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1.
Medical interventions for traumatic hyphema
Woreta, F. A., Lindsley, K. B., Gharaibeh, A., Ng, S. M., Scherer, R. W., Goldberg, M. F.
The Cochrane Database of Systematic Reviews. 2023;3(3):Cd005431
Abstract
BACKGROUND Traumatic hyphema is the entry of blood into the anterior chamber, the space between the cornea and iris, following significant injury to the eye. Hyphema may be associated with significant complications that uncommonly cause permanent vision loss. Complications include elevated intraocular pressure, corneal blood staining, anterior and posterior synechiae, and optic nerve atrophy. People with sickle cell trait or disease may be particularly susceptible to increases in intraocular pressure and optic atrophy. Rebleeding is associated with an increase in the rate and severity of complications. OBJECTIVES To assess the effectiveness of various medical interventions in the management of traumatic hyphema. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 3); MEDLINE Ovid; Embase.com; PubMed (1948 to March 2022); the ISRCTN registry; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The last date of the search was 22 March 2022. SELECTION CRITERIA Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. We included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical interventions or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions on age, gender, severity of the closed-globe trauma, or level of visual acuity at time of enrollment. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane and assessed the certainty of evidence using GRADE. MAIN RESULTS We included 23 randomized and seven quasi-randomized studies with a total of 2969 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest. We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Oral tranexamic acid appeared to provide little to no benefit on visual acuity in four trials (RR 1.12, 95% CI 1.00 to 1.25). The remaining trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty. Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60), as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two trials with 131 participants. We assessed the certainty of the evidence as low. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.33, 95% CI 0.21 to 0.53) in seven trials with 754 participants, as did aminomethylbenzoic acid (RR 0.10, 95% CI 0.02 to 0.41), as reported in one study. Evidence to support an associated reduction in risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect on the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention. The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials. We found no evidence of an effect between a single versus binocular patch on the risk of secondary hemorrhage or time to rebleed. We also found no evidence of an effect on the risk of secondary hemorrhage between ambulation and complete bed rest. AUTHORS' CONCLUSIONS We found no evidence of an effect on visual acuity of any of the interventions evaluated in this review. Although the evidence was limited, people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhage. However, hyphema took longer to clear in people treated with systemic aminocaproic acid. There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema, other than possibly to reduce the rate of secondary hemorrhage. The potentially long-term deleterious effects of secondary hemorrhage are unknown. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.
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2.
Is Antifibrinolytic Therapy Effective for Preventing Hemorrhage in Patients with Hemophilia Undergoing Dental Extractions? A Systematic Review and Meta-Analysis
Ullah, K., Mukhtar, H., Khalid, U., Sarfraz, Z., Sarfraz, A.
Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2022;28:10760296221114862
Abstract
OBJECTIVES This systematic review aims to analyze the systemic administration of antifibrinolytics (tranexamic acid and aminocaproic acid) to prevent postoperative bleeding in patients with hemophilia. METHODS This systematic review was conducted adhering to PRISMA guidelines. Only randomized controlled trials that assessed human subjects of any age or gender with any severity of hemophilia undergoing dental extractions, and systemically administered antifibrinolytic therapy compared to placebo were included. Post-operative bleeding episodes and adverse events were presented. PubMed, Cochrane, Embase, CINAHL, Web of Science, and Scopus were searched through April 15, 2022. The risk ratio (RR) and odds ratio (OR) applying 95% confidence intervals (CI) were computed using RevMan 5.4.1 (Cochrane). RESULTS Two randomized, placebo-controlled trials pooling in a total of 59 patients were pooled in this analysis. Among patients administered antifibrinolytic therapy, 84% reduced risk of post-operative bleeding was reported (RR = 0.16, 95% CI = 0.05-0.47, P = 0.0009). The chances of post-operative bleeding were reduced by 95% among the antifibrotics group (OR = 0.05, 95% CI = 0.01-0.22, P < 0.0001). CONCLUSION This review finds favorable outcomes for the routine use of antifibrinolytic therapy for dental extractions in hemophiliacs. Further trials are required to rationalize existing evidence.
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3.
Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders
Estcourt LJ, Desborough M, Brunskill SJ, Doree C, Hopewell S, Murphy MF, Stanworth SJ
The Cochrane Database of Systematic Reviews. 2016;((3)):CD009733.
Abstract
BACKGROUND People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. OBJECTIVES To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. SEARCH METHODS We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. SELECTION CRITERIA We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. DATA COLLECTION AND ANALYSIS Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. MAIN RESULTS We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants;
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4.
Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery
Coppola, A., Windyga, J., Tufano, A., Yeung, C., Di Minno, M. N.
