Aminocaproic acid in the control of haemorrhage after prostatectomy. Safety of aminocaproic acid--a controlled trial.
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Aged↗
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Incidence of thrombosis associated with epsilon-aminocaproic acid administration and with combined epsilon-aminocaproic acid and subcutaneous heparin therapy. II. A clinical study with the aid of intravenous phlebography.
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Aminocaproates↗
[The influence of fibrinolysis inhibitors on the effect of bioactive substances on the guinea pig ileum. Studies on the problem of the effect of epsilon-aminocaproic acid, acetyl-epsilon-aminocaproic acid and p-aminomethylbenzoic acid].
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Acetylcholine↗
Topically applied aminocaproic acid concentrates in the aqueous humor of the rabbit in therapeutic levels.
Systemically administered aminocaproic acid, used to reduce the incidence of secondary hemorrhage in traumatic hyphema, has been shown to accumulate in the aqueous humor of rabbits in a dose-dependent manner. Eight topical preparations of aminocaproic acid were studied to determine aqueous humor concentrations. The vehicles studied included the following: sodium chloride, 0.85 g/dL; polyvinyl alcohol, 1.4 g/dL; hydroxypropyl methylcellulose, 0.4 g/dL; benzalkonium chloride, 0.01 g/dL; ethylenediamine tetraacetic acid disodium, 0.01 g/dL; dimethyl sulfoxide, 11 and 39.6 g/dL; and carboxypolymethylene, 4 g/dL. All contained 735 g/L of aminocaproic acid except for dimethyl sulfoxide (39.6 g/dL) and carboxypolymethylene (4 g/dL), which contained 238 and 600 g/L of aminocaproic acid, respectively. Aqueous humor and plasma samples were assayed for aminocaproic acid content following topical administration. Aqueous humor concentrations of aminocaproic acid ranged from undetectable (less than 0.01 mg/dL) to 5.75 mg/dL. Plasma concentrations ranged from undetectable (less than 0.01 mg/dL) to 9.85 mg/dL. Polyvinyl alcohol (1.4 g/dL) and carboxy polymethylene (4 g/dL) provided the highest aqueous humor aminocaproic acid concentrations. The aqueous humor levels with topical aminocaproic acid administration were comparable with those achieved by systemic administration. Plasma drug levels with topical aminocaproic acid were between 5% and 33% of levels achieved by systemic aminocaproic acid. This study demonstrates that aminocaproic acid can be effectively delivered into the anterior chamber of rabbits by topical application.
Acrylic Resins↗
Systemic aminocaproic acid reduces fibrinolysis in aqueous humor.
Systemically administered aminocaproic acid has been demonstrated to reduce the incidence of secondary hemorrhage in traumatic hyphema. To directly determine the concentration of aminocaproic acid in the aqueous humor, four groups of rabbits were studied following administration of four different regimens of intravenously administered aminocaproic acid. Plasma and aqueous humor samples were assayed for drug content and antifibrinolytic activity. Peak aqueous humor concentrations of aminocaproic acid ranged from 2.5 to 33 mg/dL and varied according to the systemic dose administered. The antifibrinolytic activity paralleled the aminocaproic acid content, with a peak range from 310 to 683 s. These findings indicate a direct relationship between antifibrinolytic activity and the concentration of aminocaproic acid in aqueous humor.
Aminocaproates↗
Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation.
In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Experimental study of the prophylactic anti-influenza and interferon-inducing activity of epsilon-aminocaproic acid].
Epsilon-aminocaproic acid, an original antifibrinolytic had a rapid and prolonged protective effect, thus lowering the death rate of experimental mice contaminated with virulent strains of the influenza virus. The protective effect of the acid was observed after its intraperitoneal administration in a dose of 20 mg/mouse 24 hours before contamination by the strain with the H3N2 antigenic formula and after intranasal application of 15 mg of epsilon-aminocaproic acid divided into 2 doses 2 days before contamination by the strain with the H1N1 antigenic formula. In the animals contaminated by the H1N1 influenza virus 5 days after subcutaneous administration of the drug in a dose of 30 mg there was detected in the lungs a much lower number of the infectious viruses 3 days after the contamination. It was shown that 3 and 6 weeks after initiation of the 5-day treatment course with subcutaneous administration of epsilon-aminocaproic acid in a daily dose of 90 mg/mouse the animal resistance to the H1N1 influenza virus increased. No interferonogenic activity after administration of epsilon-aminocaproic acid was observed in the mice.
