An update on the 'danger theory' in inhibitor development in haemophilia A.

An update on the 'danger theory' in inhibitor development in haemophilia A. Expert Rev Hematol. 2019 Apr 05;: Authors: Schep SJ, Boes ML, Schutgens REG, van Vulpen LFD Abstract INTRODUCTION: Nowadays, one of the most serious treatment complications in haemophilia A is the formation of neutralizing antibodies against coagulation factor VIII (FVIII). These so-called inhibitors develop in about 30% of all patients with severe haemophilia A. Once formed, inhibitors reduce FVIII efficacy in blood coagulation, which has a negative impact on patients' health and quality of life and significantly increases haemophilia A treatment costs. The pathophysiology of inhibitor development is a complex and multi-causal process, in which both genetic factors as well as environmental factors participate. So-called 'danger signals' are considered contributors to inhibitor formation, and can be triggered by surgery, joint bleeds or infections. A pro-inflammatory tissue micro-environment is thereby established, which is characterized by the upregulation of costimulatory molecules on antigen presenting cells (APCs), that can facilitate the allo-immunization to FVIII and thereby inhibitor formation. Here, the authors will discuss evidence from (pre)clinical studies about this theory in haemophilia A. Areas covered: In this review the current knowledge regarding the 'danger theory' with regard to inhibitor development in haemophilia A is summarized. Expert o...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research