Advances in the treatment of inherited coagulation disorders

Abstract

Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.

Coping in adult patients with severe haemophilia

“…First, this study was a secondary analysis of data collected earlier in 2003–2005. There were no major treatment changes in the past 10 years for adults , new treatment opportunities (long‐acting FVIII and gene therapy) are not available yet . Therefore, we think this information on coping skills is still valid.…”

Predictors of quality of life among adolescents and young adults with a bleeding disorder

“…Therapeutic advancements [1–4], improved treatment approaches [5–8], and enhanced care delivery models [9–12] have resulted in highly active lifestyles and near-normal life expectancy for persons diagnosed with a bleeding disorder [13]. As treatments continue to improve, patient care will continue to evolve toward preventing bleeding disorder complications, such as hemophilic arthropathy, chronic pain, and inhibitor development—with the ultimate goal of attaining and maintaining high health-related quality of life (HRQoL) for those affected by the disorder [14].…”

Intracranial Hemorrhage as the First Manifestation of Severe Congenital Factor X Deficiency in a 20‐Month‐Old Male: Case Report and Review of the Literature

“…Auerswald et al. studied 102 patients with FXD and found that clinical phenotype correlates better with genotype than with factor activity. Herrmann et al.…”

“…However, until now, no case has been reported of a child with severe FXD using PCC as prophylaxis. Since 2008, a plasma‐derived FX has been on the market . Apart from an anaphylactic reaction after the first infusion, no serious complications have yet been reported Factor X concentrations of 10–20 IU/dl are generally sufficient for hemostatic control, even in the immediate postoperative period …”

“…Age at first manifestation is rather variable. Intracranial hemorrhage (ICH) occurs in 9–26% of all patients with FXD, mostly during the first month of life and often in the absence of preceding trauma …”