SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A case of a congenitally abnormal fibrinogen that resulted in surgical wound dehiscence is reported. The patient underwent successful transurethral resection for benign prostatic hypertrophy while being treated with epsilon aminocaproic acid to prevent fibrinolysis of the abnormal fibrin clot.
OBJECTIVE: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.
Diagnosis and treatment of patients with bleeding due to enhanced fibrinolysis is hampered by the absence of a rapid screen of fibrinolytic potential. The authors have developed a simple assay to assess clot structure and fibrinolysis in patient samples exposed to tissue plasminogen activator (TPA). They present the case of a forty-one-year-old man who presented with spontaneous bleeding despite normal results from coagulation screening tests, platelet count, platelet aggregation studies, platelet force development, and bleeding time. Evaluation of the patient's clot structure revealed a very weak, low-modulus, clot that rapidly dissolved in the presence of TPA. Identification of the abnormality allowed treatment with epsilon-aminocaproic acid with prompt resolution of bleeding.
UNLABELLED: Tranexamic acid is a synthetic derivative of the amino acid lysine that exerts its antifibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen molecules. Intravenously administered tranexamic acid (most commonly 10 mg/kg followed by infusion of 1 mg/kg/hour) caused reductions relative to placebo of 29 to 54% in postoperative blood losses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), with statistically significant reductions in transfusion requirements in some studies. Tranexamic acid had similar efficacy to aprotinin 2 x 10(6) kallikrein inhibitory units (KIU) and was superior to dipyridamole in the reduction of postoperative blood losses. Transfusion requirements were reduced significantly by 43% with tranexamic acid and by 60% with aprotinin in 1 study. Meta-analysis of 60 trials showed tranexamic acid and aprotinin, unlike epsilon-aminocaproic acid (EACA) and desmopressin, to reduce significantly the number of patients requiring allogeneic blood transfusions after cardiac surgery with CPB. Tranexamic acid was associated with reductions relative to placebo in mortality of 5 to 54% in patients with upper gastrointestinal bleeding. Meta-analysis indicated a reduction of 40%. Reductions of 34 to 57.9% versus placebo or control in mean menstrual blood loss occurred during tranexamic acid therapy in women with menorrhagia; the drug has also been used to good effect in placental bleeding, postpartum haemorrhage and conisation of the cervix. Tranexamic acid significantly reduced mean blood losses after oral surgery in patients with haemophilia and was effective as a mouthwash in dental patients receiving oral anticoagulants. Reductions in blood loss were also obtained with the use of the drug in patients undergoing orthotopic liver transplantation or transurethral prostatic surgery, and rates of rebleeding were reduced in patients with traumatic hyphaema. Clinical benefit has also been reported with tranexamic acid in patients with hereditary angioneurotic oedema. Tranexamic acid is well tolerated; nausea and diarrhoea are the most common adverse events. Increased risk of thrombosis with the drug has not been demonstrated in clinical trials. CONCLUSIONS: Tranexamic acid is useful in a wide range of haemorrhagic conditions. The drug reduces postoperative blood losses and transfusion requirements in a number of types of surgery, with potential cost and tolerability advantages over aprotinin, and appears to reduce rates of mortality and urgent surgery in patients with upper gastrointestinal haemorrhage. Tranexamic acid reduces menstrual blood loss and is a possible alternative to surgery in menorrhagia, and has been used successfully to control bleeding in pregnancy.
Explore the source record for details and available documents.
To determine the clinical significance of acquired alpha 2-antiplasmin deficiency in patients with bleeding disorders, I reviewed the results of assays performed on 184 patients over a 4-year period. Thirty-two evaluable patients had alpha 2-antiplasmin activity levels of less than 50% of normal (defined as severe deficiency), and 35 patients had levels between 50% and 75% of normal (mild deficiency). Records of these patients and of 32 patients who had normal levels were reviewed. Most patients with severe alpha 2-antiplasmin deficiency had either liver disease or disseminated intravascular coagulation and/or fibrinolysis, or both. There was a high incidence of severe alpha 2-antiplasmin deficiency among patients with acute promyelocytic leukemia. Five patients with pathologic bleeding had no identifiable coagulation abnormalities other than alpha 2-antiplasmin deficiency. The group with severe alpha 2-antiplasmin deficiency had a significantly higher incidence of life-threatening or fatal bleeding and the most striking laboratory evidence of hyperfibrinolysis. Using the presence of severe alpha 2-antiplasmin deficiency as an indication for therapy, epsilon-aminocaproic acid treatment was associated with cessation of life-threatening bleeding in 8 of 11 patients.
