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PubMedDate not supplied

[Reduction of intra- and post-operative bleeding after treatment with a peptide fraction derived from bovine factor VIII].

The most common post-operative complication of adenotonsillectomy is an excessive bleeding. This problem persists although the laboratory investigations may exclude hemocoagulative anomalies and the anamnesis is able to show the presence or not of genetic factors or constitutional disease. Even if the surgical operation is performed in a technical proper way, the risk of bleeding is still present. Therefore we have valued new prospects of application in pediatric O.R.L. of a peptide fraction from bovine factor VIII. This compound has proved to be able to reduce the bleeding time. We valued the action of this drug compared with that of tranexamic acid and in comparison with the results obtained before treatment. Furthermore, we have also investigated the possibility of influence of this drug on haemocoagulative parameters and we have concluded that the drug does not show any effect on them.

Adenoidectomy↗

PubMed1982

Antifibrinolytic treatment in subarachnoid haemorrhage: present state.

Two randomised controlled clinical trials in patients with recently ruptured intracranial aneurysms were undertaken using tranexamic acid (AMCA) to prevent early recurrent bleeding. In our accumulated series of 105 patients 53 were given AMCA and 52 were controls. 13% of the AMCA-treated patients and 31% of the controls rebled. In patients treated with AMCA the recurrent bleeding took place later than the rebleeding in the control patients. Vasospasm and delayed cerebral ischaemic deficits were seen more frequently in patients treated with AMCA. Total mortality from rebleeding and cerebral ischaemia was 25% in AMCA-treated patients and 19% in the controls during the six weeks' observation time. Coagulation factors remained unaffected by the drug. Local fibrinolysis in the cerebrospinal fluid decreased after one week in patients treated with AMCA. After two weeks the fibrinolytic activity was similar in AMCA-treated patients and in the controls. After experimental subarachnoid haemorrhage in 90 rabbits, AMCA was found to suppress plasminogen activator activity, mainly in the leptomeninges. This occurred however only during the first few postbleeding days. Antifibrinolytic agents only appear to reduce the risk of recurrent bleeding during the first ten day period after the primary aneurysm rupture. However they also seem to produce delayed cerebral ischaemia in patients with subarachnoid haemorrhage. Synthetic antifibrinolytics evidently shift the incidence of rebleeding curve to the right but these drugs are probably of diminished value in the subsequent weeks of risk.

4-Aminobenzoic Acid↗

PubMed1982

Effect of fibrinolysis inhibitor and chemotherapeutics on the growth of human cancers transplanted into nude mice and in tissue culture.

Effects of tranexamic acid (AMCHA) alone or together with anticancer drug on the growth of human cancers transplanted into nude mice and in tissue culture were investigated. AMCHA showed no effects on cancer cells in vitro. Fibrin deposition and host stromal reaction at the advancing border of the tumor tended to increase after AMCHA administration. These seem to contribute to the significant reduction of tumor growth rate by AMCHA in combination with an anticancer drug compared to control.

Animals↗

PubMed1983

Reduction of gastric haemorrhage by fibrinolysis inhibition - an experimental study in rats.

Gastric ulcerations were induced in rats by pyloric ligature and instillation of 1.0 N HCl. After four hours all rats had developed ulcerations. Increased release of plasminogen activators from the mucosa during these conditions has previously been demonstrated. In the present study we investigated the role of fibrinolysis inhibition versus H2-receptor blockade on the gastric bleeding. Tranexamic acid - a synthetic inhibitor of the fibrinolytic system - was found to significantly (p less than 0.01) reduce blood loss into the gastric juice by 30% measured by 51Cr labelled red blood cells; cimetidine did not reduce the gastric haemorrhage under the experimental conditions used. Both treatment regimes significantly (p less than 0.02) reduced the secretion of gastric juice. These results indicate a contribution of the fibrinolytic system in gastric bleeding from experimentally induced gastric ulcerations.

