scholarly journals Activation of bovine factor VII by hageman factor fragments

Blood ◽  
1977 ◽  
Vol 50 (4) ◽  
pp. 611-617 ◽  
Author(s):  
R Radcliffe ◽  
A Bagdasarian ◽  
R Colman ◽  
Y Nemerson
Keyword(s):  
Factor Vii ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Intrinsic Pathway ◽  
Factor Xi ◽  
Extrinsic Pathway ◽  
Hageman Factor ◽  
Amino Terminal ◽  
Activated Factor Vii

Abstract During the early events of coagulation of human blood by the intrinsic pathway, factor XII is activated to a form which can activate factor XI, and is proteolytically fragmented to smaller species (30,000 daltons and 70,000 daltons) which have lost most of the ability to activate factor XI but which can activate prekallikrein rapidly. The effect of these fragments on factor VII was studied. It was found that these Hageman factor fragments promoted rapid proteolysis of one-chain factor VII to a more active two-chain form. The amino-terminal sequences of the chains of activated factor VII were found to be Ala- Asx-Gly- and Ile-Val-Gly-, the same as were earlier observed after activation of factor VII by activated factor X. This finding indicates that initiation of coagulation by the intrinsic pathway also primes the extrinsic pathway.

scholarly journals Activation of bovine factor VII by hageman factor fragments

Blood ◽  
1977 ◽  
Vol 50 (4) ◽  
pp. 611-617 ◽  
Author(s):  
R Radcliffe ◽  
A Bagdasarian ◽  
R Colman ◽  
Y Nemerson
Keyword(s):  
Factor Vii ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Intrinsic Pathway ◽  
Factor Xi ◽  
Extrinsic Pathway ◽  
Hageman Factor ◽  
Amino Terminal ◽  
Activated Factor Vii

During the early events of coagulation of human blood by the intrinsic pathway, factor XII is activated to a form which can activate factor XI, and is proteolytically fragmented to smaller species (30,000 daltons and 70,000 daltons) which have lost most of the ability to activate factor XI but which can activate prekallikrein rapidly. The effect of these fragments on factor VII was studied. It was found that these Hageman factor fragments promoted rapid proteolysis of one-chain factor VII to a more active two-chain form. The amino-terminal sequences of the chains of activated factor VII were found to be Ala- Asx-Gly- and Ile-Val-Gly-, the same as were earlier observed after activation of factor VII by activated factor X. This finding indicates that initiation of coagulation by the intrinsic pathway also primes the extrinsic pathway.

Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

1998 ◽  
Vol 80 (08) ◽  
pp. 233-238 ◽  
Author(s):  
K. A. Mitropoulos ◽  
M. N. Nanjee ◽  
D. J. Howarth ◽  
J. C. Martin ◽  
M. P. Esnouf ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Positive Association ◽  
Factor Ix ◽  
Factor Vii ◽  
Unesterified Fatty Acid ◽  
Factor Xii ◽  
Factor X ◽  
Factor Xi ◽  
Activated Factor Vii ◽  
Normal Mean

SummaryAbetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

scholarly journals Activation of human factor VII in the initiation of tissue factor- dependent coagulation

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 685-691 ◽  
Author(s):  
LV Rao ◽  
SI Rapaport ◽  
SP Bajaj
Keyword(s):  
Tissue Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Clotting Time ◽  
Activated Factor Vii ◽  
Peptide Release ◽  
Minimal Generation

Abstract We have used activation peptide release assays to compare factor VII and activated factor VII (VIIa) activation of factor X, normal factor IX (IXN), and a variant factor IX (IXBmLE), which, after activation, is unable to back-activate factor VII. In purified systems, factor VII and VIIa each rapidly activated factor X, but after a one minute lag for factor VII. VIIa also readily activated both IXN and IXBmLE. Factor VII initially failed to activate substantial amounts of either IXN or IXBmLE; on further incubation factor VII activated IXN but not IXBmLE. Activation of IXN began when approximately 10% of factor VII had been converted to VIIa, as measured by 125I-factor VII radioactivity profiles. Adding factor VII to VIIa slowed its activation of IXBmLE. However, in the presence of factor X, factor VII alone rapidly activated IXBmLE. Unlike purified systems, 1 nmol/L VIIa added to factor VII-deficient plasma failed to activate factor IX. Increasing factor VII to 10 nmol/L (plasma concentration) either as native VII or VIIa yielded similar activation curves for factor IX and similar activation curves for factor X. Adding 5% VIIa to factor X-deficient plasma and to factor XII-deficient plasma substantially shortened the dilute tissue factor clotting time of only the former. These data support the hypothesis that factor VII/tissue factor complex initiates tissue factor-dependent clotting through a minimal generation of Xa. This Xa then rapidly back-activates a small amount of factor VII, following which the rates of activation of both factors IX and X increase dramatically.

