Recombinant Factor VIII for the Treatment of Previously Untreated Patients with Hemophilia A -- Safety, Efficacy, and Development of Inhibitors

Lusher, Jeanne M.; Arkin, Steven; Abildgaard, Charles F.; Schwartz, Richard S.

doi:10.1056/nejm199302183280701

Cited by 469 publications

(300 citation statements)

References 25 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…Low-titer inhibitors comprise 25% to 50% of observed inhibitors and approximately 10% of these are considered transient, disappearing over weeks to months despite continued treatment with fVIII. [7][8][9][10] …”

Section: How Are Inhibitors Detected?mentioning

confidence: 99%

How we treat a hemophilia A patient with a factor VIII inhibitor

Kempton

White

2009

Blood

151

144

View full text Add to dashboard Cite

The most significant complication of treatment in patients with hemophilia A is the development of alloantibodies that inhibit factor VIII activity. In the presence of inhibitory antibodies, replacement of the missing clotting factor by infusion of factor VIII becomes less effective. Once replacement therapy is ineffective, acute management of bleeding requires agents that bypass factor VIII activity. Long-term management consists of eradicating the inhibitor through immune tolerance. Despite success in the treatment of acute bleeding and inhibitor eradication, there remains an inability to predict or prevent inhibitor formation. Ideally, prediction and ultimately prevention will come with an improved understanding of how patientspecific and treatment-related factors work together to influence anti-factor VIII antibody production. (Blood. 2009;113: 11-17)

show abstract

Section: How Are Inhibitors Detected?mentioning

confidence: 99%

How we treat a hemophilia A patient with a factor VIII inhibitor

Kempton

White

2009

Blood

151

144

View full text Add to dashboard Cite

show abstract

“…In Western Europe and North America, recombinant factors have definitely become the main product used for treatment, with a constant trend towards increased consumption [13]. The first generation of recombinant products had an impeccable record of efficacy and safety [15][16][17]. Nevertheless, the manufacturers chose to implement further technological improvements leading to a substantial reduction in the content of proteins other than FVIII or FIX [18][19][20].…”

Section: From the 1990s Until Now: A New Golden Eramentioning

confidence: 99%

Back to the future: a recent history of haemophilia treatment

2008

View full text Add to dashboard Cite

Summary. In the last few decades, the management of patients with haemophilia has witnessed dramatic improvements, through the larger availability of safe plasma-derived and recombinant products for replacement therapy. Another important step forward is the progressively larger-scale implementation of primary prophylaxis in children. Currently, the main problem in patients with haemophilia is the onset of antibodies inactivating the infused clotting factor (inhibitors), even though immune tolerance regimens that are able to eradicate inhibitors and the availability of products that bypass the intrinsic coagulation defects have dramatically improved the management of these patients. Cure of haemophilia through gene transfer is being attempted, but relatively, it is far from being implemented on a large scale. It is likely that further improvements in replacement therapy will occur in the near future, through the availability of new-therapeutic tools such as factors VIII and IX with longer half-lives, more potent bypassing agents and factors extracted from the milk of transgenic animals.

show abstract

“…15 Nevertheless, patients carrying certain mutations present an incidence of inhibitor formation comparable to that of patients with severe hemophilia A. Such mutations have been located in the amino-terminal region of the A2 domain, the carboxy-terminal part of the C1 domain, and the amino-terminal part of the C2 domain.…”

Section: Introductionmentioning

confidence: 99%