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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

[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

The use of epsilon-aminocaproic acid for the management of hemophilia in dental and oral surgery patients.

The use of epsilon-aminocaproic acid has proved to be an efficient and practical method for treating hemophiliacs who require dental work. In the past, patients requiring extractions were admitted to a hospital for approximately ten days and received replacement infusions every 12 hours during their stay. This resulted in a large expense because of the cost of the material and the hospitalization itself, not to mention the trauma sustained by the patient both physically and psychologically. Also, by decreasing the number of factor infusions, the risk of complications such as the transmission of hepatitis, allergic reaction, or inhibitor formation decreased. The same protocol using a single infusion of the appropriate factor replacement with supplementary epsilon-aminocaproic acid can be used for the management of patients with other coagulation disorders such as factor IX deficiency (Christman disease), factor XI deficiency, and von Willebrand's disease. Since this paper was submitted, seven more patients have been treated using this protocol. An additional seven odontectomies, 33 extractions, operative dentistry in 18 quadrants, and alveoloplasties in two full arches have been performed. This brings the total to 23 treatment sesions with 18 patients undergoing 124 procedures. One additional minor bleeding episode occurred, resulting in a total rate of four bleeding episodes in 23 treatment sessions and 124 procedures. Our incidence of complications secondary to epsilon-aminocaproic acid specifically remains zero.

Adolescent

Nitrophenylated derivatives of epsilon-aminocaproic acid: synthesis and physico-chemical characterization.

Methods for the synthesis of the mono-, di- and tri-nitro derivatives of epsilon-aminocaproic acid are presented. Special attention is given to the purification procedure, as we have found that methods recommended in the literature do not produce a single product. Evidence is presented which shows that recrystallizing the haptens from hot ethanol produces a by-product which is the ethyl ester of the haptens. Characterization methods and physical properties of the nitro-phenylated derivates of epsilon-aminocaproic acid are summarized.

Aminocaproates

Synergistic antifibrinolytic action of the potato protease inhibitor and epsilon-aminocaproic acid.

Fibrinolysis inhibition by a mixture of potato inhibitor and E-aminocaproic acid was greater than might be expected from the sum of the antifibrinolytic effects of these inhibitors investigated separately. This inhibition was observed in studies on the plasma euglobulin fraction and in a system containing isolated elements of the fibrinolytic system. The synergistic antifibrinolytic action of the potato protease in hibitor and E-aminocaproic acid is probably due to the fact that these inhibitors have different mechanisms of action and thus there is no competition between them for the effectors in the enzyme molecule.

Aminocaproates

Aminocaproic acid in the treatment of traumatic hyphema.

Of 59 patients with traumatic hyphema studied prospectively, 32 received aminocaproic acid, an antifibrinolytic agent, to prevent secondary hemorrhage. The remaining 27 patients received placebo in an identical manner. Of the aminocaproic acid-treated patients, only one (3%) rebled, while nine patients (33%) receiving placebo suffered secondary hemorrhage. The results of this study indicate a statistically significant reduction (P less than .01) in the incidence of rebleeding in patients treated with this drug.

Adolescent

[The inhibiting effect of epsilon-aminocaproic acid on the incidence of induced tumors of the esophagus, nervous system and kidneys].

The anticarcinogenic properties of epsilon-aminocaproic acid were studied in two rat models of carcinogenesis. Esophageal tumors were induced by oral instillations of a total dose of 54 mg/kg body weight N-methyl-N-benzylnitrosamine whereas tumors of the nervous system and kidney-by transplacental injection of 75 mg/kg body weight N-ethyl-N-nitrosourea. epsilon-Aminocaproic acid given at a concentration of 1 milligram drinking water at the post-initiation stage of the carcinogenesis was shown to inhibit the induction of cancer and papilloma of the esophagus, brain glioma, peripheral nerve neurinoma and mesenchymal tumors of the kidney.

Aminocaproic Acid

Reactions of pyrzdoxal 5'-phosphate, 6-aminocaproic acid, cysteine, and penicilamine. Models for reactions of Schiff base linkages in pyridoxal 5'-phosphate-requiring enymes.

Schiff base formation, transaldimination, and reaction with aminothiols are important reactions which occur on the surface of pyridoxal-P-requiring enzymes. As a first step in assessing the role of the protein in these reactions, models for these reactions were studied in the absence of enzyme at 25 degrees, gamma/2 0.28. The reaction of 6-aminocaproic acid with pyridoxal-P to form the Schiff base N6-(P-pyridoxylidene)-aminocaproic acid was studied as a model for formation of Schiff base on the holoenzyme...

Aminocaproates

Fluorescamine use in high-performance liquid chromatographic determination of aminocaproic acid in serum.

A sensitive and specific high-performance liquid chromatographic determination of aminocaproic acid in serum is described. omega-Aminocaprylic acid is used as an internal standard. To 10 microliter of serum, 10 microliter of the internal standard solution and 50 microliter of ethanol are added. After centrifugation, a portion of the supernate is evaporated. The residue is dissolved in 750 microliter of 50 mM dibasic sodium phosphate, and then 250 microliter of fluorescamine in acetonitrile (35 mg/100 ml) is added. The reaction mixture is chromatographed using a column of octadecylsilane bonded to silica and 44% acetonitrile in 0.5 mM phosphoric acid as the eluent. Quantitation is achieved by monitoring either the absorbance of the effluent at 405 nm or the fluorescence of the compounds with a fluorometer equipped with a flowcell. The method is reproducible, simple, and fast and has a precision of 4.4%.

