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C Kluft

Publications and source records attributed to C Kluft.

At least 253 records · Page 14Linked to original sources
PubMed1984

The molecular form of alpha 2-antiplasmin with affinity for plasminogen is selectively bound to fibrin by factor XIII.

Two molecular forms of alpha 2-antiplasmin (PB = plasminogen-binding; NPB = non-PB) exist. We have studied the extent of binding of these two forms to fibrin by factor XIII. A modified crossed immunoelectrophoresis technique which separately determines both forms showed that, compared with plasma, the PB-form is reduced by 31 +/- 11% (SD) in serum of twelve individuals and the NPB form by only 6%. Laurell assay showed a reduction of 18 +/- 9% (n = 12) in total alpha 2-antiplasmin antigen (PB + NPB) in serum; the immediate plasmin inhibition test (mainly recording the PB-form) revealed 35 +/- 6% (n = 12) reduction in inhibition. Coagulation of blood, platelet-rich and platelet-poor plasma yielded comparable results. No decrease in alpha 2-antiplasmin or change in its composition was observed when factor XIII-deficient plasma was clotted. Fibrin binding was not significantly different from normal in either plasminogen-depleted or plasminogen-enriched plasma. It is concluded that the PB-form of alpha 2-antiplasmin becomes selectively bound to fibrin.

Binding Sites↗
PubMed1984

Protein C, an anticoagulant protein, is increased in healthy volunteers and surgical patients after treatment with stanozolol.

On both oral and intramuscular administration, the anabolic steroid stanozolol was found to increase protein C antigen concentrations in circulating blood. In fourteen healthy young volunteers (who received stanozolol orally, dose 10 mg/day) the average increase was 1.5-1.6 times the normal concentrations after 3-6 weeks' treatment and was accompanied by more moderate increases in the other vitamin K-dependent factors II, IX and X to 1.4, 1.4 and 1.2 times their normal concentration respectively. However, there was no change in factor VII. In sixteen elderly surgical patients, intramuscular injection (50 mg) one day prior to surgery induced a moderate increase within 24 hours (to 1.11 times the pretreatment concentration) and seven days after operation (to 1.19 times), and reduced the postoperative fall in protein C. Stanozolol administration seems to be a promising pharmacological method for increasing anticoagulant protein C levels in congenital and acquired deficiencies.

Adult↗
PubMed1984

Acute effect of smoking on fibrinolysis: increase in the activity level of circulating extrinsic (tissue-type) plasminogen activator.

The acute effect of cigarette smoking on the fibrinolytic enzyme system in blood was studied. It was found imperative to have an initial 30 min rest period, after venipuncture, to obtain a stable baseline in the fibrinolytic studies. The average heart rate, in inhaling smokers, increased from 64 to a peak of 79 beats min-1, 5-10 min after commencement of smoking. A peak in fibrinolytic activity was found to occur later, at 22.5 min. Analysis of the increase in fibrinolytic activity revealed no demonstrable activation of intrinsic systems via factor XII, nor changes in plasminogen, prekallikrein and C1-inactivator. No plasmin-alpha 2-antiplasmin complexes were detectable. The increase (P less than 0.01) was found to be due to extrinsic (tissue-type) plasminogen activator, revealed as C1-inactivator-resistant plasminogen activator activity, and further identified by quenching with anti-tissue plasminogen activator IgG. Thus, smoking appears to elicit a significant increase in the level of activity of circulating extrinsic plasminogen activator.

Adult↗
PubMed1984

Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator.

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.

Cardiopulmonary Bypass↗
PubMed1984

Effect of exercise and oral contraceptive agents on fibrinolytic potential in trained females.

