The CHS/Pfizer Care until Cure Research Program

/The CHS/Pfizer Care until Cure Research Program
The CHS/Pfizer Care until Cure Research Program2018-09-05T18:25:57+00:00

The CHS / Pfizer Care Until Cure Research Program was established in the year 2000 in collaboration with Wyeth Canada, now Pfizer. Pfizer Canada strives every day to help Canadians live healthy, balanced lives. They do that by discovering and developing innovative medicines. As a company, they’re dedicated to building healthier communities and empowering Canadians to make healthier choices every day. At Pfizer Canada, they believe that to be truly healthy, it takes more than medication.

This program allows Canadian investigators to conduct research on medical and psychosocial aspects of bleeding disorders, including outcome evaluation. Grants are awarded for clinical research in fields relevant to improving the quality of life for persons with hemophilia, persons with von Willebrand disease or other inherited bleeding disorders, persons with related conditions such as HIV or hepatitis C, and carriers of an inherited bleeding disorder.

For the 2019-2020 granting period of the program, specific areas of interest have been identified and investigators are encouraged to submit proposals within these areas. The grants review committee will allocate funding to the strongest and most relevant projects included but not limited to the areas of interest listed below.

2019-2020 AREAS OF INTEREST include and are not limited to:

  • Hemophilia A or B

1. Epidemiology / burden of disease / outcome research
2. Tailoring/Personalized Hemophilia Treatment (eg, prophylaxis regimen, pharmacokinetics, adherence and other factors)
3. The role of non-circulating & extravascular Factor IX in hemostasis
4. Mild Hemophilia: natural history, clinical outcomes, healthcare utilization and cost, quality of life and joint surveillance
5. New considerations in the management of special populations: adolescents, carriers or ageing populations
6. “Real World” Observational Data on Factor Utilization and Cost-effectiveness

    • Clinical monitoring of hemophilia treatment

1. Inhibitors, Inhibitor Management (eg, Immune tolerance), and Immunogenicity
2. Product Switching Experience: rationale for switch and clinical monitoring
3. Joint Outcomes and the Role of Point-of-care Joint Ultrasonography in the Management of Hemophilia

   • Basic Science of Gene Therapy for Hemophilia

1. Basic science, tropism, transduction efficiency & tolerability of Adeno-associated virus (AAV)
2. Epidemiology of AAV seropositivity
3. AAV antibody Titer assessment, reduction, tolerance
4. Role of immunosuppression in managing transaminitis

   • Basic Science of TFPI & Anti-TFPI Monoclonal Antibodies

1. Regulation of Coagulation
2. Basic biology of TFPI interactions with Protein C, ATIII, & Protein S
3. Cross talk among regulators interacting with TFPI (e.g. Protein S being a co-factor for both Protein C and TFPI)
4. Role of different TFPI pools in regulation of coagulation
5. Pharmacology resulting from concomitant treatments (especially antifibrinolytics) added to anti-TFPI

   • Antifibrinolytic Therapy

For the CHS / Pfizer Care Until Cure Research Program, individual grants valued at $75,000 per year will be awarded to researchers for a maximum of $150,000 which can be expended over 2 or 3 years. If a two year award is provided, the second year of funding is dependent on evidence of progress as described in the required progress report. Grant funding will begin on April 1, 2019.

Application forms for the 2019-20 granting period as well as the general criteria and conditions can be accessed by going to the sections below. Deadline to submit applications: November 15, 2018

Funds Available for Clinical Research, including Outcome Evaluation

The Canadian Hemophilia Society, in collaboration with Pfizer Canada (formerly Wyeth), has established the Care Until Cure research program to support clinical research, including outcome evaluation, to improve the quality of life of persons with hemophilia and other inherited bleeding disorders.

Eligibility

Applicants must be Canadian citizens or permanent residents and affiliated with a Canadian university or not-for-profit health-related organization. Grants will be made available for clinical research, including outcome evaluation, in fields relevant to improving the quality of life of:

  • persons with hemophilia
  • persons with von Willebrand disease or other inherited bleeding disorders
  • persons with related conditions such as HIV or hepatitis C infection
  • carriers of an inherited bleeding disorder.

For the 2019-2020 granting period of the program, specific areas of interest have been identified and investigators are encouraged to submit proposals within these areas. The grants review committee will allocate funding to the strongest and most relevant projects included but not limited to the areas of interest listed below.

2019-2020 AREAS OF INTEREST include and are not limited to:

  • Hemophilia A or B
  1. Epidemiology / burden of disease / outcome research
    2. Tailoring/Personalized Hemophilia Treatment (eg, prophylaxis regimen, pharmacokinetics, adherence and other factors)
    3. The role of non-circulating & extravascular Factor IX in hemostasis
    4. Mild Hemophilia: natural history, clinical outcomes, healthcare utilization and cost, quality of life and joint surveillance
    5. New considerations in the management of special populations: adolescents, carriers or ageing populations
    6. “Real World” Observational Data on Factor Utilization and Cost-effectiveness
  • Clinical monitoring of hemophilia treatment
  1. Inhibitors, Inhibitor Management (eg, Immune tolerance), and Immunogenicity
    2. Product Switching Experience: rationale for switch and clinical monitoring
    3. Joint Outcomes and the Role of Point-of-care Joint Ultrasonography in the Management of Hemophilia
  • Basic Science of Gene Therapy for Hemophilia
  1. Basic science, tropism, transduction efficiency & tolerability of Adeno-associated virus (AAV)
    2. Epidemiology of AAV seropositivity
    3. AAV antibody Titer assessment, reduction, tolerance
    4. Role of immunosuppression in managing transaminitis
  • Basic Science of TFPI & Anti-TFPI Monoclonal Antibodies
  1. Regulation of Coagulation
    2. Basic biology of TFPI interactions with Protein C, ATIII, & Protein S
    3. Cross talk among regulators interacting with TFPI (e.g. Protein S being a co-factor for both Protein C and TFPI)
    4. Role of different TFPI pools in regulation of coagulation
    5. Pharmacology resulting from concomitant treatments (especially antifibrinolytics) added to anti-TFPI
  • Antifibrinolytic Therapy

 

Location of Tenure 

The research will be conducted in Canada by Canadian researchers affiliated with Canadian universities and not-for-profit health-related organizations.

Grant amount / Duration of Support

Individual grants valued at $75,000 per year and per project will be awarded to researchers for a maximum of $150,000 which can be expended over 2 or 3 years. If a two year award is provided, the second year of funding is dependent on evidence of progress as described in the required progress report. Grant funding will begin on April 1, 2019.

Yearly grants will normally be disbursed in two payments in each year.

General Conditions and Application Form

Applications must be completed and submitted electronically to the Canadian Hemophilia Society and one (1) original paper copy, including signatures, must be sent to the National Office of the Canadian Hemophilia Society:

301-666 Sherbrooke Street West, Montreal, QC H3A 1E7

Please visit the pages below for General Conditions and the Application form.

Deadlines

All completed application forms and support documents must arrive at the National Office of the Canadian Hemophilia Society on or before November 15, 2018. If the CHS receives the application after the deadline date but it is postmarked on or before the deadline date, then it is considered to have been submitted on time. The names of the winners of the grants will be announced by March, 2019.

Evaluation

Applications will be reviewed by an independent peer review committee composed of Canadian medical and healthcare professionals and a patient representative. This committee will rank the applications and will make recommendations to the CHS Board of Directors on funding of the proposals. The final decisions regarding awards will be made by the CHS Board of Directors. No appeals will be considered.

1. General Conditions

1.1 Application Forms
The Application Form may be obtained by clicking on the following link: Application form.

Applications forms must be completed and submitted electronically to the Canadian Hemophilia Society (chs@hemophilia.ca) and one (1) original paper copy, including signatures, must be sent to the National Office of the Canadian Hemophilia Society:
301-666 Sherbrooke Street West, Montreal, QC H3A 1E7

1.2 Application Deadline
Completed application forms and supporting documents must arrive at the National Office of the Canadian Hemophilia Society by November 15, 2018. If the CHS receives the application after the deadline date but it is postmarked on or before the deadline date, then it is considered to have been submitted on time. The names of the successful applicants will be announced by March, 2019.

