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Factors affecting therapeutic concentration of topical aminocaproic acid in traumatic hyphema.

Epsilon-aminocaproic acid (EACA) decreases rebleeding in traumatic hyphema through antifibrinolytic activity. Therapeutic levels were achieved in aqueous humor of rabbits after topical application. Aqueous humor EACA levels were significantly higher after pretreatment with 0.5% proparacaine. Use of EACA (60%) in a carboxypolymethylene (CPM) vehicle (0.5%, 1%, 2%, 3%, and 4%) was examined. Aqueous humors levels at 4 hours ranged from 6.18-20.42 micrograms/ml. The 2% and 3% formulas achieved the highest concentrations in aqueous. Use of EACA (15%, 30%, 40%, and 60%) in 4% CPM was also studied. At 2 and 4 hours after treatment, the 30% EACA solution most effectively achieved therapeutic levels. Velcro closure devices were attached to the rabbit's eyelids, and 200 microliters of 30% EACA in 2% CPM was administered. After 3 hours the patched eyes had a mean aqueous EACA level of 60.09 micrograms/ml compared with 8.97 micrograms/ml in unpatched eyes. When dose size was studied in patched eyes, 200-microliters doses achieved aqueous levels of 60.09 micrograms/ml, and 100-microliters doses resulted in levels of 10.40 micrograms/ml. Since epithelial toxicity was observed in eyes that had been patched, the optimum topical regimen appeared to be 200 microliters of 30% EACA in 2% CPM every 6 hours in unpatched eyes.

Acrylic Resins↗

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↗

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↗

The effect of epsilon-aminocaproic acid on HemoSTATUS and kaolin-activated clotting time measurements.

UNLABELLED: New point-of-care assays have been used to identify patients with heparin resistance (i.e. heparin dose response test; Medtronic Blood Management, Parker, CO) and who have platelet dysfunction (i.e. HemoSTATUS; Medtronic Blood Management). We examined the effect of epsilon-aminocaproic acid on results from these two point-of-care tests in patients undergoing cardiac surgery. Twenty patients scheduled for elective cardiac surgical procedures were enrolled in this prospective study. HemoSTATUS clot ratio (% maximal) values in Channels (Ch) 3-6 (Ch 3: 26 +/- 25, Ch 4: 66 +/- 23, Ch 5: 84 +/- 20, Ch 6: 106 +/- 18) obtained after the IV administration of epsilon-aminocaproic acid were similar to values obtained before the administration of this agent (Ch 3: 26 +/- 20, Ch 4: 69 +/- 23, Ch 5: 86 +/- 19, Ch 6: 109 +/- 14). Slope values (86 +/- 23 s x U(-1) x mL(-1)) and projected heparin concentrations (4 +/- 1 U/mL) obtained before the administration of epsilon-aminocaproic acid were similar to slope values (88 +/- 21 s x U(-1) x mL(-1)) and projected heparin concentrations (4 +/- 1 U/mL) values obtained after administration of this agent. Our data indicate that HemoSTATUS clot ratio values and heparin dose response values are not significantly affected after IV dosing of epsilon-aminocaproic acid. IMPLICATIONS: Values from two activated coagulation time-based test systems used to identify significant heparin resistance or platelet dysfunction after cardiopulmonary bypass were not significantly affected by epsilon-aminocaproic acid administered IV.

Aged↗

Control of bleeding in patients with immune and nonimmune thrombocytopenia with aminocaproic acid.

Patients with thrombocytopenia have an increased risk of bleeding. We have used 18 courses of aminocaproic acid in 17 patients with either immune or nonimmune thrombocytopenia to successfully control hemorrhage associated with reduced platelet counts. The types of hemorrhage controlled included the following: vaginal, gastrointestinal, intracerebral, cutaneous, mucous membrane, subconjunctival, and renal, as well as that associated with dental extractions, tracheostomy, and sites of Penrose drains. The number of platelet and red blood cell transfusions administered decreased substantially following institution of aminocaproic acid therapy. We conclude that therapy with aminocaproic acid is safe and useful in the management of bleeding in patients with both immune and nonimmune thrombocytopenia.

