SEARCH · PubMed Health

Results for “Tranexamic Acid”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed2000

Antifibrinolytics for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women. Medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive treatment option. A wide variety of medications are available to reduce heavy menstrual bleeding but there is considerable variation in practice and uncertainty about the most appropriate therapy. Plasminogen activators are a group of enzymes that cause fibrinolysis (the dissolution of clots). An increase in the levels of plasminogen activators has been found in the endometrium of women with heavy menstrual bleeding compared to those with normal menstrual loss. Plasminogen activator inhibitors (antifibrinolytic agents) have therefore been promoted as a treatment for heavy menstrual bleeding. There has been a reluctance to prescribe tranexamic acid due to possible side effects of the drugs such as an increased risk of thrombogenic disease (deep venous thrombosis). Long term studies in Sweden, however, have shown that the rate of incidence of thrombosis in women treated with tranexamic acid is comparable with the spontaneous frequency of thrombosis in women. OBJECTIVES: To determine the effectiveness of antifibrinolytics in achieving a reduction in heavy menstrual bleeding. SEARCH STRATEGY: All studies which might describe randomised controlled trials of antifibrinolytic therapy for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1997, EMBASE 1980-1997 and the Cochrane Library. Companies producing antifibrinolytics and experts within the field were contacted for reference lists and information on unpublished trials. SELECTION CRITERIA: Randomised controlled trials in women of reproductive age treated with antifibrinolytic agents versus placebo, no treatment or any other medical (non-surgical) therapy for regular heavy menstrual bleeding within either the primary, family planning or specialist clinic settings. Women with post menopausal bleeding, intermenstrual bleeding, iatrogenic or pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Fifteen eligible trials were assessed by three reviewers and eight of these did not meet with the inclusion criteria. Of the seven remaining trials, four of these could be included within the meta-analysis. The remaining three trials had a crossover design and despite contacting the authors and appropriate companies, we were unable to extract the results in a format suitable to include these within the meta-analysis. However the results are included within the text of the review for discussion. MAIN RESULTS: Antifibrinolytic therapy compared to placebo showed a significant reduction in mean blood loss (WMD -94.0 [-151.4, -36.5]) and significant change in mean reduction of blood loss (WMD -110.2 [-146. 5, -73.8]). This objective improvement was not mirrored by a patient perceived improvement in monthly menstrual blood loss (RR 2.5 [0.9, 7.3]) in the one study which recorded this outcome ( approximately approximately Edlund 1995 approximately approximately ). Antifibrinolytic agents were compared to only three other medical (non-surgical) therapies: mefenamic acid, norethisterone administered in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0 [-123.4, -22.6], WMD -111.0 [-178.5, -43.5] and (WMD -100 [-143.9, -56.1] respectively) and a strong, although non-significant trend in favour of tranexamic acid in the participants' perception of an improvement in menstrual blood loss. There were no significant differences in the frequency of reported gastrointestinal side effects with tranexamic acid when compared to either NSAIDs (RR 0.9 [0.4, 2.1], oral luteal phase progestagens (RR 0.4 [0.1, 1.2]) or ethamsylate (RR 0.88 [0.3, 2.9]) when these treatments were used for heavy menstrual bleeding. (ABSTRACT TRUNCATED)

Antifibrinolytic Agents↗

PubMed1999

Aprotinin: an update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery.

UNLABELLED: Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transfusions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority during surgery because of shortages of donor blood, the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue which acts in a number of interrelated ways to provide an antifibrinolytic effect, inhibit contact activation, reduce platelet dysfunction and attenuate the inflammatory response to CPB. It is used to reduce blood loss and transfusion requirements in patients with a risk of haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion requirements compared with desmopressin. Results are less consistent with tranexamic acid: high dose aprotinin either reduces blood loss significantly more than, or to an equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage regimens consistently result in similar reductions in blood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerated, and the adverse events seen are those expected in patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in <0.1 to 0.6% of patients receiving aprotinin for the first time. The results of original reports indicating that aprotinin therapy may increase myocardial infarction rates or mortality have not been supported by more recent studies specifically designed to investigate this outcome. However, a tendency to early vein graft occlusion with aprotinin has been shown and care with anticoagulation and vessel grafts is required. No comparative tolerability data between aprotinin and the lysine analogues, aminocaproic acid and tranexamic acid, are available. CONCLUSION: Comparative tolerability and cost-effectiveness data for aprotinin and the lysine analogues are required to more fully assess their individual roles in reducing blood loss and transfusion requirements in patients undergoing CPB during OHS and/or CABG. However, clinical evidence to date supports the use of aprotinin over its competitors in patients at high risk of haemorrhage, in those for whom transfusion is unavailable or in patients who refuse allogenic transfusions.