It has been shown that physical exercise increases blood fibrinolytic potential, primarily by inducing a release of extrinsic plasminogen activator from the vessel wall. Synthetic estrogens have also been reported to influence fibrinolytic activity. The effect of exercise and the possible additional effect of oral contraceptive agents (OCA) on the fibronolytic system were studied in 20 competitive female rowers. Ten females used OCA (users), and 10 others did not (nonusers). All participants were subjected to standardized exhaustive exercise. Preexercise data revealed higher factor XII, total plasminogen, and free plasminogen levels together with a significantly lower C1-inactivator level in the group of users. No differences were observed in prekallikrein, high-molecular-weight kininogen, alpha 2-antiplasmin, alpha 2-macroglobulin, antithrombin III, and histidine-rich glycoprotein plasma levels. The factor XII-dependent fibrinolytic activator activity and the extrinsic (tissue-type) plasminogen activator were significantly higher; however, the urokinase-like fibrinolytic activator activity was significantly lower. These observations suggest a greater susceptibility to activation of the fibrinolytic pathways during OCA medication. Exercise resulted in a decrease of all factors under study but an increase in all fibrinolytic activities. No differences were observed between the two groups in the percentages of change that occurred with exercise.

Adult↗
PubMed1984

Intrinsic plasma fibrinolysis: involvement of urokinase-related activity in the factor XII-independent plasminogen proactivator pathway.

A portion of human blood fibrinolytic activity can be quenched by antibodies to urokinase. We attempted to identify this portion and its position in the three pathways (extrinsic, intrinsic factor XII dependent, and intrinsic factor XII independent) of plasminogen activator activity that have been defined in the DEFs of plasma. Activity quenching in various plasmas (including plasma adsorbed by agarose-bound AUK) demonstrated the involvement of a discrete activator activity of 40 to 50 BAU/ml with little variation among individuals (43 +/- 6 (SD) BAU/ml, n = 13). The quenching did not involve, quantitatively or qualitatively, the extrinsic (tissue-type) plasminogen activator activity varying between 1 and 146 BAU/ml in baseline plasma and in plasma obtained after stimulation by venous occlusion, exercise, or DDAVP administration. In confirmation, extrinsic activator activity was recovered in plasma adsorbed by agarose-bound AUK. The quenching also did not involve the factor XII-dependent activities; it was quantitatively normal in plasma with Hageman (n = 3) and Fletcher (n = 2) traits, and AUK did not interfere with the generation of factor XII-dependent fibrinolytic activity by addition of purified activated factor XII in plasma with Hageman trait. There was no effect of AUK on kallikrein generation, kallikrein activities, or the APPT, nor were these aspects altered in depleted plasma. In conclusion, the quenching involved the factor XII-independent system of intrinsic fibrinolysis. Addition of purified urinary urokinase did not result in restoration of missing activity in plasma adsorbed by AUK-agarose. The quenching, therefore, probably involved an apparent urokinase-related activator component in plasma.

Dextran Sulfate↗
PubMed1984

The influence of L-asparaginase therapy on the fibrinolytic system.

Fibrinolytic factors were assessed during L-asparaginase administration, to study whether their changes may predispose to a haemorrhagic or thrombotic diathesis. The total level of alpha 2-antiplasmin declined, as well as the ratio of the plasminogen-binding form of alpha 2-antiplasmin to the non-plasminogen-binding form. After cessation of L-asparaginase administration, the ratio increased to 1.6 times that of the pretreatment value. These data indicate that the plasminogen-binding form of alpha 2-antiplasmin is the form primarily synthesized in vivo. L-Asparaginase therapy reduced plasma levels of plasminogen and histidine-rich glycoprotein ( HRG ) and influenced the equilibrium between HRG , plasminogen and HRG -plasminogen complex, with a more pronounced decrease of plasminogen (62% +/- 8) and HRG (76% +/- 11) in comparison to the free-plasminogen levels (51% +/- 6). alpha 2-Macroglobulin was only slightly influenced by L-asparaginase and may consequently play a more pronounced role in inhibition. This is suggested by moderate declines in functional tests of plasmin, urokinase and tissue activator inhibition by patients plasma, and by the ratio of inhibition of these enzymes over alpha 2-antiplasmin. Thus the bleeding tendency described during L-asparaginase therapy can be ascribed not only to a temporary deficiency of coagulation factors but also to temporary alpha 2-antiplasmin deficiency.

Adolescent↗
PubMed1983

Behaviour and quantitation of extrinsic (tissue-type) plasminogen activator in human blood.