Aminocaproates

The incidence of deep vein thrombosis in prostatectomised patients following the administration of the fibrinolytic inhibitor, aminocaproic acid (EACA).

Forty patients undergoing prostatectomy for benign prostatic hypertrophy were included in a double blind trial of epsilon aminocaproic acid, and the incidence of postoperative deep vein thrombosis determined, using 125I-fibrinogen technique. There was no significant difference between the groups, the overall incidence of abnormal scans being 50 per cent, but of the patients undergoing enucleative prostatectomy 68 per cent developed significant scan findings compared with 33 per cent following transurethral surgery.

Aged

The treatment of postperfusion bleeding using epsilon-aminocaproic acid, cryoprecipitate, fresh-frozen plasma, and protamine sulfate.

The evaluation of excessive hemorrhage was carried out in 774 patients after cardiopulmonary bypass. Excessive hemorrhage was defined in any adult patient as chest tube drainage of more than 600 ml within the first eight hours after operation. Using the prothrombin time, partial thromboplastin time, fibrinogen level, and tri-F titer tests, it was possible to differentiate medical from surgical bleeding. Hyperfibrinolytic bleeding was the most frequently identifiable coagulation disorder and occurred in 159 patients (20%). All these patients were successfully treated with Amicar (epsilon-aminocaproic acid) alone, or with Amicar supplemented with cryoprecipitate or fresh-frozen plasma. Three patients (0.4%) were noted to have residual heparin and required additional protamine sulfate. Five patients (0.6%) had normal coagulation studies and required immediate reexploration. The overall blood consumption per patient was 2.1 units of packed cells. Whole blood and platelets were not used.

Aminocaproates

Prevention of early recurrence of spontaneous subarachnoid haemorrhage by epsilon-aminocaproic acid.

A controlled clinical trial of epsilon-aminocaproic acid (E.A.C.A.), 36 g/day, was undertaken to assess its effectiveness in reducing immediate recurrence in patients with spontaneous subarachnoid haemorrhage (S.A.H.) proved by lumbar puncture. Of 83 patients treated with E.A.C.A., 3 (4%) had recurrent haemorrhage, and 1 (33%) of these died. Of 82 control patients who were not given any antifibrinolytic drug, 22 (26%) had recurrent haemorrhage, and 10 (45%) of these patients died. E.A.C.A. produced a striking reduction in the early recurrence of S.A.H. No serious side-effect resulted.

Adolescent

Epsilon-aminocaproic acid (EACA).

Epsilon-aminocaproic acid (EACA) is a synthetic inhibitor of the plasmin-plasminogen system. It is the only potent antifibrinolytic agent which is commercially available in the United States. Effective blood levels of the drug are readily obtainable with either oral or intravenous administration, with very high levels of the drug being found in the urine since the drug is greatly concentrated during excretion. EACA has been used in numerous clinical situations to control bleeding and has been claimed to be an effective agent in subarachnoid hemorrhage, genitourinary bleeding from many causes, and in dental surgery in hemophiliacs. It may also be effective in several less well studied situations such as prophylaxis of bleeding episodes in hemophiliacs, control of menorrhagia, gastrointestinal bleeding, obstetrical bleeding and in bleeding following cardiac and thoracic surgery. Major side effects from EACA include hypotension, cardiac arrhythmias, rhabdomyolysis, and generation of thrombi. The incidence of thrombotic events secondary to the inhibition of the fibrinolytic system by EACA is unknown, but may be particularly increased in those patients who have some underlying predisposition to develop thrombosis. The potential benefit from the use of EACA must be weighed against the possible serious complications, particularly the development of widespread thrombi.

Aminocaproates

Epsilon aminocaproic acid (EACA) myopathy.

Two female patients developed a severe, painful proximal myopathy after taking 18--30 g of epsilon-aminocaproic acid daily for 5 weeks. Marked elevations of serum aminotransferases, creatine kinase and aldolase levels were found and the first patient had electromyographic and muscle biopsy changes of an acute monophasic, necrotising myopathy at the height of the illness. Resolution occurred in both cases on stopping the drug and the second patient had no electromyographic or muscle biopsy abnormalities 3 weeks later. Only 2 recognized cases of the condition have been reported previously but a review of the literature revealed several other possible examples.

Aged

The modification of experimental allergic encephalomyelitis with epsilon aminocaproic acid.

Epsilon aminocaproic acid, an inhibitor of plasminogen and trypsinogen activators, can decrease the severity of experimental allergic encephalomyelitis (EAE) in rats. The drug was tried because of a number of observations suggesting that neutral proteases, such as plasmin, might be chemical mediators of demyelination. The highest concentrations of plasminogen activator are found in the walls of veins and venules, around which demyelination is common in many demyelinating diseases, including MS. Indeed, the earliest lesion in MS is often demyelination with little cellular infiltration. In vitro studies have shown that neutral proteases secreted by activated macrophages selectively lyse myelin basic protein.

Aminocaproates