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PubMed1999

Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression.

BACKGROUND: Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS: New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS: Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION: These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.

Animals↗

PubMed1984

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

Conformational changes of two isozymes of Glu-plasminogen (Glu-plg I and II) induced by omega-aminoacids were studied by using fluorescence polarization and spectropolarimetry. The rotational relaxation times (Pn) of FITC labeled Glu-Plg I and II decreased in the presence of 6 aminohexanoic acid (6AHA) or tranexamic acid (t-x), which may mean increase in Brownian motion of FITC labeled region (possibly N-terminal region) of Glu-plg I and II when 6AHA or t-x binds with lysine binding sites (LBS) of these plasminogens. Glu-plg II seems to have longer rotational relaxation time compared to that of Glu-plg I, which may mean smaller extent of Brownian motion of FITC labeled region of Glu-plg II in comparison to that of Glu-plg I. The far ultraviolet circular dichroism (CD) spectra indicate that there may be some difference in the polypeptide backbone between Glu-plg I and II, possibly more of beta-structure and less of random coil structure in Glu-plg II in comparison to Glu-plg I. The presence of 6AHA or t-x gave rise to larger change of the negative ellipticity at around 208 nm in Glu-plg I in comparison to its change in Glu-plg II, which may mean the larger extent of conformational change of Glu-plg I induced by 6AHA or t-x than that of Glu-plg II.

Aminocaproates↗

PubMed1985

Participation of blood cells in exercise-induced fibrinolysis.

The fibrinolytic response to maximal exercise on a bicycle ergometer was studied in 42 normal young adults (21 males, 21 females) by euglobulin lysis and by 125I-fibrin radiometric assay of whole blood and plasma fibrinolytic activities. Increases in plasma activity by 125I-fibrin assay were similar (mean increase, 3- to 4-fold) to those observed by euglobulin lysis, and were inhibited (90-93% inhibition) by tranexamic acid at a concentration (10 mmol/l) which inhibits plasmin-mediated fibrinolysis. In addition, there was a considerable increment in the cellular phase component, evident from simultaneous 125I-fibrin assay of whole blood and plasma activities. This cellular increment occurred in 70% of subjects (16 of 21 males, and 13 of 21 females). It represented, on average, 73% of the activity increase induced in plasma by exercise, and was not inhibited by tranexamic acid. Counts of all blood cell types were increased with exercise, but there was no correlation between absolute values for or increments in counts of any cell type and the increments in cellular activity. Thus, the fibrinolytic response to exercise in the majority of normal individuals includes not only the well-known plasmin-mediated increase in plasma, which is inhibitable by tranexamic acid, but also a similar increment in cell-mediated activity, which is due to qualitative functional rather than quantitative changes in one or more as yet unidentified cell types, acting alone or in conjunction with plasma factors which are not inhibited by tranexamic acid.

Adult↗

PubMed1993

Comparison of the lysine binding functions of lipoprotein(a) and plasminogen.

Regions of apoprotein(a) of lipoprotein(a) [Lp(a)] exhibit striking primary sequence homology to the kringles of plasminogen. The kringles of plasminogen are lysine binding structures and mediate interactions of plasmin(ogen) with substrates and inhibitors. In the current study, the lysine binding properties of Lp(a) have been compared to those of plasminogen and isolated kringle 4 of plasminogen (K4). An analytical assay was implemented to quantitate the interaction of kringle-containing molecules with lysine-Sepharose beads. Radioiodinated ligands, Lp(a), plasminogen, and K4, bound to the beads, and their interactions were inhibited by lysine analogues in a dose-dependent fashion. A series of omega-aminocarboxylic acids inhibited Lp(a), plasminogen, and K4 binding to the lysine-Sepharose beads, but marked differences in the effectiveness of these compounds were observed with each ligand. In this series of compounds, 6-aminohexanoic acid was the most potent inhibitor of binding to lysine-Sepharose for all three ligands. The pH had little effect on the inhibition of plasminogen binding by these compounds. For Lp(a), a low pH caused a marked decrease in inhibition by the 5-carbon and 4-carbon omega-amino acids. In addition, tranexamic acid was 750-fold more potent than lysine in inhibiting plasminogen and 55-fold more potent for K4 binding to the beads. In contrast, the differential potency of these compounds on Lp(a) binding was only 3-fold. These results suggest that the kringles of Lp(a) possess lysine binding functions which are similar, but not identical, to those of plasminogen and its K4.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1999

Idiopathic nonhistaminergic angioedema.