Administration, Intranasal↗
Aminocaproic acid reduces the risk of secondary hemorrhage in patients with traumatic hyphema.
In a prospective, randomized, double-masked study, 34 patients (34 eyes) with nonperforating ocular injury and traumatic hyphema were treated with either aminocaproic acid (Amicar), 100 mg/kg every four hours, up to a maximum of 30 g/d, or placebo for five days. None of 21 patients who were treated with aminocaproic acid rebled, while three (23%) of 13 patients who were treated with placebo rebled. This difference was statistically significant. Of the three patients who rebled, two required surgical intervention, with one patient requiring four surgical procedures. Although complications following aminocaproic acid therapy included light-headedness, nausea and vomiting, and systemic hypotension, only one patient was withdrawn from the study because of drug-related adverse reactions. This study strongly confirms that aminocaproic acid therapy significantly reduces the incidence of secondary hemorrhage following traumatic hyphema.
Aminocaproates↗
Aminocaproic acid in prolonged hematuria of patients with sicklemia.
Forty-four episodes of sicklemic hematuria occurring in 40 patients during a 12-year period were reviewed. Seven of seven patients had evidence of a hyperactive fibrinolytic system. Fifteen of 38 pyelograms demonstrated obstruction of some portion of the collecting system by blood clots that cleared on follow-up studies (nine patients) in 2 to 37 days. Hematuria subsided spontaneously in 20 episodes. Aminocaproic acid was used in 22 patients whose hematuria prior to aminocaproic acid administration averaged twice as long as the total duration in patients undergoint spontaneous remission. Hematuria subsided in 2.2 +/- 0.3 days in the group treated with aminocaproic acid. Therapy with aminocaproic acid in this study was not associated with an increased incidence of thrombosis. Because of its potential untoward effects, however, EACA therapy in this disorder should be limited to patients with severe or prolonged hematuria.
Adolescent↗
Topical aminocaproic acid significantly reduces the incidence of secondary hemorrhage in traumatic hyphema in the rabbit model.
Systemically administered aminocaproic acid has been shown to reduce the incidence of secondary hemorrhage after traumatic hyphema. To date, no topical treatment has been shown to be effective in reducing the incidence of rebleeding in a double-masked study. Experimentally induced traumatic hyphemas in the rabbit model were treated with topical placebo gel (4% carboxypolymethylene gel only) or carboxypolymethylene gel with amino-caproic acid (treated group) in a double-masked fashion and were compared with untreated controls (control group). In both the control and placebo groups, there was a 33% rebleed rate. The treated eyes had a 10% rebleed rate that is statistically significant. The topically applied aminocaproic acid gel appears to be well tolerated locally without evidence of systemic toxicity. This study indicates that topical aminocaproic acid may be an effective alternative to systemic treatment to reduce the incidence of secondary hemorrhage in traumatic hyphema.
Acrylic Resins↗
Acute renal failure due to high-grade obstruction following therapy with epsilon-aminocaproic acid.
An 18-year-old man with mild factor VIII deficiency developed hematuria and, subsequently, acute renal failure due to high-grade urinary obstruction by clots during therapy with cryoprecipitate, epsilon-aminocaproic acid, and acetazolamide administered for ocular trauma. Discontinuation of therapy with the latter two agents and induction of a brisk diuresis with intravenous (IV) fluid therapy resulted in return of renal function concomitant with spontaneous clot passage. A review of previous literature suggests that hemophiliacs may be more susceptible than nonhemophiliacs to high-grade urinary obstruction due to clot formation when epsilon-aminocaproic acid is administered during episodes of hematuria. Acute flank pain, fever, and delayed dense nephrograms on IV pyelogram are characteristic of the syndrome and distinguish it from other forms of acute renal failure associated with epsilon-aminocaproic acid.