First time applicants are encouraged to seek advice from experienced investigators in the preparation of their applications.

Please note that the Research Proposal (Item 17 of the application) must not exceed 5000 words, excluding figures and references.

Supporting materials should include only previously published articles or materials accepted for publication.

1.3 Grant Year and Amount 
Individual grants valued at $75,000 per year and per project will be awarded to researchers for a maximum of $150,000 which can be expended over 2 or 3 years. If a two year award is provided, the second year of funding is dependent on evidence of progress as described in the required progress report. Grant funding will begin on April 1 of each year.

1.4 Grant Payments
Yearly grants will normally be disbursed in two payments in each year and sent to the financial officer of the host institution.

1.5 Research Summaries 
The Canadian Hemophilia Society (CHS) requires, within the application form, a 200-word typewritten lay description of the research to be undertaken (in non-scientific, Grade 12 readability) for inclusion in the Society’s publications should the proposal be accepted.

1.6 Notification of Grants 
Following funding decisions, successful applicants will be sent official notification informing them of the type, duration and amount of their grant. A copy of the notification is sent to the accountant at the institution concerned. The award must be acknowledged by returning an acceptance note within 15 days of the CHS notification otherwise the award will be withdrawn. Unsuccessful applicants are also advised at the conclusion of the project application review process.

1.7 Appeals 
The Research Peer Review Committee of the Canadian Hemophilia Society will make recommendations on the awarding of the grants and the final decision will be made by the CHS Board of Directors. No appeals will be considered.

2. Additional Grant Conditions and Grantee Obligations

2.1 Statement of Expenditures 
A statement of all expenditures for the grant, signed by the candidate and the financial officer of each institution, must be received at the CHS’s offices within 2 months of the end date of the grant term. An institution finance/expenditure report is acceptable to avoid duplication of effort by the researcher. Failure to fulfill this requirement may lead to exclusion from future research grant competitions. If delay is anticipated, the CHS must be informed.

2.2 Changes in the Use of the Grant
The use of funds for purposes other than stated in the application must be approved in advance by the CHS.

2.3 Unexpended Balances 
The Canadian Hemophilia Society does not permit carrying forward into the next grant year an unexpected balance in excess of $5,000. Prior written request to the CHS is required to carry forward a balance that exceeds $5,000.

2.4 Termination of the Grant 
Upon termination of the project, any unexpended balance of funds must be returned to the CHS.

2.5 Travel Expenses

A grantee may use $1,500 annually from the award for the purpose of travel in connection with the grant and, if needed, an additional amount representing one percent (1%) of the annual value of the award.

2.6 Title to Equipment
Title to any equipment obtained with the Canadian Hemophilia Society’s funds shall be held by the host institution on the condition that for a 12 month period following termination of grant, the CHS may transfer title to another institution. Prior written authorization for the transfer of funds or equipment by a grantee to another institution must be obtained from the CHS.

2.7 Interim, Final Report & Abstract Requirements
Research grant recipients are required to provide a project progress report for each year of funding allocation. This report will serve as the basis for review of the project and approval of second year funding, where applicable. The progress report will also provide supporting rationale, if required, for approval of project modifications, and/or extension requests.

Within 2 months of the end of the funding period, the Canadian Hemophilia Society requires a final report on the results of the project. The CHS also requires that the researcher provide an approximately 250-word lay abstract (Grade 12 readability) describing the outcomes of the research for inclusion in the Society’s publications and for presentation at the CHS medical and scientific symposiums.

Failure to fulfill these requirements can lead to exclusion from future research grant competitions. If delay is anticipated, the CHS must be informed.

2.8 Acknowledgement of Support
The Canadian Hemophilia Society MUST be informed of any publications that are based on research funded by the Canadian Hemophilia Society and all such publications MUST acknowledge the support of the Canadian Hemophilia Society and Pfizer Canada. Researchers are encouraged to present study results, when possible, even if preliminary, at hemophilia conferences (e.g., World Federation of Hemophilia Congress, Rendez-Vous, etc.).

2.9 Proprietary Rights

The CHS must be informed of any commercial exploitation arising from the CHS-supported activity. However, the CHS does not claim proprietary rights to inventions resulting from research supported by its funds. The onus is on the grantee to seek patent protection in collaboration with the university or institute for inventions or developments arising from the CHS-supported research.

2.10 Indirect / Overhead Costs

Grant funds must contribute towards the direct costs of the research program or project for which the funds were awarded. The Institution provides for indirect or overhead costs, such as the costs associated with facilities and basic utilities, the purchase and repair of office equipment, administration fees, insurance for equipment and research vehicles, and basic communication devices such as telephones and fax machines. The funds must be used effectively and economically, and the expenses must be essential for the research supported by the grant.

Health Charities Coalition of Canada Position Statement on Indirect Costs of Research (May 14, 2007): 

It is the policy of the Health Charities Coalition of Canada (HCCC) that health charities should not fund the indirect costs associated with the research they fund. All HCCC members have agreed not to fund indirect costs. While the HCCC recognizes that these may indeed be legitimate expenditures, we believe the funding of such costs is the responsibility of governments and not donors.

While the CHS is not a member of HCCC, it nonetheless supports the position that indirect costs associated with research it funds are the responsibility of governments and/or research institutions and not its donors.

3. Ethical considerations

3.1 Adherence to Research Guidelines
An application to the Canadian Hemophilia Society for research support constitutes a pledge on the part of the applicants and their research institutions to respect all the guidelines of the Canadian Hemophilia Society, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010 (TCPS2), the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada and the Canadian Council on Animal Care. In the event that these guidelines are not adhered to, the CHS will withhold funding.

Completed forms required for research involving human subjects, gene therapy in humans, animals and biohazards must be received by the CHS as soon as possible; funding of successful applications for research will be withheld by the CHS until full Research Ethics Board approval is provided in writing to the CHS. CHS review of the applications, by its Peer Review Committee, can proceed prior to Research Ethics Board (REB) approval.

3.2 Research Involving Human Subjects 
Each project in a research proposal involving human subjects and gene therapy in humans must submit the complete designated form, authorized by the local institutional Research Ethics Board in accordance with the TCPS2 document of the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada,and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010. The Tri-Council Policy Statement is available from the following website:www.pre.ethics.gc.ca/pdf/eng/tcps2/TCPS_2_FINAL_Web.pdf

The responsibility for filing a Clinical Trial Application ( CTA) with Health Canada for a human drug clinical trial rests with the Principal Investigator. Guidance on whether a CTA is required is found at:

www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/cta-eng.php See: Overview of the Clinical Trial Application Process and Institution/Investigator Initiated Clinical Trials.

In addition, all continuing grantees involved in human subjects must submit the complete designated form on an annual basis. Receipt of this form is required for continuation of payment by the CHS of any funds committed for the following year.

3.3 Research on Somatic Cell Gene Therapy in Humans 
The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December 2010 must be adhered to. Any research related to this area must be reviewed by the local institutional Research Ethics Board.

3.4 Care and Use of Experimental Animals 

The CHS requires that all experiments involving animals be conducted in an ethical way. The facilities for, and the care and use of animals, in any investigation the CHS supports must be in strict accordance with the guidelines set out by the Canadian Council on Animal Care (CCAC) in its publication, Guide to the Care and Use of Experimental Animals (Vol. 1, 1980 and revised in 1993; Vol. 2, 1984), available from:

The Canadian Council on Animal Care
1000 – 151 Slater St.
Ottawa, Ontario Canada K1P 5H3

Each proposal involving animals must have one copy of the designated form, completed and authorized by a local institutional Animal Care Committee, confirming its ethical acceptability (the composition of the committee is set forth in the CCAC Guide). In addition, all continuing grantees involved in research using animals must submit one complete form on an annual basis. Receipt of this form is required for continuation of payment by the CHS of any funds committed for the following year.

3.5 Research Involving Biohazards

Investigators proposing to engage in research involving animal and human pathogens and animal cells are required to comply with the Government of Canada’s Canadian Biosafety Standard (CBS), 2nd Edition, 2015 developed jointly by the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA). This standard is used by laboratory researchers and workers in facilities possessing, handling, storing or using human and terrestrial animal pathogens and toxins.

Each proposal involving research proposals covering the areas noted above must have one completed form, authorized by a local institutional committee, confirming that the level of containment implemented by the investigator meets the Canadian Biosafety Standard (CBS) requirements.

In addition, all continuing grantees participating in research involving biohazards must submit a completed form on an annual basis. Receipt of this form is required for continuation of payment by CHS of any funds committed for the following year.

Disposal of Hazardous and Radio Active Materials

3.6 Research Involving Hazardous Compounds 
Researchers are responsible for ensuring that their research conforms with the provincial statutes regarding disposal of chemical wastes. Researchers are also responsible for ensuring that research assistants and laboratory personnel are aware of any hazards posed by materials required for the research, that these personnel are adequately trained in handling and containment of such compounds, and that protective procedures are enforced, in compliance with the Occupational Health and Safety regulations of the province in which work is carried out.

3.7 Research Involving Radioactive Materials
Applicants who will be carrying out research using radioactive materials must be aware of, and comply with, all Atomic Energy Control Board regulations, recommended procedures, and safety precautions governing the use of such materials in Canada. Further information may be obtained from:

Office of Public Information
Atomic Energy Control Board

P.O. Box 1046, Station ‘B’
270 Albert Street
Ottawa, Ontario Canada K1P 5S9
Tel:  613-995-5894 Fax: 613-995-5086

Application form for Care until Cure.

For additional information, contact:
Canadian Hemophilia Society
chs@hemophilia.ca
1-800-668-2686

Canadian Hemophilia Management in the Perinatal Setting (CHiMPS)

Dr. Paul Moorehead
Janeway Children’s Health and Rehabilitation Centre – St-John’s, Newfoundland
Second year funding
Co-investigators:
Dr. Victoria Price, IWK Health Centre – Halifax, NS
Dr. Margaret Rand, Hospital for Sick Children – Toronto, ON
Dr. Julie Emberley, Janeway Children’s Health and Rehabilitation Centre – St-John’s, NL
Dr. Alfonso Iorio, McMaster University – Hamilton, ON
Dr. Tahani Ahmad, IWK Health Centre – Halifax, NS
Dr. Leonard Minuk, Cancer Care Manitoba – Winnipeg, MB
Ms. Sue Anne Hawes, IWK Health Centre – Halifax, NS
Ms. Lisa Thibeault, Kingston General Hospital – Kingston, ON
Dr. Anthony Chan, McMaster University, Hamilton, ON
Ms. Aidan Thomas, IWK Health Centre – Halifax, NS
Dr. Heather Scott, IWK Health Centre – Halifax, NS
Dr. Manohar Shroff, University of Toronto – Toronto, ON
Pregnancy, childbirth and the newborn period are times when there is a risk of significant bleeding problems for babies with hemophilia and other bleeding disorders, and for their mothers, who may also have bleeding disorders. Despite this risk, there is no standard way to provide care for these babies and their mothers, and there has been no good scientific study that shows that the care that is provided results in good outcomes. The Canadian Hemophilia Management in the Perinatal Setting (CHiMPS) study will find whether it is practical to collect information about these patients and their care. CHiMPS will also find out what medical care is being given to these patients. CHiMPS will also find out whether the care that is being given to these babies and their mothers results in low rates of bleeding complications or in low rates of exposure to unnecessary tests and medical treatments. This information will help doctors, nurses, and other health care professionals who are involved in the care of babies with bleeding disorders to develop more effective and more standardized ways of giving this care.

DDAVP vs exercise in patients with mild hemophilia A – which is better and do they work synergistically in improving hemostasis?

Dr. Manuel D. Carcao 
Hospital for Sick Children – Toronto
Second year funding (Start of project was delayed by two years)
Co-investigators:
Vanessa Bouskill, MN, RN(EC) Nurse Practitioner, Hospital for Sick Children – Toronto
Dr. Michelle Sholzberg, St. Michael’s Hospital – Toronto
To reduce the risk of bleeding, persons with hemophilia benefit from increasing their factor level in their blood. For persons with mild hemophilia A (MHA) this can be done by receiving DDAVP. DDAVP temporarily (≈12 hrs) increases the amount of FVIII in a person’s blood by shifting FVIII from sites of storage into the blood. DDAVP can be given as a nasal spray.
Our group showed that exercising for about 15 min on a stationary bicycle can increase FVIII in a similar way/extent as DDAVP. Thus exercise by itself may protect persons with MHA from bleeding and make taking DDAVP not necessary.
We wish to study this by testing 40 males (ages: 12-40) with MHA. They will be divided into two groups: Group 1 will receive DDAVP while Group 2 will undergo exercise. After that all subjects will have their blood rechecked. Then they will receive the other intervention to check if the combination of DDAVP plus exercise results in better clotting ability than just exercise or DDAVP alone.
We predict that exercise and DDAVP will result in similar effects on improving a person’s clotting ability. If successful the implications of our study will be that persons with MHA may not need to receive DDAVP but can feel reassured that they can exercise with less risk of bleeding provided that they appropriately warm up and thus raise their FVIII before engaging in sports activities that pose a risk of bleeding.

Bone Health in Symptomatic Carriers of Hemophilia A

Dr. Michelle Sholzberg
St. Michael’s Hospital – Toronto, Ontario
First year funding
Co-investigators:
Dr. Jerome Teitel, St. Michael’s Hospital
Dr. Paula James, Kingston General Hospital
Dr. Adrienne Lee, Foothills Medical Centre
Hemophilia is a genetic disorder of abnormal bleeding and men are most commonly affected. Studies have shown that men with hemophilia are more likely to have low bone strength and osteoporosis probably because of repeated bleeding into joints and muscles. Today, we know that women can also be affected by hemophilia. These women are called symptomatic hemophilia carriers. A recent study showed that carriers can also bleed into joints and that this can cause long term damage. We would like to study bone density in women who are carriers of hemophilia A around the time of menopause compared to women of the same age who are not carriers. We want to involve patients across Canada (Toronto, Kingston, Calgary) for this study. This will be the first study to explore bone health in hemophilia carriers. We think that we owe it to hemophilia carriers to better study how this genetic condition affects their bodies. We believe that our study has the potential to improve the care of hemophilia carriers worldwide.

Effects of two bouts of acute moderate-intensity exercise, repeated six hours apart, on hemostatic parameters in adult subjects with mild and moderate hemophilia A

Dr. Georges-Étienne Rivard
CHU Sainte-Justine – Montreal, Quebec
First year funding
Co-investigators:
Nichan Zourikian PT, CHU Sainte-Justine
Dr. Jean St-Louis, CHU Sainte-Justine/Maisonneuve-Rosemont
Hemophilia A is a disorder caused by decreased levels of coagulation factor VIII in the blood. It can lead to excessive bleeding following injuries, due to reduced clotting ability. Sport is recommended for individuals with hemophilia A to help improve overall health. Scientific studies suggest that a single session of exercise, such as cycling, can temporarily improve clotting ability in children and adults with mild/moderate hemophilia A. This improvement is due in part to an increased amount of factor VIII shortly after exercise. This increase may help temporarily protect against bleeds. It is not clear how long the effect lasts after exercise. This is what we want to determine. We also intend to see if two exercise sessions, instead of one, would cause a larger or longer effect. Thus, we will measure the amount of factor VIII in 40 adults (18-45 years old) with mild/moderate hemophilia A, before and after two short stationary cycling sessions, during the same day (one in the morning and one in the afternoon). Overall, our study may help to propose appropriate physical activity for each patient with mild/moderate hemophilia A, to help reduce the risk of bleeds and to improve their health.