Animals↗

PubMed1984

Fluorescence spectrophotometric studies on the conformational changes induced by omega-aminoacids in two isozymes of Glu-plasminogen (I and II).

Glu-plasminogen I (Glu-plg I: with two carbohydrate chains) and Glu-plg II (with one carbohydrate chain) were separated by a gradient elution of 6 aminohexanoic acid (6AHA) through lysine-Sepharose. Each preparation was excited with ultraviolet light of wave length at 291 nm. The intensity of fluorescence was measured at 340 nm. The intensity of fluorescence increased to a small extent at 0.02 mM of tranexamic acid (t-x) for Glu-plg I and then quickly increased from 0.1 mM of t-x to reach the peak at 0.6 mM. The intensity of fluorescence for Glu-plg II started to increase at 0.2 mM to reach the peak at 0.7 mM. No small increase of fluorescence was observed at less than 0.2 mM of t-x for Glu-plg II. Kdobs of Glu-plg I for t-x and 6AHA were 0.34 mM and 1.35 mM, respectively, whereas Kdobs of Glu-plg II for t-x and 6AHA were 0.46 mM and 3.3 mM, respectively. When Glu-plg I and II were activated by urokinase (UK) and the hydrolysis of S-2251 was measured, the extent of hydrolysis increased in the presence of t-x and 6AHA. The rate of the increase of S-2251 hydrolysis (thus activation rate of Glu-plg I and II with UK) increased in parallel with increase in fluorescence intensity of Glu-plg I and II in the presence of omega-aminoacids. In conclusion, changes in the activation rate with UK and in fluorescence intensity were observed at lower concentrations of omega-aminoacids for Glu-plg I than for Glu-plg II.

Aminocaproates↗

PubMed1981

The effects on extraction wound healing of a new drug combination introduced for use in the prevention of post-extraction complications. A preliminary report.

Fifteen extraction sockets packed with a new drug combination which includes a local anaesthetic (cincain chloride), a local antiseptic (tri-iodomethane) and two drugs with a potent antifibrinolytic activity (tranexamic acid and propyl-hydroxy-benzoic acid) in an absorbable gelatin sponge (Gelfoam) as a vehicle, were histologically assessed with special reference to the parameters related to wound healing. As a control, the same number of sockets were allowed to heal spontaneously and similarly assessed. Healing of the extraction wounds seemed to follow the normal sequence in both series, and no histological signs suggestive of a delay in the healing process could be found in any of the sockets studied. Also the mast cell count previously considered to be of importance in the connective tissue repair was found to be unaffected by the test substance. These results, together with the previously presented data on the clinical efficacy of the drug combination studied, suggest that a larger clinical study should be carried out to assess its value as a preventive measure against the development of the post-extraction symptoms, including dry socket.

Adolescent↗

PubMed1988

Determination of plasminogen activator inhibitor (PAI) capacity of human plasma in presence of oxidants: a novel principle.

