A Familial Hemorrhagic Trait Associated With a Deficiency of a Clot-Promoting Fraction of Plasma 1

Ratnoff, Oscar D.; Colopy, Joan E.

doi:10.1172/jci103109

Cited by 435 publications

(196 citation statements)

References 28 publications

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“…(17,18) During the first half of the 20th century, the remaining coagulation enzymes and co-factors were identified. (19)(20)(21)(22)(23)(24)(25) It has also become clear that coagulation proteins are primarily produced by the liver. Factors II, VII, IX, and X are vitamin K-dependent proteins, which require gamma-glutamyl carboxylation to become biologically active.…”

Section: Introductionmentioning

confidence: 99%

The blood coagulation system as a molecular machine

2003

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The human blood coagulation system comprises a series of linked glycoproteins that upon activation induce the generation of downstream enzymes ultimately forming fibrin. This process is primarily important to arrest bleeding (hemostasis). Hemostasis is a typical example of a molecular machine, where the assembly of substrates, enzymes, protein cofactors and calcium ions on a phospholipid surface markedly accelerates the rate of coagulation. Excess, pathological, coagulation activity occurs in “thrombosis”, the formation of an intravascular clot, which in the most dramatic form precipitates in the microvasculature as disseminated intravascular coagulation. Thrombosis occurs according to a biochemical machine model in the case of atherothrombosis on a ruptured atherosclerotic plaque, but may develop at a slower rate in venous thrombosis, illustrating that the coagulation machinery can act at different velocities. The separate coagulation enzymes are also important in other biological processes, including inflammation for which the rapid conversion of one coagulation factor by the other is not a prerequisite. The latter role of coagulation enzymes may be related to the old and probably maintained function of the coagulation machine in innate immunity. BioEssays 25:1220–1228, 2003. © 2003 Wiley Perioicals, Inc.

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Section: Introductionmentioning

confidence: 99%

The blood coagulation system as a molecular machine

2003

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“…Proteins that are known to be involved in contact activation of human plasma include Hageman factor (HF, blood coagulation Factor XII) (6), plasma prekallikrein (Fletcher factor) (7,8), coagulation Factor XI (plasma thromboplastin antecedent) (9), and high molecular weight (Mr) kininogen, which was recognized in studies.of Flaujeac trait (10), Fitzgerald trait (11,12), Williams trait (13), and "contact activation cofactor" (14).…”

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confidence: 99%

Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

Griffin

1978

Proc. Natl. Acad. Sci. U.S.A.

243

143

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The mechanism by which negatively charged substances such as celite, kaolin, or ellagic acid contribute to the surface-dependent activation of Hageman factor (Factor XII) was studied. Kinetic studies of the proteolytic activation of '514-labeled human Hageman factor by human plasma kallikrein, plasmin, activated Factor XI, and trypsin were performed in the presence and absence of hig molecular, weight kininogen and surface materials such as celite, kaolin, or ellagic acid. The results showed that surface-bound Hageman factor was 500 times more susceptible than soluble Hageman factor to proteolytic activation by kallikrein in the presence of high molecular weight kininogen. Surface binding of Hageman factor enhanced its cleavage by plasmin, activated Factor XI, and trypsin by 100-fold, 30-fold, and 5-fold, respectively. On a molar basis, trypsin was twice as potent as kallikrein in the cleavage of the surface-bound Hageman factor, while plasmin and activated Factor XI were an order of magnitude less potent than kallikrein. Kallikrein even at concentrations as low as 0.5 nM (i.e., 1/1000th of the concentration of prekallikrein' in plasma) was very potent in the limited proteolysis of the surface-boulid Hageman factor. These results suggest that substances classically known as "activating surfaces" promote the activation of Hageman factor indirectly by alerng its structure such that it is much more susceptible to proteolytic activation by otherplasma or cellular proteases.

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“…Curiosamente el paciente había sido sometido a dos procedimientos quirúrgicos previos sin ninguna complicación (1) . Ambos autores lograron identificar la proteína faltante como factor XII (FXII) y el hecho de que John Hageman no presentara sangrados sugería que la actividad de dichas proteí-nas era en forma de precursores inactivos (2) .…”

Section: Discusión Historiaunclassified

Tema 17-2014: La Vía De Contacto: ¿el Futuro De Los Anticoagulantes?

López¹

2014

RC_UCR-HSJD

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RESUMENDurante décadas el desarrollo de nuevos anticoagulantes se ha basado en la modificación de fármacos o moléculas previamente disponibles. La poca oferta ha ocasionado que actualmente sea aceptado no administrar anticoagulantes cuando existe una indicación clara de anticoagulación, incrementando así el riesgo de extensión del fenómeno trombótico, el síndrome postrombótico, la discapacidad a largo plazo y las recurrencias, que en conjunto causan más morbilidad y mortalidad que el sangrado secundario a sobreanticoagulación. Los nuevos anticoagulantes orales han ampliado la cantidad de pacientes potenciales, sin embargo existen más opciones viables a mediano plazo que pueden cambiar la anticoagulación tal y como la conocemos hoy en día. Se resume la evidencia disponible en cuanto a la utilización del Sistema de Contacto de la coagulación como modelo para el desarrollo de futuras opciones terapéuticas y sus implicaciones futuras. PALABRAS CLAVEAnticoagulación. Sistema de Contacto. Factor XII. ABSTRACTFor years, the development of new anticoagulant drugs has been based on modifications of previously available compounds. Currently, it is widely accepted to withhold the administration of anticoagulants even in the presence of an indication of anticoagulation, increasing the morbidity, long-term disability and relapses, which together account for more mortality than bleeding as a secondary effect. The novel oral anticoagulants have broadened the number of potential candidates; however, more options are foreseen in the future that can change clinical anticoagulation as it is prescribed today. We will summarize current knowledge on the coagulation Contact System and future therapeutic options.

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A Familial Hemorrhagic Trait Associated With a Deficiency of a Clot-Promoting Fraction of Plasma 1

Cited by 435 publications

References 28 publications

The blood coagulation system as a molecular machine

The blood coagulation system as a molecular machine

Role of surface in surface-dependent activation of Hageman factor (blood coagulation Factor XII)

Tema 17-2014: La Vía De Contacto: ¿el Futuro De Los Anticoagulantes?

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