Non-Hereditary Angioedema Treated with Tranexamic Acid

Ten patients with frequent attacks of non-hereditary angioedema were treated with tranexamic acid or placebo in a double blind manner, each period lasting 3 months. During the tranexamic acid period nine patients became symptom-free, or substantially improved, while one was unaffected (P less than 0.05). In four patients itching was a major accompanying complaint which was relieved in three. Diarrhoea and abdominal discomfort were more pronounced during tranexamic acid treatment (P less than 0.05), but only necessitated dose reduction in one patient. Four years later contact was obtained with eight of the nine responders and six were still taking tranexamic acid regularly, while in two patients the attacks were so infrequent that the drug was not taken regularly.     

Tranexamic acid: Preoperative prophylactic therapy for patients with hereditary angioneurotic edema

Short-term therapy of 96-hr duration with tranexamic acid was prophylactically effective as defined by the absence of attacks of angioedema in 14 patients with hereditary angioedema undergoing 10 dental and 4 general surgical procedures. Eight of the 14 patients had previously undergone dental extractions without prophylactic therapy with antifibrinolytic agents and each had experienced one or more attacks of angioedema. Seven of these 8 patients had a cumulative experience of 13 episodes of laryngeal edema after dental extractions and the eighth had a bout of cutaneous angioedema. Although the number of dental extractions conducted without prophylactic antifibrinolytic therapy cannot be accurately defined in retrospect, the prominence of laryngeal edema in this circumstance is striking when compared with the absence of attacks in the presence of prophylaxis with tranexamic acid. Methyltestosterone and impeded androgens are now known to be effective prophylaxis for spontaneous and, presumably, postoperative attacks when employed chronically because their administration is associated with correction of the biochemical defect of hereditary angioneurotic edema, but their chronic administration to children and women of childbearing age requires further definition because of their potential pituitary suppressive action. Tranexamic acid prophylaxis makes it possible to offer to untreated patients with hereditary angioneurotic edema dental work and other operative procedures that in the past were withheld or conducted with considerable risk.     

Activation of the contact system and fibrinolysis in autoimmune acquired angioedema: A rationale for prophylactic use of tranexamic acid

Cl-inhibitor deficiency results in bouts of mucocutaneous edema and may be inherited (hereditary angioedema) or acquired (acquired angioedema [AAE]). The two forms have the same clinical picture but differ in the response to treatment. Prophylaxis with antifibrinolytic agents produces better results in the acquired form than in the inherited form, in which androgen derivatives are more effective. It is hypothesized that activation of the contact and fibrinolytic systems is involved in the pathogenesis of attacks. We evaluated these two systems in plasma from eight patients with AAE and anti-Cl-inhibitor autoantibodies (autoimmune AAE) by measuring the cleavage of high molecular weight kininogen and the complexes formed by plasmin and its inhibitor α₂-antiplasmin. We also measured complement parameters, autoantibody titer, and cleaved Cl-inhibitor (relative molecular mass = 96,000), because autoantibodies to Cl-inhibitor are known to facilitate its cleavage by proteases. Plasma was obtained from patients in remission, during prophylactic treatment with the antifibrinolytic agent tranexamic acid (2 to 4.5 gm/day) and also from two patients during acute attacks of edema. Levels of cleaved high molecular weight kininogen and antiplasmin-plasmin complexes in patients with AAE were both higher in basal conditions, during treatment, and during acute attacks than those in normal subjects (p < 0.001). The cleaved inactive form of Cl-inhibitor was also present in all patients in all three conditions. Therapy with antifibrinolytic agents reduced the frequency and intensity of symptoms without significantly changing any of the biochemical parameters. Our data demonstrate that in patients with autoimmune AAE there is continuous activation of contact and fibrinolytic systems, which might be counteracted by antifibrinolytic agents, as indicated by the favorable effects of prophylactic treatment with tranexamic acid.     