Primary defect of C1-inhibitor (C1-INH), the regulatory protein of the initial classical pathway of complement, is the cause of hereditary angioedema. Clinical symptoms involve potentially fatal obstruction of the upper respiratory tract, abdominal pains, and subcutaneous edemas. Since the description of functional tests for C1-INH two types of hereditary defect have been known: type I and type II. Sixteen patients with the type I of hereditary angioedema were diagnosed and treated in our hospital. The onset of the disease occurred between 1.5-12 y. of age. Clinical symptoms were observed in skin, gastrointestinal and respiratory tracts. Mean concentration of C1-INH in sera of 16 patients was 3.25 mg/dl, below 8.75 mg/dl that is the critical for well-functioning C1-INH. Inhibitory activity of C1-INH for C1 esterase in plasma was zero in most of the patients, while it was 0.94 +/- 0.20 U/ml in plasma samples of 91 healthy blood donors. Three modalities of treatment are available: substitution with C1-INH concentrate in acute attacks and antifibrinolytic and/or anabolic drugs for prophylaxis. We have obtained good therapeutic results with epsilon-aminocaproic acid (antifibrinolytic), 2g daily during 3 months, with 6 months intervals.
BACKGROUND: Reexploration of the mediastinum for bleeding is required in 3% to 7% of patients after cardiac operation, with many proving to have no surgically correctable cause. In spite of a "negative exploration," the bleeding often ceases. We propose the hypothesis that such a negative exploration can be therapeutic by reducing marked fibrinolytic activity in the mediastinal cavity. METHODS: Fibrinolytic activity in shed mediastinal blood was compared with that in the system blood in 5 patients after cardiac operation by measuring fibrinogen, fibrin degradation product, plasminogen activator inhibitor-1, and alpha2-antiplasmin levels. RESULTS: Fibrinolytic activity in mediastinal blood was markedly increased when compared with paired systemic venous blood. This was indicated by the mediastinal blood's lower fibrinogen levels (0.47 versus 1.91 U/mL; p < 0.001), very high levels of fibrin degradation products (1,350 versus 200 ng/mL; p < 0.05), and higher levels of plasminogen activator inhibitor-1 (55.5 versus 28.1 ng/mL; p < 0.005). Decreased levels of alpha2-antiplasmin were also observed in the mediastinum (0.50 versus 0.61 U/mL; p < 0.05). CONCLUSIONS: Our data confirm that fibrinolytic activity can be extremely high in the mediastinum in response to clot formation. This may explain the hemostatic effects of a negative reexploration, where irrigation and the removal of clots may reduce the fibrinolytic process; this may allow the bleeding ends of capillaries and small vessels to thrombose. Decreased levels of alpha2-antiplasmin observed suggest that lysine analogs, such as epsilon-aminocaproic acid, may have a beneficial role when locally delivered into the mediastinum.
A 20-year-old male was injured in his right eye by the stopper of a bottle filled with carbonated fruit juice. The contusion caused a recurrent hyphema which lasted approximately 6 weeks and responded to epsilon-aminocaproic acid treatment. Among the investigations for coagulation and fibrinolysis, the only pathological laboratory finding was a shortened plasma euglobulin clot lysis time (1.5 h) which returned to normal (4--5 h) following the epsilon-aminocaproic and treatment.
An analysis of the effects of adrenal cortical steroids on the response of the vascular system to bacterial endotoxin has shown that glucocorticoids (cortisone, triamcinolone) are capable of preparing the system for the generalized Shwartzman reaction. On the other hand, the mineralocorticoid desoxycorticosterone acetate does not have this capability. The mechanism of preparation by glucocorticoids has been studied. Administering insulin, with maintenance of normal blood sugar, had no effect on the extent of glomerular capillary thrombosis. Blockade, however, of alpha-adrenergic receptor sites by Dibenzyline caused a significant reduction of the thrombosis. In addition, cortisone-treated animals did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated (by ellagic acid) and fibrinolysis inhibited (by epsilon-aminocaproic acid). It is concluded that glucocorticoids prepare for the generalized Shwartzman reaction by increasing the sensitivity of the microcirculation to stimulation of alpha-adrenergic receptor sites.
The metabolism of [2-14C]N-nitrosohexamethyleneimine in male MRC-Wistar rats was studied and some of the major urinary metabolites were identified. The extent of total oxidation to 14CO2 was 18.1% in 24 hours and radioactivity incorporation was observed in various tissues; that in the liver was the highest. Analysis of urine after 24 hours showed that 36.7% of the radioactivity administered was excreted by this route, with a minimum of 11 products present. Hexamethyleneimine (HX), epsilon-caprolactam, epsilon-aminocaproic acid, and 6-aminocaprohydroxamic acid were the identified metabolites. Of the remaining products, two appeared to result from HX metabolism and one was a glucuronide conjugate. No parent compound was found.
An 82 year old man developed antibodies against coagulation factor VIII:C without any apparent cause. Bleeding from the soft tissue cavity could not be controlled by factor VIII:C concentrates, immunosuppression with steroids and intravenous immunoglobulin therapy in the standard dosages. However, a single injection of Epsilon Aminocaproic Acid (EACA) instilled into the cavity under aseptic precautions achieved lasting hemostasis with resultant wound healing.
