Identifying nonresponsive bleeding episodes in patients with hemophilia and inhibitors : a consensus definition

Introduction: In patients with hemophilia and inhibitors, timely identification of bleeding episodes that are nonresponsive to bypassing therapy with either Factor Eight Inhibitor Bypassing Activity (FEIBA; Baxter AG, Vienna, Austria) or recombinant activated factor VII (rFVIIa; NovoSeven®, Novo Nordisk A/S, Bagsvaerd, Denmark) is essential to optimize patient outcomes. Currently, the lack of validated laboratory markers of efficacy increases the challenge of assessing treatment response. Differential responses to bypassing therapy necessitate the availability of both agents for comprehensive inhibitor management. Methods: An international panel of seven physicians met in December 2008 to develop a consensus definition for joint and muscle bleeds that are initially nonresponsive to bypassing therapy. A modified National Institutes of Health Consensus Development Conference method was used. Results: It was agreed that identification of nonresponsiveness to therapy should be based on both subjective and objective assessments. Subjective criteria include qualitative assessments made by the patient or parent, such as pain level and the patient’s perception of active bleeding. Objective criteria include physician assessments (e.g. pain, swelling, and mobility), imaging studies, when applicable, and laboratory parameters such as thrombin generation and thromboelastography (these have yet to be validated). A non–limb-threatening joint or muscle bleed can be considered nonresponsive to bypassing therapy if indicated by these criteria at or after 24 h from the start of treatment. Conclusions: Early and accurate identification of nonresponsive bleeds is essential in order to provide appropriate treatment strategies, which may include changing therapies. This consensus definition is intended to guide the course of treatment for patients with hemophilia and inhibitors; however, it should not replace clinical judgment