A new functional assay of PAI-activity in human plasma is described. Hitherto known assays for fast acting PAI have some disadvantages: predilution and/or acidification steps of the sample to afford the required inactivation of alpha-2-antiplasmin (A2-PI). This approach in contrast implicates test performance in presence of chloramine T (CT), an oxidant that destroys plasma antiplasmin activity without impairing significantly the activity of urokinase (u-PA) or plasmin. The following reaction conditions were found optimal: 50 microliter of undiluted plasma, anticoagulated with citrate or EDTA, were first incubated with 1 IU u-PA in a Tris-buffer, pH 8.4 and then with Glu-plasminogen (0.85 mumol/l final), CT (2.5 mmol/l final), tranexamic acid (0.9 mmol/l final) for 5 min. at 37 degrees C. After addition of 0.3 mmol/l of the chromogenic plasmin substrate H-D-Nva-CHA-Lys-pNA (pNA = para nitroanilide) and of NaCl (250 mmol/l final) a linear kinetic with delta A405/t in the range of 0.2/min for normal plasma was recorded. In an endpoint version of the test the chromogenic substrate can be added together with plasminogen resulting an A/t2-kinetic. Dilution studies showed a linear calibration curve from 0 to 14 arbitrary u-PA inhibiting units (AU)/ml plasma. By means of PAI-standard plasmas PAI-capacity values of 20 healthy volunteers (10 males/10 females) (x = 26 years, sigma = 4.2) were determined. They ranged from 0.4 - 6.9 (x = 1.3, sigma = 0.9) AU/ml plasma. Plasma samples containing more than 14 AU/ml were prediluted with PAI-deficient plasma. Intra- and inter-assay coefficients of variation (CV) were determined to be 1.3 +/- 0.6 and 4.3 +/- 0.5%, respectively. The values of this assay correlate well with those obtained by acidification of the samples. However, the possibility of measuring plasma PAI (and PA) activities by means of a simple and direct approach can be considered as an important progress with regard to routine hospital practice. The presented oxidative inactivation of A2-PI mimics the leukocyte attack phase, suggesting that activated leukocytes create a microenvironment of uncontrolled plasmin activity.

Adult↗

PubMed1981

The role of antifibrinolytic therapy in the preoperative management of recently ruptured intracranial aneurysms.

In a retrospective study of the use of antifibrinolytic therapy in a series of patients with recently ruptured intracranial aneurysms, 131 patients were selected based on the following criteria: commencement of therapy within 3 days of the last subarachnoid hemorrhage (SAH); continuation of therapy for at least 6 days; and apparently uncomplicated surgery. Two main modalities of antifibrinolytic therapy were used: Group A, tranexamic acid (AMCA) 3 gm daily plus aprotinin k.i.u. (kallikrein inactivating units) daily (82 cases); Group B, AMCA 6 gm daily (41 cases). The remaining 8 patients were treated with epsilon-aminocaproic acid alone or in combination with aprotinin and were not considered to constitute a large enough group for statistical comparison. The rest of the preoperative treatment consisted of bed rest; mild sedation; antihypertensives, if the blood pressure exceeded 160 mm Hg; and osmotic diuretics as needed. The mean interval between last SAH and operation was about 13 days in both groups. The rates of rebleeding and thromboembolism were similar in the two groups but the rates of ischemic complications and post-SAH hydrocephalus were higher in Group B. The difference in the rate of severe cerebral ischemic complications was statistically significant (11 of 82 in Group A versus 12 of 41 in Group B, p less than 0.02), and in the main they were present preoperatively. The rates of rebleeding (approximately 10%) and of death from rebleeding (approximately 5%) are lower than in other published series on the natural history of this condition. In cases in which antifibrinolytics are indicated, present evidence indicates that low-dose AMCA plus aprotinin seems to be a rational combination for lowering the rebleeding, ischemic complication, and post-SAH hydrocephalus rates.

Adult↗

PubMed1983

Comparison between antifibrinolytic and antiprostaglandin treatment in the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices.

The effects of a fibrinolysis inhibitor (tranexamic acid, TA) and prostaglandin synthesis inhibitor (diclofenac sodium, DS) were compared in the reduction of excessive menstrual blood loss in 19 women with an intrauterine contraceptive device (IUCD). These women (mean blood loss before treatment to 135.1 +/- 18.9 SE ml, range 70-294 ml) were treated in random order with TA (1.5 g three times daily for 5 days starting on the first day of menstruation for two periods), and with DS (50 mg three times on the first day followed by 25 mg three times daily for 4 days, for two periods), or with placebo (one period) in a double-blind trial. The placebo treatment did not change menstrual blood loss (128.3 +/- 15.6 ml). The TA treatment decreased blood loss to 59.4 +/- 7.7 ml (P less than 0.001) and the DS treatment to 102.1 +/- 13.6 ml (P less than 0.01). Neither treatment abolished pelvic discomfort during menstruation or shortened its duration. Various side-effects were noted by 12 women during 19 TA treatments and by five women during six DS treatments. Thus, while TA is generally far more effective, DS gave pronounced decreases in menstrual bleeding in some women and had less frequent side-effects.