The Cochrane Database of Systematic Reviews. 2015;(2):Cd009961
Abstract
BACKGROUND In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. OBJECTIVES To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. SELECTION CRITERIA Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. DATA COLLECTION AND ANALYSIS Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. MAIN RESULTS Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 μg/kg) was compared with a low-dose regimen (35 μg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. AUTHORS' CONCLUSIONS There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.
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5.
Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study
Geisthoff UW, Seyfert UT, Kubler M, Bieg B, Plinkert PK, Konig J
Thrombosis Research. 2014;134((3):):565-71.
Abstract
INTRODUCTION Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. MATERIALS AND METHODS In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3months for a total of 6months. RESULTS 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. CONCLUSION Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright 2014 Elsevier Ltd. All rights reserved.
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Efficacy of tranexamic acid mouthwash as an alternative for factor replacement in gingival bleeding during dental scaling in cases of hemophilia: A randomized clinical trial
Nuvvula S, Gaddam KR, Kamatham R
Contemporary Clinical Dentistry. 2014;5((1):):49-53.
Abstract
OBJECTIVE The objective of the following study is to evaluate freshly prepared tranexamic acid mouth wash (FTAMW) as an alternative to factor replacement therapy (FRT) in controlling gingival bleeding in hemophiliacs during dental scaling. MATERIALS AND METHODS Experimental treatment regime (ETR) involved saline transfusion followed by FTAMW and the control treatment regime (CTR) involved FRT followed by placebo mouthwash. A total of 22 hemophiliacs randomly received dental scaling under either CTR or ETR at two different visits, following a split mouth design. They were instructed to use the rendered mouthwash 4 times a day for 5 days and record the mouthwash usage and bleeding episodes in a logbook. The difference in the bleeding episodes was analyzed using Chi-square test with the level of significance predetermined at 0.05. RESULTS Totally 19 patients completed the study. Seven patients reported no bleeding either in ETR or CTR; five patients noticed bleeding in CTR, but not in ETR. Three patients noticed bleeding in ETR, but not in CTR. Patients reported ease in usage and cost-effectiveness of ETR. CONCLUSION FTAMW was found to be an effective alternative to FRT in controlling gingival hemorrhage in hemophiliacs during dental scaling.
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7.
Effectiveness in controlling haemorrhage after dental scaling in people with haemophilia by using tranexamic acid mouthwash
Lee AP, Boyle CA, Savidge GF, Fiske J
British Dental Journal. 2005;198((1):):33-8; discussion 26.
Abstract
AIMS: To compare the effectiveness of tranexamic acid mouthwash (TAMW) in controlling gingival haemorrhage after dental scaling with that of using factor replacement therapy (FRT) prior to dental scaling in people with haemophilia. DESIGN Double-blind cross-over randomised control trial. SETTING Dedicated hospital dental practice for patients with inherited bleeding disorders. METHOD Sixteen patients with haemophilia who required dental scaling participated in this pilot study. The experimental treatment regime (ETR) involved transfusing each patient with saline before scaling both quadrants on one side of the mouth followed by oral rinsing with TAMW four times daily for up to eight days. The control regime (CR) involved giving each patient FRT before scaling the opposite side of the mouth followed by use of a placebo TAMW. Each patient underwent both treatments in a random-ised sequence. Both the operator and the patients were unaware of which were the ETR and CR episodes. On both occasions the patient kept a log book of the rinsing regime and any post-operative bleeding. Additionally, a structured post-treatment telephone interview was conducted to assess the effectiveness and the patient acceptability of the ETR. RESULTS Thirteen patients completed the study. No statistically significant difference was found in gingival bleeding and mouthwashing frequencies between the ETR and the CR (p > 0. 05). Five patients reported no gingival bleeding with either the ETR or the CR. No patient, using either regime, required extra FRT due to gingival haemorrhage. All subjects found the ETR acceptable and easy and reported feeling safe in using TAMW alone to control gingival bleeding after dental scaling. CONCLUSION TAMW use after dental scaling was as effective as using FRT beforehand in controlling gingival haemorrhage for people with haemophilia.
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8.
Lack of efficacy of tranexamic acid in thrombocytopenic bleeding
Fricke W, Alling D, Kimball J, Griffith P, Klein H
Transfusion. 1991;31((4):):345-8.
Abstract
A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. Our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia.
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9.
Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease
Forbes CD, Barr RD, Reid G, Thomson C, Prentice CR, McNicol GP, Douglas AS
British Medical Journal. 1972;2((5809):):311-3.
Abstract
In a double-blind trial tranexamic acid (AMCA, Cyclokapron), 1 g three times a day for five days, significantly reduced blood loss and transfusion requirements after dental extraction in patients with haemophilia and Christmas disease. No side effects were seen in either group of patients. Screening tests showed no toxic action of tranexamic acid on the liver, kidney, or heart.