A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of epsilon-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX C18 column (150 mm x 2.0 mm, i.d., 3 microm particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 microl/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.
6-Aminocaproic Acid ; Acetonitriles ; Administration, Oral ; Animals ; Calibration ; Mass Spectrometry* ; Methanol ; Normetanephrine ; Pharmacokinetics ; Plasma* ; Rats* ; Zinc

It is recognized that rebleeding of traumatic hyphema may predispose patients to several complications including decreased visual acuity. We reviewed the medical records of 92 patients(92 eyes) with the diagnosis of nonperforating traumatic hyphema. The relative efficiencies of Aminocaproic acid and systemic Predisolone for reducing rate of rebleeding and their side effects were evaluated under the statistical analysis. Fourty-seven patients received an oral dosage of 50 mg/kg of Aminocaproic acid every 4 hours for 5 days(up to a maximum 30 gm/day), and fourty-five patients took an oral dosage of 0.6 mg/kg of Prednisolone daily in two devided doses. The frequency of rebleeding was not statistically significantly different between the aminocaproic acid treated group(4.3%, 2/47 patients) and the prednisolone treated group(6.7%, 3/45 patients). The developing rates of their acute adverse reaction were statistically different between the aminocaproic acid treated group(44.7%, 21/47 patients) and the prednisolone treated group(20%, 9/45 patients).
Aminocaproic Acid* ; Diagnosis ; Humans ; Hyphema* ; Medical Records ; Prednisolone* ; Visual Acuity

9 classic hemophilacs in Severance Hospital, Yonsei University from Dec. '77 to Aug. '79 were reviewed and analysed and the following results were obtained. 1. Intracranial hemorrhage is required the most immediate emergent therapy in hemophiliacs and computerized transverse axial tomogarhy may be essential for the accurate and noninvasive diagnosis and for the effective emergency treatment. 2. To conserve supplies of therapeutic materials and to decrease the possibility of transmitting hepatitis and other diseases with blood products, it is desirable to reduce the amount of blood products with the use of epsilone aminocaproic acid, and epsilone aminocaproic acid may be useful in extraction and/or other non-dental injury with hemophiliacs.
Aminocaproic Acid ; Diagnosis ; Emergencies* ; Emergency Treatment ; Equipment and Supplies ; Hemophilia A* ; Hepatitis ; Intracranial Hemorrhages

Introduction: Thromboelastography (TEG) provides an overall assessment of the platelet-coagulation protein cascade interaction. The information generated from the TEG is rapidly obtained and made useful to guide replacement therapy. The purpose of this study was to evaluate the efficacy of the TEG as its guided blood replacement therapy and pharmacological therapy during liver transplantation. METHODS: This study was carried out in 13 consecutive patients who were subjected to TEG-guided replacement therapy during liver transplantation. A prepared mixture of blood products used for continuous replacement therapy was a fluid composed of red blood cells(2 units), fresh frozen plasma (2 units), and normal saline(500 ml). The pharmacological therapy was performed by comparing TEG of untreated blood and blood treated with antifibrinolytic and heparin neutralizing agent. Based on the findings of TEG, platelet concentrates were given. The TEG samples were obtained at various intervals. Additional TEG tracing was obtained as needed to see the effect of therapeutic intervention. RESULTS: In all patients the reaction time was kept in an acceptable range in the preanhepatic stage by administration of the mixture of blood products. Heparin-induced anticoagulation was observed in 3 cases in the anhepatic stage and in 11 cases upon reperfusion. Fibrinolysis was seen in all but one patients: 8% in the preanhepatic stage, 41% in the anhepatic stage, 69% at reperfusion, and 2% in the postanhepatic stage. Early and aggressive treatment with epsilon-aminocaproic acid effectively inhibited fibrinolysis without complications. Ten patients needed platelet transfusion in the postanhepatic stage with significant improvement in the TEG. CONCLUSIONS: The results of this study suggest that TEG monitoring and TEG-guided replacement and pharmacological therapy are clinically effective in maintaining blood coagulability.
Aminocaproic Acid ; Blood Platelets ; Fibrinolysis ; Heparin ; Humans ; Liver Transplantation* ; Liver* ; Plasma ; Platelet Transfusion ; Reaction Time ; Reperfusion ; Thrombelastography ; Transplantation

Traumatic hyphema accounts for about 6.7% of ocular trauma and its visual threatening associated ocular injuries are commotio retinae, retinal detachment, macular hole. cataract and rebleeding. The authors reviewed the medical records of 98 patients (98 eyes) having been admitted to the Joongang Gil Hospital between March 1989 and February 1991 with the diagnosis of nonperforating traumatic hyphema. Prospective study was performed as to the effect of epsilon-aminocaproic acid (EACA) in the clearance time of blood clot in the anterior chamber and the frequency of rebleeding. The avlrage clearance time of blood clot was significantly longer in the EACA treated group (5.8 days) than in the control group (3.5 days)(t-Test P<0.01). The frequency of rebleeding was not statistically significantly different between the EACA treated group (3.9%, 2/52 patients) and the control group (87%, 4/46 patients)(X2-Test P>0.05).
Aminocaproic Acid ; Anterior Chamber ; Cataract ; Diagnosis ; Humans ; Hyphema* ; Medical Records ; Prospective Studies ; Retina ; Retinal Detachment ; Retinal Perforations

