Heavy menstrual bleeding in adolescents: incidence, diagnostics, and management practices in primary care.

Background: Heavy menstrual bleeding (HMB), self-reported by 37% of adolescents, can be the first sign of a bleeding disorder (BD) during adolescence. The Dutch general practitioner (GP) guideline demands laboratory diagnostics and referral for patients at risk for a BD. How often adolescents consult the GP for HMB and which diagnostic and management strategies are used are unknown. Objectives: This study aims to estimate the incidence of HMB in adolescents in primary care and to identify diagnostic and management practices for HMB, considering the HMB GP guideline. Methods: Retrospective analyses of a GP network database containing over 200 Dutch GPs were performed. Adolescents aged 10 to 21 years, with a new diagnosis of HMB between 2010 and 2020, and a 6-month follow-up were eligible. The incidence rate and diagnostic and therapeutic strategy data were extracted. Results: We identified 1879 new diagnoses of HMB in adolescents. The average incidence rate was 7.91 per 1000 person-years. No diagnostic studies were performed in 67%. Laboratory studies were mainly restricted to hemoglobin levels (31%). Full coagulation screening occurred in 1.3%, and ferritin levels in 10%. Medication was prescribed in 65%; mostly hormonal treatment (56%) and/or nonsteroidal antiinflammatory drugs (NSAIDs) (18%). The referral rate was higher after >2 follow-up visits (6.7%) vs after 1 GP visit for HMB (1.6%; Odds ratio: 8.8; 95% CI: 5.1-15), mostly to gynecologists (>85%). Conclusion: According to this GP database study, few adolescents visit their GP with HMB despite its high self-reported incidence. Most adolescents were prescribed hormonal contraception without further diagnostics. Referral was rare and mostly occurred after multiple follow-up visits.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

BACKGROUND: Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease (VWD). The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. This is an update of a previously published Cochrane Review. OBJECTIVES: Primarily, we aim to assess the efficacy of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or VWD undergoing oral or dental procedures.Secondary objectives are to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or VWD and to establish the effects of these agents on bleeding in oral or dental procedures for each of these patient populations. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase, Cinahl and the Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 01 March 2019. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people with haemophilia or VWD undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid (EACA)) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardised forms. MAIN RESULTS: While there were no eligible trials in people with VWD identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of EACA published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference (RD) of -0.64 (95% confidence interval (CI) -0.93 to - 0.36) and the EACA trial a RD of -0.50 (95% CI 0.77 to -0.22). The combined RD of both trials was -0.57 (95% CI -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping EACA (combined RD of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the EACA trial, but overall the risk of bias appeared to be low for both trials. AUTHORS' CONCLUSIONS: Despite the discovery of a beneficial effect of systemically administered tranexamic acid and EACA in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with VWD.

Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions.

BACKGROUND: Individuals on continuous treatment with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) are at increased risk of bleeding complications during and after oral or dental procedures. Anticoagulant treatment is preferably continued at the same dose, since dose reduction or discontinuation of treatment is associated with an increased risk of thromboembolism. The use of haemostatic measures during or after the procedure (or both) could enable continuation of the oral anticoagulant treatment. OBJECTIVES: We aimed to assess the efficacy of antifibrinolytic agents for preventing bleeding complications in people on oral anticoagulants undergoing minor oral surgery or dental extractions. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders 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. We searched PubMed, Embase and the Cochrane Library. Additional searches were performed using ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), the CINAHL database of nursing and allied health services, the open access ProQuest dissertation database, papers and reports from the American College of Clinical Pharmacy (ACCP) and abstract books from annual scientific conferences.Date of last search: 04 January 2018. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people on continuous treatment with VKAs or DOACs undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid (TXA) or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained from potentially relevant abstracts and two authors independently assessed these for inclusion based of the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. The quality of the evidence was assessed using GRADE. MAIN RESULTS: No eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures were identified.Three randomised trials and one quasi-randomised trial (follow-up in all was seven days) in people on continuous treatment with VKAs were included with a total of 253 participants (mean age 60 years). Two trials published in 1989 and 1993 compared the antifibrinolytic agent TXA with placebo in people using VKAs. Two other trials were published in 1999 and 2015 and compared TXA with gelatin sponge and sutures, and dry gauze compression, respectively. In all included trials, those who were treated with VKAs had international normalised ratio (INR) values within the therapeutic range and TXA was applied locally, not systemically.The two trials from 1989 and 1993 comparing TXA with placebo showed a statistically significant beneficial effect regarding the number of major postoperative bleeding episodes requiring intervention, with a pooled risk difference (RD) of -0.25 (95% confidence interval (CI) -0.36 to -0.14) (128 participants) (moderate-quality evidence). For the two trials that compared TXA with either gelatin sponge and sutures or with dry gauze compression, there was no difference between the TXA and the standard care group, RD 0.02 (95% CI -0.07 to 0.11) (125 participants) (moderate-quality evidence). The combined RD of all included trials was -0.13 (95% CI -0.30 to 0.05) (moderate-quality evidence). There were no side effects of antifibrinolytic therapy that required treatment withdrawal (128 participants) (moderate-quality evidence). Despite heterogeneity between trials with respect to the different haemostatic measures used in the control groups, the trials were comparable regarding design and baseline participant characteristics.Overall, we considered the risk of bias to be low in the trials comparing TXA with placebo and moderate in the trials comparing TXA with alternative haemostatic measures. AUTHORS' CONCLUSIONS: Based on the results of this Cochrane Review, there seems to be a beneficial effect of locally applied TXA in preventing oral bleeding in people on continuous treatment with VKAs undergoing minor oral surgery or dental extractions. However, the small number of identified randomised controlled trials, the relatively small number of participants included in the trials and the differences in standard therapy and treatment regimens between trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in this population.We were unable to identify any eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures. Therefore, a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

BACKGROUND: Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. OBJECTIVES: The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. MAIN RESULTS: While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. AUTHORS' CONCLUSIONS: Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.