scholarly journals Activation of human factor VII in the initiation of tissue factor- dependent coagulation

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 685-691 ◽  
Author(s):  
LV Rao ◽  
SI Rapaport ◽  
SP Bajaj
Keyword(s):  
Tissue Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Clotting Time ◽  
Activated Factor Vii ◽  
Peptide Release ◽  
Minimal Generation

We have used activation peptide release assays to compare factor VII and activated factor VII (VIIa) activation of factor X, normal factor IX (IXN), and a variant factor IX (IXBmLE), which, after activation, is unable to back-activate factor VII. In purified systems, factor VII and VIIa each rapidly activated factor X, but after a one minute lag for factor VII. VIIa also readily activated both IXN and IXBmLE. Factor VII initially failed to activate substantial amounts of either IXN or IXBmLE; on further incubation factor VII activated IXN but not IXBmLE. Activation of IXN began when approximately 10% of factor VII had been converted to VIIa, as measured by 125I-factor VII radioactivity profiles. Adding factor VII to VIIa slowed its activation of IXBmLE. However, in the presence of factor X, factor VII alone rapidly activated IXBmLE. Unlike purified systems, 1 nmol/L VIIa added to factor VII-deficient plasma failed to activate factor IX. Increasing factor VII to 10 nmol/L (plasma concentration) either as native VII or VIIa yielded similar activation curves for factor IX and similar activation curves for factor X. Adding 5% VIIa to factor X-deficient plasma and to factor XII-deficient plasma substantially shortened the dilute tissue factor clotting time of only the former. These data support the hypothesis that factor VII/tissue factor complex initiates tissue factor-dependent clotting through a minimal generation of Xa. This Xa then rapidly back-activates a small amount of factor VII, following which the rates of activation of both factors IX and X increase dramatically.

scholarly journals Activation of human factor VII during clotting in vitro

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 218-226 ◽  
Author(s):  
LV Rao ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Glass Tube ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Normal Plasma

Abstract We have studied factor VII activation by measuring the ratio of factor VII clotting to coupled amidolytic activity (VIIc/VIIam) and cleavage of 125I-factor VII. In purified systems, a low concentration of Xa or a higher concentration of IXa rapidly activated 125I-factor VII, yielding a VIIc/VIIam ratio of 25 and similar gel profiles of heavy and light chain peaks of VIIa. On further incubation, VIIa activity diminished and a third 125I-peak appeared. When normal blood containing added 125I- factor VII was clotted in a glass tube, the VIIc/VIIam ratio rose fivefold, and 20% of the 125I-factor VII was cleaved. Clotting normal plasma in an activated partial thromboplastin time (APTT) system yielded a VIIc/VIIam ratio of 25 and over 90% cleavage of 125I-factor VII. Clotting factor XII-deficient plasma preincubated with antibodies to factor X in an APTT system with added XIa yielded a VIIc/VIIam ratio of 19 and about 60% cleavage, which indicates that IXa, at a concentration achievable in plasma, can effectively activate factor VII. Clotting normal plasma with undiluted tissue factor yielded a VIIc/VIIam ratio of 15 to 20 and 60% cleavage of 125I-factor VII, whereas clotting plasma with diluted tissue factor activated factor VII only minimally. We conclude that both Xa and IXa can function as significant activators of factor VII in in vitro clotting mixtures but believe that only small amounts of factor VII may be activated in vivo during hemostasis.

scholarly journals Activation of human factor VII during clotting in vitro

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 218-226 ◽  
Author(s):  
LV Rao ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Glass Tube ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Factor Xii ◽  
Factor X ◽  
Normal Plasma

