Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

Journal Article · Fri Jun 01 04:00:00 EDT 1984 · Blood; (United States)

OSTI ID:6800378

Morrison, S A; Jesty, J

A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin.

• Research Organization: Health Sciences Center, SUNY, Stony Brook, NY
• OSTI ID: 6800378
• Journal Information: Blood; (United States), Journal Name: Blood; (United States) Vol. 63:6; ISSN BLOOA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
AMINES
ANIMALS
ANTICOAGULANTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD COAGULATION FACTORS
BLOOD PLASMA
BODY FLUIDS
CALCIUM
CARBOHYDRATES
CATTLE
COAGULANTS
DOMESTIC ANIMALS
DRUGS
ELEMENTS
ENZYME ACTIVITY
ENZYME INHIBITORS
HEMATOLOGIC AGENTS
HEPARIN
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
MATERIALS
METALS
MUCOPOLYSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHYSIOLOGY
POLYSACCHARIDES
PRIMATES
REACTION KINETICS
RUMINANTS
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES