Implications of emerging pathogens in the management of haemophilia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72878/1/j.1365-2516.2006.01193.x.pd

New treatment paradigm for hemophilia poses challenges for legacy bioassays

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151338/1/jth14550_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151338/2/jth14550.pd

Strategies towards a longer acting factor VIII

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74903/1/j.1365-2516.2006.01260.x.pd

Not in the genotype: can unexplained hemophilia A result from “micro(RNA) management”?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154344/1/trf15668_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154344/2/trf15668.pd

The role of telemedicine in the delivery of health care in the COVID‐19 pandemic

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162731/2/hae14044.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162731/1/hae14044_am.pd

New high-technology products for the treatment of haemophilia

This review will focus on new technologies in development that promise to lead to further advances in haemophilia therapeutics. There has been continued interest in the bioengineering of recombinant factor VIII (rFVIII) and factor IX (rFIX) with improved function to overcome some of the limitations in current treatment, the high costs of therapy and to increase availability to a broader world haemophilia population. Bioengineered forms of rFVIII, rFIX or alternative haemostatic molecules may ultimately have an impact on improving the efficacy of therapeutic strategies for the haemophilias by improving biosynthesis and secretion, functional activity, half-life and immunogenicity. Preventing and suppressing inhibitors to factor (F) VIII remain a challenge for both clinicians and scientists. Recent experiments have shown that it is possible to obtain anti-idiotypic antibodies with a number of desirable properties: (i) strong binding avidity to FVIII inhibitors; (ii) neutralization of inhibitory activity both in vitro and in vivo ; (iii) cross-reactivity with antibodies from unrelated patients, and (iv) no interference with FVIII function. An alternative, although complementary approach, makes use of peptides derived from filamentous-phage random libraries. Mimotopes of FVIII can be obtained, which bind to the paratope of inhibitory activity and neutralize their activity both in vitro and in vivo . In this paper, we review advanced genetic strategies for haemophilia therapy. Until recently the traditional concept for gene transfer of inherited and acquired haematological diseases has been focused on how best to obtain stable insertion of a cDNA into a target-cell genome, allowing expression of a therapeutic protein. However, as gene-transfer vector systems continue to improve, the requirement for regulated gene transcription and hence regulated protein expression will become more critical. Inappropriate protein expression levels or expression of transferred cDNAs in non-intended cell types or tissues may lead to target-cell toxicity or activation of unwanted host immune responses. Regulated protein expression requires that the transferred gene be transferred with its own regulatory cassette that allows for gene transcription and translation approaching that of the normal gene in its endogenous context. New molecular techniques, in particular the use of RNA molecules, now allow for transcription of corrective genes that mimic the normal state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75577/1/j.1365-2516.2004.00996.x.pd

International workshop on immune tolerance induction: consensus recommendations 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73382/1/j.1365-2516.2007.01497.x.pd

Progress in the molecular biology of inherited bleeding disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73391/1/j.1365-2516.2008.01718.x.pd

Reduction of inhibitor titres by infusion of FVIII gene transduced tolerogenic dendritic cells in haemophilic mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72521/1/j.1365-2516.2009.01996_2.x.pd

Biological mechanisms underlying inter‐individual variation in factor VIII clearance in haemophilia

Previous studies have highlighted marked inter‐individual variations in factor VIII (FVIII) clearance between patients with haemophilia (PWH). The half‐life of infused FVIII has been reported to vary from as little as 5.3 hours in some adult PWH, up to as long as 28.8 hours in other individuals. These differences in clearance kinetics have been consistently observed using a number of different plasma‐derived and recombinant FVIII products. Furthermore, recent studies have demonstrated that half‐life for extended half‐life (EHL‐) FVIII products also demonstrates significant inter‐patient variation. Since time spent with FVIII trough levels <1% has been shown to be associated with increased bleeding risk in PWH on prophylaxis therapy, this variability in FVIII clearance clearly has major clinical significance. Recent studies have provided significant novel insights into the cellular basis underlying FVIII clearance pathways. In addition, accumulating data have shown that endogenous plasma VWF levels, ABO blood group and age, all play important roles in regulating FVIII half‐life in PWH. Indeed, multiple regression analysis suggests that together these factors account for approximately 34% of the total inter‐individual variation in FVIII clearance observed between subjects with severe haemophilia A. In this review, we consider these and other putative modulators of FVIII half‐life, and discuss the biological mechanisms through which these factors impact upon FVIII clearance in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156160/2/hae14078.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156160/1/hae14078_am.pd