We have studied factor VII activation by measuring the ratio of factor VII clotting to coupled amidolytic activity (VIIc/VIIam) and cleavage of 125I-factor VII. In purified systems, a low concentration of Xa or a higher concentration of IXa rapidly activated 125I-factor VII, yielding a VIIc/VIIam ratio of 25 and similar gel profiles of heavy and light chain peaks of VIIa. On further incubation, VIIa activity diminished and a third 125I-peak appeared. When normal blood containing added 125I- factor VII was clotted in a glass tube, the VIIc/VIIam ratio rose fivefold, and 20% of the 125I-factor VII was cleaved. Clotting normal plasma in an activated partial thromboplastin time (APTT) system yielded a VIIc/VIIam ratio of 25 and over 90% cleavage of 125I-factor VII. Clotting factor XII-deficient plasma preincubated with antibodies to factor X in an APTT system with added XIa yielded a VIIc/VIIam ratio of 19 and about 60% cleavage, which indicates that IXa, at a concentration achievable in plasma, can effectively activate factor VII. Clotting normal plasma with undiluted tissue factor yielded a VIIc/VIIam ratio of 15 to 20 and 60% cleavage of 125I-factor VII, whereas clotting plasma with diluted tissue factor activated factor VII only minimally. We conclude that both Xa and IXa can function as significant activators of factor VII in in vitro clotting mixtures but believe that only small amounts of factor VII may be activated in vivo during hemostasis.

scholarly journals Activation of Hageman Factor (HF, Factor XII) by Sephadex-Ellagic Acid Mixtures

1977 ◽  
Author(s):  
O. D. Ratnoff ◽  
H. Saito
Keyword(s):  
Ellagic Acid ◽  
Partial Thromboplastin Time ◽  
Factor Xii ◽  
Intrinsic Pathway ◽  
Clotting Factors ◽  
Factor Xi ◽  
Molecular Changes ◽  
Hageman Factor ◽  
Procoagulant Effect ◽  
Fletcher Factor

In the intrinsic pathway of clotting, PTA (Factor XI) is activated by activated HF. Whether activation of HF requires the presence of prekallikrein (Fletcher factor) and high M. W.(HMW) kininogen (Fitzgerald factor), or whether these agents act after activation of HF is disputed. Purified HF activates PTA in the absence of prekallikrein, but this may reflect molecular changes in HF during purification.Sephadex G10 or G15 was mixed with ellagic acid and freed of excess ellagic acid by washing. A mixture of normal plasma, or plasma deficient in HF, prekallikrein, HMW kininogen or PTA, and Sephadex-ellagic acid was centrifuged at 31000 xg. Each supernatant plasma except that deficient in HF shortened the abnormally long partial thromboplastin time (PTT) of HF-deficient plasma. Plasma simultaneously depleted of HMW kininogen, prekallikrein and PTA also shortened the PTT of HF-deficient plasma and of plasma depleted of HF and prekallikrein (albeit minimal clotting times were reached more slowly in the latter case) but had virtually no procoagulant effect upon the PTT of plasma depleted of HF and HMW kin inogen.Thus, exposure of HF in plasma to Sephadex-ellagic acid generated a clot-promoting form of HF in the absence of other clotting factors, but its full expression requited the presence of HMW kininogen.

scholarly journals Activation of human factor VII by activated factors IX and X

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1143-1150 ◽  
Author(s):  
DR Masys ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Human Factors ◽  
Factor Viii ◽  
Active Site ◽  
Human Factor ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Factor X ◽  
Activated Factor Vii

Factor VII clotting activity increases about five-fold when blood is clotted in glass. Prior studies suggested that this results from activation induced by activated factor IX (IXa). However, in purified systems containing phospholipid and calcium, activated factor X (Xa) is known to activate factor VII rapidly. Therefore, we studied activation of factor VII by IXa and X, in systems using purified human factors. Concentrations of IXa and Xa were calculated from total activated protein concentrations rather than from active site concentrations. In the presence of phospolipid and calcium, both IXa and Xa activated factor VII 25-fold; however, Xa was roughly 800 times more efficient than IXa. Without added phospholipid, activation of factor VII by both Xa and IXa was markedly slowed, and Xa was roughly 20 times more efficient than IXa. When both phospholipid and calcium were omitted, activation of factor VII by either enzyme was negligible. Adding normal prothrombin, but not decarboxylated prothrombin, substantially slowed activation of factor VII by both Xa and IXa. Adding thrombin-activated factor VIII and antithrombin-III did not change rates of factor VII activation by either enzyme. These results from purified systems do not provide an explanation for the prior data from plasma systems.