Aprotinin↗

PubMed1988

The effect of antifibrinolytic agents on wound healing.

The effect on the tensile strength of healing wounds of 2 of the most commonly used antifibrinolytic substances, tranexamic acid and epsilon-aminocaproic acid, has been studied in white rats. 2 symmetrical linear lines were made on the dorsal skin, in 1 of which was injected 1 ml of the test solution. The incisions were closed with interrupted sutures, and after 7 days the animal was sacrificed, the wound excised and its tensile strength determined. The results showed tranexamic acid (1 ml of a solution containing 100 mg/ml) to have a positive effect on wound healing, whereas epsilon-aminocaproic acid (1 ml of a solution containing 400 mg/ml) had a negative effect. When both agents were compared in the same animal, wounds in tissue injected with tranexamic acid had a higher tensile strength than those made in tissue pre-treated with epsilon-aminocaproic acid. Even compared at the same ionic strength, similar results were obtained. It is clear from this investigation that, unlike epsilon-aminocaproic acid, tranexamic acid has a positive effect on wound healing, and that this effect is not due to the antifibrinolytic properties, as both are powerful fibrinolytic inhibitors.

Aminocaproates↗

PubMedDate not supplied

[Stomatologic approach in patients with congenital coagulation deficit].

BACKGROUND: The purpose of the present paper was to resolve postoperative bleeding after oral surgery in patients with congenital coagulative defects, avoid transfusion of clotting factors and improve the patient's quality of life. METHODS: Since 1988, 1598 oral surgery procedures have been performed on patients with congenital coagulative defects treated with a protocol including pre- and postoperative tranexamic acid rinses. RESULTS: The use of tranexamic acid mouth washing has obtained effective hemostasis in 86% of cases and only 4% of surgical procedures required clotting factor transfusions. CONCLUSIONS: The results suggest that mouth washing with tranexamic acid prevents excessive oral bleeding in patients with congenital deficit of the coagulation system. Furthermore, a total elimination of the granulation tissue, that reduces the possibility of activation of the fibrinolytic mechanism, is also important.

Antifibrinolytic Agents↗

PubMed2006

Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery?

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, epsilon-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; epsilon-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28-0.64) for aprotinin and 0.17 (0.11-0.24) for tranexamic acid. Results suggest a dose-effect relation with tranexamic acid. Epsilon-aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.

Adult↗

PubMed1981

Secondary-site binding of Glu-plasmin, Lys-plasmin and miniplasmin to fibrin.

Active-site-inhibited plasmin was prepared by inhibition with d-valyl-l-phenylalanyl-l-lysylchloromethane or by bovine pancreatic trypsin inhibitor (Kunitz inhibitor). Active-site-inhibited Glu-plasmin binds far more strongly to fibrin than Glu-plasminogen [native human plasminogen with N-terminal glutamic acid (residues 1-790)]. This binding is decreased by alpha(2)-plasmin inhibitor and tranexamic acid, and is, in the latter case, related to saturation of a strong lysine-binding site. In contrast, alpha(2)-plasmin inhibitor and tranexamic acid have only weak effects on the binding of Glu-plasminogen to fibrin. This demonstrates that its strong lysine-binding site is of minor importance to its binding to fibrin. Active-site-inhibited Lys-plasmin and Lys-plasminogen (Glu-plasminogen lacking the N-terminal residues Glu(1)-Lys(76), Glu(1)-Arg(67) or Glu(1)-Lys(77))display binding to fibrin similar to that of active-site inhibited Glu-plasmin. In addition, alpha(2)-plasmin inhibitor or tranexamic acid similarly decrease their binding to fibrin. Glu-plasminogen and active-site-inhibited Glu-plasmin have the same gross conformation, and conversion into their respective Lys- forms produces a similar marked change in conformation [Violand, Sodetz & Castellino (1975) Arch. Biochem. Biophys.170, 300-305]. Our results indicate that this change is not essential to the degree of binding to fibrin or to the effect of alpha(2)-plasmin inhibitor and tranexamic acid on this binding. The conversion of miniplasminogen (Glu-plasminogen lacking the N-terminal residues Glu(1)-Val(441)) into active-site-inhibited miniplasmin makes no difference to the degree of binding to fibrin, which is similarly decreased by the addition of tranexamic acid and unaffected by alpha(2)-plasmin inhibitor. Active-site-inhibited Glu-plasmin, Lys-plasmin and miniplasmin have lower fibrin-binding values in a plasma system than in a purified system. Results with miniplasmin(ogen) indicate that plasma proteins other than alpha(2)-plasmin inhibitor and histidine-rich glycoprotein decrease the binding of plasmin(ogen) to fibrin.