Canadian Hemophilia Management in the Perinatal Setting (CHiMPS)

Dr. Paul Moorehead
Janeway Children’s Health and Rehabilitation Centre – St-John’s, Newfoundland
First year funding

Co-investigators:
Dr. Victoria Price, IWK Health Centre – Halifax, NS
Dr. Margaret Rand, Hospital for Sick Children – Toronto, ON
Dr. Julie Emberley, Janeway Children’s Health and Rehabilitation Centre – St-John’s, NL
Dr. Alfonso Iorio, McMaster University – Hamilton, ON
Dr. Tahani Ahmad, IWK Health Centre – Halifax, NS
Dr. Leonard Minuk, Cancer Care Manitoba – Winnipeg, MB
Ms. Sue Anne Hawes, IWK Health Centre – Halifax, NS
Ms. Lisa Thibeault, Kingston General Hospital – Kingston, ON
Dr. Anthony Chan, McMaster University, Hamilton, ON
Ms. Aidan Thomas, IWK Health Centre – Halifax, NS
Dr. Heather Scott, IWK Health Centre – Halifax, NS
Dr. Manohar Shroff, University of Toronto – Toronto, ON

Pregnancy, childbirth and the newborn period are times when there is a risk of significant bleeding problems for babies with hemophilia and other bleeding disorders, and for their mothers, who may also have bleeding disorders. Despite this risk, there is no standard way to provide care for these babies and their mothers, and there has been no good scientific study that shows that the care that is provided results in good outcomes. The Canadian Hemophilia Management in the Perinatal Setting (CHiMPS) study will find whether it is practical to collect information about these patients and their care. CHiMPS will also find out what medical care is being given to these patients. CHiMPS will also find out whether the care that is being given to these babies and their mothers results in low rates of bleeding complications or in low rates of exposure to unnecessary tests and medical treatments. This information will help doctors, nurses, and other health care professionals who are involved in the care of babies with bleeding disorders to develop more effective and more standardized ways of giving this care.


Assessing the usability and user experience of the Canadian Bleeding Disorders Registry (CBDR) and MyCBDR

Prof. Nancy Heddle
McMaster University – Hamilton, Ontario
Second year funding
Co-investigators:
Dr. Alfonso Iorio, McMaster University
Ms. Shannon Lane, McMaster University
Dr. Arun Keepanasseril, McMaster University
Ms. Theresa Almonte, Hamilton Health Sciences
Ms. Kay Decker, Hamilton Health Sciences

The Canadian Hemophilia Assessment and Resources Management Information System (CHARMS) was implemented across Canada in 2000 to help manage hemophilia and track coagulation factor concentrate use among patients. Over the years, the need for a more efficient and effective system became apparent. A new, web-based system, comprised of two components, the Canadian Bleeding Disorders Registry (CBDR) and MyCBDR, was introduced to replace CHARMS; it is being rolled out across the country. The ease of use and acceptability of this new system to Canadian end users (HTC staff, people with hemophilia and caregivers) is important and unknown. A study will be conducted to assess the usability and user experience of CBDR/MyCBDR. Participants will be invited to attend a “think aloud” session where they will complete a series of system tasks while describing what they are seeing, thinking and doing. The think aloud exercise will be followed by a brief interview and questionnaire. The assessment will be repeated three months later after the participant has had a chance to use the system in their usual setting to determine whether perceptions of ease of use change over time. This study will help identify any difficulties with the system.


Outcomes indicators of transitional care in adolescents with hemophilia

Outcomes indicators of transitional care in adolescents with hemophilia: a Delphi survey of Canadian hemophilia care providers and patient focus groups

Dr. Haowei (Linda) Sun
University of British Columbia – Vancouver, British Columbia
Second year funding
Co-investigators:
Dr. Vicky Breakey, McMaster University
Dr. Shannon Jackson, University of British Columbia
Dr. John Wu, University of British Columbia

Adolescents with chronic disease such as hemophilia face multiple challenges during transition from pediatric to adult care. There is a lack of studies evaluating the outcomes following transition in adolescents and young adults with hemophilia, hence it is unclear which outcomes are the best indicators of successful transition. A Delphi survey of Canadian hemophilia care providers and patient focus groups will be conducted to identify the most important and feasible clinical and patient-reported outcome indicators of effective transition. Results will lead to the development of a Hemophilia Transition Outcome instrument, which will help inform future studies evaluating the success of hemophilia transition.


DDAVP vs exercise in patients with mild hemophilia A – which is better and do they work synergistically in improving hemostasis?

Dr. Manuel D. Carcao 
Hospital for Sick Children – Toronto
First year funding (Start of project was delayed by two years)
Co-investigators:
Vanessa Bouskill, MN, RN(EC) Nurse Practitioner, Hospital for Sick Children – Toronto
Dr. Michelle Sholzberg, St. Michael’s Hospital – Toronto

To reduce the risk of bleeding, persons with hemophilia benefit from increasing their factor level in their blood. For persons with mild hemophilia A (MHA) this can be done by receiving DDAVP. DDAVP temporarily (≈12 hrs) increases the amount of FVIII in a person’s blood by shifting FVIII from sites of storage into the blood. DDAVP can be given as a nasal spray.

Our group showed that exercising for about 15 min on a stationary bicycle can increase FVIII in a similar way/extent as DDAVP. Thus exercise by itself may protect persons with MHA from bleeding and make taking DDAVP not necessary.

We wish to study this by testing 40 males (ages: 12-40) with MHA. They will be divided into two groups: Group 1 will receive DDAVP while Group 2 will undergo exercise. After that all subjects will have their blood rechecked. Then they will receive the other intervention to check if the combination of DDAVP plus exercise results in better clotting ability than just exercise or DDAVP alone.

We predict that exercise and DDAVP will result in similar effects on improving a person’s clotting ability. If successful the implications of our study will be that persons with MHA may not need to receive DDAVP but can feel reassured that they can exercise with less risk of bleeding provided that they appropriately warm up and thus raise their FVIII before engaging in sports activities that pose a risk of bleeding.

DDAVP vs exercise in patients with mild hemophilia A – which is better and do they work synergistically in improving hemostasis?

Dr. Manuel D. Carcao 
Hospital for Sick Children – Toronto
First year funding (Start of project was delayed by one year)

Co-investigators:
Vanessa Bouskill, MN, RN(EC) Nurse Practitioner, Hospital for Sick Children – Toronto
Dr. Michelle Sholzberg, St. Michael’s Hospital – Toronto

To reduce the risk of bleeding, persons with hemophilia benefit from increasing their factor level in their blood. For persons with mild hemophilia A (MHA) this can be done by receiving DDAVP. DDAVP temporarily (≈12 hrs) increases the amount of FVIII in a person’s blood by shifting FVIII from sites of storage into the blood. DDAVP can be given as a nasal spray.

Our group showed that exercising for about 15 min on a stationary bicycle can increase FVIII in a similar way/extent as DDAVP. Thus exercise by itself may protect persons with MHA from bleeding and make taking DDAVP not necessary.

We wish to study this by testing 40 males (ages: 12-40) with MHA. They will be divided into two groups: Group 1 will receive DDAVP while Group 2 will undergo exercise. After that all subjects will have their blood rechecked. Then they will receive the other intervention to check if the combination of DDAVP plus exercise results in better clotting ability than just exercise or DDAVP alone.

We predict that exercise and DDAVP will result in similar effects on improving a person’s clotting ability. If successful the implications of our study will be that persons with MHA may not need to receive DDAVP but can feel reassured that they can exercise with less risk of bleeding provided that they appropriately warm up and thus raise their FVIII before engaging in sports activities that pose a risk of bleeding.


Outcomes indicators of transitional care in adolescents with hemophilia

Outcomes indicators of transitional care in adolescents with hemophilia: a Delphi survey of Canadian hemophilia care providers and patient focus groups

Dr. Haowei (Linda) Sun
University of British Columbia – Vancouver, British Columbia
First year funding

Co-investigators:
Dr. Vicky Breakey, McMaster University
Dr. Shannon Jackson, University of British Columbia
Dr. John Wu, University of British Columbia

Adolescents with chronic disease such as hemophilia face multiple challenges during transition from pediatric to adult care. There is a lack of studies evaluating the outcomes following transition in adolescents and young adults with hemophilia, hence it is unclear which outcomes are the best indicators of successful transition. A Delphi survey of Canadian hemophilia care providers and patient focus groups will be conducted to identify the most important and feasible clinical and patient-reported outcome indicators of effective transition. Results will lead to the development of a Hemophilia Transition Outcome instrument, which will help inform future studies evaluating the success of hemophilia transition.