PURPOSE: We sought to describe the characteristics of a group of patients with idiopathic nonhistaminergic angioedema and their response to prophylactic treatment with tranexamic acid. METHODS: We identified 25 patients (15 men and 10 women; age at diagnosis 16 to 77 years) who had idiopathic nonurticarial angioedema that was not prevented by histamine-1 (H1) blockers. Known causes of angioedema were excluded by clinical history, physical examination, and diagnostic tests. RESULTS: The median age at the onset of symptoms was 35 years (range 8 to 66). The frequency of attacks was > 12 per year for 16 patients, six to 11 per year for 6 patients, and one to five per year for 3 patients. All patients had cutaneous attacks, 13 (52%) reported swellings of the pharynx or larynx, and 5 (20%) had symptoms consistent with bowel angioedema. Because of the similarities between these patients and patients who are deficient in C1 inhibitor, the 15 patients with severe and frequent attacks were started on prophylactic treatment with the antifibrinolytic agent tranexamic acid, 1 g three times a day orally for 3 months, tapered according to its effectiveness. The symptoms of 11 patients decreased to less than one attack per year, and the remaining 4 patients had partial remissions (less than 4 attacks per year). Fourteen patients are still being treated with tranexamic acid. CONCLUSION: Patients with idiopathic nonhistaminergic angioedema appear to have similar clinical features and response to treatment with tranexamic acid as those who are deficient in C1 inhibitor. This suggests that those two forms of angioedema might have, at least in part, a similar pathogenesis.

Adolescent↗

PubMed1996

Influence of early fibrinolysis inhibition on thrombus formation following microvascular trauma.

The effect of the fibrinolysis inhibitor tranexamic acid on early thrombus formation following microvascular trauma was investigated in the central arteries of ears in 86 rabbits (in all 172 vessels), divided into four separate blind randomised studies. In the first part a common end-to-end anastomosis was done and in the last three studies a severe trauma-arteriotomy/intimectomy was performed. Parameters studied were vessel bleeding times, patency rates, weights of intraluminal thrombotic material, haematocrit and plasma fibrinolytic activity. In the first study consisting of 14 control animals and 18 animals treated with 14 mg/kg bw of tranexamic acid, end-to-end anastomosis was performed on the central artery of one ear and on the central vein of the other ear. In the second, third, and fourth studies consisting of 18, 20, and 16 control vessels and the same number of corresponding vessels in treated animals a 7-mm longitudinal arteriotomy followed by a deep 5-mm-long intimectomy was performed. The second and third treated groups were given 14 mg/kg bw of tranexamic acid 5 min and 1 h, respectively, before reflow and the fourth group 28 mg/kg bw 5 min before reflow. The difference between the second and third studies was the addition, to mimic clinical situations, of 8.5 ml saline/kg bw 2 h before reflow in the third study. In conclusion, treatment with a single clinical dose, 14 mg/kg of tranexamic acid, did not influence vessel bleeding times or thrombus formation in the anastomotic or severe trauma models and seems safe to use. Not even a double clinical dose, 28 mg/kg, influenced thrombus formation in a statistically significant way.

Anastomosis, Surgical↗

PubMed2004

Response of rat prostate and lung tumors to ionizing radiation combined with the angiogenesis inhibitor AMCA.