Adult↗

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↗

Epsilon aminocaproic acid in paediatric cardiac surgery to reduce postoperative blood loss.

We have studied the efficacy of epsilon aminocaproic acid in reducing postoperative blood loss in infants and children with congenital cyanotic cardiac anomalies undergoing corrective operative procedures. This prospective study was carried out on 170 infants and children randomly divided into two equal groups. Group A acted as the control group and received normal saline as placebo while group B patients received epsilon aminocaproic acid (100 mg/kg body wt) intravenously slowly soon after anaesthetic induction followed by 100 mg/kg in the cardiopulmonary bypass pump at the time of starting of cardiopulmonary bypass and 100 mg/kg after weaning from bypass over a period of 3 h. In group A the time for sternal closure after separation from bypass and administration of protamine was 75.18 +/- 5.5 min and in group B 50.7 +/- 5.2, (P < 0.001). Blood loss at 24 h in group A was 42.6 +/- 6.9 ml/kg/24 h and in group B 23.7 +/- 5.8 ml/kg/24 h, (P < 0.001). The need for packed red cells in group A was 21.8 +/- 7.1 ml/kg/24 h and in group B 10.7 +/- 7.8 ml/kg/24 h, (P < 0.001). The need for platelet concentrate in group A was 22.0 +/- 6.7 ml/kg/24 h and group B 6.2 +/- 3.2 ml/kg/24 h, (P < 0.001). Fibrin degradation products (split) in group A was 8.2 +/- 0.8 micrograms/ml, and group B 3.8 +/- 1.3 micrograms/ml, (P < 0.001). Reexploration rate was also considerably reduced in group B, 5 of 85 (6%) compared to group A, 13 of 85 (15%), (P < 0.001). It was found that epsilon aminocaproic acid is effective in reducing postoperative blood loss, packed red cells and plasma product requirements in paediatric patients undergoing corrective surgical procedures for congenital cyanotic heart diseases.

Aminocaproic Acid↗

Measurement of fibrinolytic activity after epsilon-aminocaproic acid administration in rats (Rattus norvegicus).

The antifibrinolytic agent, epsilon-aminocaproic acid was administered to rats via either intraperitoneal injection or intravenous infusion. Time-response and dose-response studies of the resultant plasma levels of fibrinolytic activity were measured by a modification of a standard fibrin plate technique. The modified technique involved the addition of human plasma to rat plasma in a ratio of 10:1 (rat:human). The plasma levels of fibrinolytic activity reflected plasma concentrations of epsilon-aminocaproic acid.

Aminocaproates↗

Can epsilon-aminocaproic acid balance the off-pump bleeding advantage?

BACKGROUND: Aprotinin improved the control of bleeding in patients undergoing surgery with cardiopulmunary bypass, but its use was halted because of the risk of bovine spongiform encephalopathy. We then started to use epsilon-aminocaproic acid and the results in the control of bleeding were satisfactory. To assess its effectiveness in the control of postoperative bleeding precisely, we compared the results for patients operated on for myocardial revascularization on-pump and treated with epsilon-aminocaproic acid with those for patients who decidedly bleed less: off-pump patients. METHODS: Two groups of patients who had had either on- or off-pump double aortocoronary bypass surgery were retrospectively reviewed for postoperative bleeding. These two almost homogeneous group had two grafts only: left anterior descending and circumflex arteries operated on with cardiopulmonary bypass and treated with the epsilon-aminocaproic acid, and left anterior descending and right coronary arteries operated on off-pump. RESULTS: Postoperative bleeding through chest drainage at 4 h was 265+/-91.7 mL in the off-pump group and 328.4+/-131.4 mL in the on-pump group (p=0.004). But at 24 h it was 671.6+/-311.5 mL in the off-pump group and 827.8+/-514.4 mL in the on-pump group (p=0.07). CONCLUSIONS: epsilon-Aminocaproic acid is effective in controlling postoperative bleeding in patients operated on for myocardial revascularization with the aid of cardiopulmonary bypass.

