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 Small molecule library 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. “
“Summary. Antibody responses to clotting factor concentrates remain a major treatment limitation. In conjucation with ongoing clinical studies, the pathogenesis and potential treatment of clotting factor immune responses is being evaluated in a variety of animal models. In 2010, the most important treatment-related complication of coagulation factor replacement is the development of neutralizing antibodies to the therapeutic protein. This complication occurs in approximately 25% of haemophilia selleck compound A (HA) patients and 3% of haemophilia B subjects. While significant progress has been made in our understanding of the pathogenic mechanisms involved in this phenomenon, much remains to be learnt. The investigation of the immune selleck products response to coagulation factor exposure in human haemophiliacs is limited by a number of biological and practical considerations. Thus, while it remains critical to continue the evaluation of this treatment complication in human populations, this experimental approach will need to be complemented with
observations made in animal models of haemophilia. This chapter focuses on three specific aspects of the immune response to factors VIII (FVIII) and factor IX (FIX): the development of novel transgenic mouse models to facilitate the characterization of this process, the study of tolerance mechanisms in haemophilic mice and finally, the association of inhibitors with haemophilia gene therapy studies. About 25% of patients with severe HA develop neutralizing antibodies against FVIII, after replacement therapy [1,2]. The antibody response to FVIII is a polyclonal IgG response that is not restricted isotypically. Although IgG4 is frequently the major component of anti-FVIII antibodies, all IgG subclasses have been found [3,4]. While the antibodies against FVIII are well characterized [5–8], limited information is available on the regulation of the antibody response. In particular, the reason why some patients develop antibodies while others do not is far from clear.