AIM: To determine whether radiation combined with Trans-4-AminoMethyl Cyclohexane carboxylic Acid (AMCA, or tranexamic acid, Cyklokapron) results in a better tumor response than radiation alone. MATERIALS AND METHODS: We evaluated the responses of the L44 lung tumor in BN rats and R3327-MATLyLu (MLL) prostate tumor in Copenhagen rats, to single and fractionated X-ray doses with and without AMCA (1.5 g/kg). Tumors were grown subcutaneously in the flank of the animal. AMCA was administered subcutaneously twice daily for at least 2 weeks. Response to treatment was evaluated according to excess growth delay and specific growth delay. RESULTS: L44 and MLL tumors treated with AMCA only experienced a non-significant growth delay. L44 tumors treated with 4 daily dose fractions of 2.5 Gy had a significant excess and specific growth delay when treated with AMCA, the enhancement ratio was 1.6-1.7. The enhancement ratio based on the calculated excess biologically effective dose of the linear-quadratic concept was 1.4-1.5. MLL tumors treated with a single dose of 20 Gy and AMCA had no significant excess growth delay. CONCLUSION: The enhancement ratio of 1.4-1.7 for the L44 tumor, but not for the MLL tumor, due to AMCA treatment, indicates that AMCA may potentiate the anti-tumor effect of ionizing radiation in distinct tumor types.

Angiogenesis Inhibitors↗

PubMed2003

Pharmacological approaches to reducing allogeneic blood exposure.

This article discusses evidence for the role of pharmacological interventions such as the protease inhibitor aprotinin (Trasylol), lysine analogue anti-fibrinolytics [tranexamic acid (Cyclokapron) and epsilon aminocaproic acid (Amicar)], DDAVP (Desmopressin) and recombinant Factor VIIa (NovoSeven), in preventing the need for blood and blood-component therapies after major (cardiac, hepatic and orthopaedic/trauma) surgery. The data show that aprotinin is consistently effective in reducing globally the transfusion burden in cardiac and hepatic surgical procedures. However, there are little data to support its use in routine elective orthopaedic surgery. Multiple studies have failed to show an increased risk for myocardial ischaemia or infarction with aprotinin, and there may even be a reduced incidence of perioperative stroke in patients undergoing cardiac surgery. An increased probability of a hypersensitivity reaction when the drug is readministered within a 6-month period remains a significant issue. The data for the lysine analogue anti-fibrinolytics show no evidence of efficacy in reducing the transfusion burden for epsilon aminocaproic acid and inconsistent results with tranexamic acid in cardiac and hepatic surgery. As with aprotinin therapy, there is a paucity of data to support their use in routine elective orthopaedic surgery. There are no data to support the routine use of DDAVP to reduce the transfusion burden. Limited data suggest that this drug may be effective when a defect in platelet function is demonstrated. This aspect deserves further investigation. Recombinant activated Factor VII (rFVIIa) has proven benefit for its licensed indication to reduce bleeding in haemophiliacs with inhibitors to Factors VIII and IX. Reports of benefit in other instances are largely anecdotal. Hence, at this time it is therefore speculative and premature to suggest whether there is a place for this agent in routine clinical practice. No adequately powered, placebo-controlled prospective studies are available to investigate the safety of the lysine analogues, DDAVP or rFVIIa in cardiac, hepatic or orthopaedic surgery.

Blood Loss, Surgical↗

PubMed1999

Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study.

OBJECTIVE: To determine whether an educational package could influence the management of menorrhagia, increase the appropriateness of choice of non-hormonal treatment, and reduce referral rates from primary to secondary care. DESIGN: Randomised controlled trial. SETTING: General practices in East Anglia. SUBJECTS: 100 practices (348 doctors) in primary care were recruited and randomised to intervention (54) and control (46). INTERVENTIONS: An educational package based on principles of "academic detailing" with independent academics was given in small practice based interactive groups with a visual presentation, a printed evidence based summary, a graphic management flow chart, and a follow up meeting at 6 months. OUTCOME MEASURES: All practices recorded consultation details, treatments offered, and outcomes for women with regular heavy menstrual loss (menorrhagia) over 1 year. RESULTS: 1001 consultation data sheets for menorrhagia were returned. There were significantly fewer referrals (20% v 29%; odds ratio 0. 64; 95% confidence interval 0.41 to 0.99) and a significantly higher use of tranexamic acid (odds ratio 2.38; 1.61 to 3.49) in the intervention group but no overall difference in norethisterone treatment compared with controls. There were more referrals when tranexamic acid was given with norethisterone than when it was given alone. Those practices reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid. CONCLUSIONS: The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Intraoperative antifibrinolysis and blood-saving techniques in cardiac surgery. Prospective trial of 3 antifibrinolytic drugs.