The authors attempted to analyse the factors influencing the mortality involved in aneurysm surgery based on 38 cases of intracranial surgery for anterior communicating aneurysms, and obtained the following conclusion. 1. The surgical results are much better when the aneurysm surgery is delayed over one week after the occurrence of aneurysmal rupture, if there is no evidence of intracerebral hematoma. Administration of a massive dosage of epsilon aminocaproic acid in the waiting period prior to aneurysm surgery seems to be effective for preventing recurrence of bleeding from the aneurysm. 2. The direction of the anterior communicating aneurysm should be clearly visualized on a cerebral angiogram so that the most effective aneurysmal approach can be selected in surgery. 3. Microsurgery and hypotension in aneurysm surgery minimize brain damage in the exposure of aneurysm and provide accurate isolation of the aneurismal neck from the parent vessel in aneurysmal neck ligation. 4. Proximal ligation of the anterior cerebral artery is also an effective procedure to prevent recurrent hemorrhage from anterior communicating aneurysm.
Aminocaproic Acid ; Aneurysm* ; Anterior Cerebral Artery ; Brain ; Hematoma ; Hemorrhage ; Humans ; Hypotension ; Ligation ; Microsurgery ; Mortality ; Neck ; Parents ; Recurrence ; Rupture

BACKGROUND: Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method. METHODS: Five electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Thirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level. CONCLUSIONS The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.
Aminocaproic Acid ; therapeutic use ; Antifibrinolytic Agents ; therapeutic use ; Aprotinin ; therapeutic use ; Humans ; Randomized Controlled Trials as Topic ; Spine ; surgery ; Tranexamic Acid ; therapeutic use

OBJECTIVE: To systematically evaluate the hemostatic efficacy of tranexamic acid and ε-aminocaproic acid in total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Randomized controlled trials (RCT) and retrospective case-control studies about tranexamic acid and ε-aminocaproic acid for the comparison of THA or TKA were searched electronically in PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP from the time of building databases to July 2020. Two investigators carried out literature screening and data extraction according to the inclusion and exclusion criteria respectively. The methodological quality of the included randomized controlled studies was evaluated through the Cochrane Handbook, and the methodological quality of the included retrospective case-control studies was evaluated through the NOS scale. Blood loss, the incidence of thrombosis complications, per capita input of hemoglobin were Meta-analyzed by Review Manager 5.3 software. RESULTS: A total of 6 articles were included, including 4 RCTs and 2 retrospective case-control studies. A total of 3 174 patients, including 1 353 in the tranexamic acid group and 1 821 in the ε-aminocaproic acid group. Meta-analysis results showed that there were no difference statistical significance in blood loss [MD=-88.60, 95%CI(-260.30, 83.10), P=0.31], blood transfusion rate [OR=1.48, 95%CI(0.96, 2.27), P=0.08], thrombotic complications [OR=0.80, 95%CI(0.07, 8.83), P=0.85], per capita hemoglobin input [MD=0.04, 95%CI(-0.02, 0.10), P=0.18] between tranexamic acid group and ε-aminocaproic acid group during THA. While in TKA, the blood loss of the tranexamic acid group was less than that of the ε-aminocaproic acid group [MD=-147.13, 95%CI(-216.52, -77.74), P<0.0001], the difference was statistically significant. The blood transfusion rate [OR=1.30, 95%CI(0.74, 2.28), P=0.37], thrombotic complications [OR=0.95, 95%CI(0.38, 2.36), P=0.92], per capita hemoglobin input [MD=-0.00, 95%CI(-0.05, 0.06), P=0.48], tourniquet time [MD=1.54, 95%CI(-2.07, 5.14), P=0.40] were similar between two groups, the difference was not statistically significant. CONCLUSION In THA, tranexamic acid and ε-aminocaproic acid have similar hemostatic effects, while in TKA, tranexamic acid can effectively reduce the patient's blood loss and has a better hemostatic effect. Tranexamic acid is recommended as one of the first choice hemostatic drugs for TKA.
Aminocaproic Acid/therapeutic use* ; Antifibrinolytic Agents/therapeutic use* ; Arthroplasty, Replacement, Hip/methods* ; Arthroplasty, Replacement, Knee/methods* ; Blood Loss, Surgical/prevention & control* ; Hemoglobins ; Hemostatics ; Humans ; Tranexamic Acid/therapeutic use*

