Abstract: 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. 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.

Plain-language summary: We searched for randomised controlled trials comparing the efficacy (mortality, blood loss, need for re-intervention, subjective assessment of efficacy, duration and dose of therapy) and the safety of any type of treatment given to people with congenital bleeding disorders during any type of surgery. We found four trials to be included in this review. Two trials evaluated 59 people with haemophilia A or B receiving antifibrinolytic drugs (agents that reduce the breakdown of clots) or placebo in addition to the initial standard treatment before dental extractions. The remaining two trials evaluated 53 people with haemophilia A or B and inhibitors (antibodies that act against the factor concentrate therapy) receiving an different clotting concentrate, recombinant activated factor VII, both during and after surgery. These two trials evaluated different treatment options: high-dose compared with low-dose and a single large (bolus) infusion compared with continuous infusion. The trials included in this review provide some information in two specific situations in people with congenital bleeding disorders undergoing surgery. However, on the whole, there is not enough evidence from trials to define the best treatments for the various types of disease and types of surgery. Further trials would be useful to improve our knowledge but are difficult to carry out and currently do not appear to be a clinical priority. Indeed, both major and minor surgery are safely performed in clinical practice in these individuals based on local experience and data from uncontrolled studies.