Spatiotemporal dynamics of contact activation factors of blood coagulation

• Published in: Biochimica et biophysica acta Vol. 1569; no. 1; pp. 86 - 104
• Main Authors: Kondratovich, Andrei Yu, Pokhilko, Alexandra V, Ataullakhanov, Fazoil I
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2002
• Subjects: Algorithms; Binding Sites; Blood Coagulation; Citrated plasma; Cluster Analysis; Contact activation system; Coumarins; Enzyme Activation; Factor XIa; Factor XIa - chemistry; Glass; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Kallikrein; Kinetics; Models, Theoretical; Plasma Kallikrein - chemistry; Polystyrenes; Spatiotemporal dynamics; Temperature; Time Factors; α 2MG, α 2-macroglobulin; Blood coagulation; Citrated plasma; PRP, platelet-rich plasma; LBTI, lima bean trypsin inhibitor; Kallikrein; PFP, platelet-free plasma; AMC, 4-methyl-7-aminocoumarin; PPP, platelet-poor plasma; kall–α 2MG, kallikrein–α 2-macroglobulin complex; Factor XIa; HMWK, high molecular weight kininogen; Contact activation system; Spatiotemporal dynamics; SBTI, soybean trypsin inhibitor
• DOI: 10.1016/S0304-4165(01)00247-1
• ISSN: 0304-4165; 0006-3002

A new in vitro model is proposed for studying the spatiotemporal distributions of activated clotting factors, in which clotting is activated in a thin layer of nonstirred plasma supplemented with a fluorogenic substrate and is monitored by fluorescence from its cleavage product. Analysis of the spatiotemporal dynamics of factor XIa and kallikrein in glass-activated human plasma provides evidence that both contact factors remain restricted to the glass surface and possibly a narrow boundary zone (<0.1 mm). The kinetics of factor XIa and kallikrein studied by a new method (in nonstirred plasma) coincided with those studied fluorimetrically with full stirring: their concentrations rapidly rose for the first few minutes after activation and then slowly declined. Factor XI and prekallikrein activation is likely to be restricted by the limited number of sites available for binding to the surface. The maximum concentration of the active factors was estimated at 2×10 8 molecules per mm 2 at the glass surface (irrespective of stirring). At the plastic surface, this value was 15–30 times lower.