Search PubMed⌕ Search

Biomedical subjects

V Ellis

Publications and source records attributed to V Ellis.

At least 73 records · Page 4Linked to original sources
PubMed1986

The influence of DDAVP infusion on the coagulation and fibrinolytic response to surgery.

The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p less than 0.005, ECLT p less than 0.0125, by Student's t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p less than 0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p less than 0.005) than control at all stages of operation and a significant shortening (5 sec p less than 0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage.

Adult↗
PubMed1986

Pentosan polysulphate: activation of heparin cofactor II or antithrombin III according to molecular weight fractionation.

The relative potency of pentosan polysulphate in activation of heparin cofactor II/thrombin interaction has been compared to heparin and dermatan sulphate and found to be within the same order. A skewed distribution of molecular weight forms was observed upon gel filtration of pentosan polysulphate with an average molecular weight of 4500 daltons. Two peaks of activity were observed in activation of heparin cofactor II. The greatest activity was observed in high molecular weight fractions (5-fold greater than that of average molecular weight) and a concentration-dependent profile indicated a template mechanism of action. A lower peak of activity was observed at average molecular weight and the effect of increasing concentrations of this material on activity indicated a mechanism involving binding to proteinase inhibitor or proteinase alone. Potentiation of antithrombin III/thrombin interaction was observed only in fractions greater than the average molecular weight. Concentration-dependent profiles indicated binding to antithrombin III and thrombin was a requisite of activation. A fraction of low molecular weight showed no property of activation of antithrombin III or heparin cofactor II/thrombin interaction. Three fractions of high, average and low molecular weights tested in clotting assays showed relative potencies corresponding to those observed in the purified systems.

Antithrombin III↗
PubMed1986

The acceleration of the inhibition of platelet prothrombinase complex by heparin.

The influence of heparin on the inhibition of factor Xa has been studied under conditions where factor Xa is bound to collagen-thrombin-stimulated platelets to form the prothrombinase complex. Unfractionated heparin was found to cause a concentration-dependent acceleration of the inhibition of the platelet prothrombinase complex up to a maximum rate constant of 4.1 X 10(7) M-1 X min-1 at heparin concentrations of 0.2 microM and above. This is equivalent to a 4800-fold acceleration over the rate constant for the inhibition in the absence of heparin, and is 6.8-fold lower than the rate constant for the inhibition of uncomplexed factor Xa in the presence of saturating concentrations of heparin which was determined as 2.8 X 10(8) M-1 X min-1. The effects of three Mr fractions of heparin were also studied. These were a gel-filtered heparin of Mr 15000, a gel-filtered heparin of Mr 6000 and a heparin oligosaccharide (primarily 8-10 monosaccharide units) prepared by nitrous acid depolymerization, each with high affinity for antithrombin III. These fractions all accelerated the rate of the antithrombin III inhibition of the platelet prothrombinase complex, with maximum rate constants of 6.8 X 10(7), 1.4 X 10(7) and 9.8 X 10(6) M-1 X min-1, respectively. On comparison with the effect of these heparin fractions on the rate of inhibition of uncomplexed factor Xa a progressively increasing disparity between the rate of inhibition of uncomplexed and complexed factor Xa was observed, rising from 1.7-fold with the oligosaccharide to 6.8-fold with the unfractionated heparin. A possible mechanism for this differential activity between uncomplexed and complexed factor Xa with the various heparin fractions is discussed in terms of an involvement of heparin binding to factor Xa.

Antithrombin III↗
PubMed1985

Mechanisms of inhibition of platelet coagulant activity.

The plasma proteinase inhibitors are relatively ineffective in the inhibition of the activity of the platelet prothrombinase complex, due to the low rates of inhibition, and possibly due to the indirect protection from the potentiating effect of the vascular endothelium. The plasma proteinase inhibitors are more effective at inhibiting thrombin, thereby preventing the feedback activation of platelets and factor V and subsequent prothrombinase complex development. This may constitute a mechanism for the control of the development of the prothrombinase complex on the platelet surface. The protein C-thrombomodulin mechanism for the destruction of factor Va activity probably constitutes a major inhibitory mechanism for the prothrombinase complex in vivo.

