The role of proconvertin and stuart factor in the inactivation of tissue thromboplastin by serum

Hermansky, F; Vítek, J

doi:10.1007/bf02171149

Cited by 7 publications

(5 citation statements)

References 3 publications

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“…Thomas also showed that the inhibitory ef fect of serum was calcium dependent and reversible. Similar results were later ob tained by other investigators using in vitro clotting assays [17][18][19][20]. Eventually, Hjort [2] provided evidence that the inhibitory effect of serum was directed against the combined activity of factor VII and TP (the convertin reagent), but did not affect the activity of the TP reagent, or the factor VII reagent (the proconvertin reagent) alone.…”

Section: The Effects Of Serum On Tissue Extractssupporting

confidence: 73%

Extrinsic Pathway Inhibitor – The Key to Feedback Control of Blood Coagulation Initiated by Tissue Thromboplastin

Sandset¹,

Abildgaard²

1991

Pathophysiol Haemos Thromb

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Extrinsic pathway inhibitor (EPI) is a Kunitz type serine protease inhibitor. EPI is a potent inhibitor of the factor VIIa/thromboplastin (TP) complex in the presence of factor Xa and is also a direct inhibitor of factor Xa. The inhibitory mechanism is complex and is currently thought to involve, in a first step, the formation of a EPI-factor Xa complex, and, in a second step, the formation a quaternary EPI-factor Xa-factor VIIa-TP complex. In the blood vessels, EPI is confined to three different pools. A major pool of EPI is bound to the endothelial surface, and this fraction may be released by heparin. Plasma contains a second, but smaller pool of EPI (≈ 10–50% of the endothelial surface pool) at a concentration of 50–100ng/ml. This pool consists mostly of EPI-lipoprotein complexes and only less than 10% is carrier-free EPI. A third pool of EPI is confined to platelets ( < 10% of the plasma pool). The biological role of these pools has not yet been clarified, but some evidence suggest that the carrier-free EPI is biologically most active. In patients, disseminated intravascular coagulation may continue despite normal or even elevated EPI levels. However, evidence has now been provided to indicate that EPI can inhibit factor VIIa/TP complexes formed in vivo to prevent the effect of limited amounts of TP. Taken together, the present knowledge of EPI indicates that EPI functions as a key inhibitor to feedback control of blood coagulation initiated by TP.

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Section: The Effects Of Serum On Tissue Extractssupporting

confidence: 73%

Extrinsic Pathway Inhibitor – The Key to Feedback Control of Blood Coagulation Initiated by Tissue Thromboplastin

Sandset¹,

Abildgaard²

1991

Pathophysiol Haemos Thromb

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“…Thomas (3) also noted that the inhibitory effect of serum required the presence of calcium ions, that the inhibitor appeared to bind to thromboplastin, and that the effect could be reversed by calcium ion chelators. The calcium ion requirement and reversibility of the thromboplastin inhibition were subsequently confirmed by in vitro coagulation assays (5–9). In 1957, Hjort (10) reported that the previously described serum inhibitor of thromboplastin recognized the factor VIIa-Ca 2+ -tissue factor complex, which he termed convertin, rather than factor VII (proconvertin) or thromboplastin alone.…”

Section: Introductionmentioning

confidence: 91%

Tissue factor pathway inhibitor: structure-function

Broze

Girard²

2012

Front Biosci

147

212

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An inhibitor of tissue factor-induced coagulation was rediscovered in the 1980’s and subsequently named tissue factor pathway inhibitor (TFPI). Three isoforms of TFPI are transcribed through alternative mRNA splicing: TFPIα, which contains an acidic aminoterminus followed by three tandem Kunitz-type protease inhibitor domains and a basic carboxyterminus; TFPIβ, in which the Kunitz-3 and carboxyterminus of TFPIα are replaced with a different carboxyterminus containing a glycosyl phosphatidyl inositol (GPI) anchor; and TFPIδ, which is truncated following the Kunitz-2 domain. The microvascular endothelium is thought to be the principal source of TFPI and TFPIα is the predominant isoform expressed in humans. TFPIα, apparently attached to the surface of the endothelium in an indirect GPI-anchor-dependent fashion, represents the greatest in vivo reservoir of TFPI. The Kunitz-2 domain of TFPI is responsible for factor Xa inhibition and the Kunitz-1 domain is responsible for factor Xa-dependent inhibition of the factor VIIa/tissue factor catalytic complex. The anticoagulant activity of TFPI in one-stage coagulation assays is due mainly to its inhibition of factor Xa through a process that is enhanced by protein S and dependent upon the Kunitz-3 and carboxyterminal domains of full-length TFPIα. Carboxyterminal truncated forms of TFPI as well as TFPIα in plasma, however, inhibit factor VIIa/tissue factor in two-stage assay systems. Studies in gene-disrupted mice demonstrate the physiological importance of TFPI.

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“…Thomas also noted that this inhibitory effect of serum required the presence of calcium ions, that the inhibitor appeared to bind to the thromboplastin, and that the inhibition could be reversed by calcium ion chelators. The calcium requirement and reversibility of the thromboplastin inhibition were later confirmed by using in vitro coagulation assays (Mann & Hurn, 1949; McClaughry, 1950; Lanchantin & Ware, 1953;Berry, 1957;Hermansky & Vitek, 1960). In a landmark study, Hjort (1957) showed that the serum inhibitor recognized the factor VII-Ca2+-thromboplastin complex, which he called "convertin'', rather than factor VII or thromboplastin alone and, using indirect means, suggested that the binding of the inhibitor to convertin was also calcium dependent.…”

Section: Laci Historymentioning

confidence: 98%

Regulation of coagulation by a multivalent Kunitz-type inhibitor

Broze¹,

Girard²,

Novotny³

1990

Biochemistry

371

233

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^Jlood coagulation proceeds through a series of reactions in which plasma zymogens of serine enzymes are sequentially activated by limited proteolytic cleavage. Mechanistically, the initiation of coagulation has been separated into two pathways, "extrinsic" and "intrinsic", that converge at the activation of factor X with subsequent generation of thrombin proceeding through a single, "common", pathway (MacFarlane, 1964; Davie & Ratnoff, 1964) (Figure 1). In the extrinsic pathway, factor VIIa bound to its cofactor, tissue factor (TF), can activate factor X directly. In the intrinsic pathway, exposure

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The role of proconvertin and stuart factor in the inactivation of tissue thromboplastin by serum

Cited by 7 publications

References 3 publications

Extrinsic Pathway Inhibitor – The Key to Feedback Control of Blood Coagulation Initiated by Tissue Thromboplastin

Extrinsic Pathway Inhibitor – The Key to Feedback Control of Blood Coagulation Initiated by Tissue Thromboplastin

Tissue factor pathway inhibitor: structure-function

Regulation of coagulation by a multivalent Kunitz-type inhibitor

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