Hemostatic effect of tranexamic acid mouthwash in anticoagulant-treated patients undergoing oral surgery

We carried out a placebo-controlled, double-blind, randomized study of the hemostatic effect of tranexamic acid mouthwash after oral surgery in 39 patients receiving anticoagulant agents because of the presence of cardiac valvular stenosis, a prosthetic cardiac valve, or a vascular prosthesis. Surgery was performed with no change in the level of anticoagulant therapy, and treatment with the anticoagulant agent was continued after surgery. Before it was sutured, the operative field was irrigated in 19 patients with 10 ml of a 4.8 percent aqueous solution of tranexamic acid (an inhibitor of fibrinolysis) and in 20 patients with a placebo solution. For seven days thereafter, patients were instructed to rinse their mouths with 10 ml of the assigned solution for two minutes four times a day. There were no significant differences between the two treatment groups in base-line variables, including the level of anticoagulation at the time of surgery. Eight patients in the placebo group had a total of 10 postoperative bleeding episodes, whereas only 1 patient in the tranexamic acid group had a bleeding episode (P = 0.01). There were no systemic side effects. We conclude that local antifibrinolytic therapy is effective in preventing bleeding after oral surgery in patients who are being treated with anticoagulants.     

Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding

We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.     

氨甲环酸在全膝关节置换中的应用进展

全膝关节置换术(TKA)是目前晚期膝关节病变的终末治疗手段,但是伴发大量的术后失血,严重影响术后康复及患者满意度。氨甲环酸(TXA)作为一种抗纤溶药物,能够阻断纤溶酶原向纤溶酶转化,进而抑制纤维蛋白的溶解,可有效减少术后失血。但是目前临床上对氨甲环酸在全膝关节置换术中应用的用药途径、剂量、次数以及安全性尚未形成统一的标准。因此,本文就上述内容的最新研究进展进行综述。     

Treatment for hereditary angioedema with normal C1‐INH and specific mutations in the F12 gene (HAE‐FXII)

Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE‐FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE‐FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE‐FXII. Potential triggers included estrogen‐containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin‐converting enzyme inhibitors. Drug treatment comprised plasma‐derived C1 inhibitor (pdC1‐INH) for acute swelling attacks and progestins, tranexamic acid, and danazol for the prevention of attacks. Discontinuation of eOC was effective in 25 (89.3%) of 28 women and led to a reduction in the number of attacks (about 90%). After ending hormonal replacement therapy, three of eight women became symptom‐free. Three women with exacerbation of HAE‐FXII during intake of quinapril or enalapril had no further HAE‐FXII attacks after discontinuation of those drugs. Eleven women were treated with pdC1‐INH for 143 facial attacks. The duration of the treated facial attacks (mean: 26.6 h; SD: 10.1 h) was significantly shorter than that of the previous 88 untreated facial attacks in the same women (mean: 64.1 h; SD: 28.0 h; P < 0.01). The mean reduction in attack frequency was 99.8% under progestins after discontinuing eOC (16 women), 93.8% under tranexamic acid (four women), and 100% under danazol (three women). For patients with HAE‐FXII, various treatment options are available which completely or at least partially reduce the number or duration of attacks.     

Management of pregnancy in hereditary angioedema in a resource constrained setting: Our experience at Chandigarh,North India

Hereditary angioedema (HAE) is a rare genetic disorder distinguished clinically by recurrent episodes of non-pruritic swelling. Although pregnancy has been considered a trigger, it may have variable effect on frequency of attacks of HAE. C1-inhibitor (C1-INH) is the treatment of choice for management of HAE during pregnancy. However, because of non-availability of C1-INH therapy in developing countries, fresh-frozen plasma (FFP) and tranexamic acid remain the drugs of choice in pregnancy for treatment of acute attacks and for prophylaxis respectively. There is paucity of data on outcome of pregnancy with patients with HAE from developing countries such as India where all the first line medications are not available.A retrospective review was done including four HAE patients who conceived (with a total of 9 pregnancies). Our results suggest that frequency of attacks may increase during pregnancy especially during second trimester and post-delivery (during breastfeeding). However, HAE attacks are rare at the time of delivery.In resource limited settings, treatment with FFP/tranexamic acid needs to be individualised.     