Animals↗
PubMed1984

Inhibition of prothrombinase complex by plasma proteinase inhibitors.

The rate of inactivation of human coagulation factor Xa by the plasma proteinase inhibitors antithrombin III and alpha 1-antitrypsin has been studied in the presence of the accessory components which constitute the prothrombinase complex. The rate of inactivation of factor Xa by antithrombin III was found to be decreased in the presence of phospholipid vesicles with high affinity for factor Xa. The second-order rate constant for the reaction fell from 6.21 X 10(4) to 3.40 X 10(4) M-1 min-1 in the presence of 20 microM phospholipid. Purified factor Va had no effect on the rate of inactivation of factor Xa in the absence of phospholipid. In the presence of phospholipid, factor Va increased the protective effect displayed by phospholipid, further reducing the rate constant to 2.20 X 10(4) M-1 min-1. The rate of inactivation of factor Xa by alpha 1-antitrypsin was unaffected under these conditions. Platelet-bound prothrombinase complex was formed by incubation of factor Xa with washed human platelets activated by a mixture of collagen and thrombin. The prothrombinase activity was inhibited by antithrombin III was a second-order rate constant of 0.85 X 10(4) M-1 min-1. This rate was obtained in both the presence and absence of exogenous factor Va. Platelet factor 3 vesicles, isolated from platelet aggregation supernatants, also formed prothrombinase complex in the presence of factor Va, and this was inhibited by antithrombin III at the same rate as the platelet-bound complex. There was no protection of the platelet-bound prothrombinase complex from inhibition by alpha 1-antitrypsin.

Animals↗
PubMed1984

[Respite care].

Explore the source record for details and available documents.

Family↗
PubMed1983

The effect of divalent metal cations on the inhibition of human coagulation factor Xa by plasma proteinase inhibitors.

The inactivation of human coagulation factor Xa by the plasma proteinase inhibitors alpha 1-antitrypsin, antithrombin III and alpha 2-macroglobulin in purified systems was found to be accelerated by the divalent cations Ca2+, Mn2+ and Mg2+. The rate constant for the inhibition of factor Xa by antithrombin III rose from 2.62 X 10(4) M-1 X min-1 in the absence of divalent cations to a maximum of 6.40 X 10(4) M-1 X min-1 at 5 mM Ca2+, 8.10 X 10(4) M-1 X min-1 at 5 mM Mn2+, with a slight decrease in rate at higher cation concentrations. Mg2+ caused a gradual rise in rate constant to 5.65 X 10(4) M-1 X min-1 at 20 mM. The rate constant for the inhibition of factor Xa by alpha 1-antitrypsin in the absence of divalent cations was 5.80 X 10(3) M-1 X min-1. Ca2+ increased the rate to 1.50 X 10(4) M-1 X min-1 at 5 mM and Mn2+ to 2.40 X 10(4) M-1 X min-1 at 6 mM. The rate constant for these cations again decreased at higher concentrations. Mg2+ caused a gradual rise in rate constant to 1.08 X 10(4) M-1 X min-1 at 10 mM. The rate constant for the factor Xa-alpha 2-macroglobulin reaction was raised from 6.70 X 10(3) M-1 X min-1 in the absence of divalent cations to a maximum of 4.15 X 10(4) M-1 X min-1 at 4 mM Ca2+, with a decrease to 3.05 X 10(4) M-1 at 10 mM. These increases in reaction rate were correlated to the binding of divalent cations to factor Xa by studying changes in the intrinsic fluorescence and dimerization of factor Xa. The changes in fluorescence suggested a conformational change in factor Xa which may be responsible for the increased rate of reaction, whilst the decrease in rate constant at higher concentrations of Ca2+ and Mn2+ may be due to factor Xa dimerization.

Calcium↗
PubMed1983

Anticoagulant and antiheparin activities of a pentosan polysulphate.