Assessing the usability and user experience of the Canadian Bleeding Disorders Registry (CBDR) and MyCBDR

Prof. Nancy Heddle
McMaster University – Hamilton, Ontario
First year funding

Co-investigators:
Dr. Alfonso Iorio, McMaster University
Ms. Shannon Lane, McMaster University
Dr. Arun Keepanasseril, McMaster University
Ms. Theresa Almonte, Hamilton Health Sciences
Ms. Kay Decker, Hamilton Health Sciences

The Canadian Hemophilia Assessment and Resources Management Information System (CHARMS) was implemented across Canada in 2000 to help manage hemophilia and track coagulation factor concentrate use among patients. Over the years, the need for a more efficient and effective system became apparent. A new, web-based system, comprised of two components, the Canadian Bleeding Disorders Registry (CBDR) and MyCBDR, was introduced to replace CHARMS; it is being rolled out across the country. The ease of use and acceptability of this new system to Canadian end users (HTC staff, people with hemophilia and caregivers) is important and unknown. A study will be conducted to assess the usability and user experience of CBDR/MyCBDR. Participants will be invited to attend a “think aloud” session where they will complete a series of system tasks while describing what they are seeing, thinking and doing. The think aloud exercise will be followed by a brief interview and questionnaire. The assessment will be repeated three months later after the participant has had a chance to use the system in their usual setting to determine whether perceptions of ease of use change over time. This study will help identify any difficulties with the system.

HR-pQCT: a novel imaging technology detects microarchitectural skeletal pathology in hemophilia patients

Dr. Adrienne Lee
University of Calgary (Alberta)
Second year funding

Co-investigators:
Dr. Man-Chiu Poon, University of Calgary
Dr. Steven Boyd, University of Calgary
Dr. Gregory Kline, University of Calgary

Comprehensive care of hemophilia patients has resulted in significant improvements in survival, preservation of joint function, and quality of life. Thus, the focus is now shifting to issues of the aging hemophilia patient. Osteoporosis is emerging as a unique concern in persons with hemophilia (PWH) and several studies demonstrate a significant proportion of PWH with low bone mineral density (BMD) developing at an early age. Low BMD predisposes to bone fractures, a consequence that would be difficult and expensive to manage in PWH due to the underlying bleeding disorder. Why hemophilia persons are developing low BMD is unclear since this is normally a disease of postmenopausal women. The goal of this project is to utilize a new imaging technology called HR-pQCT (high resolution peripheral quantitative computed tomography) that visualizes the bone structure in 3D. This information along with bone metabolism markers can tells us about bone strength, the changes in bone density, and potentially the reason why these changes occur in PWH. We hope the results of our study will help identify aging PWH individuals with bone quality deficits who are at risk of fracture and may benefit from early preventative measures.

DDAVP vs exercise in patients with mild hemophilia A – which is better and do they work synergistically in improving hemostasis?

Dr. Manuel D. Carcao
Hospital for Sick Children – Toronto
First year funding

Co-investigators:
Vanessa Bouskill, MN, RN(EC) Nurse Practitioner, Hospital for Sick Children – Toronto
Dr. Michelle Sholzberg, St. Michael’s Hospital – Toronto

To reduce the risk of bleeding, persons with hemophilia benefit from increasing their factor level in their blood. For persons with mild hemophilia A (MHA) this can be done by receiving DDAVP. DDAVP temporarily (≈12 hrs) increases the amount of FVIII in a person’s blood by shifting FVIII from sites of storage into the blood. DDAVP can be given as a nasal spray.

Our group showed that exercising for about 15 min on a stationary bicycle can increase FVIII in a similar way/extent as DDAVP. Thus exercise by itself may protect persons with MHA from bleeding and make taking DDAVP not necessary.

We wish to study this by testing 40 males (ages: 12-40) with MHA. They will be divided into two groups: Group 1 will receive DDAVP while Group 2 will undergo exercise. After that all subjects will have their blood rechecked. Then they will receive the other intervention to check if the combination of DDAVP plus exercise results in better clotting ability than just exercise or DDAVP alone.

We predict that exercise and DDAVP will result in similar effects on improving a person’s clotting ability. If successful the implications of our study will be that persons with MHA may not need to receive DDAVP but can feel reassured that they can exercise with less risk of bleeding provided that they appropriately warm up and thus raise their FVIII before engaging in sports activities that pose a risk of bleeding.

Hemophilic arthropathy of the ankle: at what age can it be detected?

Kathy Mulder, PT  
Health Sciences Centre – Winnipeg
One year funding.

Co-investigators:
Dr. Kristy Witmeier, Centre for Health care Innovation – Winnipeg Regional Health Authority
Matthew Thiessen, PT, Health Sciences Centre – Winnipeg

The aim of the project is to review the joint health scores for the ankles of all subjects who participated in the Canadian Escalating Dose Prophylaxis Study. Ankle joints are often affected in people with hemophilia. Chronic pain and loss of mobility can begin at an early age. Degeneration usually progresses quickly and necessitates the use of special footwear, mobility aids and joint surgery.
We have observed that there may be two key periods when children are more likely to show signs of ankle involvement. The purpose of this project is to analyze the joint scores in detail to determine if this is so.

If there is a discernible pattern, it may be possible to tailor interventions, such as factor prophylaxis, physiotherapy, footwear modifications and activity selection, to provide better protection for the ankles during critical periods of growth and development with an aim to delaying or preventing chronic joint disease in ankles.

Living with and managing hemophilia from diagnosis and through key care transitions: The journey for families of children with hemophilia

Dr. Roberta Woodgate
University of Manitoba – Winnipeg, Manitoba
Second year funding

Co-investigator: Dr. Milena Pirnat

The purpose of this study is to arrive at an increased understanding of the experiences and needs of families of children with hemophilia as they learn to live with and manage hemophilia from diagnosis through other key care transitions. Thirty families will be recruited with the intent to involve parents as well as their children with hemophilia. Data collection methods include interviews combined with photovoice, which is a process that involves participants taking photographs to document their experiences. The significance of this innovative study is threefold.

First, this study will improve our understanding of the experiences and needs of families of children with hemophilia as they learn to live with and manage hemophilia from diagnosis through other key care transitions by listening to their voices. Second, children with hemophilia and their parents will have meaningful involvement and play an active role in defining issues, considering solutions, and identifying priorities specific to families of children with hemophilia. Third, the knowledge gleaned from this study may be used to inform and improve existing services and programs as well as develop new services and programs that are meant to enhance how families of children with hemophilia manage and deal with hemophilia.

HR-pQCT: a novel imaging technology detects microarchitectural skeletal pathology in hemophilia patients

Dr. Adrienne Lee
University of Calgary (Alberta)
First year funding

Co-investigators:
Dr. Man-Chiu Poon, University of Calgary
Dr. Steven Boyd, University of Calgary
Dr. Gregory Kline, University of Calgary

Comprehensive care of hemophilia patients has resulted in significant improvements in survival, preservation of joint function, and quality of life. Thus, the focus is now shifting to issues of the aging hemophilia patient. Osteoporosis is emerging as a unique concern in persons with hemophilia (PWH) and several studies demonstrate a significant proportion of PWH with low bone mineral density (BMD) developing at an early age. Low BMD predisposes to bone fractures, a consequence that would be difficult and expensive to manage in PWH due to the underlying bleeding disorder. Why hemophilia persons are developing low BMD is unclear since this is normally a disease of postmenopausal women. The goal of this project is to utilize a new imaging technology called HR-pQCT (high resolution peripheral quantitative computed tomography) that visualizes the bone structure in 3D. This information along with bone metabolism markers can tells us about bone strength, the changes in bone density, and potentially the reason why these changes occur in PWH. We hope the results of our study will help identify aging PWH individuals with bone quality deficits who are at risk of fracture and may benefit from early preventative measures.