aminocaproic acid, which inhibits the production of fibrinolysin, and Plasma, which provides the necessary ingredients for collagen synthesis. GMI has advantages of low immunogenicity and increased longevity. It has been known to induce fibroblast activity and promote new collagen synthesis. We used 34 Sprague-Dawley rats which were bred under the same condition and duration. 18 of experimental animals were undergone cardiac puncture, and their blood were collected, centrifugated, and stored in freezer. Out of 16 animals, control group were injected with 2ml plasma into the subcutaneous tissue of Lt. scapular, while experimental group were implanted of 2ml GMI into the Rt. same area. Experimental animals were sacrificed at the 3rd day, 5th day, 1st week and 2nd week respectively after implantation of GMI. To observe the histopathologic change of GMI and surrounding tissue reaction of GMI, we had examined with H&E staining, immunohistochemical staining with vimentin, alpha-SMA, S-100 under LM and SEM. The obtained results were as follows; 1. In LM study, the inflammatory cell infiltrations and granulation tissue formation were observed, and muscle tissues were well attached with adipose tissues in the control group. In the experimental group, inflammatory cell infiltrations had been observed by the 2nd week and irregular adipiose tissues and well differentiated mesenchymal tissues were examined. 2. In immunohistochemical study, the experimental group of alpha-SMA study, there were a prominent positive response on endothelial development of granulation tissues and mesenchymal tissues compare with the control group. In vimentin study, positive response on mescenchymal fibroblast continued to 2nd week, but negative in the control group. In S-100 study, both groups were positively responded on irregular adipose tissues. 3. In SEM study, collagen fibers were embedded by the plasma by the 5th day in the control group, and in the 3rd day experiment GMI were resorved but communited with collagen fiber till the 1st week. Collagen fibers were infilt-rated into GMI at the 2nd week and the infilltrated GMI were conglomerated with the mature adipose cells and the collagen fibers. From the above results, GMI implantation in the subcutaneous tissue of Sprague-Dawley rat, the mild infiltration of inflammatory cells were showed till 2nd week and the granulation tissues were observed. GMI were nearly resorbed till 2nd week, but well attached with adipose tissue and collagen fibers. The endothelium and fibroblasts were actively proliferated. Adipose tissues and mesenchymal tissue cells were observed. As already expressed, GMI showed resorptive change in course of time without any early immune reaction, and seemed to induce fibroblast activity and promote new collagen synthesis.]]>
Adipose Tissue ; Aminocaproic Acid ; Animals ; Cicatrix ; Collagen ; Endothelium ; Fibrinolysin ; Fibroblasts ; Gelatin ; Granulation Tissue ; Longevity ; Plasma ; Punctures ; Rats ; Rats, Sprague-Dawley ; Subcutaneous Tissue ; Vimentin

OBJECTIVETo investigate the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin (BCG) on preventing recurrence of superficial bladder transitional cell carcinoma (BTCC) after surgical management.

METHODSA total of 326 cases of superficial BTCC undergoing transurethral resection of bladder tumor (TURBT) or partial cystectomy were divided into 5 groups. Then the different dosage BCG with or without antifibrinolytic agents was regular instilled into bladders (once a week, then once a month after 6 times). Group A including 66 cases received intravesical instillation of 100-120 mg BCG plus 100 mg para-aminomethyl benzoic acid (PAMBA). Group B including 64 cases: instillation of 50-60 mg BCG plus 100 mg PAMBA; Group C including 65 cases: 100-120 mg BCG plus 2.0 g epsilon-aminocaproic acid (EACA); Group D including 64 cases: 50-60 mg BCG plus 2.0 g EACA; Group E (control group) including 67 cases: 100-120 mg BCG. All the cases had been followed up for 4 to 69 months (mean, 28.5 months). Not only was cystoscopy performed every 3 months, but also biopsy was carried out to identify recurrence when necessary. Side effect was recorded after instillation.

RESULTSThe rate of tumor recurrence of Group A, Group B, Group C and Group D was 12%, 10%, 9%, 9% respectively, which was significantly lower than that of Group E (30%) (chi(2) = 5.699, 6.818, 7.380, 7.867, P = 0.017, 0.009, 0.007, 0.005). And there was no significant difference of tumor recurrence rate between Group A and Group B or between Group C and Group D (Group A and Group C: high dosage BCG plus antifibrinolytic agents, while Group B and Group D: low dosage BCG plus antifibrinolytic agents) (P > 0.05). But the side effects developing in Group B and Group D after BCG instillation were less than those in Group A and Group C.

CONCLUSIONSThe efficacy of BCG on prevention the recurrence of superficial BTCC can be enhanced when combined with antifibrinolytic agents. Even if the dosage of BCG was reduced by half, the efficacy didn't changed. A new approach of low dosage BCG plus antifibrinolytic agents is recommended in the prophylaxis of recurrence of bladder cancer.

4-Aminobenzoic Acid ; administration & dosage ; Adjuvants, Immunologic ; therapeutic use ; Administration, Intravesical ; Adult ; Aged ; Aged, 80 and over ; Aminocaproic Acid ; administration & dosage ; Antifibrinolytic Agents ; therapeutic use ; BCG Vaccine ; therapeutic use ; Carcinoma, Transitional Cell ; drug therapy ; surgery ; Combined Modality Therapy ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Urinary Bladder Neoplasms ; drug therapy ; surgery ; para-Aminobenzoates