Thrombin formation and neutralization by antithrombin III in animals receiving repeated intravenous injections of tissue thromboplastin

1986 ◽  
Vol 101 (5) ◽  
pp. 571-573
Author(s):  
V. E. Pastorova
Keyword(s):  
Antithrombin Iii ◽  
Intravenous Injections ◽  
Tissue Thromboplastin ◽  
Thrombin Formation

scholarly journals Hereditary Antithrombin III Deficiency. Evidence of Increased Thrombin Formation in the Early Stage of Hemostasis

1977 ◽  
Author(s):  
F. Josso ◽  
M. H. Aurousseau ◽  
A. M. Fischer ◽  
M. D. Dautzenberg ◽  
S. Beguin
Keyword(s):  
Antithrombin Iii ◽  
Early Stage ◽  
Young Male ◽  
Massive Pulmonary Embolism ◽  
New Family ◽  
Mild Deficiency ◽  
Antithrombin Iii Deficiency ◽  
Thrombin Formation

High incidence of thromboembolism in observed in families with antithrombin III deficiency, despite the rather moderate defect (25 to 50 per cent) observed in the affected subjects, considered as heterozygous for the disease. The mechanism by which such a mild deficiency may promote thrombosis still remains unknown.A new family with antirhrombin III deficiency is reported, including three affected generations. Three young male adults of a same sibship died from massive pulmonary embolism aged from 22 to 28 years. In four living members of the family, three of which had antecedents of thrombophlebitis, antithrombin III level was close to 50 per cent by all assay methods used. Electro-phoretic and immunochemical studies failed to demonstrate any qualitative defect of the antithrombin III molecule.In these patients the only abnormalities of hemostasis lied in the early stage of the hemostatic pathway. In vitro, thrombin formation occured very rapidly after initiation of coagulation, as demonstrated by the kinetics of thrombin generation and factors V and VIII activation. In vivo, factors V and VIII were activated during bleeding much more rapidly than in controls and this activation was not suppressed by low doses of heparin (10 u./kg) as in the controls.These findings indicate that antithrombin III acts chiefly in the regulation balance of the early stages of hemostasis and thrombosis.

Heparin-coating of extracorporea circuits reduces thrombin formation in patients undergoing cardiopulmonary bypass

Perfusion ◽  
1991 ◽  
Vol 6 (3) ◽  
pp. 221-225 ◽  
Author(s):  
YJ Gu ◽  
W. van Oeveren ◽  
Kwhj van der Kamp ◽  
C. Akkerman ◽  
PW Boonstra ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Antithrombin Iii ◽  
Artery Bypass ◽  
Control Group ◽  
Second Phase ◽  
Control Groups ◽  
Heparin Coating ◽  
Systemic Heparinization ◽  
Extracorporeal Circuits ◽  
Thrombin Formation

This clinical study was performed to evaluate the inhibiting effects of heparin- coated extracorporeal circuits on thrombin formation during cardiopulmonary bypass (CPB). Thirty patients undergoing coronary artery bypass grafting were randomly divided into two groups with (Duraflo II, n=15) orwithout (control, n=15) the use of heparin-coated circuits. Standard systemic heparinization was performed in all the patients before CPB. The results showed that thrombin formation during the first phase of CPB was inhibited by heparin-coating identified by the significantly lower concentrations of thrombin-antithrombin III (TAT) complex formed in plasma in the Duraflo II group than in the control group (p <0.05). Heparin concentrations were higher in the Duraflo II group than in the control group at the end of CPB ( p <0.05). However, after release of the aortic crossclamp in the second phase of CPB, thrombin became strongly activated in both the Duraflo II and the control groups indicated by a sharp increase of TAT complex as well as fibrinopeptide A. Thus, Duraflo II heparin-coating reduces thrombin formation in the early phase of CPB, however, this beneficial effect was counteracted after aortic crossclamp release by material-independent stimuli. Therefore, adequate systemic heparinization is still required despite improved haemocompatibility of the circuits offered by heparin-coating.

scholarly journals Experimental Studies on Factor VIII Inhibitor Bypassing Activity