Binding Sites↗

PubMed2004

Haemostatic management of intraoral bleeding in patients with congenital deficiency of alpha2-plasmin inhibitor or plasminogen activator inhibitor-1.

Haemostatic management of intraoral bleeding was investigated in patients with congenital alpha2-plasmin inhibitor (alpha2-PI) deficiency or congenital plasminogen activator inhibitor- 1 (PAI-1) deficiency. When extracting teeth from patients with congenital alpha2-PI deficiency, we advocate that 7.5-10 mg kg(-1) of tranexamic acid be administered orally every 6 h, starting 3 h before surgery and continuing for about 7 days. For the treatment of continuous bleeding, such as post-extraction bleeding, 20 mg kg(-1) of tranexamic acid should be administered intravenously, and after achieving local haemostasis 7.5 mg kg(-1) of tranexamic acid should be administered orally every 6 h for several days. In addition, when treating haematoma caused by labial or gingival laceration or buccal or mandibular contusion, haemostasis should be achieved by administering 7.5-10 mg kg(-1) of tranexamic acid every 6 h. Tranexamic acid can also be used for haemostatic management of intraoral bleeding in patients with congenital PAI-1 deficiency, but is less effective when compared with use in patients with congenital alpha2-PI deficiency. Continuous infusion of 1.5 mg kg(-1) h(-1) of tranexamic acid is necessary for impacted tooth extraction requiring gingival incision or removal of local bone.

Adult↗

PubMed2004

Intraoperative moderate acute normovolemic hemodilution associated with a comprehensive blood-sparing protocol in off-pump coronary surgery.

UNLABELLED: We evaluated the blood-sparing effects of intraoperative moderate acute normovolemic hemodilution (ANH) combined with intraoperative tranexamic acid treatment and shed blood reinfusion in patients undergoing off-pump coronary artery bypass (OPCAB). One-hundred consecutive OPCAB patients (baseline hematocrit >34%) were prospectively randomized to tranexamic acid treatment (control group; 50 patients) or to tranexamic acid treatment plus normovolemic (1:1 replacement with colloids) withdrawal of 17% +/- 2% of the circulating blood volume (ANH group; 50 patients). All patients had shed blood reinfused with intraoperative bleeding in excess of 250 mL. The requirement for allogeneic transfusions, based on strict a priori defined criteria, was the primary end point of the study. Hematochemical evaluations, bleeding, major complications, and other outcomes were also recorded. Demographics, baseline hematochemical data, and operative characteristics were similar in the two groups. Patients in the ANH group had a median of 850 mL of blood withdrawn and showed a lower intraoperative minimum hematocrit (31% vs 37%; P < 0.0001). Two patients in the ANH group versus 10 patients in the control group (odds ratio, 0.17; 95% confidence interval, 0.03-0.89; P = 0.028) required transfusion of a significantly smaller number of packed red blood cell units (5 vs 24; P < 0.001). Postoperative hematochemical variables, bleeding, and outcomes were similar in the two groups of patients. Moderate ANH, combined with tranexamic acid administration and on-demand shed blood reinfusion, may reduce allogeneic transfusion requirements in OPCAB patients. IMPLICATIONS: We studied the blood-sparing effects of moderate acute normovolemic hemodilution (ANH) in 100 patients undergoing off-pump coronary surgery (OPCAB). Combined with tranexamic acid administration and shed blood reinfusion when the intraoperative bleeding exceeded 250 mL, ANH was effective in reducing the number of OPCAB patients who required allogeneic transfusions and the number of packed red blood cell units transfused.

Aged↗

PubMed1984

Antifibrinolytic treatment in subarachnoid hemorrhage.

We enrolled 479 patients with subarachnoid hemorrhage in a multicenter, randomized, double-blind, placebo-controlled trial to determine whether treatment with the antifibrinolytic agent tranexamic acid improves outcome by preventing rebleeding. At three months there was no statistical difference between the outcomes in the tranexamic acid group and the control group. Of the 173 patients who died, 84 had received tranexamic acid and 89 placebo (95 per cent confidence interval for the difference in mortality rate, -6 to 11 per cent). Similarly, when analysis was restricted to patients with an angiographically demonstrated aneurysm, there was no significant difference between the groups. This absence of effect was not due to a lack of antifibrinolytic action, since the rate of rebleeding was reduced from 24 per cent in the control group to 9 per cent in the tranexamic acid-treated group (chi-square = 18.07, P less than 0.001), but resulted from a concurrent increase in the incidence of ischemic complications (15 per cent in the control group and 24 per cent in the tranexamic acid group; chi-square = 8.07, P less than 0.01). We conclude that until some method can be found to minimize ischemic complications, tranexamic acid is of no benefit in patients with subarachnoid hemorrhage.