Acute Kidney Injury↗
[Bleeding after extracorporeal circulation and epsilon-aminocaproic acid].
In order to assess the efficacy of epsilon aminocaproic acid in reducing bleeding after extracorporeal circulation for aorto-coronary bypass grafting, a double blind study was carried out in 57 patients. The efficiency of epsilon aminocaproic acid was assessed by the fibrinolytic activity as measured by a Von Kaulla test one hour after injection of protamine, by the amount of blood transfusions required and by the measurement of blood losses between the end of the injection of protamine and transfer of the patient to the intensive care unit, and then during the first 24 h following operation. No significant difference (p less than 0.05) between the group of treated patients and the group with placebo could be found concerning the postoperative bleeding, the amount of blood transfusions necessary and the occurrence of fibrinolysis. It was therefore concluded that there was no reason to routinely use epsilon aminocaproic acid after aorto-coronary bypass grafting.
Aged↗
Studies of angiotensin I converting enzyme: effects of kinins, bacitracin, gamma-aminobutyric and epsilon-aminocaproic acids, and related compounds on substrate binding and catalysis in vitro.
Bradykinin and 22 of its analogs were evaluated for their abilities to inhibit the hydrolysis of [3H]hippurylglycylglycine by purified porcine kidney angiotensin I converting enzyme. The mean inhibitory concentration (IC50) for bradykinin was 1.2 +/- 0.2 X 10(-6) M. Except for Ile-Ser-bradykinin and [Sar4]-bradykinin, none of the kinin analogs were more potent in this regard than bradykinin. Bacitracin, gamma-aminobutyric acid, epsilon-aminocaproic acid, and structurally related compounds were also tested. The IC50 value for bacitracin was 1.9 +/- 0.4 X 10(-4) M, gamma-aminobutyric acid, 83.4 +/- 7.2 mM, and for epsilon-aminocaproic acid, 7.0 +/- 1.4 mM. Compounds were also evaluated for their abilities to prevent 125I-labelled [Tyr1]-kallidin binding to angiotensin I converting enzyme inhibited by EDTA. The IC50 values for bradykinin, bacitracin, gamma-aminobutyric acid, and epsilon-aminocaproic acid were 1.6 +/- 0.3 X 10(-8) M, 2.6 +/- 0.9 X 10(-6) M, greater than 291 mM, and 13.2 +/- 3.9 mM, respectively.
Aminocaproates↗
Epsilon-aminocaproic acid in the treatment of patients with acute promyelocytic leukemia and acquired alpha-2-plasmin inhibitor deficiency.
Patients with acute promyelocytic leukemia often develop bleeding diatheses during treatment. In seven patients who had this disease, the plasma level of alpha-2-plasmin inhibitor was the best predictor of severity of coagulopathy and bleeding. Clinical bleeding occurred when alpha-2-plasmin inhibitor levels measured less than 30% of normal levels. Patients with acute promyelocytic leukemia who had acquired deficiencies of alpha-2-plasmin inhibitor were considered to have deficits similar to those in persons congenitally deficient in alpha-2-plasmin inhibitor, and were assumed to be at increased risk for bleeding. Treatment with the fibrinolytic inhibitor, epsilon-aminocaproic acid, along with heparin resulted in prompt cessation of bleeding, reversal of laboratory evidence of fibrinolysis, and a decreased need for blood product support. The only thrombotic complication--thrombosis around a central venous catheter--resolved when treatment with epsilon-aminocaproic acid was discontinued. Epsilon-aminocaproic acid is a safe and effective therapy for those patients with acute promyelocytic leukemia who develop coagulopathy associated with low levels of alpha-2-plasmin inhibitor.
Aminocaproates↗
[Tooth extraction in patients suffering from hemophilia A under the cover of cryoprecipitates and epsilon-aminocaproic acid].
