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Introduction: Rare acquired bleeding disorders include a wide spectrum of coagulopathies characterized by spontaneous or post-trauma and post-surgery hemorrhages in patients without a previous personal or family history of bleeding., Areas Covered: This review, based on a Medline/PubMed search during the last 20 years, will focus mainly on rare acquired bleeding disorders caused by autoantibodies against coagulation factors, including autoantibodies against factor VIII (acquired hemophilia A), von Willebrand factor (acquired von Willebrand syndrome) and other coagulation factors (factors V, X, XI, and XIII). The pathogenic, laboratory, and clinical features of these rare hemorrhagic conditions will be discussed, with particular attention to their management., Expert Opinion: The treatment of rare acquired bleeding disorders includes the control of bleeding and the elimination of the autoantibody and of the underlying disease, when present. As the bleeding clinical phenotype is often severe, the management of affected patients is particularly challenging. Thus, while an early diagnosis of the acquired coagulopathy is essential to start the most appropriate treatment and to improve patients' outcomes, the support of specialized centers is equally important to provide a correct management of such complicated cases.

Introduction : Hemophilia A and B are congenital bleeding disorders. The current standard management of patients with severe hemophilia is prophylaxis which is given intravenously two or three times weekly; however, this is associated with a significant burden on the quality of life of the patient. The main attempts to improve the management of hemophilia is hence through the development of a new generation of products with properties facilitating prophylaxis and/or a better control of bleeding. Areas covered : This review describes the preclinical and phase 1/2 studies investigating the innovative products for the management of hemophilia patients with or without coagulation factor inhibitors. Expert opinion : Numerous innovative therapeutics, including factor concentrates and non-clotting factor-based therapies with extended half-life, are under clinical investigation. Among replacement therapies for hemophilia A, the results from phase 1/2 studies indicate that the most interesting products are those bioengineered using XTEN fusion technology. The anti-tissue factor pathway inhibitor antibody concizumab is the most innovative and interesting agent among non-clotting factor products. If the results of ongoing trials confirm the preliminary positive results, these promising agents will provide further improvements in the management and quality of life of patients with hemophilia.

One of the most serious complications of the treatment of severe haemophilia A is the development of alloantibodies against exogenous factor VIII (FVIII). Inhibitors render factor replacement therapy ineffective, exposing patients to a remarkably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in newer haemostatic therapies that are not based on the replacement of the deficient FVIII. This review will focus on the most interesting among these innovative therapies, emicizumab, and will provide an update on its current stage of clinical development.

The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions. This narrative review will deal with inhibitors arising in patients with inherited bleeding disorders other than "classical" hemophilia, focusing in particular on those developing in patients with congenital deficiency of coagulation factor V, factor VII, factor XI, and factor XIII., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function., Methods: We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments., Results: The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently., Conclusion: The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

The Health Commission of the Conference between the Italian State and Regions recognized the need to establish an institutional accreditation model for Haemophilia Centres (HCs) to be implemented by 21 Regions in order to provide patients with haemophilia and allied inherited coagulations disorders with high and uniform standards of care. The Italian National Blood Centre, on behalf of the Commission, convened a panel of clinicians, patients, experts, representatives from Regions and Ministry of Health. The agreed methodology included: systematic literature review and best practice collection, analysis of provisions and regulations of currently available services, priority setting, definition of principles and criteria for the development of recommendations on the optimal requirements for HCs. The result was the formulation of two recommendations sets. Two sets of recommendations were produced. The first concerns regional policy planning, in which the following aspects of comprehensive haemophilia care should be considered for implementation: monitoring and auditing, multidisciplinary approach to clinical care, protocols for emergency management, home treatment and its monitoring, patient registries, drug availability and procurement, recruitment and training of health care professionals. The second set concerns the accreditation process and lists 23 organizational requirements for level 1 HCs and 4 additional requirements for level 2 HCs. These recommendations help to provide Italian Regional Health Authorities with an organizational framework for the provision of comprehensive care to patients with inherited coagulation disorders based on current scientific evidence., (© 2013 John Wiley & Sons Ltd.)

Background: Deficiency or dysfunction of coagulation factor VIII (FVIII) is the underlying cause of haemophilia A. Haemophilic patients are at present treated with plasma-derived FVIII (pdFVIII) or recombinant FVIII (rFVIII) in order to correct their clotting deficiency. pdFVIII concentrates are exclusively produced from human plasma upon pooling from multiple donors. It is not know whether the presence of excess of other plasma proteins, in addition to von Willebrand factor, could stimulate untoward immune responses in the recipient. Thus, information regarding the presence of contaminants in commercial products is of concern., Materials and Methods: Two commercially available pdFVIII concentrates were characterized through SDS-PAGE and mass spectrometry Emoclot and Beriate., Results: The components of two pdFVIII products considered in this study were well identified by mass spectrometry analysis, in both cases we found abundant components coming from blood plasma, and some other contaminants. Only in Beriate we also found truncated form of pdFVIII., Conclusion: The two pdFVIII examined showed the presence of vWF, Fibrinogen in excess, and other substances that could be considered as contaminants or impurities.