Functional assay of extrinsic (tissue-type) plasminogen activator (EPA) in plasma on fibrin plates was evaluated. Using specific quenching antibodies, we demonstrated the method to be specific for EPA under all conditions tested. Contributions of urokinases and intrinsic activators were excluded. The quantity of EPA in blood samples, as compared with purified uterine tissue activator, shows 1 blood activator unit (BAU) to be comparable to 0.93 ng. The median values for EPA activity for healthy volunteers were: baseline, 1.9 BAU/ml (n = 123); diurnal, 5.5 BAU/ml (n = 12); DDAVP administration, 11.7 BAU/ml (n = 39); exhaustive exercise, 25 BAU/ml (n = 24); venous occlusion (15 min), 35 BAU/ml (n = 61). A large inter-individual variation in EPA activity was found, while individual baseline values tended to be constant for periods of weeks. In vitro in blood EPA activity shows a disappearance of 50% in about 90 min at 37 degrees C; EPA activity in euglobulin fractions is stable for less than or equal to 2 hr at 37 degrees C. A rapid decrease in EPA activity occurs in vivo, as noted after extracorporal circulation and exercise stimulation (t1/2 decay, 2-5 min).

Adult↗
PubMed1983

Hydrogels by irradiation of a synthetic heparinoid polyelectrolyte.

Gamma irradiation of aqueous solutions of a synthetic heparinoid polyelectrolyte results in the formation of hydrogels, varying in water content and mechanical strength. The equilibrium water content and the mechanical strength of the hydrogels are dependent on the initial polyelectrolyte concentration, the molecular weight of the polyelectrolyte, the percentage of double bonds in the polyelectrolyte and the radiation dose. The polyelectrolyte hydrogels do not deplete Antithrombin III from blood and there is no activation of factor XII according to an in vitro kallikrein generation test. However, in a very sensitive test for factor XII activation (contact promoted shortening of the thrombotest) a slight activation of this factor was observed.

Biocompatible Materials↗
PubMed1982

The suitability of various plasmin preparations for the functional assay of alpha 2-antiplasmin in plasma.

Various plasmin preparations were tested for their suitability for use in the assay of alpha 2-antiplasmin in blood plasma by the immediate plasmin inhibition test. Activation of plasminogen, viz., 1-Glu-plasminogen and/or 77-Lys-plasminogen, by immobilized urokinase results in plasmin preparations suitable for this alpha 2-antiplasmin test. Plasmins obtained by "spontaneous" activation procedures in glycerol containing solutions, however, appeared not to be suitable. In this second group, the behaviour of the plasmins resembles that of 442-Val-plasmin (miniplasmin), which is known to show a low inactivation rate with alpha 2-antiplasmin due to the absence of lysine-binding sites in the plasmin molecule. Evidence is presented that, in the nonsuitable plasmins, the lysine-binding sites, although not completely absent, have at least partly lost their functional integrity.

Blood Coagulation Tests↗
PubMed1982

A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma.

An indirect spectrophotometric assay for extrinsic plasminogen activator has been devised, which is based on the parabolic assay of Drapier et al. (5). The system contains activator, plasminogen, the synthetic plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251, Kabi) and a mixture of soluble fibrinogen fragments prepared by treatment of fibrinogen with cyanogen bromide. The addition of these fibrinogen fragments considerably enhances the sensitivity and specificity of the method owing to specific stimulation of the plasminogen activation by extrinsic plasminogen activator. The assay conditions were optimized and the application for extrinsic plasminogen activator measurements in plasma euglobulin fractions is demonstrated.

Fibrin↗
PubMed1982

Decreased levels of histidine-rich glycoprotein (HRG) and increased levels of free plasminogen in women on oral contraceptives low in estrogen.

Determinations by immunologic methods of histidine-rich glycoprotein (HRG) and plasminogen, were made in plasma samples collected during one normal or hormone induced cycle in 15 young, normal women and in 11 women using oral contraceptives with 30 micrograms ethinyl estradiol and 150 micrograms levo-norgestrel. The hormone group showed an increase in plasminogen level to about 150% of normal, while the concentration of HRG was decreased to about 75% of normal. This resulted in a considerable relative increase in the concentration of free plasminogen in the hormone group (calculated from the equilibrium: HRG . plasminogen in equilibrium HRG + plasminogen, using KD = 1.0 microM), representing a doubling of that in the normal group. Hence, more plasminogen is available for binding to fibrin and activation in the hormone group.

Adult↗