Adult↗

PubMed1979

Early postoperative changes in graft thickness after penetrating keratoplasty. Influence of host corneal disorder on time course.

In 172 patients the thickness of the corneal graft was followed with frequent measurements during the first 14 days after operation. Three different graft thickness time courses were observed. Patients with keratitis, stromal dystrophy and corrosion or mechanical lesion showed a secondary rise in graft thickness on the 6th postoperative day, while patients with keratoconus and those treated with tranexamic acid showed no rise on the 6th day. Patients with Fuchs' dystrophy differed from the other groups in not reaching the maximal thickness until the 3rd postoperative day. The possible correlation of these three time courses with changes in the fibrinolytic system is discussed.

Age Factors↗

PubMed1991

Serpin-serine protease binding kinetics: alpha 2-antiplasmin as a model inhibitor.

We have examined in detail the kinetics of binding of the serpin alpha 2-antiplasmin to the serine proteases alpha-chymotrypsin and plasmin. These represent model systems for serpin binding. We find, in contrast to earlier published results with alpha 2-antiplasmin and plasmin, that binding is reversible, and slow binding kinetics can be observed, under appropriate conditions. Binding follows a two-step process with both enzymes, with the formation of an initial loose complex which then proceeds to a tightly bound complex. In the absence of lysine and analogues, equilibrium between alpha 2-antiplasmin and plasmin is achieved rapidly, with an overall inhibition constant (Ki') of 0.3 pM. In the presence of tranexamic acid or 6-aminohexanoic acid, lysine analogues that mimic the effects of fibrin, plasmin binding kinetics are changed such that equilibrium is reached slowly following a lag phase after mixing of enzyme and inhibitor. The Ki' is also affected, rising to 2 pM in the presence of 6-aminohexanoic acid concentrations above 15 mM. Thus extrapolation to the in vivo situation indicates that complex formation in the presence of fibrin will be delayed, allowing a burst of enzyme activity following plasmin generation, but a tight, pseudoirreversible complex will result eventually. Chymotrypsin is more weakly inhibited by alpha 2-antiplasmin, exhibiting an overall Ki' of 0.1 nM, after two-stage complex formation. The inhibition constant for the initial loose complex (Ki) is very similar for both enzymes. The difference in binding strength between the two enzymes is accounted for by the dissociation rate constant of the second step of complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproic Acid↗

PubMed1980

Irradiation and gastro-intestinal fibrinolysis: an experimental study in the rat.

Tissue fibrinolysis in the rat stomach and transverse colon was studied after X-ray irradiation of the abdomen. Tissue biopsies were examined on unheated fibrin plates and with a histochemical technique modified from Todd. A significantly increased fibrinolytic activity was found in the mucosa of the stomach and colon 3 days after irradiation, while fibrinolysis localized to submucosal vessels was unchanged. Mucosal fibrinolysis in the stomach was significantly inhibited by intragastric administration of tranexamic acid.

Animals↗

PubMed2003

Protease inhibitors in the treatment of hereditary angioedema.

Deficiency of C1 Inhibitor leads to unopposed activation of complement, with localized, unpredictable, and sometimes life-threatening attacks of angioedema. Treatment with plasma-derived C1 Inhibitor rapidly aborts attacks, and may be lifesaving, but is expensive, requires use of a pooled blood product, may need to be repeated and may not be effective in autoantibody mediated angioedema. The antifibrinolytic agents aprotinin, tranexamic acid, and epsilon-aminocaproic acid are useful for prophylaxis and treatment of angioedema, likely by inhibiting plasmin. Specific drugs to replace the deficient C1 Inh have not been reported. The kallikrein inhibitor DX-88 (Dyax) has received orphan drug status in Europe and is undergoing clinical trial in Europe and the USA.