Diagnostic and therapeutic problems associated with hereditary deficiency of the C1 esterase inhibitor

Six patients in a family with a history of hereditary angioedema reported swelling of the extremities and recurrent abdominal pain occurring spontaneously or after trauma. Attacks of oedema involving the airways, the greatest danger with this disorder, were present only in one case. This autosomal dominant disease is due to deficient activity of the inhibitor of the first component of complement. Low levels of C4, and absence of C1 esterase inhibitor confirm the diagnosis. Two asymptomatic cases with the appropriate biochemical abnormality are reported in this study. For short term prophylaxis of attacks (before surgery especially), fresh frozen plasma is used, or better still, C1 esterase inhibitor. For long term prophylaxis of attacks antifibrinolytic and hormonal drugs are used: in two cases, the authors obtained good results with methyltestosterone after failure of tranexamic acid.     

Treatment of hereditary angioedema

Summary The purpose of this study was to report the results of different treatments in 20 patients with hereditary angioedema. Effectiveness of tranexamic acid in preventing swellings was evaluated in 15 patients: in all but 3 subjects tranexamic acid was effective without serious side effects. 15 severe attacks of edema were managed with intravenous infusions of either kallikrein inhibitor (8 cases) or concentrate of C 1 esterase inhibitor (7 cases). In only 1 case was the kallikrein inhibitor unsuccessful. C 1 esterase inhibitor concentrate proved highly effective in the treatment of acute attacks (the result was lacking in one patient because of too low dosage of the drug). No side effects were observed with both treatments, but improvement was more rapidly achieved with infusion of C 1 esterase inhibitor. The serum levels of C 4 and C 1 esterase inhibitor and the activity of C 1 esterase inhibitor before and after long-term prophylaxis and acute attacks treatment were investigated.     

Comparison of tranexamic acid (Transamin) and traditional therapy for sudden deafness

The effectiveness of tranexamic acid treatment for sudden deafness was studied in detail. The results of treatment with tranexamic acid administration in 19 cases (25 ears) of sudden deafness and two historical control groups using various treatments were compared by the chi square contingency test. The data suggested that tranexamic acid treatment may be superior to traditional treatments especially if treatment is begun early. Among ears treated with tranexamic acid, 11 ears (44%) were healed or recovered remarkably, 8 ears (32%) recovered slightly and 6 ears (24%) were unchanged or worsened. Fibrinolysis in the inner ear may be the pathophysiology of sudden deafness. Treatment with tranexamic acid starting within 4 days after onset of symptoms was most effective in patients whose initial audiogram was flat or concave, initial average hearing loss at 5 frequencies (250 Hz, 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz) was between 23 dB and 76 dB (mean; 45.1 dB) and was not accompanied by dizziness.     

静脉输注氨甲环酸对全膝关节置换后隐性失血的影响

背景：人工全膝关节置换过程中,止血带的使用、手术创伤等因素会导致纤溶系统的异常激活,是术后失血的主要原因。氨甲环酸是一类抗纤溶药物,在人工全膝关节置换中使用,可减少置换后显性失血、总失血量,并降低异体血输血率。然而,氨甲环酸对人工全膝关节置换后隐性失血的影响尚未明确。 目的：观察静脉输注氨甲环酸对初次全膝关节置换后隐性失血的影响。 方法：回顾性分析2013年6至12月北京大学第三医院行初次单侧全膝关节置换54例患者的临床资料,按照是否使用氨甲环酸分为两组。氨甲环酸组22例在术中经静脉给予总量2 g的氨甲环酸,对照组32例使用等量生理盐水。两组患者置换后均口服利伐沙班抗凝。记录患者置换前及置换后连续5 d的血红蛋白、血红细胞压积,采用Gross方程计算总失血量和隐性失血量,比较两组间失血量的差异性。置换后1周行下肢静脉超声检查,判断有无下肢深静脉血栓形成。 结果与结论：两组患者一般资料、围术期情况等比较差异均无显著性意义(P > 0.05)。氨甲环酸组患者置换后引流量、显性失血量、总失血量、自体血回输量、异体血输注量均明显少于对照组,差异有显著性意义(P < 0.05)。根据Gross方程计算隐性失血量,氨甲环酸组为(302.9±189.9) mL,对照组为(596.8±271.4) mL,差异有显著性意义(P < 0.05)。置换后两组各发生1例下肢肌间静脉血栓。提示静脉输注氨甲环酸能显著减少单侧全膝关节置换后隐性失血量,降低异体血输血量,同时不增加下肢静脉血栓的发生率。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