Living with and managing hemophilia from diagnosis and through key care transitions: The journey for families of children with hemophilia

Dr. Roberta Woodgate
University of Manitoba – Winnipeg, Manitoba
First year funding

Co-Investigator: Dr. Milena Pirnat

The purpose of this study is to arrive at an increased understanding of the experiences and needs of families of children with hemophilia as they learn to live with and manage hemophilia from diagnosis through other key care transitions. Thirty families will be recruited with the intent to involve parents as well as their children with hemophilia. Data collection methods include interviews combined with photovoice, which is a process that involves participants taking photographs to document their experiences. The significance of this innovative study is threefold.
First, this study will improve our understanding of the experiences and needs of families of children with hemophilia as they learn to live with and manage hemophilia from diagnosis through other key care transitions by listening to their voices. Second, children with hemophilia and their parents will have meaningful involvement and play an active role in defining issues, considering solutions, and identifying priorities specific to families of children with hemophilia. Third, the knowledge gleaned from this study may be used to inform and improve existing services and programs as well as develop new services and programs that are meant to enhance how families of children with hemophilia manage and deal with hemophilia.

Assessing differential immunogenicities of factor VIII molecules

Assessing differential immunogenicities of factor VIII molecules: Do previously treated hemophilia A patients represent a valid model? A clinical epidemiology investigational approach

Dr. Angela Barbara
McMaster University – Hamilton, Ontario
One year funding

Co-Investigator: Dr. Alfonso Iorio

The biggest problem in treating people with hemophilia A is the development of inhibitors. Inhibitors stop the standard treatment of replacement with missing clotting factor from working. Testing new hemophilia A drugs to make sure that they do cause patients to develop inhibitors has found mixed results. Some have suggested that changing from one drug to another drug increases the chances of getting an inhibitor. Because it was assumed inhibitors develop soon after treatment, usually in young kids, the best model for studying inhibitiors after a switch has been in previously treated patients (PTPs). However, recent evidence shows a constant lifelong rate of inhibitors. So, we challenge the idea that a product switch is most likely causing inhibitors in PTPs by reassessing published cases.

Development and evaluation of an innovative Web-based Educational Program to promote self-management for teens with hemophilia

Dr. Jennifer Stinson
The Hospital for Sick Children – Toronto, Ontario
Second year funding.

Co-Investigators: Dr. V Blanchette; Dr. V. Breakey; Mr. Danial Ignas

In recent years, the importance of smooth transition of care from pediatric to adult care has received increasing attention. Pediatric hematologists who care for teens with childhood-onset hematological conditions, such as hemophilia, face challenges in supporting transition to ensure that these young people are educated and able to manage their medical conditions as adults. This program of research aims to develop an innovative web-based self-management and transition care program to meet the needs of young people with hemophilia. The proposed research includes a usability study to test the user-friendlessness of the website and a pilot study to assess the feasbility of the web-based educational intervention for adolescents with hemophilia. Data from the pilot study will guide the development of a randomized controlled trial that will assess the effectiveness of the intervention on important clinical health outcomes. The knowledge gained through this work will be transferable across chronic conditions affecting adolescents and will be useful for developing similar programs to improve transition of care. For youth with hemophilia, it will provide ongoing education and support through transition of care and beyond.

Bone mineral density in Canadian children with severe hemophilia A or B: A multi-centre, cross-sectional, observational study

Ms. Cecily Bos, PT 
Hamilton Health Sciences  and
Dr. Anthony K. Chan
McMaster University
Second year funding.

Co-investigators: Dr. Colin Webber; Dr. Kathryn Weber

Recent research has shown that bone mineral density, a measure of bone strength, may be lower among people with hemophilia than among those without this disease. The majority of this research has been done in countries where the treatment for hemophilia differs from the standard of care in Canada. This study is being done to find out whether Canadian children and youth with severe hemophilia A and B have lower BMD than their healthier peers.

People with hemophilia do not have sufficient amounts of certain blood components (called coagulation factors) to help the blood clot. Current treatment strategies offer a greatly improved quality of life and the expectation of a lifestyle similar to the rest of the population. These strategies can vary, but the standard of care in Canada for patients with severe hemophilia A and B is to regularly infuse the missing factor to prevent bleeding.

In the first study of its kind in Canada, researchers will explore any association between BMD and factor replacement therapy, joint health, bleeding history, and physical activity levels by evaluating bone scans of children and youth with severe hemophilia A and B across the country.

von Willebrand Disease plasma and platelets: Functional characterization of quantitative and qualitative von Willebrand factor mutations.

Dr. Paula James
Queens University
Second year funding.

Co-investigators: Dr. W. Kahr; Dr. S. Robinson

In this study, we propose to perform a detailed analysis of two unique Canadian families; one with individuals with both Type 1 and Type 3 von Willebrand disease (VWD) and one with Type 2B VWD.  VWD is the most common, inherited bleeding disorder known in humans and causes excessive bleeding from skin and mucous membranes and in its most severe form, Type 3 VWD, bleeding into muscles and joints as well.  We believe that only through detailed study will we improve our understanding of this disease, an understanding that we hope will ultimately lead us to better treatments for individuals affected with VWD.  We have identified two interesting VWF mutations in these families and will investigate the significance of those mutations in our laboratories.  Investigators from three Canadian centers will be involved: Dr. Paula James from Queen’s University, Dr. Walter Kahr from The Hospital for Sick Children and Dr. Sue Robinson from QEII Health Sciences Center.  We believe the comprehensive set of experiments included in this proposal will allow for the synergistic interaction of the three Canadian centers, improving our understanding of  VWD.

von Willebrand Disease plasma and platelets: Functional characterization of quantitative and qualitative von Willebrand factor mutations

Dr. Paula James
Medicine & Pathology and Molecular Medicine
Queens University – Kingston, Ontario
First year funding

Co-investigators: Dr Walter Kahr; Dr Sue Robinson

In this study, we propose to perform a detailed analysis of two unique Canadian families; one with individuals with both Type 1 and Type 3 von Willebrand disease (VWD) and one with Type 2B VWD.  VWD is the most common, inherited bleeding disorder known in humans and causes excessive bleeding from skin and mucous membranes and in its most severe form, Type 3 VWD, bleeding into muscles and joints as well.  We believe that only through detailed study will we improve our understanding of this disease, an understanding that we hope will ultimately lead us to better treatments for individuals affected with VWD.  We have identified two interesting VWF mutations in these families and will investigate the significance of those mutations in our laboratories.  Investigators from three Canadian centers will be involved: Dr. Paula James from Queen’s University, Dr. Walter Kahr from The Hospital for Sick Children and Dr. Sue Robinson from QEII Health Sciences Center.  We believe the comprehensive set of experiments included in this proposal will allow for the synergistic interaction of the three Canadian centers, improving our understanding of  VWD.

Bone mineral density in Canadian children with severe hemophilia A or B: A multi-centre, cross-sectional, observational study.

Cecily Bos, PT 
Hemophilia Department
Hamilton Health Sciences – Hamilton, Ontario

and

Dr Anthony K. Chan
Hemophilia (pediatric)
McMaster University – Hamilton, Ontario

First year funding

Co-investigators: Dr Colin Webber; Dr Kathryn Webert

Recent research has shown that bone mineral density, a measure of bone strength, may be lower among people with hemophilia than among those without this disease. The majority of this research has been done in countries where the treatment for hemophilia differs from the standard of care in Canada. This study is being done to find out whether Canadian children and youth with severe hemophilia A and B have lower BMD than their health peers.

People with hemophilia do not have sufficient amounts of certain blood components (called coagulation factors) to help the blood clot. Current treatment strategies offer a greatly improved quality of life and the expectation of a lifestyle similar to the rest of the population. These strategies can vary, but the standard of care in Canada for patients with severe hemophilia A and B is to regularly infuse the missing factor to prevent bleeding.

In the first study of its kind in Canada, researchers will explore any association between BMD and factor replacement therapy, joint health, bleeding history, and physical activity levels by evaluating bone scans of children and youth with severe hemophilia A and B across the country.

