New Perspectives in Hemophilia Treatment
Open Access
- 1 January 2005
- journal article
- Published by American Society of Hematology in Hematology-American Society Hematology Education Program
- Vol. 2005 (1) , 429-435
- https://doi.org/10.1182/asheducation-2005.1.429
Abstract
A variety of factor concentrates are currently available for replacement therapy for patients with hemophilia. These differ by several parameters, including source (pooled from pooled blood vs recombinant), purity, pathogen inactivation, and by the presence or absence of extraneous proteins such as albumin. The choice of replacement product reflects both safety issues of pathogen transmission or inhibitor development, and personal preferences of the patient and the physician. In general, currently available products are viral pathogen-free, although there is debate about the risk of transmission of parvovirus B19 and prion pathogens. Because of this very small risk, recombinant factor is the treatment of choice in previously untreated patients. In addition, a subset of concentrates contain factor that is activated during manufacture, yielding activated products that can be used in the treatment of patients with inhibitors. Such activated products, especially recombinant factor VIIa (rFVIIa), have also acquired several off-label indications in the management of bleeding in non-hemophiliac patients. The management of hemophilia patients with inhibitors is an ongoing challenge. Immune tolerance induction using a desensitization technique is successful in up to 90% of patients with alloantibodies against factor VIII, with greatest success seen in patients with low titer inhibitors who are treated soon after detection of an alloantibody and in whom treatment includes administration of immunosuppression along with repeated infusions of high titer concentrates. Such therapy is less successful in patients with factor IX alloantibodies. Non-hemophiliac patients with acquired inhibitors represent a unique patient population that requires special management. These patients have a mortality rate that approaches 25% because of the association of acquired inhibitors with severe bleeding complications, occurrence in a largely elderly population, and the frequent presence of an underlying, often serious, primary medical condition. Treatment consists of immunosuppression with steroids, chemotherapy, or intravenous immunoglobulin. Recent studies using rituximab for selective B-cell depletion in these patients have been very promising, although prospective controlled studies have not yet been performed. Finally, although hemophilia A and B appear to be ideal diseases to target with gene therapy approaches, the promise of this therapy remains to be realized.Keywords
This publication has 12 references indexed in Scilit:
- Treatment of acquired hemophilia by the Bonn-Malmö Protocol: documentation of an in vivo immunomodulating conceptBlood, 2005
- Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activityJournal of Thrombosis and Haemostasis, 2004
- Pathogenic antibodies to coagulation factors. Part one: Factor VIII and Factor IXJournal of Thrombosis and Haemostasis, 2004
- Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophiliaBlood, 2004
- The epidemiology of inhibitors in haemophilia A: a systematic reviewHaemophilia, 2003
- The future of recombinant coagulation factorsJournal of Thrombosis and Haemostasis, 2003
- Inhibitor Development in Previously Untreated Patients with Hemophilia A: A Prospective Long-Term Follow-Up Comparing Plasma-Derived and Recombinant ProductsSeminars in Thrombosis and Hemostasis, 2002
- Recombinant Activated Factor VII (rFVIIa): Characterization, Manufacturing, and Clinical DevelopmentSeminars in Thrombosis and Hemostasis, 2001
- The diagnosis and management of factor VIII and IX inhibitors: a guideline from the UK Haemophilia Centre Doctors' Organization (UKHCDO)British Journal of Haematology, 2000
- The Inhibitor Antibody Response Is More Complex in Hemophilia A Patients Than in Most Nonhemophiliacs With Factor VIII AutoantibodiesBlood, 1997