The effect of tranexamic acid in fibrin sealant on adhesion formation in the rat

The objective of the research was to determine the effect of the type, dose, and volume of anti-fibrinolytic agents (tranexamic acid, aprotinin) added to fibrin formulations, on adhesion development. Adhesions were induced in 228 male rats by creating apposing parietal and visceral peritoneal defects. Animals were randomized to receive no treatment or a fibrin formulation containing aprotinin or tranexamic acid. Seven days later the incidence of adhesions, and the force and energy required to detach them, were determined. Adhesions developed in 13/13 rats in the control and aprotinin groups. Treatment with fibrin (100 mg/ml tranexamic acid) resulted in adhesions in 4/14 rats (as strips, p < or = 0.0005), 4/10 rats (as spray, p < or = 0.0036), and 12/15 rats (by drip). The reduction of adhesions was dependent on the concentration of tranexamic acid with strip and spray application. Using commercial formulations, tranexamic-acid-containing fibrin (10/15, p = 0.042), but not aprotinin-containing fibrin (13/15), reduced the incidence of side-wall adhesions from 15/15 in controls. Fibrin containing either tranexamic or aprotinin reduced the incidence and severity of adhesions. This effect was greater when tranexamic acid was used and was dependent on the mode of administration, the volume, and to a degree, the concentration of tranexamic acid.     

Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients.

BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine the benefits and risks of long-term treatment with danazol. METHODS: Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before and during danazol treatment, and adverse effects to the treatment were noted. Data were collected by using standardized questionnaires. RESULTS: In all, 111 of 118 patients responded to danazol. During treatment, 54 of the 118 patients (45.8%) became symptom free or had 1 attack or less per year. In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring of patients is mandatory. However, many patients accept the adverse effects of prophylactic treatment to avoid the distressing and sometimes life-threatening attacks of this condition.     

Rate of improvement during and across three treatments for panic disorder with or without agoraphobia: Cognitive behavioral therapy,selective serotonin reuptake inhibitor or both combined

Background

Existing literature on panic disorder (PD) yields no data regarding the differential rates of improvement during Cognitive Behavioral Therapy (CBT), Selective Serotonin Reuptake Inhibitor (SSRI) or both combined (CBT+SSRI).

Method

Patients were randomized to CBT, SSRI or CBT+SSRI which each lasted one year including three months of medication taper. Participating patients kept record of the frequency of panic attacks throughout the full year of treatment. Rate of improvement on panic frequency and the relationship between rate of improvement and baseline agoraphobia (AG) were examined.

Results

A significant decline in frequency of panic attacks was observed for each treatment modality. SSRI and CBT+SSRI were associated with a significant faster rate of improvement as compared to CBT. Gains were maintained after tapering medication. For patients with moderate or severe AG, CBT+SSRI was associated with a more rapid improvement on panic frequency as compared to patients receiving either mono-treatment.

Limitations

Frequency of panic attacks was not assessed beyond the full year of treatment. Second, only one process variable was used.

Conclusions

Patients with PD respond well to each treatment as indicated by a significant decline in panic attacks. CBT is associated with a slower rate of improvement as compared to SSRI and CBT+SSRI. Discontinuation of SSRI treatment does not result in a revival of frequency of panic attacks. Our data suggest that for patients without or with only mild AG, SSRI-only will suffice. For patients with moderate or severe AG, the combined CBT+SSRI treatment is recommended.     

Reducing blood loss in primary knee arthroplasty: a prospective randomised controlled trial of tranexamic acid and fibrin spray

A prospective, randomised controlled trial compared the effects of two medications intended to reduce blood loss from total knee arthroplasty. Patients were randomised to one of the following three treatment groups: 10mg/kg tranexamic acid at given at induction of anaesthesia, 10 ml of fibrin spray administered topically during surgery, or to a control group receiving neither treatment. Sixty six patients underwent elective cemented total knee arthroplasty; computer navigation was used in all cases. There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups (p=0.181). There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups(p=0.181). The fibrin spray led to a significant reduction in blood loss compared to control (p=0.007). The effect of tranexamic acid did not reach significance (p=0.173). We conclude that fibrin spray was effective in reducing blood loss but that with a study of this power, we were unable to detect an effect of tranexamic acid in cemented navigated total knee replacement at the dose used.     

Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease

Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment. Four patients transformed into acute myeloid leukemia or myelodysplastic syndromes; three of these patients had essential thrombocythemia, and one had a myeloproliferative syndrome. Two patients died of solid cancers. Five out of 53 evaluable patients (9%) had pretreatment clonal cytogenetic abnormalities involving chromosomes 1, 9, 20, and 21. At follow-up, during or after hydroxyurea treatment, 15% had cytogenetic abnormalities, an unexpectedly low frequency compared to the previously reported frequency in patients with polycythemia vera treated with alkylating agents. None of our patients who developed cytogenetic clonal changes during hydroxyurea therapy had polycythemia vera. However, follow-up is too short to draw any conclusions about the mutagenic potential of hydroxyurea compared to alkylating agents.     

桃红四物汤联合氨甲环酸对人工股骨头置换术后 隐形失血的影响

目的 探讨桃红四物汤联合氨甲环酸对人工股骨头置换术后隐性失血的影响。方法 选取2017年3月~2018年10月我院行人工股骨头置换的股骨颈骨折老年患者58例,随机分为对照组32例和中药组26例。对照组采用利伐沙班+氨甲环酸治疗,中药组在对照组的基础上加用桃红四物汤治疗。对比两组患者输血率、隐性失血量、术后肿胀情况及并发症情况。结果 中药组与对照组输血率比较（15.38% vs 12.50%）、隐性失血量比较[（38.25±5.21）ml vs （40.12±6.14）ml],差异无统计学意义（P＞0.05）。两组术后第1天、第10天、第14天患肢肿胀情况比较,差异无统计学意义（P＞0.05）。中药组术后第3天肿胀变化为（41.02±4.96）mm,小于对照组的（56.56±5.26）mm,第7天肿胀变化为（22.08±3.90）mm,小于对照组的（30.54±6.11）mm,差异均有统计学意义（P＜0.05）。两组患者术后3个月内随访,未发生肺栓塞及下肢深静脉血栓。结论 桃红四物汤作为活血化瘀代表方与氨甲环酸合用,不增加患者出血及输血风险,并具有促进术后消肿的优势。     

Pharmacological therapy for abnormal uterine bleeding

Pharmacological therapies for the treatment of abnormal uterine bleeding are effective and generally well tolerated. This review presents an evidence-based approach to medical therapy. Selection depends on the etiology and amount of bleeding, need for contraception or preservation of fertility, perimenopause status, and medication efficacy and adverse effects.Available nonhormonal agents include nonsteroidal anti-inflammatory agents, which reduce bleeding by 25% to 35% and improve dysmenorrhea through reduced prostaglandin levels; tranexamic acid, which inhibits plasminogen activator with a 40% to 60% reduction in menstrual blood loss; and intranasal desmopressin, which is an antifibrinolytic for women with an underlying bleeding disorder (eg, von Willebrand disease).Hormonal regimens cause the inhibition of endometrial growth. Cyclic progestogen therapy for 21 days results in a significant reduction in menstrual blood loss. Limited data suggest that oral contraceptives reduce menstrual blood loss by 40% to 50% with decreased breast tenderness and dysmenorrhea and a reduction in risk of uterine and ovarian cancer. The progestin-releasing intrauterine devices are effective up to 97% by 6 months and provide relief of dysmenorrhea and contraception. Long-acting progestogen injections produce amenorrhea and provide contraception but are associated with irregular spotting and reversible bone loss. Danazol leads to endometrial atrophy with a reduced menstrual loss; androgenic adverse effects may be lessened with lower doses or vaginal use. Gonadotrophin agonists lead to ovarian suppression and are used to shrink fibroids or the endometrium preoperatively but are limited by hypoestrogenic adverse events. Emergency use of parenteral conjugated estrogens has a 70% chance of stopping abnormal bleeding but an increased risk of thrombosis.