Development and evaluation of an innovative Web-based Educational Program to promote self-management for teens with hemophilia

Dr. Jennifer Stinson
The Hospital for Sick Children – Toronto, Ontario
First year funding

Co-investigators: Dr. V. Blanchette; Dr. V. Breakey; Mr. Danial Ignas

In recent years, the importance of smooth transition of care from pediatric to adult care has received increasing attention. Pediatric hematologists who care for teens with childhood-onset hematological conditions, such as hemophilia, face challenges in supporting transition to ensure that these young people are educated and able to manage their medical conditions as adults. This program of research aims to develop an innovative web-based self-management and transition care program to meet the needs of young people with hemophilia. The proposed research includes a usability study to test the user-friendlessness of the website and a pilot study to assess the feasbility of the web-based educational intervention for adolescents with hemophilia. Data from the pilot study will guide the development of a randomized controlled trial that will assess the effectiveness of the intervention on important clinical health outcomes. The knowledge gained through this work will be transferable across chronic conditions affecting adolescents and will be useful for developing similar programs to improve transition of care. For youth with hemophilia, it will provide ongoing education and support through transition of care and beyond.

The Assessment of the Minimal Effective and Tolerated Dose of Tranexamic Acid in Women with Menorrhagia who have Bleeding Disorders

Dr. Katherine Sue Robinson
Dept. of Medicine, Division of Adult
QEII Health Sciences Center – Halifax, Nova Scotia
Co Principal Investigator:
Dr. Victoria Price
IWK Health Center- Halifax, Nova Scotia
Second year funding

Co-Investigators: Dr. Tamara Macdonald, Prof. Mohamed Abdolell, Dr. Eileen Mcbride, Dr. Nancy Van Eyk, Dr. Joan Wenning.

Many women have heavy periods and this can be associated with low blood, tiredness and inability to carry out normal activities.  Approximately 10-30 % of these women will have an underlying bleeding disorder. There is a drug called tranexamic acid which is commonly used and is effective in reducing menstrual flow. However, up to 1/3 of women have side affects and they are more common at higher doses.  In the medical literature, there are different dosing schedules and there is one commonly recommended in Canada.   Women with underlying bleeding disorders may require higher doses of this medication compared to those who do not. In our study, we want to find the lowest effective dose of tranexamic acid for girls and women with heavy periods who have bleeding disorders and we think this will be lower then the usual recommended dose. If our results support this, it may contribute to changing how we presently prescribe this medication and may provide a better option for women with heavy periods in particular those with bleeding disorders. We have just started a Women with Bleeding Disorders Clinic and hope that this project will lead to better care for our patients and more research in the future.

Project extended until Fall 2011.

Understanding Health and Treatment Decision-Making Among Young People with Hemophilia: A Youth Perspective

Dr. Kathryn Webert
Department of Medicine
McMaster University – Hamilton, Ontario
Second year funding

Co-Investigators:  Prof. Nancy Heddle, Dr. Anthony Chan, Dr. Irwin Walker, Ms. Shannon Lane.

The first generation of young people with hemophilia to have grown up using primary prophylaxis are ‘coming of age’ and making the transition from childhood to adolescence and early adulthood.  At this point, they may decide to continue with prophylaxis or switch to on-demand therapy. There is no clear evidence suggesting that either one of these treatments is superior in adulthood and nothing is known about how young people make the decision about which treatment to use as they mature.  We know that patient decision-making about medical treatment involves considering the scientific evidence, but it is also influenced by patients’ attitudes, life experiences, feelings about their disease, values and beliefs.  This research is concerned with understanding these non-medical aspects of decision-making around hemophilia treatments. To find out what the main factors are in their decision-making, we will conduct interviews and a focus group with 15 – 29-year old patients with hemophilia in Southern Ontario, followed by 3 focus groups of similar patients from across Canada. The results of this research will help us to understand how young people with hemophilia make decisions about their treatment, and will be used to develop strategies for discussing treatment choices with this age group.

Project extended until May 2011.

Development of a clinical history assessment tool for bleeding disorders

Dr. Catherine Hayward
McMaster University and Hamilton Health Sciences
Dept. of Pathology and Molecular Medicine
McMaster University Medical Center – Hamilton, Ontario
Second year funding

Co-Investigators: Dr. Menaka Pai, Ms. Nancy Heddle, Dr. Richard Cook.

Bleeding problems are common in the general population, but they can be challenging to assess. This is because healthy people can experience some types of bleeding (e.g. mild bruises and nosebleeds) and because abnormal bleeding is sometimes mild in severity. To assess patients with possible bleeding problems, doctors traditionally ask many questions about excessive bleeding. Patients often find it difficult to answer so many questions during an appointment, and doctors are unsure which questions are most important. A brief, standardized questionnaire would be helpful to ensure that patients are asked important questions, using language that is easy to understand.

Our research group has collected a large amount of information on the symptoms and laboratory findings for over 300 patients with bleeding problems. We propose to use statistical methods to analyze this information and develop a brief questionnaire. We will give this questionnaire to a large group of patients and healthy people to fill out, to explore what symptoms are common in patients with the most common types of bleeding disorders (undefined bleeding disorders and platelet secretion defects), and what their risks of bleeding are. I am optimistic that the questionnaire will help doctors decide which patients have blood clotting problems, and need to have further investigations done. It will also help us learn more about the most common types of bleeding disorders, and how they can impact patients’ lives. This research has potential to improve patient care, by generating evidence on the best way to assess bleeding symptoms, how they manifest in different types of bleeding disorders, and how to optimize treatment of bleeding.

Project extended until Summer 2011.

Non-steroidal anti-inflammatory drugs and menorrhagia revisited

Dr. Rochelle Winikoff, FRCP
Staff hematologist
CHU Sainte-Justine – Montreal, Quebec
Second year funding (2008 funding and work deferred into 2009/10/11 because of delay in ethics approval. Project expected to be terminated in 2011.)

Co-investigators: Dr. Sylvain Chemtob, Dr. Michèle David, Dr. Diane Francoeur, Dr. Georges-Étienne Rivard

Heavy menstrual bleeding (menorrhagia) is an important health care problem. It is a common condition that results in considerable morbidity and cost to society. Non-steroidal anti-inflammatory drugs (NSAIDS) can successfully decrease menstrual blood flow in women with menorrhagia. They work largely by blocking the production of prostaglandins which are chemical substances responsible for controlling blood flow in the uterus. NSAIDS are not widely used for this purpose mainly because the response is often modest and or unpredictible. The variable response to NSAIDS among women with menorrhagia is not well understood. Our goal is to optimize therapy for menorrhagia by identifying a subgroup of women that is most likely to respond well to NSAIDS and to establish a clear place for NSAIDS in the treatment of menorrhagia. We hypothesize that a subset of women with menorrhagia related to high levels of prostacyclin (a substance that causes dilation of blood vessels) will have a superior response to NSAID therapy than those without. The presence of other prostaglandin related menstrual symptoms may also be important clinical predictors of response to NSAIDS in women with menorrhgia. In this study adult women with menorrhagia will be treated with an NSAID for two consecutive menstrual periods and their clinical response assessed. Potential clinical predictors of response to NSAID treatment will be collected  including baseline prostaglandin urinary measures. Clinical predictors of response to NSAID treatment will be then be determined. The results of this study should help clinicians identify women for whom NSAID therapy should be considered upfront to treat menorrhagia. Clinical indices including baseline prostacyclin measurements could be a part of the initial clinical evaluation for menorrhagia and could help distinguish between women with menorrhagia who are likely to respond to treatment with NSAIDS and those who are not, in whom alternative therapies may be more beneficial. A similar treatment strategy could eventually be applied to women with menorrhagia related to bleeding disorders.