Seventy one persons (67 children and 4 of their mothers) who came to the out-patient department of our hospital because of recurrent edemas of subcutaneous tissue and mucous membranes were the subjects of study. Serum haemolytic activity of complement and concentration of C1-esterase inhibitor, C1q, C4 and C3 were measured. Twenty six persons were related: altogether 12 families were studied, mostly sisters and brothers. In six patients (k 8.5% of the group studied) inherited type I defect of C1-inhibitor was detected and the diagnosis of angioneurotic edema confirmed. The results of complement determination in these patients (5 girls and 1 mother) were compared to the rest of the group and to healthy blood donors and showed clear differences in concentrations of C1-inhibitor, C1q, C4 and in haemolytic activity. Treatment consisted of fibrinolysis inhibitor, epsilon-aminocaproic acid and of antihistamine drugs. The value of this kind of therapy in the treatment of a very well responding child is discussed.
A case is reported in which a young man suffering from hereditary angioedema was admitted with severe airway obstruction due to groww pharyngeal and laryngeal oedema. Tracheostomy was necessary. The rationale of treatment with epsilon aminocaproic acid, tranexamic acid and fresh frozen plasma is discussed. The patient subsequently underwent dental extractions under general anaesthesia with tracheal intubation without complications.
Bleeding remains an important complication after repeat and complicated cardiac surgery. Although aprotinin has recently been approved by the Food and Drug Administration for use as an antifibrinolytic agent, many surgeons continue to have concerns about its added cost and potential side effects. We review here the current state of antifibrinolytic therapy for excessive bleeding in cardiothoracic surgery and suggest the use of a single intravenous dose of 10 g of epsilon-aminocaproic acid immediately before cardiopulmonary bypass as a safe, inexpensive, and effective alternative to aprotinin. Further clinical and laboratory studies are needed to confirm or modify this protocol.
To evaluate the effect of 1-deamino-8-D-arginine vasopressin (DDAVP) in various bleeding disorders, 10 micrograms/m2 DDAVP was administered to subjects with von Willebrand disease (13), platelet function defects (12), von Willebrand disease and platelet defects together (8), or isolated prolongation of the bleeding time (5). DDAVP shortened the bleeding time similarly in all patient groups. Shortening of the bleeding time was also observed in 2 patients with aspirin-induced platelet defects and in 2 normal subjects. DDAVP administration was associated with falls in the platelet count, mean platelet volume, and partial thromboplastin time, and rises in platelet adhesion, factor VIII coagulant activity, factor VIII related antigen, and von Willebrand factor activity. The basal bleeding time was the only predictor of the magnitude of the bleeding-time correction. Normal haemostatis was achieved with DDAVP plus epsilon-aminocaproic acid and no blood product support during operations in 18 patients with bleeding disorders.
The binding of an amino acid, glycine (Gly), alanine (Ala), epsilon-aminocaproic acid (-AC), monosodium glutamate (GluNa), or lysine (Lys), to starch was examined by a biomolecular interaction analyzer (IAsys). A starch sample (ATS) hydrolyzed to an extent of 1% hydrolysis rate with 15% sulfuric acid was used as a model starch for the binding examination. The reducing end of ATS was oxidized by the Somogyi reagent, and the conversion of the reducing end to the carboxyl group of ATS was confirmed by a carboxylic acid fluorescence labeling reagent. The oxidized ATS was immobilized to the amino group of a sensor cuvette by using water-soluble carbodiimide and N-hydroxysuccinimide through an amide bond. The IAsys examination showed that Gly, Ala, and epsilon-AC scarcely bound to the immobilized starch chains but that GluNa and Lys favorably bound with their increasing concentrations. The relative binding index (RBI) of each amino acid was defined by the ratio of the slope of the linear regression equation between the binding response and the concentration for each amino acid to that for Gly. Because the relationships between the RBI and the pasting characteristics (pasting temperature, peak viscosity, breakdown, and swelling index) could each be expressed by a linear regression equation with a high correlation coefficient, it is concluded that the regulation of the pasting behavior of starch with an amino acid is caused by binding of the amino acid to the starch chains.
To elucidate the mechanism of taurine transport across the hepatic plasma membranes, rat liver sinusoidal plasma membrane vesicles were isolated and the transport process was analyzed. In the presence of a sodium gradient across the membranes (vesicle inside less than vesicle outside), an overshooting uptake of taurine occurred. In the presence of other ion gradients (K+, Li+, and choline+), taurine uptake was very small and no such overshoot was observed. Sodium-dependent uptake of taurine occurred into an osmotically active intravesicular space. Taurine uptake was stimulated by preloading vesicles with unlabeled taurine (transstimulation) in the presence of NaCl, but not in the presence of KCl. Sodium-dependent transport followed saturation kinetics with respect to taurine concentration; double-reciprocal plots of uptake versus taurine concentration gave a straight line from which an apparent Km value of 0.38 mM and Vmax of 0.27 nmol/20 s x mg of protein were obtained. Valinomycin-induced K+-diffusion potential failed to enhance the rate of taurine uptake, suggesting that taurine transport does not depend on membrane potential. Taurine transport was inhibited by structurally related omega-amino acids, such as beta-alanine and gamma-aminobutyric acid, but not by glycine, epsilon-aminocaproic acid, or other alpha-amino acids, such as L-alanine. These results suggest that Na+-dependent uptake of taurine might occur across the hepatic sinusoidal plasma membranes via a transport system that is specific for omega-amino acids having 2-3 carbon chain length.