Cerebral Angiography↗

PubMed2006

The role of antifibrinolytic agents in gynecologic cancer surgery.

OBJECTIVE: To compare the effects of crystalloid and colloid solutions, tranexamic acid and epsilon-aminocaproic acid on the need for allogenic blood transfusion and on coagulation and fibrinolysis parameters. METHODS: We conducted the study in the Anesthesiology and Reanimation Department of Hacettepe University Medical Faculty, Ankara, Turkey between March 2004 and April 2005. The study included 105 patients, classified by the American Society of Anesthesiology as physical status groups I-II, undergoing gynecologic cancer treatment. We divided them into 5 groups: group I (crystalloid) received crystalloid solutions, group II (colloid) received colloid solutions, group III (tranexamic acid) received 10 mg x kg(-1) tranexamic acid, and group 5 (epsilon-aminocaproic acid) received 100 mg x kg(-1) epsilon-aminocaproic acid. All patients bleeding amount was measured and recorded perioperatively, and at the 12th and 24th hours postoperatively. We then evaluated the patients' hemoglobin, hematocrit, activated thromboplastin time, international normalized ration, fibrinogen, and thrombocyte count and symptoms of pulmonary embolism. RESULTS: In comparing the amount of bleeding, the bleeding in the tranexamic acid group was 30.8% less than the crystalloid group (p<0.05), 33.3% less than the colloid group (p<0.05), and 23.9% less than the epsilon-aminocaproic acid group (p<0.05). CONCLUSION: When the negative effects of blood transfusions were considered, tranexamic acid administration can be recommended for decreasing the need for blood transfusion in gynecologic cancer surgery.

Aminocaproic Acid↗

PubMed2000

Comparison of blood-conservation strategies in cardiac surgery patients at high risk for bleeding.

BACKGROUND: Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. METHODS: In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). RESULTS: There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. CONCLUSIONS: The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.

Adult↗

PubMed1997

Enzyme-controlling medicines: introduction.

A short history of the research work of S. Okamoto and co-workers, for the previous 50 years, is briefly described. In the 1950s, when the physiologic role of fibrinolysis had not been established, they began to seek for compounds that inhibit the action of plasmin. They examined approximately 200 lysine derivatives and discovered epsilon aminocaproic acid (EACA) and tranexamic acid (t-AMCHA). In the 1970s, we selected thrombin as the target enzyme to be controlled; structure-activity relationship studies, taking arginine as the skeleton structure, led to the discovery of the selective thrombin inhibitor No. 205 (4-ethyl-1-[N2-(5-dimethylamino-1-naphthalenesulfonyl)-L-arginyl]- 1-piperidine), and further attempts to minimize the toxicity finally led to No. 805 (argatroban, MD-805, (2R,4R)-4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)-sulfo nyl]-L-arginyl)-2-piperidine carboxylic acid). Argatroban, without any cofactor, inhibits thrombin competitively. The high selectivity of the action of argatroban is promising for treating thrombosis in clinical practice. More recently, taking advantage of our knowledge obtained through previous studies, active center-directed plasmin inhibitors and a selective inhibitor of kallikrein have been found.

Aminocaproic Acid↗

PubMed1988

Management of traumatic hyphema in children. An analysis of 340 cases.

Three hundred forty children with nonperforating traumatic hyphema were examined to verify or refute the possible protective action of the antifibrinolytic agent, tranexamic acid, against rebleeding. In the retrospective study group, 219 children were treated with strict bed rest, binocular patching, and sedation but did not receive antifibrinolytic agents. In the prospective study group, 121 children received systemically administered tranexamic acid; some of these children were confined to bed rest (26 cases) and some were allowed free ambulation within their rooms (95 cases). In the children who were treated with bed rest but who did not receive the antifibrinolytic agent, the frequency of secondary hemorrhage was 9.6%. Tranexamic acid reduced the incidence of secondary hemorrhage significantly: none of 26 eyes of patients who received systemically administered tranexamic acid and were confined to bed rest rebled, and only one (1.1%) of 95 eyes of children who received tranexamic acid and were allowed free ambulation in the hospital rebled.