Aged↗

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↗

Intraocular pressure increase associated with epsilon-aminocaproic acid therapy for traumatic hyphema.

We treated five patients receiving epsilon-aminocaproic acid who demonstrated sudden and accelerated clot dissolution with accompanying increases in intraocular pressure 24 to 96 hours after discontinuing treatment. All of these patients required additional ocular hypotensive medications and one patient required anterior chamber washout for persistently increased intraocular pressure. These findings suggest that certain patients with hyphema may be at risk for significant intraocular pressure increases following cessation of epsilon-aminocaproic acid therapy.

Adolescent↗

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↗

[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↗

epsilon-Aminocaproic acid esters as transdermal penetration enhancing agents.

The synthesis of epsilon-aminocaproic acid esters is described. Two representative members from a group of five of the 1-alkyl homologues synthetized as flexible analogues of 1-alkylazacyclohepatanone derivatives were evaluated in vitro for their effectiveness on the transport of theophylline through the excised human cadaver skin in comparison with Azone. The 1-octyl- and 1-dodecyl-epsilon-aminocaproic acid esters (OCEAC and DDEAC) show excellent penetration enhancement. Donor samples contained 2.5% theophylline and 1% enhancers tested in three different vehicles. Fluxes of theophylline were increased with OCEAC about 19 times from olive oil, 45 times from water, and about 38 times from water-propylene glycol (3:2) vehicle toward controls (with DDEAC about 17, 39, and 35 times, respectively) and they were markedly higher than Azone under the given conditions. Acute LD50's (i.p. in mice) of OCEAC (DDEAC) were 245 mg/kg (352 mg/kg), with a slightly lower toxicity than Azone. OCEAC and DDEAC did not exhibit acute dermal irritation in vivo on rabbits at a 5% concentration in white petrolatum.

Administration, Cutaneous↗

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↗

Characteristics and functional outcome of traumatic hyphema without routine administration of epsilon-aminocaproic acid.

BACKGROUND: The prevalence of traumatic hyphema as well as the distribution of its severity varies among different patient populations. Treatment recommendations in the literature differ significantly among various published reports. This lack of a uniformly accepted treatment probably reflects the different characteristics of this pathology among the populations investigated and cells for a population-adjusted treatment recommendation. OBJECTIVES: To report the characteristics and functional outcome of patients with traumatic hyphema and to discuss possible recommendations regarding the use of epsilon-aminocaproic acid. METHODS: A prospective, non-randomized study was conducted in 154 consecutive patients with traumatic hyphema, including data collection of ophthalmic status at various time points, the presence or absence of secondary hemorrhage, and final visual acuity. RESULTS: Of the 154 eyes studied over 3 years, nearly 90% had hyphema of grade 1 or less, 5 (3.25%) experienced rebleeding, and 2 (1.3%)--neither of which rebled--needed surgical intervention. None of the four patients who experienced final visual acuity of 6/40 or less suffered rebleeding. CONCLUSION: The use of epsilon-aminocaproic acid in the studied population was unjustified and routine use of epsilon-aminocaproic acid in our patient population is probably not indicated. A treatment policy regarding epsilon-aminocaproic acid use should be adjusted to the population being treated.

Adolescent↗

Rhabdomyolysis during treatment with epsilon-aminocaproic acid.

Severe rhabdomyolysis and acute renal failure occurred in a patient receiving epsilon-aminocaproic acid. The lack of evidence of vascular involvement in the muscle biopsy specimen suggests that epsilon-aminocaproic acid may have direct myotoxicity. This drug may produce a spectrum of muscle disease from mild myopathy to life-threatening rhabdomyolysis.

Adult↗