Rapid increase of fibrinolytic activity in pig and rat after exclusion of the liver from the circulation and its control by various organs.

Liver-bypass in the pig and the rat instantly results in a marked increase of fibrinolytic activity. Within 1--2 hours this increase is followed in rats by a normalization. A new increase can be obtained by intravenous Carbachol injection. Removal of organs results to various degrees -- most pronounced after bilateral nephrectomy -- in reduction of control value of fibrinolytic activity before liver-bypass. In rats with adrenalectomy plus splenectomy there is no normalization of liver-bypass-induced increased fibrinolytic activity.

The powerful urinary procoagulant and its relation to renal diseases.

Human urine and urine of various animals contains a powerful procoagulant which converts prothrombin in presence of factors V, VII, X, and phospholipids or thrombocytes into thrombin. In human beings its content of the urine is markedly reduced or totally absent in kidney diseases, but normal in hemophilic patients. Only 0.2 ml urine are required for its assessment. In experimental kidney diseases in rabbits and rats there is an inverse relationship between procoagulant and protein excretion. In the test tube 1 part of urine corrects the clotting of 5-10 parts of hemophilic plasma, even in the presence of very strong coagulation inhibitors.

[On the normalization of the content of human urine of procoagulant after renal transplantation (author's transl)]. / Uber die Normalisierung des Gehaltes menschlichen Urins an Prokoagulans nach Nierenübertragung.

With human urine a very active procoagulant is excreted which converts prothrombin into thrombin in the presence of factor V, phospholipids and calcium chloride. In kidney diseases, its excretion is considerably reduced or totally absent. A negative correlation exists between these diseases and protein excretion. Kidney transplantation results in a normalization, however showing a trend which is not always parallel with the normalization of the blood creatinine levels. During the post-transplantation period, an occasional temporary, but very clear reduction with abnormal values of the kidney function tests can be observed. It is presumed that the procoagulant excretion could represent a hitherto unexplored function of the tubuli.

Structure-activity relationship in synthetic fibrinolytics. 2-Phenethynylcyclopropanecarboxylates.

The fibrinolytic activity of nine 2-phenethynylcyclopropanecarboxylates was measured in the hanging clot test. The structure-activity relationship is given by log 1/C equals 0.54 log P + 2.01 where P is the octanol-water partition coefficient of the carboxylate ion pair and C is the molar concentration of the drug. The equation obtained for the cyclopropanecarboxylates is compared with similar equations for benzoates, salicylates, and N-phenylanthranilates.

Conjugated estrogens and hypercoagulability.

A group of 11 menopausal women receiving 1.25 mg. of conjugated estrogens daily had coagulation tests to determine the development of hypercoagulability after taking 5 and 21 tablets. There was no essential change in thrombin generation or fibrinolytic activity as measured by euglobin lysis time. There was a shift toward hypercoagulability in all three parameters of the thrombelastograms. The decrease of the antithrombin III activity was not as pronounced following the administration of conjugated estrogens as had been the change associated with oral contraceptives. Fibrin monomers were observed in some women during the first week of Premarin therapy.

In vitro inhibition of aggregation of human erythrocytes by synthetic fibrinolytic compounds.

It has been shown that a variety of synthetic organic anions which induce fibrinolytic activity in human plasma in vitro and which in addition inhibit collagen-induced aggregation of human platelets, also exert to various degrees an inhibition of dextran, fibrinogen and gelatin induced aggregation of human erythrocytes and of the pathologically accelerated erythrocyte sedimentation rate. Since increased erythrocyte aggregation is contributing to thrombogenesis, ability to prevent erythrocyte aggregation is a desirable feature for synthetic antithrombotic compounds. They should exert three actions: induce fibrinolytic activity, prevent platelet aggregation, and inhibit erythrocyte aggregation. This communication refers to prototypes of such compounds.

The impedance machine: a new bedside coagulation recording device.

A new continuously recording bedside coagulation screening device is described. The instrument, called an empedance machine, functions by measuring the changing mechanical impedance exerted on a minutely vibrating probe by the progressing fibrin formation of the specimen to be analyzed. The impedance machine works with 0.04-0.4 ml both of whole blood or plasma. During the recordings, the clotting process can be observed in the specimens which are transilluminated. The rugged machine is extremely simple to handle. The two parts which come in contact with blood are disposable. Various examples (recordings) for clinical and experimental applicaton are given and discussed.