Cold Promoted Activation of Factor VII

1972 ◽  
Vol 28 (02) ◽  
pp. 194-205 ◽  
Author(s):  
H Gjønnæss
Keyword(s):  
Intrinsic Factor ◽  
Coagulation Factors ◽  
The Other ◽  
Factor Vii ◽  
Factor Xii ◽  
Factor X ◽  
Reaction Sequence ◽  
Activated Factor Vii ◽  
Control Plasma

SummaryThe cold promoted shortening of the thrombotest times induced by incubation of plasma with prekallikrein activators for 20 hours at 0° C is due to activation of factor VII. No change was recorded for the other coagulation factors. The activation was strong, as the presence of 1 per cent cold activated factor VII reduced the thrombotest time of factor VII deficient plasma from 115 to 38.7 seconds.The activation of factor X by the cold activated factor VII occurred in the course of seconds, in the presence of calcium and thromboplastin. Cold promoted activation of factor VII also implied reduced cephalin time, probably via traces of thrombin inducing intrinsic factor X activator activity during the clotting test.Generation of cold promoted activator activity (CPA) was independent of coagulation factors V, VIII, IX, X, XI, and calcium, but factor XII was a prerequisite. Of factor VII even traces were sufficient for the generation of CPA. The activation of the kallikrein system, that occurs in parallel with the cold promoted activation of factor VII, occurred both in factor VII deficient plasma and in ordinary control plasma. In the reaction sequence, the activation of factor VII therefore is less likely to be the first step, it possibly is a result of activation of the kallikrein system.

Herpes Simplex Virus Initiates the Intrinsic Pathway of Coagulation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3173-3173
Author(s):  
Edwin S Gershom ◽  
Michael R Sutherland ◽  
Pete Lollar ◽  
Ed L. Pryzdial
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Current Work ◽  
Vascular Pathology ◽  
Factor Vii ◽  
Factor Xii ◽  
Contact Activation ◽  
Intrinsic Pathway ◽  
Extrinsic Pathway ◽  
Simplex Virus

Abstract Abstract 3173 Poster Board III-113 A hemostatic response to vascular injury is initiated by the extrinsic pathway of coagulation and amplified by the intrinsic pathway. We previously reported that purified herpes simplex virus type-1 (HSV1) has constitutive extrinsic pathway tissue factor (TF) and anionic phospholipid on its surface derived from the host cell, and can consequently bypass strict cellular control of coagulation. The current work addresses the hypothesis that HSV1-induced plasma coagulation also involves intrinsic pathway, factor VIII (FVIII), and upstream contact activation pathway, factor XII (FXII). HSV1-initiated clotting was accelerated when purified FVIII was added to FVIII-deficient plasma. The involvement of FVIII was confirmed by an inhibitory anti-FVIII antibody (Ab), which attenuated HSV1-initiated clotting of normal plasma. High HSV1 concentrations predictably reduced the effect of FVIII due to the availability of excess viral TF. To further define clotting mechanisms initiated by HSV1, the extrinsic pathway was disabled using factor VII-deficient plasma. The intrinsic pathway may be triggered by contact activation of FXII by kallikrein when bound to a suitable surface. Here we found that an inhibitor of activated FXII, corn trypsin inhibitor, and anti-FXII Ab attenuated HSV1-initiated clotting. Direct activation of purified FXII by the virus was not observed. Supporting the involvement of kallikrein in FXII activation due to HSV1, anti-kallikrein Ab was also inhibitory. The current work shows that HSV1 can trigger and amplify coagulation through the intrinsic and contact activation pathways, and suggests an additional mechanism that may explain prior reports linking virus infection to vascular pathology. Disclosures No relevant conflicts of interest to declare.

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