Ancrod (Arvin) on slow intravenous administration converts fibrinogen into fibrin at a rate which does not cause intravascular thrombosis. The fibrin is eliminated from the circulation and the blood is thus rendered incoagulable. To test the efficacy of ancrod in the prevention of thrombosis after prosthetic replacement of the heart valves, the tricuspid valve was replaced with a polypropylene mitral valve in 17 calves, using cardiopulmonary bypass. Five calves were eliminated from the study. Eleven calves were treated with ancrod, and one untreated calf was used as a control. Four out of five prosthetic valves in calves treated with ancrod for up to 72 hours were free of thrombus formation, and one out of three at one week. In the long-term study, fibrinogen titres rose after varying intervals, in spite of continual treatment with ancrod. This `escape9 of fibrinogen titres from the control of ancrod may be due to species resistance or to the development of immunity. Further study is in progress to elucidate this point and to gain further knowledge for the clinical application of ancrod.
Clinical observations indicated a prompt cessation of episcleral capillary bleeding after exposure of those tissues to aqueous humor during intraocular surgery. Based on this observation, both aqueous and vitreous humors were obtained from eyes provided by an eye bank and from human eyes prior to intraocular surgery. Samples of cerebrospinal fluid also were obtained from two patients, one with optic atrophy and another with nutritional amblyopia. A total of 49 specimens were studied. Aqueous humor shortened the average ear lobe puncture bleeding time from 4.74 +/- 0.2 to 1.13 +/- 0.1 minutes. Varying dilutions of aqueous humor, up to a dilution of 1:16, shortened prothrombin and partial thromboplastin times when compared with normal control plasma without aqueous. Vitreous humor shortened partial thromboplastin time but had no effect on prothrombin time. The effect of cerebrospinal fluid on prothrombin and partial thromboplastin times was similar to the aqueous, but to a lesser degree.
An Allen correction and a polychromatic analysis are about equally effective in minimizing effects of interference by bilirubin and triglyceride turbidity in the direct spectrophotometry of serum hemoglobin: interference from bilirubin is nearly eliminated, that from turbidity substantially decreased. The limit of detectability of hemoglobin is 8 mg/L in the presence of a moderate concentration of bilirubin. A change in hemoglobin concentration as small as 16 mg/L can be detected in serum having a concentration near the upper limit of the reference interval, i.e., at the medical decision level. The polychromatic formula gives concentration estimates approximately 5% greater than those of the Allen correction. The formula for the Allen correction is hemoglobin (mg/L) = 1.68 mA415 - 0.84 mA380 - 0.84 mA450 . That for the polychromatic analysis is hemoglobin (mg/L) = 1.65 mA415 - 0.93 mA380 - 0.73 mA470 .
Summary: When Arvin is administered to patients, there is a rapid fall in plasma plasminogen concentration and fibrin degradation products appear in the blood which can be detected both by their anticoagulant effect and by their reaction with anti‐fibrinogen serum. There is a minimal but inconstant increase in the concentration of plasminogen activator and circulating plasmin cannot be detected. These findings are similar to those recorded in the defibrination syndrome and are explained by the assumption that both plasminogen and activator are adsorbed onto intravascular fibrin micro‐clots. Local plasmin release would then cause lysis of fibrin with the appearance of fibrin degradation products. There is no apparent reason why this mechanism should assist in the lysis of coexisting preformed thrombi. The apparent rapid lysis of thrombi which has been observed in some patients treated with Arvin can be explained if such thrombi are not static, but represent a balance between fibrin deposition and fibrinolysis. Therapeutic defibrination, by preventing extension of the thrombus, would allow the normal fibrinolytic mechanism to produce dissolution of the thrombus.
A simple procedure has been developed for the isolation of coagulation factor VIII (F VIII) from plasma in a form which induces a monospecific antibody in rabbits. Amino acid precipitation from plasma was followed by gel filtration on Sepharose 4B and further purification was achieved by affinity chromatography on heparin-Sepharose. The material so isolated was identified by immunoelectrophoresis and lacked coagulant activity. The antiserum produced in rabbits inhibited F VIII coagulant activity and von Willebrand factor activity as measured by ristocetin platelet agglutination. The isolated IgG fraction insolubilised with CNBr-Sepharose 4B retained the ability to complex with F VIII. This complex possessed F VIII coagulant activity which could be removed in 0.6 M NaCl and dissociated in 8 M urea.
The effects of altered fibrinogen concentrations on fibrinogen synthesis in rabbits were evaluated by determining the rate of appearance of [75Se]selenomethionine (75SeM) in circulating fibrinogen. Fibrinogen levels were maintained at twice normal by infusion of homologous fibrinogen for either 1 or 6 days before the intravenous injection of 20 micronCi of 75SeM, and the rate of appearance of labeled fibrinogen was measured during the subsequent 24 h. In both groups, synthesis was unchanged. Five hours after induction of partial defibrinogenation by the infusion of bovine thrombin, fibrinogen synthesis was increased threefold. Stimulation was not attributable to decreased fibrinogen concentrations; synthesis was increased equally when levels were maintained above normal by infusion of fibrinogen before administration of thrombin. Heat-inactivated thrombin and diisopropylfluorophosphate-inactivated thrombin did not stimulate fibrinogen synthesis. Thrombin produced elevated titers of fibrinogen-fibrin degradation products (FDP-fdp). However, fibrinogen synthesis was not increased in rabbits that had received FDP-fdp from thrombin-treated donors. These data suggest that neither the fibrinogen concentration nor FDP-fdp influenced fibrinogen synthesis.
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