1977 ◽  
Author(s):  
H. Vinazzer
Keyword(s):  
Factor Viii ◽  
Calcium Chloride ◽  
Experimental Studies ◽  
Factor Xa ◽  
Factor Viii Inhibitor ◽  
Factor V ◽  
Factor X ◽  
Tissue Thromboplastin ◽  
Viii Inhibitor ◽  
Thrombin Formation

The exact action of factor VIII inhibitor bypassing activity (FEIBA) is still unclear. For this reason, a series of experimental studies was carried out. Procoagulant activities were examined by standard one-stage methods while factor Xa and thrombin were measured by chromogenic substrates. Activities of factors II, VII, IX, and X were similar to PPSB fractions. In addition, low factor V activity and a phospholipid were detected. No activated factor X was present in FEIBA but there was a trace amount of 2.1 NIH units of thrombin per 100 FEIBA units. On addition of calcium chloride slow thrombin formation could be observed which however, reached 1100 NIH units of thrombin per 100 FEIBA units within an incubation time of 10 min. The velocity of thrombin formation was greatly enhanced by addition of a PTT reagent and of thromboplastin respectively. Factor Xa on the other hand, was neither formed after addition of calcium chloride nor by a PTT reagent. Tissue thromboplastin however, activated Xa from FEIBA in the same manner as a PTT reagent plus barium sulfate plasma. From these results, the conclusion could be drawn that thrombin could readily be made available from FEIBA while activation of Xa either needed the complete endogenous pathway or the presence of tissue thromboplastin. The procoagulant activity of FEIBA therefore, could be attributed to direct thrombin formation. By this process, an activation of the clotting mechanism in plasmas deficient in endogenous coagulation factors, and a complete independence from the presence or absence of a specific antibody could be explained.

scholarly journals Interaction between human tissue thromboplastin and human antithrombin III.

1989 ◽  
Vol 37 (11) ◽  
pp. 2984-2987 ◽  
Author(s):  
Keizo HIRAHARA ◽  
Tetsuro MATSUISHI ◽  
Nobuo SUZUKI ◽  
Munetsugu KURATA
Keyword(s):  
Human Tissue ◽  
Antithrombin Iii ◽  
Tissue Thromboplastin

Tissue Thromboplastin Induced Reversible DIC and Heparin-Enhanced Inhibitors in Dogs

1986 ◽  
Vol 55 (01) ◽  
pp. 078-085 ◽  
Author(s):  
German A Marbet ◽  
Michael J Griffith
Keyword(s):  
Antithrombin Iii ◽  
Ex Vivo ◽  
Order Rate Constant ◽  
Thrombin Inhibitors ◽  
Heparin Cofactor Ii ◽  
First Order ◽  
Tissue Thromboplastin ◽  
Pseudo First Order ◽  
Homologous Tissue

SummaryReversible acute disseminated intravascular coagulation (DIC) has been induced in dogs by intravenous injection of homologous tissue thromboplastin. There was no measurable consumption of antithrombin III and heparin cofactor II even if fibrinogen was reduced during DIC by more than 80% of its baseline. The prothrombin level remained practically constant. These data correspond to the generation of a few nanomoles of thrombin in vivo with subsequent pseudo-first order inactivation by the major thrombin inhibitors. An ex vivo measure of the pseudo-first order rate constant (dynamic thrombin inhibitory capacity, DTIC) was a sensitive probe of circulating heparin. There was no change of DTIC during DIC in the absence of exogenous heparin suggesting that heparin-like endogenous glycosaminoglycans were not released in substantial amounts. Pretreatment with heparin efficiently inhibited the development of tissue thromboplastin induced DIC. This animal model may serve as a tool for the study of glycosaminoglycan anticoagulants in vivo.

scholarly journals Synergistic effect of antithrombin III, activated protein C and heparin on the inhibition of the tissue thromboplastin-mediated coagulation.

