The WFH reaches out to people with von Willebrand disease (vWD) and rare bleeding disorders.
The WFH’s recent strategic review identified an unmet need amongst people with other inherited bleeding disorders, such as vWD, rare factor deficiencies, and platelet disorders, which are often undiagnosed or misdiagnosed. In response, we are expanding our activities to improve treatment for people with these disorders.
Accordingly, we have established a new working party chaired by Dr. Paula Bolton-Maggs (U.K.) to focus on vWD and rare disorders. Dr. Bolton-Maggs is eminently qualified for this role, having made significant contributions to research on factor XI deficiency in particular. She also wrote a recent WFH monograph on the treatment of rare disorders. (Monograph #39: The Rare Coagulation Disorders, available at www.wfh.org )
A number of important initiatives involving WFH volunteers are already underway. The international registry of rare bleeding disorders (www.rbdd.org) has expanded our knowledge about the prevalence and clinical manifestations of these conditions. Unlike hemophilia, most of these disorders can be inherited by both males and females and the prevalence of these disorders is particularly high in parts of the world where marriages between close relatives, such as cousins, is not unusual.
The bleeding manifestations of the different rare coagulation factor disorders vary considerably and are often quite different from classical hemophilia. For example, hemarthrosis (joint bleeding) is quite rare in most of the rarer disorders, whilst other symptoms, such as menorrhagia, epistaxis, and soft tissue or mucosal bleeds typically predominate. Deficiencies of some coagulation factors, especially factor XIII, are strongly linked to an increased risk of internal head bleeds.
Laboratory diagnosis is very important in such cases and assays are based on the basic prothrombin time (PT) and activated partial thromboplastin time (aPTT) assays. In this context I have no doubt that expansion of the WFH-WHO International External Quality Assessment Scheme will help to improve future diagnosis of these cases. An understanding of the molecular basis of these disorders will also open up the possibility of carrier testing and antenatal diagnosis.
There is also an urgent need for safe treatment products. The rarity of the conditions often means it is not cost effective for commercial companies to perform the extensive clinical trials required by the regulatory authorities for the granting of a product license.
Recombinant activated factor VII is a rare exception although it is too expensive for many countries to use. Various brands of plasma-derived preparations of fibrinogen (factor I), factor VII, factor XI, and factor XIII are available from a few manufacturers, usually only on a named-patient basis. Prothrombin complex concentrates containing the four vitamin-K dependent coagulation factors (II, VII, IX, and X) are intended for the reversal of anticoagulation with warfarin and similar drugs but may be useful in the management of factor II (prothrombin) and X deficiency.
Although fresh frozen plasma contains all coagulation factors, it is best to use coagulation factor concentrates where possible as these can be subjected to virucidal inactivation/removal steps, which render them much safer. The same is true of cryoprecipitate, which is also a good source of fibrinogen, von Willebrand factor, factor VIII and factor XIII. The recent development of a viral inactivation process applicable to cryoprecipitate is welcome news. No factor V concentrate is currently available, so fresh plasma remains the only choice at present.
In summary , the WFH recognizes the need to broaden its work to encompass the rare bleeding disorders as well as hemophilia. We aim to gather information on the prevalence of these conditions and to enhance laboratory diagnosis and promote the development of safe treatment products.
Dr. Paul Giangrande
Vice President Medical
Last Updated: January 2007 |
