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.

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 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.

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.

The Influence of the Thyroid Function on the Metabolic Rate of Prothrombin, Factor VII, and Factor X in the Rat

1976 ◽  
Vol 35 (03) ◽  
pp. 607-619 ◽  
Author(s):  
Allan T. van Oosterom ◽  
Herman Mattie ◽  
Wim Th Hermens ◽  
Jan J. Veltkamp
Keyword(s):  
Metabolic Rate ◽  
Thyroid Function ◽  
Coagulation Factors ◽  
Biologically Active ◽  
Factor Vii ◽  
Synthesis Rate ◽  
Apparent Difference ◽  
Vitamin K1 ◽  
Factor X ◽  
Significant Difference

SummaryThe influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability.No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study.The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation.The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred.An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.

HAEMOSTATIC CHANGES INDUCED BY TWO LOW DOSE TRIPHASIC ORAL CONTRACEPTIVES

1987 ◽  
Author(s):  
S J Machin ◽  
I J Mackie ◽  
K Walshe ◽  
M D Gillmer
Keyword(s):  
Oral Contraceptives ◽  
Protein C ◽  
Low Dose ◽  
Factor Vii ◽  
Cycle Period ◽  
Factor Xii ◽  
Factor X ◽  
Combined Oral Contraceptives ◽  
First Time ◽  
Protein C Activity

The haemostatic system was investigated in 26 women taking cyclically administered triphasic combined oral contraceptives for the first time during their first six cycles. Fourteen women received Logynon (mean dose 32.4μg ethinyloestradiol, 92pg progestagen) and 12 received SHD 415G (Schering) which contains a mean dosage of 32.4μg ethinyloestradiol and 78pg gestodene, a recently developed progesterone. The Logynon group showed a significant increase (p<0.005) in fibrinogen (pre-mean 284.4 g/1; after 1 cycle 347.3 g/1, after 6 cycles 318.6 g/1) , factor VII (65.8 u/1 to 73.9 u/1 to 83.2 u/1), factor XII (1.74 u/1 to 2.41 u/1, to 2.25 u/1), plasminogen (100.9 u/1 to 135.1 u/1 to 126.3 u/1); decrease in ATIII (115.9 u/1 to 103.1 u/1 to 93.4 u/1) but no significant change in factor X (98.4 u/1 to 108.9 u/1 to 102.4) or protein C (0.85 u/1 to 0.88 u/1 to 0.94 u/1) activity. The SHD 415G group showed similar changes with an increase in fibrinogen (247.9 g/1 to 330.8 g/1 to 373 .1 g/1), factor VII (63.1 u/1 to 73.1 u/1 to 90.3 u/1, factor X (98.3 u/1 to 112.0 u/1 to 124.4 u/1), factor XII (1.46 u/1, to 1.93 u/1, to 2.03 u/1), plasminogen (110.8 u/1 to 125.4 u/1 to 136.7 u/1); decrease in ATIII (113.1 u/1 to 96.3 u/1 to 89.7 u/1), but no change in protein C (0.84 u/1 to - 0.78 u/1 to 0.85 u/1) activity. These changes were apparent after the first cycle of therapy and the differences were maintained over the six cycle period. There was no increase in protein C activity despite changes in the other vitamin K dependent proteins factors VII and X. Both low oestrogen dose triphasic pills caused similar prothrombotic changes which were not modified by the new progesterone, gestodene.

scholarly journals Evidence for the presence of tissue factor activity on subendothelium

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 968-975
Author(s):  
HJ Weiss ◽  
VT Turitto ◽  
HR Baumgartner ◽  
Y Nemerson ◽  
T Hoffmann
Keyword(s):  
Tissue Factor ◽  
Umbilical Artery ◽  
Factor Viia ◽  
Rabbit Aorta ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor X ◽  
Factor Activity ◽  
Fibrin Deposition ◽  
Tissue Factor Activity

By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.

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.

Neonatal Polycythemia: A Disorder Associated With Hyperviscosity, Normal Coagulation Findings And Thrombocytopenia

1981 ◽  
Author(s):  
J Katz ◽  
E Rodriguez ◽  
C Madani ◽  
D Hicks ◽  
H E Branson
Keyword(s):  
Plasma Exchange ◽  
Gestational Age ◽  
Degradation Products ◽  
Factor Ix ◽  
Factor Vii ◽  
Large For Gestational Age ◽  
Factor Xii ◽  
Factor X ◽  
Platelet Counts ◽  
Before And After

Thirty-two newborns with elevated capillary hematocrits >65% were studied. Twenty-two newborns required plasmaexchange transfusion. All had central (venous) hematocrits >65% and had symptoms referrable to complications associated with this syndrome. Of the 22, 15 were appropriate-for-gestational age, 5 were small-for-gestational age, and 2 were large-for-gestational age. Viscosity measurements in the 10 newborns who did not require plasma-exchanges showed increased viscosity in 2 in the slow shear rates associated with bloodflow in the smaller vessels. Coagulation data before and after plasma exchange did not show a hypercoagulable state: PT-14.2±0.7 and 12.9±1.2 secs, PTT 49.9±3.6 and 42.2±3.2 secs, factor VII 73±5 and 78±5%, factor VIII 103±10 and 94±10%, AT III levels were low 14±1.2 and 17±1.3 mg/dl, fibrin degradation products were <10μg/ml, fibrin monomer was not detected, plasminogen levels were 5±0.8 and 7±0.9mg/dl, fibrinogen levels were 203±9.8 and 200±11.8 mg%. Vitamin K dependent factors were reduced factor V 44±6 and 49±11%, factor VII 77±5 and 86±5%, factor IX 28±2 and 42±3%, factor X 35±4 and 62±6%, factor XI 55±5 and 84±9%, factor XII 47±5 and 63±5%. Statistical significant differences were found only with factors IX, X, XI and XII. Thrombocytopenia was present in 6 patients (20% incidence) and post plasma exchange the platelet counts rose significantly and in 2 patients within 3 days reached normal levels. No statistical difference in the platelet counts were noted before and after the plasma-exchange and were similar to the levels determined in 10 newborn controls. Neonatal polycythemia with thrombocytopenia may indicate a more severe disorder, with hematocrits in the 6 patients >70%. It is suggested that the mechanism of the thrombocytopenia may be aggregates of platelets that deaggregate following plasmaexchange. The complications associated with neonatal polycythemia appear related to hyperviscosity, erythrocyte and platelet “sludging” in the smaller vessels.

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