Haemophilia Care in Martinique: From 1982 to 2015

Abstract Introduction: Hemophilia A (HA) and B (HB) are the most common congenital bleeding disorders, characterised by missing clotting factor VIII (FVIII) for HA or factor IX (FIX) for HB, associated with specific mutations for the corresponding genes. This is the first article to focus on a localised specific hemophiliac population in the French West Indies. Methods: Clinical, biological, genetic and socio-demographic data were collected at the Martinique Regional Centre for the Treatment of Hemophilia. Results: Nowadays patients with hemophilia and von Willebrand diseases can benefit from clinical and paramedical care comparable to what prevails in mainland France. 130 hemophilia patients were diagnosed in Martinique. This study provides the first global report on epidemiological characteristics of hemophilia in Martinique. Hemophilia treatment center was established in 2000, implementation of care services, number and diagnoses of hemophilia patients, frequency of complications such as inhibitors, HIV and hepatitis C infection, and underlying genetic mutations are described. Conclusion : These original data support that the French West Indies island of Martinique has the highest rate of HA and HB in the world compared to other countries. The establishment of a treatment center now provides standard of care to this population and may be a model for similar approaches in other French overseas regions. Disclosures No relevant conflicts of interest to declare.

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Prevalence of Hepatitis C Infection and Virus Clearance in Patients with Hemophilia

Blood ◽

10.1182/blood.v126.23.4706.4706 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4706-4706

Author(s):

Kamila Izabela Cisak ◽

Jianmin Pan ◽

Shesh Nath Rai ◽

Patricia Ashby ◽

Vivek R. Sharma

Keyword(s):

Viral Load ◽

Hepatitis C ◽

Factor Viii ◽

The United States ◽

Treatment Center ◽

Clotting Factor ◽

Hepatitis C Infection ◽

Clotting Factors ◽

Virus Clearance ◽

Viii And Ix

Abstract Introduction Hemophilia A and B are hereditary genetic disorders caused by deficiency of clotting factor VIII and IX respectively. Infusions of clotting factors constitute the mainstay of treatment. Before availability of recombinant factor VIII and IX, patients with hemophilia received products derived from human plasma and were at risk of blood-borne infections exposure. Since then, ongoing advances have yielded not only safer recombinant clotting factors but also effective treatment of infections. Hepatitis C infection and its complications constitute a common cause of morbidity and mortality in older hemophilia patients. In the last few years, FDA approved various antiviral medications which allow achievement of sustained virologic response and even cure hepatitis C infection. Goal of our study is to show prevalence of hepatitis C infection and virus clearance at our hemophilia treatment center. Methods We performed retrospective chart review of patients followed at a single hemophilia treatment center in the United States. We included 59 patients with factor VIII or IX deficiency, age 30 and older, followed in clinic between 2005 and 2014. Patients with acquired hemophilia were excluded from study. Data was collected from physician notes and laboratory tests results which included hepatitis C antibodies and viral load. Results 39 (66.1%) patients had history of hepatitis C infection. 21 (35.6%) patients had detectable hepatitis C viral load [95% CI 0.24-0.49] while 18 (30.5%) patients cleared the virus [95% CI 0.19-0.44]. Conclusions Our study showed that 66.1% of hemophilia patients followed at our institution had current or past hepatitis C infection. More than half of them were virus carriers during their last viral load check. Many of them had refused interferon-based treatment due to the requirement of being on it for long duration and concerns about side effects. Others had received the treatment but failed it. This constituted as much as 35.6% of hemophilia patients at our hemophilia treatment center. Availability of the newer antiviral agents that are better tolerated and yield high cure rates provide an opportunity to further reduce the disease burden in these patients. Disclosures No relevant conflicts of interest to declare.

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Genetic Characterization of Hemophilia and Implications for Novel Therapies

Blood ◽

10.1182/blood.v116.21.sci-9.sci-9 ◽

2010 ◽

Vol 116 (21) ◽

pp. SCI-9-SCI-9 ◽

Cited By ~ 1

Author(s):

David Lillicrap

Keyword(s):

Gene Transfer ◽

Phase I ◽

Half Life ◽

Genetic Characterization ◽

Viral Vector ◽

Conflicts Of Interest ◽

Coagulation Factor ◽

Factor Ix ◽

Clotting Factor

Abstract Abstract SCI-9 The genes encoding factor VIII (FVIII) and factor IX (FIX) were cloned 25 years ago. Since then, substantial translational application of this knowledge has been witnessed. First, genetic analysis of hemophilia has enabled a detailed understanding of the types and patterns of mutation responsible for these conditions. This knowledge has provided important biological insights into the mechanisms underlying mutation generation and has also formed the basis for precise molecular diagnosis for hemophilia carriers and potentially affected fetuses. In addition, the hemophilic genotype is the best-characterized and strongest predictor for the development of inhibitor generation in previously untreated patients. The second benefit deriving from the genetic characterization of the hemophilias has been the production of recombinant coagulation factor concentrates. Over the past 20 years, the use of recombinant factor concentrates has increased dramatically and we are currently witnessing a flurry of activity to develop second-generation, enhanced concentrates. The major objective of these projects is to facilitate clotting factor prophylaxis through the production of concentrates whose half-lives are extended, thus reducing the frequency of factor administration. These endeavors are utilizing a variety of approaches, but most are focused on either chemical modification of the factors through polymer conjugates or the generation of fusion proteins with immunoglobulin or albumin to take advantage of the recycling function of the neonatal Fc receptor. The first wave of these new products is now undergoing early phase clinical studies, and while substantial benefits for FIX half-life extension appear achievable, FVIII half-life modification may be more challenging. Finally, molecular genetic knowledge of the hemophilias has resulted in the pursuit of strategies to utilize genetic approaches to effect long-term “cures” of the disease. These initiatives have resulted in several small phase I/II trials of viral vector-based gene transfer but have also formed the basis of mutation-specific therapies such as a translational read-through approach being undertaken in patients with nonsense mutations. Currently, two phase I/II trials are in progress with liver-directed AAV FIX gene transfer in which two different AAV serotypes are being evaluated. These studies follow on from two previous AAV clinical trials in which the major obstacle to clinical benefit appears to have been the host immune response to the vector. There is considerable interest in the outcomes of these new studies. Disclosures: No relevant conflicts of interest to declare.

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Integration of Ambulatory Clinical Pharmacy Services in a Gastroenterology Clinic for Management of Hepatitis C Infection: A Pilot Study

INNOVATIONS in pharmacy ◽

10.24926/iip.v8i2.517 ◽

2017 ◽

Vol 8 (2) ◽

Author(s):

Erika Bower ◽

Haley Holtan ◽

George Konstantinides ◽

Shannon Reidt

Keyword(s):

Patient Satisfaction ◽

Conflicts Of Interest ◽

Demographic Data ◽

Medication Management ◽

Satisfaction Survey ◽

Original Research ◽

Staff Satisfaction ◽

Hepatitis C Infection ◽

Clinical Pharmacists ◽

Satisfaction Surveys

Purpose: The purpose of this study is to describe implementation of comprehensive medication management (CMM) services in a gastroenterology (GI) clinic for HCV patients on direct acting antivirals (DAAs), and to evaluate services in terms of identification of medication related problems (MRPs), patient satisfaction, and provider satisfaction. Methods: Six months of visit data was retrospectively collected to determine demographic data and to analyze pharmacist’s identification of MRPs. Patient satisfaction surveys were collected using a thirteen question validated pharmacist-satisfaction survey. After pilot completion, a twelve-question survey was sent to all GI clinic staff members to evaluate overall staff satisfaction with services. Results: Ninety-four CMM visits were completed. A total of 246 MRPs were identified with an average of 2.6 MRPs per visit. Seventy-eight MRPs were related to appropriate indication, 27 to efficacy, 30 to safety, and 109 to adherence. Forty MRPs were related to drug-drug interactions. Patient satisfaction surveys revealed that 86% of respondents rated the quality of care and services from the clinical pharmacist as "Excellent". Patients better understood and felt confident with therapy. All staff satisfaction survey respondents strongly agreed or agreed that the pharmacist made valuable contributions to the clinic and patient care. All also strongly agreed that pharmacy’s CMM services were an essential component to the management of HCV. Conclusion: Data supports continued involvement of clinical pharmacists within the clinic to promote safety and efficacy of DAAs. Patient and staff satisfaction survey results further illustrate the importance and value that CMM provided by clinical pharmacists can provide. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties. Type: Original Research

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Participation for Innovation: Survey of Motivation for Clinical Studies Evaluating New Treatments for Hemophilia

Blood ◽

10.1182/blood.v118.21.4778.4778 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4778-4778

Author(s):

Severine Henrard ◽

Niko Speybroeck ◽

Catherine M Lambert ◽

Cedric R. Hermans

Keyword(s):

Clinical Trials ◽

Side Effects ◽

Clinical Research ◽

Clinical Studies ◽

Conflicts Of Interest ◽

Developed Countries ◽

Active Participation ◽

Treatment Center ◽

Clotting Factor ◽

New Treatments

Abstract Abstract 4778 Over the last 50 years, clinical research into new treatments has helped to transform the care of individuals with hemophilia. Life expectancy for severe hemophiliacs has indeed increased from 11 years in the 1960s to more than 60 years today and many patients with hemophilia are now able to lead an active and fulfilled life. All this has been possible largely through the commitment of people with hemophilia to active participation in clinical research. While much has been achieved, much remains to be accomplished such as the development and validation of longer acting clotting factor concentrates, new bypassing agents and the validation of treatment strategies aiming at preventing or reducing the risk of inhibitor development. Although many clinical trials are currently ongoing around the world, most of them are facing difficulties in recruiting candidate patients, mainly in developed countries. In this context, there is a major need to improve the patients' awareness of the importance of clinical research in hemophilia and highlight the opportunities of an active participation in clinical trials. A survey was launched to evaluate the motivation of patients with hemophilia for clinical studies and identify factors which might influence their willingness to participate. A specific questionnaire was sent to 189 patients with hemophilia (127 adults and 62 children) regularly attending the hemophilia treatment Center of the Cliniques Universitaires Saint-Luc, Brussels, Belgium. Different aspects such as socio-demographic status, familial situation, current hemophilia treatment, knowledge about principles and perceived benefits and risks of clinical studies, positive and negative factors for motivation were extensively addressed. Preliminary results show that most patients have a limited knowledge about the general principles of clinical research. Patients on prophylaxis show a higher motivation to participate than patients treated on demand. Patients are mainly concerned by possible side effects of new treatments. The time lost from school or work refrains many motivated patients from an active participation. Moreover, very few patients are ready to take part in phase 1 trial fearing unknown reactions or side-effects. This survey, which will soon be extended to several hemophilia centers in Europe, highlights the importance to raise awareness and provide better knowledge about the modalities, the risks and benefits of clinical research. Disclosures: No relevant conflicts of interest to declare.

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Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648807 ◽

1994 ◽

Vol 72 (01) ◽

pp. 033-038 ◽

Cited By ~ 7

Author(s):

N Schinaia ◽

A M G Ghirardini ◽

M G Mazzucconi ◽

G Tagariello ◽

M Morfini ◽

...

Keyword(s):

Cumulative Incidence ◽

National Registry ◽

Factor Ix ◽

Clotting Factor ◽

Coagulation Disorders ◽

Factors Associated ◽

Kaplan Meier ◽

Significant Difference ◽

Congenital Coagulation Disorders ◽

Clotting Factor Concentrates

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

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The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649437 ◽

1966 ◽

Vol 15 (03/04) ◽

pp. 349-364 ◽

Cited By ~ 5

Author(s):

A.H Özge ◽

H.C Rowsell ◽

H.G Downie ◽

J.F Mustard

Keyword(s):

Body Weight ◽

Factor Viii ◽

Factor Ix ◽

Clotting Factor ◽

Blood Ph ◽

Order Of Magnitude ◽

Dose Dependent ◽

Generation Test ◽

Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

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‘Colonial livery’ and the chemise à la reine, 1779–1784

Costume ◽

10.3366/cost.2018.0069 ◽

2018 ◽

Vol 52 (2) ◽

pp. 217-239 ◽

Cited By ~ 1

Author(s):

Jane Ashelford

Keyword(s):

West Indies ◽

Jane Austen ◽

French West Indies ◽

Cotton Industry ◽

Saint Domingue ◽

Marie Antoinette ◽

White Elite

When Jane Austen wrote in January 1801 that ‘Mrs Powlett was at once expensively and nakedly dressed’, the fashion for muslin dresses had existed for some eighteen years. This article examines the crucial period between 1779 and 1784 when the muslin garment, which became known as the chemise à la reine, was developed and refined. Originating in the French West Indies, the gaulle was the ‘colonial livery’ worn by the wives of the white elite, the ‘grands blancs’, and first appeared as a costume in a ballet performed in Paris in 1779. The version worn by Queen Marie Antoinette in Vigée Le Brun's controversial portrait of 1783 provoked, according to the Baron de Frénilly, ‘a revolution in dress’ which eventually destabilized society. The article focuses on the role played by Saint-Domingue, France's most valuable overseas possession, in the transference of the gaulle from colonial to metropolitan fashion, and how the colony became one of the major providers of unprocessed cotton to the French cotton industry.

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