Aminocaproic Acid↗

PubMed1981

A new combination of drugs intended to be used as a preventive measure for the postextraction complications. A preliminary report.

Fifteen extraction sockets packed with a new drug combination, including a local anesthetic (cincain chloride), a local antiseptic (tri-iodomethane) and two drugs with a potent antifibrinolytic activity (tranexamic acid and propyl-hydroxybenzoic acid) in Gelfoam as a vehicle, were assessed clinically with special reference to the development of the postextraction symptoms, dry socket included. As a control series, 15 extraction sockets allowed to undergo a spontaneous healing were similarly evaluated. All the sockets in both series were found to heal according to the normal sequence. There were, however, statistically highly significant differences between the two series with regard to the clotting time, postextraction pain and the need for adjunct analgesics, in favor of the sockets packed with the compound in test. The observed beneficial effects of the test compound are discussed in the light of the recently elucidated etiologic and pathogenetic mechanisms leading to the development of dry socket, and a conclusion is drawn that the present results, although preliminary due to the limited number of patients, advocate further evaluation of the new drug combination and its applicability in the prevention of the troublesome postextraction complications, including dry socket.

Adolescent↗

PubMed1978

Management of late corneal graft problems.

Immediately after an operation the corneal graft is taken care of by the surgeon, but after a certain period of time the control lies in the hands of the general ophthalmologist. Examples of the management of different kinds of postoperative complications are presented. Early correct treatment of any graft problem is of decisive importance. Careful slit-lamp examination and measurement of graft thickness is stressed and the prompt use of systemic and subconjunctival steroids is recommended for incipient graft failure. Systemic tranexamic acid may also be useful.

Adrenal Cortex Hormones↗

PubMed1979

[Actinic prurigo. Treatment with antifibribolytics].

Preceded by a brief commentary about the clinical characteristics of actinic prurigo, the qualities of anantifibrinolytic medication and its possible machanism of action in allergic conditions and atopias are analysed. An earlier experience with five familiar cases of actinic prurigo given 1 g of tranexamic acid or 3 g E. ACA, within a period of three months has been effective remarkally exceeding the results obtained with other therapeutic agents. The proposed therapeutic scheme may or may not be, modified, according to the response to the response of each individual case.

Adolescent↗

PubMed1975

[Study of a large family with hereditary angioneurotic edema].

A large kindred (156 members) with hereditary angioneurotic edema is reported. 44 members of the family exhibit typical symptoms of the disease: recurring edemas of the skin and episodes of abdominal pain accompanied by vomiting due to mucosal edema in the stomach and intestine. In 32 patients complement studies were performed which in 28 cases revealed decreased levels of C1-inhibitor and almost normal values for C3 concentration. Among 21 members of the family who had never had symptoms of the disease, 7 also had low levels of C1-inhibitor. In 6 of 16 women, attacks often occur in conjunction with menstruation. In 9 of 10 women the symptoms of the disease had worsened during their first pregnancy. 8 patients have been successfully treated with tranexamic acid for 7-20 months.

Adolescent↗

PubMed1978

Anti-fibrinolytic therapy of giant hypertrophic gastritis (Menetrier's disease).

In five cases of giant hypertrophic gastritis (Menetrier's disease) biopsied gastric mucosa was examined for fibrinolytic activity; in all cases there was marked elevation of the activity due mainly to tissue plasminogen activator. The patients were given antifibrinolytic therapy with oral tranexamic acid (trans-4-aminomethyl cyclohexane carboxylic acid; trans-AMCHA), and four of the patients showed marked improvement of their hypoproteinemia as well as their mucosal disorders. One patient, who showed moderate increase of serum protein level but no reduction of the mucosal disorder, finally received gastrectomy. It was concluded that antifibrinolytic therapy seemed to block the vicious circle of 'membrane disorders', 'increased tissue fibrinolysis', 'increased vascular permeability' and 'hypoproteinemia' in Menetrier's disease.

Adult↗