Sixty consecutive patients undergoing elective open-heart surgery were prospectively enrolled in a study to compare the efficacy of 3 different antifibrinolytic drugs to reduce postoperative bleeding and to reduce homologous blood requirements in combination with blood-saving techniques and restrictive indications for blood transfusion. The patients were randomized to 1 of 4 intraoperative treatment regimens: 1) control (no antifibrinolytic therapy); 2) epsilon-aminocaproic acid (10 g IV at induction of anesthesia, followed by infusion of 2 g/h for 5 hours); 3) tranexamic acid (10 mg/kg IV within 30 minutes after induction of anesthesia, followed by infusion of 1 mg/kg per hour for 10 hours); or 4) high-dose aprotinin (2 million KIU IV at induction of anesthesia and 2 million KIU added to the extracorporeal circuit, followed by infusion of 500 thousand KIU/h during surgery). Hemoconcentration and reinfusion of blood drained from the operative field and the extracorporeal circuit after operation were used in all patients. Indications for blood transfusion were hypotension, tachycardia, or both, with hemoglobin values < 8.5 g/dL; or severe anemia with hemoglobin values < 7 g/dL. Compared with the blood loss in the control group, patients receiving aprotinin and epsilon-aminocaproic acid showed significantly less postoperative blood loss at 1 hour (control, 128 +/- 94 mL; aprotinin, 54 +/- 47 mL, p = 0.01; and epsilon-aminocaproic acid, 69 +/- 35 mL, p = 0.03); this trend continued at 24 hours after operation (control, 724 +/- 280 mL; aprotinin, 344 +/- 106 mL, p < 0.0001; and epsilon-aminocaproic acid, 509 +/- 148 mL, p = 0.01). Aprotinin was significantly more efficient than epsilon-aminocaproic acid (p=0.002). Tranexamic acid did not have a statistically significant effect on blood loss. Homologous blood requirements were not significantly different among the groups; postoperative hematologic values and coagulation times were also comparable. Despite the efficacy of aprotinin and epsilon-aminocaproic acid shown in the present study, the blood requirements were not significantly different from those that are found when transfusions are restricted, autotransfusions are used, and blood from the operative field and extracorporeal circuit is concentrated and reinfused. Therefore, intraoperative antifibrinolysis may not be indicated in routine cardiac surgery when other blood-saving techniques are adopted.

Adult↗

PubMed1981

Treatment of ulcerative colitis by the direct administration of an antifibrinolytic agent as an enema.

Fibrinolytic activity in biopsied colonic mucosa was examined in patients with ulcerative colitis, and most cases were found to have increased tissue fibrinolysis -- due mainly to tissue plasminogen activator -- in the affected mucosa. Five cases, 4 with elevated tissue fibrinolysis and 1 normal, were treated with an antifibrinolytic agent, tranexamic acid (trans-AMCHA) administered as an enema, to inhibit fibrinolysis of the affected mucosa directly. In patients with elevated mucosal fibrinolysis, 2 showed complete remission after tranexamic acid enema alone, and there was one remission in response to combination treatment with oral prednisolone. One case with slightly elevated mucosal fibrinolysis showed clinical improvement, although the radiological findings were unchanged. No response was observed in one case with normal tissue fibrinolysis. It is concluded that tranexamic acid may show a therapeutic effect in ulcerative colitis with elevated mucosal fibrinolysis when administered via an enema, which allows direct contact of the drug with the affected mucosa.

Adolescent↗

PubMed2006

The use of antifibrinolytic agents in total hip arthroplasty: a meta-analysis.