Bed Rest↗

PubMed2003

[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)

Fibrinolytic Agents↗

PubMed1993

[The use of antifibrinolytics in heart surgery. 3 prospective studies].

In order to assess the validity of antifibrinolytic treatments in cardiac surgery, three successive controlled randomized double-blind studies were carried out in patients undergoing a first (n = 60) or repeat surgical procedure because of a valvular or coronary disease. The first study aimed at stating the value of low doses of aprotinin compared with "classical" ones and a placebo. The second study was planned to compare tranexamic acid with low-dosed aprotinin and a placebo. The last study applied to reiterated procedures and compared tranexamic acid with classical and reduced aprotinin dosages, without a placebo group. Effects were estimated on postoperative bleeding, blood transfusions, platelets function and possible complications such as thrombosis or seric creatinine elevation. A reduced bleeding was observed in the non-placebo groups of studies I and II. The 3d study did not show any significant differences in this respect between the three methods. Tranexamic acid was found as effective as aprotinin on platelets function. No significant changes of seric creatinine was observed from preoperative to 4th postoperative day. A valvular non-obstructive thrombosis occurred on the second postoperative week in the tranexamic acid group.

Antifibrinolytic Agents↗

PubMed1992

Effects of antifibrinolytic agents on the life span of fibrin sealant.

Fibrin sealant, a biologic glue consisting of fibrinogen and thrombin, has been used in a variety of surgical procedures. The usefulness of fibrin sealant may be prolonged by the addition of antifibrinolytic agents. This study compared the efficacy of transexamic acid (30 mg/ml), epsilon-aminocaproic acid (25 mg/ml), and aprotinin (3000 KIU/ml) to provide data on the choice of an appropriate antifibrinolytic agent for use with fibrin sealant. By use of a modified in vitro plasma euglobulin lysis time (hours), all agents were found to be superior (n = 10 for each agent, P < 0.05, analysis of variance for completely randomized design followed by Dunnett's test for multiple comparisons) to control. Lysis times (mean +/- SE) were (control) 50.9 +/- 0.5, (tranexamic acid) 402.6 +/- 25.4, (epsilon-aminocaproic acid) 433.5 +/- 21.2, and (aprotinin) 393.9 +/- 26.0. Using the in vivo implantation of fibrin sealant supplemented with 125I-fibrinogen in the rat peritoneum significant improvement in percentage clot (mean +/- SE) remaining was found (P < 0.05, analysis for repeated measures followed by tests for multiple comparisons) under the following conditions: at 3 hr by weight (n = 15), tranexamic acid (70.13 +/- 2.02%) was superior to aprotinin (61.22 +/- 2.21%) and control (61.28 +/- 2.36%); at 3 hr by radioactivity counts (n = 19), tranexamic acid (76.29 +/- 0.75%) was superior to epsilon-aminocaproic acid (72.52 +/- 1.28%) and aprotinin (73.84 +/- 0.78%); at 72 hr by radioactivity counts (n = 10), aprotinin (27.30 +/- 2.45%) was superior to epsilon-aminocaproic acid 19.76 +/- 3.09% and control (20.38 +/- 3.01%). These data suggest the early (3-hr) superiority of tranexamic acid as an inhibitor of plasminogen activation and the late (72-hr) effectiveness of aprotinin as an inhibitor of plasmin. The possibility of a synergistic effect of tranexamic acid and aprotinin is suggested.

Adhesives↗

PubMed1996

Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents for dental extractions in hemophilia B.

This study evaluated the safety and efficacy of combined treatment with epsilon-aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX (MAb factor IX) for prophylaxis against bleeding in eight hemophilia B patients undergoing nine dental extraction procedures. All patients achieved excellent hemostasis without clinical evidence of thrombosis. There were no significant changes in hemoglobin or hematocrit or in markers of hemostatic system activation (prothrombin fragment F1+2, fibrinopeptide A, and fragment B beta 15-42) after surgery. Thus, a highly purified factor IX concentrate and antifibrinolytic therapy can be effectively and safely combined in hemophilia B patients undergoing dental extractions.

Adult↗

PubMed1987

Antifibrinolytic agents in subarachnoid haemorrhage.

For many years clinicians have used antifibrinolytic agents to try to reduce rebleeding after subarachnoid haemorrhage. Early studies of their effectiveness produced conflicting results. This paper re-evaluates the available trials and considers benefits in the light of potential complications. Present evidence conclusively demonstrates that epsilon-aminocaproic acid and tranexamic acid administered in standard dosage, reduce the risk of rebleeding but, as a result of an increased incidence of ischaemic complications, do not benefit patients' outcome.

Antifibrinolytic Agents↗