Tooth extractions were carried out in 75 patients with haemophilia A after infusion of a single dose of cryoprecipitate and 4 g of epsilon-aminocaproic acid. During the 7-10 day period of follow-up, the patients received epsilon-aminocaproic acid by mouth. In 32 of 44 patients with severe or moderate haemophilia and in 22 of 31 patients with mild haemophilia, healing was uneventful and no bleeding complications occurred. Only in 5 patients with severe haemophilia and in 1 patient with mild heamophilia bleeding from tooth sockets was extensive enough to require further replacement therapy. The results show that epsilon-aminocaproic acid in conjunction with a single infusion of cryoprecipitate can insure hemostasis after dental extraction in patients with haemophilia A.
Adolescent↗
Quantitative determination of the binding of epsilon-aminocaproic acid to native plasminogen.
The binding of epsilon-amino[14C]caproic acid (6-aminohexanoic acid, EACA) to native human plasminogen was determined using the ultrafiltration technique of Paulus (Paulus, H. (1969) Anal. Biochem. 32, 91-100) at free ligand concentrations ranging from 2 micrometer to 16 mM. One strong binding site (Kd = 0.009 mM) and approximately five weaker ones (Kd = 5 mM) were found. The constants were obtained by fitting the experimental points to the simple assumption of two sets of noninteracting sites. The distinct separation of the two kinds of sites allowed the correlation of the well known epsilon-aminocaproic acid-induced conformational transition in plasminogen with the saturation of the weaker group of binding sites by this ligand. The conformational transition was monitored by measurements of the sedimentation coefficient, as was done by others earlier. The midpoint of the transition occurred at approximately 3.3 mM free ligand. A dissociation constant of 0.32 mM was also obtained for L-lysine by measurements of the competition between this compound and labeled epsilon-aminocaproic acid for the strong binding site. The correlation between epsilon-aminocaproic acid binding and effects of the compound on various physical and functional properties is discussed. A discussion of the possible sources of error encountered in the technique used is also included.
Aminocaproates↗
Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate.
There appears to be no clinically significant difference in blood loss or transfusion requirements after transurethral resection of the prostate (TURP) when intravesical 0.5% aminocaproic acid is compared with 0.9% sodium chloride irrigation in patients during the first three days after surgery. This is probably because early post-TURP bleeding is due to inadequate hemostasis or perforation of the prostatic capsule, and not excessive local or systemic fibrinolysis. However, we suggest that intravesical aminocaproic acid might be a useful alternative to systemic antifibrinolytic therapy in patients with delayed, recurrent, excessive post-prostatectomy bleeding, which is thought to be due to fibrinolysis. Since aminocaproic acid is not systemically absorbed after bladder instillation, intravesical administration causes few side effects and does not necessitate screening patients for disseminated intravascular coagulation prior to treatment.
Aged↗
Effects of heparin and epsilon-aminocaproic acid in dogs on plasmin-125-I generation in response to urokinase injections and venous injury.
The isotopic method described previously for quantification of plasmin- (125)I by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin- (125)I and plasminogen- (125)I. It was found that the euglobulin precipitation method precipitates 72.4+/-2.1 (sd)% of both plasmin- (125)I and plasminogen- (125)I. Using this method and plasminogen- (125)I as a tracer, studies were first made of the effects of heparin and epsilon-aminocaproic acid in dogs on plasmin- (125)I generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin- (125)I generation; and third, in vitro studies of plasminogen- (125)I affinity to fibrin and its activation in blood clots. The venous injury was produced by the damage of venous endothelium by an injection of 90% phenol and the thrombosis by a thrombin injection into an occluded vein. Heparin and epsilon-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin- (125)I generation by the urokinase injection. Similar inhibitory effects of heparin and epsilon-aminocaproic acid were observed on plasmin- (125)I generation in response to venous injury. The venous occlusion caused a small degree of plasmin- (125)I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin- (125)I. The in vitro studies showed that plasminogen- (125)I does not have a specific affinity to fibrin and is incorporated into blood clots in approximately equal concentrations as those in serum during clotting processes, and that blood clots per se do not stimulate plasmin- (125)I generation. These results suggest that injured veins release considerable amounts of vascular plasminogen activators into circulation and that these play an important role in thrombus dissolution in vivo.
Aminocaproates↗