Search PubMed⌕ Search

PubMed · 16113749

Chromogenic methods in coagulation diagnostics.

Abstract

Chromogenic peptide substrates were developed more than 30 years ago. Although the use of chromogenic substrate methods in coagulation and fibrinolysis diagnostics was not as rapidly implemented as initially believed, they are now well established for several analytes such as antithrombin, FVIII, protein C, plasminogen, plasmin inhibitor, heparins, and pentasaccharides. The advent of direct thrombin and factor Xa inhibitors has stimulated the development of new, specific chromogenic methods and these may find their way into routine use if these new drug candidates will prove to be valid replacements for coumarin derivatives. A large number of chromogenic research methods for other analytes were developed, too. The current interest in global chromogenic methods for thrombin generation and the protein C pathway may turn out as clinically important and thus enter into routine use.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Rosén. 2005. Chromogenic methods in coagulation diagnostics.. https://doi.org/10.1267/h%C3%A4mo05030259

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Analysis of inhibition rate enhancement by covalent linkage of antithrombin to heparin as a potential predictor of reaction mechanism.

Antithrombin (AT) inhibition of coagulation enzymes is catalyzed by unfractionated heparin (UFH) and other heparinoids. Reaction proceeds either via conformational activation of the inhibitor or template-mediated binding of both inhibitor and protease. We investigated if the relative inhibition rates of AT + UFH and covalent AT-heparin conjugate (ATH) with coagulation factors might be indicative of the mechanism involved. Rates were determined by discontinuous assay and mechanisms were probed by a variety of binding studies with UFH or ATH heparin chains. Rates were increased more than 2-fold with ATH over AT + UFH in reactions with thrombin, factor (F) VIIa + tissue factor + Ca2+ + lipid, FIXa and FXIa, but not with FXa or FXIIa. In comparison, UFH or ATH heparin binding (evidence of a template mechanism) was only observed with thrombin, tissue factor, FIXa and FXIa. Thus, inhibition rate enhancement by conjugation of AT with heparin were predictive of inhibitor.enzyme template bridging by heparin. Rationales behind this novel concept are discussed.

Antithrombins↗

{4(S)-(Piperidin-1-ylcarbonyl)-4-[3-(trifluoromethyl)phenylsulfonamido]butyl}guanidinium chloride: a model of a graftable thrombin inhibitor.

In the title compound, C18H27F3N5O3S+.Cl-, the guanidine group forms N-H...Cl hydrogen bonds, with four N...Cl distances in the range 3.164 (3)-3.337 (4) A. In the crystal packing, the cations are further linked by N-H...O and C-H...O interactions. The structure is compared with that of argatroban complexed with thrombin and is the subject of docking studies in the active site of thrombin.

Antithrombins↗