Effectiveness and safety of the use of antifibrinolytic agents in total-knee arthroplasty: A meta-analysis.

BACKGROUND: Antifibrinolytic agents have been successfully used to reduce blood transfusion demand in patients undergoing elective knee arthroplasty. The purpose of this study was to investigate different antifibrinolytic agents for patients undergoing total-knee arthroplasty (TKA). METHODS: We searched the randomized controlled trials assessing the effect of antifibrinolytic agents on TKA in MEDLINE, PubMed, Embase, and the Cochrane Library. Participants are divided into antifibrinolytic agent group and control group under TKA. Double extraction technology is used and the quality of its methodology is evaluated before analysis. Outcomes analyzed included blood loss, number of blood transfusions, rates of blood transfusion, and deep vein thrombosis (DVT). RESULTS: A total of 28 randomized controlled trials involving 1899 patients were included in this study. Compared with the control group, the antifibrinolytic agents group exhibited significantly reduced the amounts of total blood loss (weighted mean difference [WMD] with 95% confidence interval [CI]: -272.19, -338.25 to -206.4), postoperative blood loss (WMD with 95% CI: -102.83, -157.64 to -46.02), average units of blood transfusion (risk ratio with 95% CI: 0.7, 0.12 to 0.24), and average blood transfusion volumes (WMD with 95% CI: -1.34, -1.47 to -1,21). Antifibrinolytic agents significantly reduced the rate of blood transfusions and did not increase the occurrence risk of intraoperative blood loss and DVT. Several limitations should also be acknowledged such as the heterogeneity among the studies. CONCLUSION: The application of antifibrinolytic agents can significantly reduce blood loss and blood transfusion requirements. Additionally, these agents did not increase the risk of DVT in patients undergoing TKAs.

Reversing anticoagulation in the hemorrhaging patient.

PURPOSE OF REVIEW: Anticoagulants in general, but especially the relatively new direct oral anticoagulants and platelet inhibitors, pose a great challenge for physicians in the hemorrhaging patient. The aim of the present review is to provide an overview on recent studies dealing with the reversal of anticoagulation in the hemorrhaging patient and to describe our therapeutic emergency strategy for those patients. RECENT FINDINGS: A specific antidote for dabigatran is already on the market and antidotes for the direct and indirect factor Xa inhibitors are in development. Moreover, bleeding under platelet inhibitors remains critical with very little evidence on effective reversal strategies. SUMMARY: To reverse anticoagulation in the hemorrhaging patient, specific antidotes should be the first option if available, followed by four-factor prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor seven as the emergency strategy. Fibrinogen concentrate, antifibrinolytics and oral charcoal, respectively, can be considered as an additional measure. Massive blood loss and thrombocytopenia should be treated independently according to the respective, local guidelines for (massive) transfusion of blood and blood products.

Safety of tranexamic acid in women with heavy menstrual bleeding: an open-label extension study.

AIMS: An open-label, extension clinical study was conducted to assess the safety of a novel, oral formulation of tranexamic acid (TA) in women with cyclic heavy menstrual bleeding. PATIENTS & METHODS: Eligible patients who completed either a three- or six-cycle double-blinded clinical trial of TA were offered enrollment into a study of nine cycles with TA (1.3 g orally three times/day for a maximum of 5 days per cycle). Safety was assessed by the incidence of treatment-emergent adverse events, ophthalmologic examinations and ECGs, among other evaluations. RESULTS: The most commonly reported treatment-emergent adverse events were menstrual discomfort (46.2%), headache (43.9%) and back pain (23.1%). A small proportion of participants (3.8%) reported ocular adverse events, but there was no evidence of ocular toxicity. No prothrombotic effects were observed. CONCLUSION: During nine menstrual cycles of treatment, this novel formulation of TA was well tolerated and exhibited a favorable safety profile supporting its use as a therapy for cyclic heavy menstrual bleeding.

Tranexamic acid: a novel oral formulation for the treatment of heavy menstrual bleeding.

Tranexamic acid, a synthetic lysine derivative, is an antifibrinolytic drug that prevents the breakdown of fibrin by competitively blocking binding sites of plasminogen. Tranexamic acid is often considered a first-line treatment for the management of heavy menstrual bleeding (HMB). A new oral formulation of tranexamic acid provides a nonhormonal HMB therapy that is safe, effective and well tolerated; is administered only during menstruation; addresses the excessive fibrinolysis implicated in many cases of HMB; and improves women's health-related quality of life by reducing limitations on physical, social and leisure activities. This article provides a summary of the clinical development, therapeutic efficacy and tolerability profile of this novel formulation of tranexamic acid for the treatment of HMB.

The use of vitamin K in patients on anticoagulant therapy: a practical guide.

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

Thrombolytic therapy. State of the art.

Thrombolytic agents have become the corner stone in the treatment of acute myocardial infarction. However, the current agents are far from perfect. New thrombolytic drugs have been designed to overcome these shortcomings. Development of these agents has focused not only on increasing plasma half-life and thus allowing single-bolus administration, but also on improving fibrin specificity and resistance to plasminogen activator inhibitor. The safety and efficacy of several of these promising thrombolytic drugs have been evaluated in large-scale trials, which are discussed in the present review. Parallel to these advances, alternatives to standard thrombolytic regimens have been developed. New trials evaluating the combination of reduced-dose fibrinolytics with different regimens of antithrombotic agents will optimize future reperfusion strategies.

Synovectomy with rifampicine in haemophilic haemarthrosis.

The purpose of this paper was to assess the effectiveness of intra-articular injected rifampicine in haemophilic patients in order to achieve synovectomy by preventing repeated intra-articular bleeding. We have used this technique in haemophilic patients previously and reported our results on 13 cases [1]. Two hundred and fifty milligrams of rifampicine was injected into the elbow and ankle joints and 500 mg was injected into knee joints with 3-10 mL of lidocaine, depending on the joint size. The injections were repeated once a week for 7 weeks. Patients were only covered with antihaemophilic factor on the day of the injection at 30% above their coagulation level. We evaluated the results using two measures: subjective reports from the patient and objective assessment by the examiner. In the subjective reports the patient graded the results from their own perspective from 1 (poor) to 10 (excellent): 1-3, poor; 4-6, fair; 7-8, good; and 9-10, excellent. In the objective reports the grading was: excellent ('dry joint', full function, no haemarthrosis, no synovitis); good (clinical improvement, synovitis, reduction of haemarthroses, full function); fair synovitis (reduction of haemarthroses, no change in function); poor synovitis (persistent haemarthroses). This paper reports on the results of 38 patients with 39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees, nine elbows and eight ankles. Subjectively, there were excellent results in 21 joints (11 knees, six elbows and four ankles) good results in 15 joints (eight knees, three elbows and four ankles), fair results in two knees and a poor result in one knee. Objectively, results obtained were excellent in 20 joints (11 knees, six elbows and three ankles); good in 17 (nine knees, three elbows and five ankles); fair in one knee and poor in one knee.