RESUMEN
We investigated the effect on thrombin generation in plasma of the pentasaccharide that represent the AT III/binding site in heparin. This compound has no effect on the breakdown of thrombin in plasma. It dose-dependently inhibits the formation of thrombin in both the intrinsic and the extrinsic pathway. If coagulation is triggered by the complete prothrombinase complex (phospholipid--factor Va--factor Xa) under conditions in which the large majority of factor Xa is bound to the complex, the inhibition of prothrombinase activity is only minor. If no factor Va is present or if the prothrombinase activity is triggered by adding complete tenase (PL-FVIIIa-FIXa) or incomplete tenase (PL-FIXa) to the plasma the inhibition by pentasaccharide is of the same magnitude as that in the intrinsic or extrinsic system. We conclude that the pentasaccharide inhibits blood coagulation by catalysing the inactivation of free factor Xa. In contrast to classical heparin it does inhibit the peak of thrombin formation in platelet rich plasma, probably because it is less subject to inactivation by heparin binding proteins from platelets than classical heparin is.
Asunto(s)
Oligosacáridos/farmacología , Trombina/sangre , Activación Enzimática/efectos de los fármacos , Humanos , Oligosacáridos/síntesis química , Tiempo de Trombina , Tromboplastina/aislamiento & purificaciónRESUMEN
We evaluated a recently developed commercial assay for quantifying thrombin-antithrombin III (TAT) complexes in human plasma. The assay is precise (within-assay CV less than 10%, between-assay CV less than 13%), and sensitive (detection limit 0.7 micrograms of TAT per liter of plasma). Measurements for healthy volunteers yielded a normal reference (95 percentile) interval of 0.8 to 5.0 micrograms/L (n = 50, mean 2.1 micrograms/L, range 1.1 to 7.5 micrograms/L). TAT concentrations were increased in 25 of the 41 patients who fulfilled the clinical criteria of disseminated intravascular coagulation (DIC, overall mean 15.8 micrograms/L) and in 30 of the 35 patients with deep-vein thrombosis of the leg (overall mean 9.4 micrograms/L). We assessed the accuracy of the TAT assay by comparison with established criteria for the laboratory diagnosis of DIC involving various cutoff values for antithrombin III, factor V, fibrinogen, platelet count, fibrin/fibrinogen degradation products, and activated partial thromboplastin time. The low specificity of the TAT assay with regard to some of these criteria indicates that the latter are probably insensitive.
Asunto(s)
Antitrombina III/sangre , Trombina/sangre , Coagulación Intravascular Diseminada/sangre , Humanos , Métodos , Flebitis/sangreRESUMEN
In this study, we successfully performed local thrombolysis in 6 patients with peripheral arterial occlusions by using a novel high-molecular-weight urokinase. Mean duration of recanalization was 12.8 hours, mean fibrinogen consumption was relatively low (42%), reptilase time was relatively long (mean increase by 47%). These findings would suggest that the substance is highly effective, though systemic adverse reactions are mild.
Asunto(s)
Fibrinolíticos/uso terapéutico , Trombosis/tratamiento farmacológico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Batroxobina , Estabilidad de Medicamentos , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Peso Molecular , Trombina/sangreRESUMEN
Heparan with a low affinity for antithrombin III has previously been demonstrated to inhibit thrombin generation in both normal plasma and plasma depleted of antithrombin III. In addition, standard heparin and heparin with a low affinity for antithrombin III have been demonstrated to have equivalent inhibitory actions on thrombin generation in plasma depleted of antithrombin III. These observations prompted the investigation of the effects of four normal vessel wall glycosaminoglycans (heparan sulfate, dermatan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate) on the intrinsic pathway generation of thrombin and factor Xa and on the inactivation of thrombin and factor Xa in plasma. Heparan sulfate inhibited thrombin generation and accelerated the inactivation of added thrombin and factor Xa in normal plasma but not in antithrombin III-depleted plasma. In contrast, dermatan sulfate inhibited thrombin generation in both normal and antithrombin III-depleted plasma. In addition, heparan sulfate was an effective inhibitor of factor Xa generation, while dermatan sulfate was not. Neither chondroitin-4-sulfate nor chondroitin-6-sulfate inhibited the generation of thrombin or factor Xa nor did they accelerate the inactivation of factor Xa or thrombin by plasma. These results suggest that heparan sulfate acts primarily by potentiating antithrombin III, while dermatan sulfate acts by potentiating heparin cofactor II. The inhibition of thrombin generation by heparan sulfate and dermatan sulfate thus appears to occur by complementary pathways, both of which may contribute to the anticoagulation of blood in vivo.