficacy were performed with a human thrombosis model employing non-anticoagulated blood from severe homozygous FVII-deficient patients and healthy individuals at blood-flow conditions mimicking those in healthy and diseased vessels. Additional validation included an anti-TF monoclonal antibody, recombinant TF pathway inhibitor, recombinant inactivated-active site FVIIa and all-trans retinoic acid.

Role of ADP and thromboxanes in human thrombus formation in ex vivo models.

Adenosine diphosphate (ADP) and prostaglandin derivatives play important roles in thrombogenesis. Their roles in platelet function have been extensively studied for more than three and two decades, respectively. Of further importance for thrombogenesis, and perhaps for atherogenesis as well, is that these compounds are involved in the regulation of vascular wall tone, both as constrictors and dilators.

Characterization of a monoclonal antibody with specificity for holo-transcobalamin.

Background: Holotranscobalamin, cobalamin-saturated transcobalamin, is the minor fraction of circulating cobalamin (vitamin B12), which is available for cellular uptake and hence is physiologically relevant. Currently, no method allows simple, direct quantification of holotranscobalamin. We now report on the identification and characterization of a monoclonal antibody with a unique specificity for holotranscobalamin.