1989 ◽  
Vol 37 (3) ◽  
pp. 692-696 ◽  
Author(s):  
Keizo HIRAHARA ◽  
Yuko ETOH ◽  
Tetsuro MATSUISHI ◽  
Nobuo SUZUKI ◽  
Munetsugu KURATA
Keyword(s):  
Synergistic Effect ◽  
Protein C ◽  
Antithrombin Iii ◽  
Activated Protein C ◽  
Tissue Thromboplastin

scholarly journals Factor IXa Inhibition Contributes to the Heparin Effect

1991 ◽  
Vol 66 (03) ◽  
pp. 306-309 ◽  
Author(s):  
Suzette Béguin ◽  
Frédérique Dol ◽  
H Coenraad Hemker
Keyword(s):  
Antithrombin Iii ◽  
Dermatan Sulfate ◽  
Factor Xa ◽  
Inhibitory Effect ◽  
Heparin Cofactor Ii ◽  
Factor Ixa ◽  
Factor Viiia ◽  
At Iii ◽  
Inhibition Of Thrombin ◽  
Thrombin Formation

SummaryWe investigated whether the inactivation of factor IXa contributes to the partial inhibition of thrombin formation that is observed at therapeutic concentrations of heparin. The action of standard unfractionated heparin (0.05 U/ml) on thrombin formation in the intrinsic system was compared to that of a mixture of dermatan sulfate (DS) and a synthetic pentasaccharide (PS). DS enhances the action of heparin cofactor II which inhibits thrombin only. PS specifically enhances the anti-factor Xa activity of antithrombin III (AT III). The concentrations of DS and PS were chosen so as to obtain equal anti-thrombin and anti-factor Xa activities as in 0.05 U/ml heparin. An extra inhibitory effect of heparin over the mixture is observed in situations where free factor IXa, not bound to factor VIIIa and phospholipid, limits the rate of thrombin formation, notably in contact activated plasma. We conclude that the inactivation of free factor IXa by heparin contributes importantly to the inhibition of thrombin formation in the intrinsic system such as e.g. measured in the activated partial thromboplastin time.

Prothrombin Fragment 1+2, Thrombin- Antithrombin III-Complexes and Fibrinopeptide A in Spontaneously Clotting Whole Blood In Vitro

1994 ◽  
Vol 71 (01) ◽  
pp. 049-053 ◽  
Author(s):  
Thomas Herren ◽  
P Werner Straub ◽  
André Haeberli
Keyword(s):  
Whole Blood ◽  
Antithrombin Iii ◽  
In Vitro Studies ◽  
Healthy Controls ◽  
Fibrinopeptide A ◽  
Prothrombin Fragment ◽  
Fibrin Formation ◽  
Thrombin Formation

SummaryPrevious in vitro studies using spontaneously clotting whole blood revealed thrombin formation and high fibrinopeptide A (FPA) concentrations measured during incubation time. This occurred in spite of normal concentrations of thrombin antagonists present in the blood of the healthy subjects examined. However, there are several reports showing that in vivo increased thrombin- anti thrombin III-complex (TAT) concentrations and relatively low FPA concentrations may occur e. g. in patients with (pre)thrombotic disorders. These in vivo findings indicate more effective thrombin inhibition by antithrombin III, with almost no fibrin formation. To find an explanation for the differences observed in vitro and in vivo, we extended the in vitro studies by measuring concentrations of prothrombin fragment 1 + 2 (F1 + 2), TAT and FPA at several time points until 30 min. Our goal was to test whether thrombin at least initially is neutralized by antithrombin III, resulting in a lack of fibrin formation, either in the absence or in the presence of heparin (0.2 and 0.5 U/ml whole blood, respectively).In the absence of heparin a simultaneous increase in the concentrations of F1+2, TAT and FPA was observed. Thrombin was only partially neutralized by antithrombin III and large amounts of fibrin were formed. The addition of heparin virtually suppressed thrombin formation since the F1 + 2 concentration remained low. Moreover, the small amounts of thrombin formed were neutralized by antithrombin III to a greater extent than in the absence of heparin. Thus, in the presence of heparin less fibrin was produced as evidenced by significantly lower FPA concentrations.Experiments using blood of two patients with antithrombin III deficiency showed that fibrin formation was not different from the healthy controls in spite of the significantly higher initial F1 + 2 concentration measured. During incubation, the patients tended to form more thrombin, of which proportionally less was neutralized by antithrombin III, and more fibrin as compared to the healthy controls. Heparin addition suppressed thrombin formation less efficiently.

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