Total hip arthroplasty is associated with significant blood loss that often requires allogenic blood transfusions. Tranexamic acid and aprotinin have been shown to reduce blood loss and transfusions in clinical trials with variable results. This meta-analysis evaluates whether tranexamic acid and aprotinin significantly reduces blood loss and transfusion requirements in total hip arthroplasty. Thirteen clinical trials were identified. Combined, these agents were significant across all outcome measures in reducing blood loss and transfusions. Separately, only aprotinin was found to be significant. The data also showed that aprotinin (tranexamic acid is inconclusive) is only beneficial in revision total hip arthroplasty. Therefore, only aprotinin is effective in reducing both blood loss and transfusion requirements without an increase in thromboembolic complications in patients undergoing revision total hip arthroplasty.

Antifibrinolytic Agents↗

PubMed1980

Local inhibition of the fibrinolytic system in patients with massive upper gastrointestinal hemorrhage.

The effect or oral tranexamic acid on massive upper gastrointestinal hemorrhage was evaluated in a randomized double-blind study. Totally 50 patients entered the trial and seven were excluded, leaving 22 placebo treated and 21 tranexamic acid treated for analysis. The groups were comparable regarding sex, age, diagnosis, and initial laboratory data. Transfusions requirements and operation frequency did not differ. Mortality was slightly reduced and death delayed in tranexamic acid treated patients.

Administration, Oral↗

PubMed1995

Pharmacological manipulation of gastric juice: thrombelastographic assessment and implications for treatment of gastrointestinal haemorrhage.

The impairment of formation and maintenance of a formed fibrin clot contributes to the prolonged bleeding and high incidence of rebleeding in upper gastrointestinal haemorrhage. To investigate the basis for the use of drug therapy in gastric bleeding, this study used thrombelastography to determine the effects of pharmacological manipulation of gastric juice on coagulation and fibrinolysis. The thrombelastograph is a mechanical device that provides a visual assessment of all stages of coagulation and fibrinolysis. The effects of fresh and pharmacologically changed gastric juice was assessed after its addition to fresh whole blood in the thrombelastograph cuvette. Pharmacological manipulation was achieved through alkalisation or through addition of tranexamic acid, aprotinin, or sucralfate. Fresh gastric juice delayed clot formation, decreased maximum clot amplitude, and stimulated clot lysis. Alkalisation inhibited the lytic effects of fresh gastric juice and improved the induced abnormalities in coagulation. Tranexamic acid partially inhibited gastric juice induced clot lysis but did not exhibit a beneficial effect on coagulation. Sucralfate, and to a lesser extent aprotinin significantly inhibited fibrinolysis but exacerbated the detrimental effect of gastric juice on the parameters of coagulation. Alkalisation of gastric juice reduces the adverse effect on coagulation and fibrinolysis. Tranexamic acid, aprotinin, and sucralfate can all reduce or inhibit clot lysis, but the adverse effects on clot formation may outweigh any potential benefit in the treatment of gastrointestinal bleeding.

Aprotinin↗

PubMed2005

In vivo biological performance of composites combining micro-macroporous biphasic calcium phosphate granules and fibrin sealant.

INTRODUCTION: Fibrin glues are currently used by surgeons and can facilitate the handling of biomaterials. Combining fibrin glue with calcium phosphate bioceramics gives a mouldable composite that cements the granules into the implantation site. In addition to the mechanical aspect of the composite, it has been suggested that the mixture also promotes wound healing. These human blood derivatives contain natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic substances. We compared the bioactivity of two composites combining calcium phosphate granules with two different types of fibrin glue, one with aprotinin and the other with tranexamic acid. MATERIALS AND METHODS: The composite was composed of fibrin glue (Tissucol) and 1 to 2 mm granules of biphasic calcium phosphate granules (MBCP) with a volume ratio of 1 for 2. Bone cavities were drilled in 12 New Zealand rabbits and filled with a composite with aprotinin-fibrin glue on the right condyle and one with tranexamic acid-fibrin glue on the left condyle. The rabbits were randomized into two groups: 3 and 6 weeks of delay. Light microscopy, scanning electron microscopy and image analysis were performed. RESULTS: No adverse reactions were observed in either sample. Bony ingrowth associated with bioceramic resorption by osteoclastic TRAP-positive cells was noted. No significant difference was observed between the two composites. The bony ingrowth and ceramic resorption were qualitatively and quantitatively similar with both composites. CONCLUSION: This study demonstrated that the choice of a natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic agent in the fibrin sealant associated with calcium phosphate granules and used as a bone substitute had no effect on the bioactivity of the composite. It remained efficient in bone reconstruction, no adverse effects were observed, and the bony ingrowth was qualitatively and quantitatively equivalent with the two types of fibrin sealant.

