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A M Fischer

Publications and source records attributed to A M Fischer.

80 records · Page 5Linked to original sources
PubMed1982

A comparison of pentosan polysulphate (SP54) and heparin. I: Mechanism of action on blood coagulation.

The effects of SP54 on inhibition of thrombin, factor Xa and factor IXa, in the presence and absence of antithrombin III (At III), have been examined and compared to those of heparin. SP54 potentiated inhibition of thrombin and Xa by purified At III, but crossed immunoelectrophoresis data indicated that these effects were mediated by binding to the enzyme, rather than to At III. Relatively high concentrations of SP54 were required for inhibition of thrombin and Xa in plasma, but at concentrations less than 2 micrograms/ml there was a marked suppression of the intrinsic activation of factor X. This effect was shown to be independent of At III, and to be due largely to inhibition of factor IXa. Prothrombin activation by factor Xa and phospholipid was also suppressed by SP54 in the absence of At III, and its effect on the APTT was also shown to be independent of At III. It is concluded that a relatively low concentrations the anticoagulant actions of SP54 are mainly due to these At III-independent pathways.

Animals↗
PubMed1982

A comparison of pentosan polysulphate and heparin. II: Effects of subcutaneous injection.

A comparison has been made between the effects of pentosan polysulphate (SP54) and mucosal heparin following subcutaneous injection in man. Unlike heparin, pentosan polysulphate has relatively little effect in vivo as measured by anti-factor Xa clotting assay and none by an anti-Xa amidolytic assay (S-2222). However, pentosan polysulphate is at least as potent as heparin on a weight basis in producing activation of lipoprotein lipase, shortening of the euglobulin clot lysis time and impairing the generation of factor Xa. Our data indicate that pentosan polysulphate has more marked effects in vivo than in vitro, that the action of the drug on clotting is mediated mainly via an At III-independent pathway, and that its effects are not confined to the coagulation system.

Blood Coagulation↗
PubMed1982

[Prevention of thrombosis by Hemoclar. Preliminary results of a test in a patient with antithrombin III deficiency].

We report here preliminary results of a study comparing the effect of Hemoclar and antithrombin III (AT III) in a patient with an AT III congenital deficiency. Both drugs inhibit thrombin generation in the patient's plasma. Unlike AT III, Hemoclar also inhibits factor Xa generation. This led us to propose the use of Hemoclar, which acts via an AT III independent pathway, to prevent thrombosis in A III deficient patients.

Adult↗
PubMed1981

Respective roles of antithrombin III and alpha 2 macroglobulin in thrombin inactivation.

In order to investigate the mechanism of thrombin inactivation in the presence of both antithrombin III (AT III) and alpha 2-macroglobulin (alpha 2 M), thrombin and the inhibitors have been purified from human material and thrombin inactivation studied using purified reagents either alone or added to defibrinated plasma. Comparison of clotting and amidolytic activities of residual thrombin allowed to measure the amount of thrombin bound to alpha 2 M. In a purified reagent system as well as in plasma, part of exogenous thrombin is bound to alpha 2 M. The amount of bound thrombin is related to alpha 2 M concentration. Conversely, previous plasma alpha 2 M depletion by immunoabsorption increases the consumption of heparin-cofactor activity by exogenous thrombi. Thus AT III and alpha 2 M compete for thrombin inactivation. This finding could be of practical interest in clinical situations associating high plasma alpha 2 M levels and a decrease of AT III concentrations.

Antithrombin III↗
PubMed1979

[Heparin inhibition of the antithrombin activity of alpha-2-macroglobulin].

The interaction between thrombin and alpha-2-macroglobulin was studied on human purified materials, either in the presence or in the absence of heparin, by kinetic analysis of thrombin inhibition and polyacrylamide gel electrophoresis. In the absence of heparin, binding of thrombin to alpha-2-macroglobulin, shown by electrophoresis, leads to the loss of the coagulant property of the enzyme. In the presence of heparin the rate of inhibition of thrombin clotting activity by alpha-2-macroglobulin is strongly decreased. Heparin binds to thrombin, impairing the formation of thrombin-alpha-2-macroglobulin complex. These data show that heparin paradoxically protects thrombin from inhibition by alpha-2-macroglobulin whereas it increases the enzyme inhibition by antithrombin III. Such a phenomenon could be of practical interest for treatment of thrombosis in patients with high plasma level of alpha-2-macroglobulin and low level of antithrombin III, such as occurs in the nephrotic syndrome.

Heparin↗