Pentosan polysulphate (PPS, Hemoclar, MW 6,700) was observed to have a low affinity for ATIII-Sepharose eluting at 0.3M NaCl. Tested in vitro it had, as previously reported, a low potency as an anticoagulant, about 10 times less than heparin on a weight for weight basis. Only the KCCT was affected by low concentrations of PPS unlike heparin by which both thrombin time and KCCT were affected. Upon injection of PPS subcutaneously (50mg) the heparin activity measured by chromogenic anti factor Xa and by KCCT was in the ratio of 2:1. When injected intravenously (40mg) into 3 healthy volunteers a significant prolongation of a modified prothrombin time was observed in 2 subjects. When PPS was added to heparin containing plasma it was observed to completely inhibit heparin at low concentrations (2:1 on a weight to weight basis) when measured in the thrombin and prothrombin time but not in the KCCT. The antiheparin effect of PPS was also observed in a purified system in obviating the heparin potentiation of the rate of inhibition of thrombin by antithrombin III. Observations showed that at higher concentrations of PPS it acted by directly inhibiting thrombin without the intervention of antithrombin III but also to potentiate the rate of fibrin monomer polymerization.

Anticoagulants↗
PubMed1983

Platelet activation during steady state sickle cell disease.

Previous reports have given conflicting conclusions of the role platelets may play in initiating vaso-occlusive sickle cell crisis. Seven patients homozygous for sickle cell hemoglobin, and seven age, race and sex matched controls were each studied on at least two occasions in a six week period of normal health. The number of platelets circulating as aggregates, the plasma concentration of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were significantly elevated compared with controls. These findings were confirmed with a second series of fourteen patients and nine controls. Patient's platelets in plasma adjusted for both platelet number and citrate concentration aggregated more in response to low concentrations (0.4 and 1 microM) but less to higher concentrations (4 and 20 microM) of ADP and needed significantly more prostacyclin (PGI2) to inhibit ADP induced aggregation than did platelets from control subjects. There was no significant difference in plasma concentration of fibrinopeptide A and thromboxane (Tx)B2, nor in the platelet generation of TxB2 and release of serotonin and beta TG induced by aggregating agents. Thus, the platelets of patients with sickle cell anemia in the steady state are readily activated and respond in vivo by increased formation of aggregates and release of beta TG and PF-4.

Adenosine Diphosphate↗
PubMed1982

Inhibition of human factor Xa by various plasma protease inhibitors.

The inhibitory effects of the plasma protease inhibitors antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin on the activity of human factor Xa have been studied using purified proteins. The rate of inhibition was determined by measuring the residual factor Xa activity at timed intervals utilizing the synthetic peptide susbtrate Bz-Ile-Glu(piperidyl)-Gly-Arg-pNA. Kinetic analysis with varying molar concentrations of inhibitors demonstrated that the inhibition of factor Xa by antithromin III, alpha 2-macroglobulin and alpha 1-antitrypsin followed second-order kinetics. Calculated values of the rate constants for the inhibition of factor Xa by antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin were 5.8 . 10(4), 4.00 . 10(4) and 1.36 . 10(4) M -1 . min -1, respectively. The plasma concentrations of the inhibitors can be used to assess their potential relative effectiveness against factor Xa. In plasma this was found as alpha 1-antitrypsin greater than antithrombin III greater than alpha 2-macroglobulin in the ratio 4.64: 2.08: 1.0. Cephalin was shown to inhibit the rate of reaction between factor Xa and antithrombin III.

Antithrombin III↗
PubMed1982

An acquired coagulation inhibitor to factor II.

An elderly woman with a bleeding problem associated with prolonged PTT, PT and thrombin time but with normal snake venom time was found to have very high levels of plasma antithrombin. The antithrombin activity was isolated and characterized and found to be an IgG which directly inhibited thrombin and also precipitated prothrombin. The concentration in plasma of the gamma-globulin inhibitory activity was equivalent per ml to 80 NIH units of thrombin. Corticosteroid and immunosuppressive treatment reduced the level of the inhibitor with remission of bleeding symptoms.

Aged↗