Identifying non-responsive bleeding episodes in patients with haemophilia and inhibitors: a consensus definition

Assessing response to treatment with bypassing agents presents a substantial challenge in the treatment of patients with haemophilia and inhibitors. Rapid and accurate identification of bleeding episodes that are non-responsive to bypassing therapy with either Factor Eight Inhibitor Bypassing Activity (FEIBA; Baxter AG) or recombinant activated factor VII (rFVIIa; NovoSeven (R), Novo Nordisk A/S) is essential to guide treatment decisions and optimize patient outcomes through early intervention. Although both bypassing agents are effective, differential responses to therapy necessitate multiple therapeutic options. This article provides a consensus definition for non-life-threatening joint and muscle bleeds that are non-responsive to bypassing agents. An international panel of seven physicians met in December 2008 to develop the consensus definition using a modified National Institutes of Health Consensus Development Conference method. The consequent definition of non-life-threatening bleeding episodes that are non-responsive to bypassing treatment provides a global picture of the condition of the patient during such an event. Identification of non-responsiveness is based on various criteria: pain, swelling/tension, mobility, patient perception and laboratory parameters. Criteria can be assessed subjectively by the patient/parent and/or objectively by the clinician. Although the precise timing of each determination should be at the discretion of the physician, bleeds should be considered non-responsive if the clinical situation meets the specified criteria 24 h from the start of treatment. Although it is not intended to replace clinical judgment, this definition can guide the optimal course of treatment for patients with haemophilia and inhibitors.