Treatment of Factor VIII Inhibitors: Products and Strategies

Bg, Macik

doi:10.1055/s-2007-994002

Cited by 38 publications

(27 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, APCCs such as FEIBA (Factor Eight Inhibitor Bypassing Activity) represent a well–established approach to the prophylaxis and treatment of bleeding episodes in haemophilia patients who have inhibitors (alloantibodies) against FVIII. APCCs, including FEIBA, were developed in the early 1970s [4, 5]. Although FVIII inhibitor bypassing activity has been demonstrated both in vitro and in vivo, today – more than 25 years after its discovery – the active principle is still the subject of scientific debate [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Factor Xa and Prothrombin: Mechanism of Action of FEIBA

Turecek¹,

Váradi²,

Gritsch³

et al. 1999

Vox Sanguinis

View full text Add to dashboard Cite

A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high–titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)–deficient dog and controlled bleeding in rabbits with antibody–induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.

show abstract

Section: Introductionmentioning

confidence: 99%

Factor Xa and Prothrombin: Mechanism of Action of FEIBA

Turecek¹,

Váradi²,

Gritsch³

et al. 1999

Vox Sanguinis

View full text Add to dashboard Cite

show abstract

“…The frequency of the presence of such inhibitors is up to 30% in patients with severe hemophilia A [3]. The alloimmune response exposes the patients to a higher risk of mortality [4]. A number of factors have been identified in the recent years that may be responsible for the occurrence of alloantibody inhibitor and have been discussed in detail by Ghosh et al in this issue.…”

Section: The Occurrence Of Anti-fviii Antibodiesmentioning

confidence: 99%

Varied Immune Response to FVIII: Presence of Proteolytic Antibodies Directed to Factor VIII in Different Human Pathologies

Wootla

Rao

Friboulet

et al. 2009

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation of the complement and its activation, and activation of effector cells. In addition to this plethora of functions, antibodies are capable of expressing enzymatic activity. Antibodies with catalytic function are a result of the productive interplay between the highly evolved machinery of the immune system and the chemical framework used to induce them (antigens). Catalytic antibodies are immunoglobulins with an ability to catalyze the reactions involving the antigen for which they are specific. Catalytic immunoglobulins of the IgM and IgG isotypes have been detected in the serum of healthy donors. In addition, catalytic immunoglobulins of the IgA isotype have been detected in the milk of healthy mothers. Conversely, antigen-specific hydrolytic antibodies have been reported in a number of inflammatory, autoimmune, and neoplastic disorders. The pathophysiological occurrence and relevance of catalytic antibodies remains a debated issue. Through the description of the hydrolysis of coagulation factor VIII as model target antigen, we propose that catalytic antibodies directed to the coagulation factor VIII may play a beneficial or a deleterious role depending on the immuno-inflammatory condition under which they occur.

show abstract

“…Thus far, therapeutic interventions in these situations have included overcoming the inhibitors with large doses of factor VIII; however, this is only feasible when the inhibitor titer is relatively low (Maick 1993;Nillson et al 1993). Other approaches have included the use of activated and non-activated Electronic supplementary material The online version of this article (doi:10.1007/s10529-010-0227-7) contains supplementary material, which is available to authorized users.…”

Section: Introductionmentioning

confidence: 99%

“…Other approaches have included the use of activated and non-activated Electronic supplementary material The online version of this article (doi:10.1007/s10529-010-0227-7) contains supplementary material, which is available to authorized users. prothrombin complex concentrates, porcine factor VIII (Bray et al 1994;Hay et al 1994) and plasmapheresis with or without adsorption of antibody (Maick 1993). All these interventions can have significant disadvantages including high cost, unpredictability of response, transmission of blood-derived infections, thromboembolic complications, and in the case of porcine factor VIII, development of antiporcine antibodies.…”

Section: Introductionmentioning

confidence: 99%

High-level expression of functional recombinant human coagulation factor VII in insect cells

et al. 2010

View full text Add to dashboard Cite

Recombinant coagulation factor VII (FVII) is used as a potential therapeutic intervention in hemophilia patients who produce antibodies against the coagulation factors. Mammalian cell lines provide low levels of expression, however, the Spodoptera frugiperda Sf9 cell line and baculovirus expression system are powerful systems for high-level expression of recombinant proteins, but due to the lack of endogenous vitamin K-dependent carboxylase, expression of functional FVII using this system is impossible. In the present study, we report a simple but versatile method to overcome the defect for high-level expression of the functional recombinant coagulation FVII in Sf9 cells. This method involves simultaneous expression of both human gamma-carboxylase (hGC) and human FVII genes in the host. It may be possible to express other vitamin K-dependent coagulation factors using this method in the future.

show abstract

Treatment of Factor VIII Inhibitors: Products and Strategies

Cited by 38 publications

References 87 publications

Factor Xa and Prothrombin: Mechanism of Action of FEIBA

Factor Xa and Prothrombin: Mechanism of Action of FEIBA

Varied Immune Response to FVIII: Presence of Proteolytic Antibodies Directed to Factor VIII in Different Human Pathologies

High-level expression of functional recombinant human coagulation factor VII in insect cells

Contact Info

Product

Resources

About