Hemophilia Research Today is a free monthly online journal that collates and summarizes the latest research about Hemophilia, including details on genetics, causes, symptoms, blood transfusion.

How I treat age-related morbidities in elderly persons with hemophilia.

Mannucci PM, Schutgens RE, Santagostino E, Mauser-Bunschoten EP

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy. pmmannucci@libero.it

In persons with hemophilia, life expectancy is now approaching that of the general male population, at least in countries that can afford regular replacement therapy with coagulation factor concentrates. The new challenges for comprehensive treatment centers are thus to provide optimal health care for this aging population of patients, who often present not only with the comorbidities typically associated with hemophilia (arthropathy, chronic pain, blood-borne infections), but also with common age-related illnesses such as cardiovascular disease and cancer. There are no evidence-based guidelines for the management of these conditions, which often require drugs that interfere with hemostasis, enhance the bleeding tendency, and warrant more intensive replacement therapy. At the moment, elderly patients with hemophilia affected by other diseases should be managed like their age-group peers without hemophilia, provided replacement therapy is tailored to the heightened risk of bleeding associated with the need for invasive procedures and drugs that further compromise the deranged hemostasis. More detailed advice is provided on the schedules of replacement therapy needed to tackle cardiovascular diseases, such as acute coronary syndromes and nonvalvular atrial fibrillation, because these conditions will become more and more frequent challenges for the comprehensive treatment centers.

Published 18 December 2009 in Blood, 114(26): 5256-63.
Full-text of this article is available online (may require subscription).

Articles on Hemophilia published 7 December 2009:

Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy.   Blood, 114(20): 4373-82.

One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly ... [Abstract] [Full-text]

Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model.   Blood, 114(20): 4562-5.

Production of recombinant B-domain-deleted canine factor VIII (cFVIII-BDD) unexpectedly revealed superior protein yields with 3-fold increased specific activity relative to human FVIII-BDD (hFVIII-BDD). We also determined that activated cFVIII-BDD is more stable than activated hFVIII-BDD. Furthermore, cFVIII-BDD is efficient at inducing hemostasis in human plasma containing FVIII inhibitors. Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease phenotype with a ... [Abstract] [Full-text]

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The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created enormous interest in applying this process to the development of cellular medicine for degenerative and genetic diseases. Because the liver is the primary site of factor VIII (FVIII) synthesis, we hypothesized that the partial replacement of mutated liver cells by healthy cells in hemophilia A mice could manage the severity of the bleeding disorder. We perturbed the host liver with acetaminophen to facilitate the ... [Abstract] [Full-text]

Articles on Hemophilia published 25 September 2009:

Enhanced efficacy of recombinant FVIII in noncovalent complex with PEGylated liposome in hemophilia A mice.   Blood, 114(13): 2802-11.

Recombinant FVIII formulated in PEG-ylated liposomes (rFVIII-PEG-Lip) was reported to increase the bleed-free days from 7 to 13 days (at 35 IU/kg rFVIII) in severe hemophilia A patients. To understand the underlying mechanism, we sought to recapitulate its efficacy in hemophilia A mice. Animals treated with rFVIII-PEG-Lip achieved approximately 30% higher survival relative to rFVIII after tail vein transection inflicted 24 hours after dosing. The efficacy of rFVIII-PEG-Lip represents an ... [Abstract] [Full-text]

Articles on Hemophilia published 16 September 2009:

Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A.   Eur J Clin Pharmacol, 65(10): 989-98.

PURPOSE: The three aims of this investigation were (1) to develop a population pharmacokinetic (PK) model for factor VIII (FVIII) in haemophilia A patients, with estimates of inter-occasion and inter-individual variance, (2) to investigate whether appropriate dosing of FVIII for regular prophylaxis can be calculated according to patient characteristics, and (3) to present dosing recommendations for initiating prophylactic treatment. METHODS: A population PK model was developed using data from ... [Abstract] [Full-text]

Articles on Hemophilia published 2 September 2009:

High frequencies of exposure to the novel human parvovirus PARV4 in hemophiliacs and injection drug users, as detected by a serological assay for PARV4 antibodies.   J Infect Dis, 200(7): 1119-25.

BACKGROUND: PARV4 is a human parvovirus that was first detected in and cloned from an individual with a human immunodeficiency virus (HIV) seroconversion-like illness and that subsequently persisted in the lymphoid tissue and bone marrow. In contrast to human parvovirus B19 infections, PARV4 infections are most frequently detected in injection drug users (IDUs), particularly those who are coinfected with HIV type 1 (HIV-1). To investigate the routes of transmission of PARV4 and to ascertain ... [Abstract] [Full-text]

Articles on Hemophilia published 31 August 2009:

An assessment of the relative influence of pain coping, negative thoughts about pain, and pain acceptance on health-related quality of life among people with hemophilia.   Pain, 145(1): 169-75.

Many people with hemophilia are affected by chronic arthritic joint pain as well as acute bleeding pain. In this cross-sectional study, 209 men with hemophilia A or B completed the Hemophilia Pain Coping Questionnaire (HPCQ), the Chronic Pain Acceptance Questionnaire (CPAQ), and the RAND 36-item Health Survey (SF-36), a measure of health-related quality of life. Multiple regression was used to test the influence of active pain coping, passive adherence coping, and negative thoughts about pain ... [Abstract] [Full-text]

Articles on Hemophilia published 27 August 2009:

Haemophilia imaging: a review.   Skeletal Radiol, 38(10): 949-57.

Haemophilia disorders are characterised by a blood coagulation anomaly leading to prolonged and excessive bleeding. Imaging provides an essential role in the investigation of both the musculoskeletal and the non-musculoskeletal complications of haemophilia. Our institution is home to a large tertiary referral centre for haemophilia treatment. Using our broad experience, we present a multi-modality pictorial review of the musculoskeletal manifestations of haemophilia, including haemophilic ... [Abstract] [Full-text]

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