Animals↗

PubMed1989

Effects of fibrinolytic inhibitors on mortality from upper gastrointestinal haemorrhage.

OBJECTIVE: To see whether fibrinolytic inhibitors are of value when given to patients with upper gastrointestinal haemorrhage. DESIGN: Meta-analysis of six randomised double blind placebo controlled trials. Two methods used for obtaining an overall estimate of effect, including a random effects model incorporating any heterogeneity of outcome in the estimate of the overall treatment effect. SETTING: Inpatient care in hospitals in the United Kingdom, Sweden, and Australia. PATIENTS: 1267 Patients admitted to hospital with primary diagnosis of acute upper gastrointestinal haemorrhage. Five of the six trials included a high proportion of elderly patients. Most patients were bleeding from peptic ulcers in the stomach and duodenum (43-88%) or gastric erosions (4-23%). A variable proportion had a degree of clinical shock at entry. INTERVENTIONS: Tranexamic acid 3-6 g/day given intravenously for two or three days followed by 3-6 g/day by mouth for a further three to five days (four trials) or 4.5-12 g/day by mouth for two to seven days (two trials). END POINTS: Frequency of recurrent haemorrhage, need for surgery, and death. MAIN RESULTS: Treatment with tranexamic acid was associated with a 20-30% reduction in the rate of rebleeding, a 30-40% reduction (95% confidence interval 10% to 60%) in mortality. CONCLUSIONS: Treatment with tranexamic acid may be of value to patients considered to be at risk of dying after an upper gastrointestinal haemorrhage.

Clinical Trials as Topic↗

PubMed2004

[Therapeutic approach of hereditary angioedema].

PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH). Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families) with HAE and their evolution. METHODS: Ten patients (1-38 years old) with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50) for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10); low serum C4 level (8/10); undetectable CH50 (3/10) and low CH50 levels (6/10); low APH50 levels (2/10). Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although HAE is caused by the same defect and affects members of the same family, various approaches have been taken to treat these patients. We observed different alternatives of prophylactic therapy for HAE, of which some did not require drug therapy.

Adolescent↗

PubMed2000

Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia.

OBJECTIVES: Good surgical technique and other interventions can reduce immediate and long-term blood loss which is a common complication of surgery for cervical intra-epithelial neoplasia. The objective of this review was to assess the effect of interventions to reduce blood loss due to surgery for cervical intra-epithelial neoplasia. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register. SELECTION CRITERIA: Randomised and quasi-randomised trials of vasopressin, tranexamic acid, haemostatic sutures or Monsel's solution in women who have had surgery for intra-epithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data. MAIN RESULTS: Seven trials were included. Vasopressin had a beneficial effect on peri-operative bleeding. Prophylactic tranexamic acid reduced haemorrhage after knife and laser cone biopsy. Packing with Monsel's solution resulted in less peri-operative blood loss and secondary haemorrhages than routine suturing. Elective suturing also appeared to increase the risk of amenorrhoea and dysmenorrhoea. Vaginal packing increased satisfactory colposcopy rates at follow-up and reduced post-surgical stenosis. REVIEWER'S CONCLUSIONS: Bleeding associated with surgery of the cervix appears to be reduced by vasopressin, which is used under local rather than general anaesthetic. Tranexamic acid appears to be beneficial after knife and laser cone biopsy. There are not enough data to assess the effects on primary haemorrhage. There is some evidence that haemostatic suturing has an adverse effect on blood loss, cervical stenosis and satisfactory colposcopy.

Blood Loss, Surgical↗