[The treatment of herpes zoster with hemocoagulase (Bothrops Jararaca venom)].
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Fibrinogen Zurich I is characterized by an abnormal fibrin monomer polymerization. It consists of two fractions of molecules, one with a normal aggregation and one not aggregating at all and interfering with the aggregation of the normal population. Using a radioimmunoassay for fibrinopeptide A, only approximately half of the expected fibrinopeptide A could be recovered after thrombin or Defibrase proteolysis. The defective fibrinopeptide A release could be confirmed by measurement of the N-terminal Gly/Tyr ratio. It is likely that the abnormal fibrin monomer aggregation of the abnormal fraction of fibrinogen Zurich I is due to the defective fibrinopeptide A release of this fraction.
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Various attempts have been made in the past to remove fibrinogen from plasma fractions rich in factor VIII. Present studies indicated the Defibrase, a preparation of a thrombin-like enzyme from the venom of Bothrops atrox, might be successfully employed for this purpose. Addition of Defibrase to plasma or low-purity factor VIII concentrates allows for the complete removal of fibrinogen without any apparent reduction in the activity. It was also shown that treatment with Defibrase neither decreases the stability of factor VIII nor apparently affects its antigens properties.
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To test the validity of a proposed two step fibrin assembly mechanism and directly visualize the molecular species present at various stages of fibrin formation, we have carried out an electron microscopic investigation. Assembly conditions duplicated those of a recent light scattering study and specimens were prepared at different time points with the use of a negative staining technique recently employed to visualize the trinodular structure of fibrinogen. Under near-physiological buffer conditions, protofibrils structurally similar to those postulated by Ferry have been found at early stages of fibrin assembly. In parallel with the light scattering results, a dramatic increase in fiber diameter was found in specimens prepared during the postulated lateral association stage of gelation. Light scattering and electron microscopic results both showed that high ionic strength reduces the rate and extent of fiber formation. Reptilase cleavage is shown to result in typical cross striated fibrin.
Dextran has been shown to alter the mechanical properties and lysability of fibrin. The present study was undertaken to determine whether it would also influence the ability of polymerizing fibrin to activate platelets. Human fibrinogen, with or without the presence of dextran, was incubated with either human thrombin or reptilase at 37 C. Macroscopically evident fibrils first appeared at 7 1/2 to 8 minutes in fibrinogen solution not containing dextran and at 2 1/2 to 3 minutes in solution containing dextran. Both solutions caused aggregation of washed human platelets, but the one containing dextran was less potent (P less than 0.005). Similarly, polymerizing fibrin, under the influence of dextran, was a less potent stimulator of platelet release of labeled serotonin. Scanning electron microscopy showed decreased platelet adhesion to fibrin polymerized in the presence of dextran. Inclusion of dextran in plasminogen-rich bovine fibrin clots facilitated their lysis by urokinase. Apparently, dextran not only increases the lysability of fibrin but also alters the platelet-activating activity of polymerizing fibrin.
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Circulating anticoagulants are unusual in drug-induced syndromes. We evaluated the prolonged thrombin time of plasma from a patient with a procainamide-induced syndrome. This defect was shown to be due to a circulating anticoagulant that was not of fibrin or fibrinogen origin and that prolonged thrombin and reptilase clotting times of plasma. Subclinical doses of heparin sodium induced hemorrhagic manifestations in this patient. Following cessation of heparin therapy, the circulating anticoagulant persisted but the bleeding tendency abated. All clinical and laboratory manifestations of this syndrome abated gradually following cessation of procainamide therapy.
Most techniques of clot detection do not give information about the mechanical properties of the forming clot. A procedure was developed by which the dynamic loss modulus, or mechanical impedance, of a solution of fibrinogen could be continuously monitored during clot development. This method was then applied to the analysis of purified preparations of normal fibrinogen and two dysfibrinogens. Both thrombin and reptilase were used as clotting agents, and unique tracings of clot impedance vs. time were generated for each dysfibrinogen. The functional defect was known in each case, and the clot impedance tracings were able to distinguish between abnormalities in the release of fibrinopeptides A and B. Mechanical impedance measurements were shown to complement other types of analyses now used in the characterization of dysfibrinogens. In particular, they distinguished between dysfibrinogens that appeared similar by more conventional laboratory methods.
Hemostasiologic effects of intravenous application of Reptilase were investigated in a randomized double blind study in the course of normal abdominal and vaginal hysterectomies. Coagulation factors and thrombocytes were checked before, after, 40 minutes after as well as 24 hours after the operation. Significant shortening of the clot observation time resulted 40 minutes after the injection of 1 ml Reptilase. A small but highly significant decrease of thrombocytes was observed 40 minutes after the end of the operation when Reptilase was injected. Further coagulation screening tests: Quick test, PTT and thrombin time were without statistically differences in both patients groups from the beginning till 24 hours after the operation. A significant decrease in Factor V concentrations resulted 40 minutes after the injection of Reptilase, whereas no changes were seen in the placebo patient group. Too, Factor XIII values and Antithrombin 3 concentrations decreased after the administration of Reptilase. There was no abnormal raise of fibrin-monomers in both groups. Enhanced fibrinolysis with elevated FDP-levels were measured in none of the cases. The administration of Reptilase induced a short lasting augmentation of blood coagulation but without any signs of disseminated intravascular coagulation.