Non-steroidal anti-inflammatory drugs and menorrhagia revisited

Dr. Rochelle Winikoff, FRCP
Staff hematologist
CHU Sainte-Justine – Montreal, Quebec
Second year funding (2008 funding and work deferred into 2009 because of delay in ethics approval)

Co-investigators: Dr. Sylvain Chemtob, Dr. Michèle David, Dr. Diane Francoeur, Dr. Georges-Étienne Rivard

Heavy menstrual bleeding (menorrhagia) is an important health care problem. It is a common condition that results in considerable morbidity and cost to society. Non-steroidal anti-inflammatory drugs (NSAIDS) can successfully decrease menstrual blood flow in women with menorrhagia. They work largely by blocking the production of prostaglandins which are chemical substances responsible for controlling blood flow in the uterus. NSAIDS are not widely used for this purpose mainly because the response is often modest and or unpredictible. The variable response to NSAIDS among women with menorrhagia is not well understood. Our goal is to optimize therapy for menorrhagia by identifying a subgroup of women that is most likely to respond well to NSAIDS and to establish a clear place for NSAIDS in the treatment of menorrhagia. We hypothesize that a subset of women with menorrhagia related to high levels of prostacyclin (a substance that causes dilation of blood vessels) will have a superior response to NSAID therapy than those without. The presence of other prostaglandin related menstrual symptoms may also be important clinical predictors of response to NSAIDS in women with menorrhgia. In this study adult women with menorrhagia will be treated with an NSAID for two consecutive menstrual periods and their clinical response assessed. Potential clinical predictors of response to NSAID treatment will be collected  including baseline prostaglandin urinary measures. Clinical predictors of response to NSAID treatment will be then be determined. The results of this study should help clinicians identify women for whom NSAID therapy should be considered upfront to treat menorrhagia. Clinical indices including baseline prostacyclin measurements could be a part of the initial clinical evaluation for menorrhagia and could help distinguish between women with menorrhagia who are likely to respond to treatment with NSAIDS and those who are not, in whom alternative therapies may be more beneficial. A similar treatment strategy could eventually be applied to women with menorrhagia related to bleeding disorders.

Development of a clinical history assessment tool for bleeding disorders

Dr. Catherine Hayward
McMaster University and Hamilton Health Sciences
Dept. of Pathology and Molecular Medicine
McMaster University Medical Center – Hamilton, Ontario
First year funding

Co-Investigators: Dr. Menaka Pai, Ms. Nancy Heddle, Dr. Richard Cook.

Bleeding problems are common in the general population, but they can be challenging to assess. This is because healthy people can experience some types of bleeding (e.g. mild bruises and nosebleeds) and because abnormal bleeding is sometimes mild in severity. To assess patients with possible bleeding problems, doctors traditionally ask many questions about excessive bleeding. Patients often find it difficult to answer so many questions during an appointment, and doctors are unsure which questions are most important. A brief, standardized questionnaire would be helpful to ensure that patients are asked important questions, using language that is easy to understand.

Our research group has collected a large amount of information on the symptoms and laboratory findings for over 300 patients with bleeding problems. We propose to use statistical methods to analyze this information and develop a brief questionnaire. We will give this questionnaire to a large group of patients and healthy people to fill out, to explore what symptoms are common in patients with the most common types of bleeding disorders (undefined bleeding disorders and platelet secretion defects), and what their risks of bleeding are. I am optimistic that the questionnaire will help doctors decide which patients have blood clotting problems, and need to have further investigations done. It will also help us learn more about the most common types of bleeding disorders, and how they can impact patients’ lives. This research has potential to improve patient care, by generating evidence on the best way to assess bleeding symptoms, how they manifest in different types of bleeding disorders, and how to optimize treatment of bleeding.

Understanding Health and Treatment Decision-Making Among Young People with Hemophilia: A Youth Perspective

Dr. Kathryn Webert
Department of Medicine
McMaster University – Hamilton, Ontario
First year funding

Co-Investigators:  Prof. Nancy Heddle, Dr. Anthony Chan, Dr. Irwin Walker, Ms. Shannon Lane.

The first generation of young people with hemophilia to have grown up using primary prophylaxis are ‘coming of age’ and making the transition from childhood to adolescence and early adulthood.  At this point, they may decide to continue with prophylaxis or switch to on-demand therapy. There is no clear evidence suggesting that either one of these treatments is superior in adulthood and nothing is known about how young people make the decision about which treatment to use as they mature.  We know that patient decision-making about medical treatment involves considering the scientific evidence, but it is also influenced by patients’ attitudes, life experiences, feelings about their disease, values and beliefs.  This research is concerned with understanding these non-medical aspects of decision-making around hemophilia treatments. To find out what the main factors are in their decision-making, we will conduct interviews and a focus group with 15 – 29-year old patients with hemophilia in Southern Ontario, followed by 3 focus groups of similar patients from across Canada. The results of this research will help us to understand how young people with hemophilia make decisions about their treatment, and will be used to develop strategies for discussing treatment choices with this age group.

The Assessment of the Minimal Effective and Tolerated Dose of Tranexamic Acid in Women with Menorrhagia who have Bleeding Disorders

Dr. Katherine Sue Robinson
Dept. of Medicine, Division of Adult
QEII Health Sciences Center – Halifax, Nova Scotia
Co Principal Investigator:
Dr. Victoria Price
IWK Health Center- Halifax, Nova Scotia
First year funding

Co-Investigators: Dr. Tamara Macdonald, Prof. Mohamed Abdolell, Dr. Eileen Mcbride, Dr. Nancy Van Eyk, Dr. Joan Wenning.

Many women have heavy periods and this can be associated with low blood, tiredness and inability to carry out normal activities.  Approximately 10-30 % of these women will have an underlying bleeding disorder. There is a drug called tranexamic acid which is commonly used and is effective in reducing menstrual flow. However, up to 1/3 of women have side affects and they are more common at higher doses.  In the medical literature, there are different dosing schedules and there is one commonly recommended in Canada.   Women with underlying bleeding disorders may require higher doses of this medication compared to those who do not. In our study, we want to find the lowest effective dose of tranexamic acid for girls and women with heavy periods who have bleeding disorders and we think this will be lower then the usual recommended dose. If our results support this, it may contribute to changing how we presently prescribe this medication and may provide a better option for women with heavy periods in particular those with bleeding disorders. We have just started a Women with Bleeding Disorders Clinic and hope that this project will lead to better care for our patients and more research in the future.

The prevalence of symptomatic pediatric VWD

Dr. Paula James, FRCPC
Assistant Professor
Queen’s University – Kingston, Ontario
Second year funding

Co-investigators: Dr. Victor Blanchette (CO-PI), Dr. David Lillicrap, Dr. Mariana Silva, Dr. Margaret Rand, Dr. Leonardo Brandao

Von Willebrand disease (VWD) is an inherited bleeding disorder that causes bleeding from mucous membranes (ie: nosebleeds, bleeding gums and heavy menstrual periods) and easy bruising. Diagnosing the condition can be very difficult, particularly in children. Although bruises and nosebleeds are common among children with VWD, very young children may not have had a chance to manifest other characteristic bleeding symptoms, such as heavy menstrual periods or bleeding after surgery. To compound this, it is often difficult for patients to recognize whether certain symptoms are normal or abnormal and most of the attempts to address this by creating standardized bleeding questionnaires have been focused on the adult population.

In the current study, we propose to address the issue of the symptomatic prevalence of VWD in children by investigating children who have symptoms of bleeding or bruising for VWD. Additionally, we propose to validate a commonly used (modified) adult bleeding questionnaire in children during the course of this study. We will accomplish this by screening between 10,000 and 15,000 children attending a pediatric outpatient centre for bleeding or bruising symptoms. Those that report a problem with bleeding or bruising symptoms will be further evaluated using a bleeding questionnaire. Children with positive bleeding scores will then be investigated with VWF laboratory studies. The bleeding questionnaire will also be administered to a group of ~300 normal children to allow for the validation of the questionnaire. This study will be carried out by investigators who have recently completed a complementary study, performed primarily on adults, evaluating the prevalence of VWD at the level of primary care.

Non-steroidal anti-inflammatory drugs and menorrhagia revisited

Dr. Rochelle Winikoff, FRCP
Staff hematologist
CHU Sainte-Justine – Montreal, Quebec
Second year funding

Co-investigators: Dr. Sylvain Chemtob, Dr. Michèle David, Dr. Diane Francoeur, Dr. Georges-Étienne Rivard

Menorrhagia is a common clinical problem to which there is no standard medical treatment approach. It is estimated that about 30% of women complain of menorrhagia and it is the main presenting complaint in women referred to gynecologists. Non-steroidal anti-inflammatory drugs (NSAIDS), which non-specifically inhibit cyclooxygenase (COX), are effective in approximately 50 to 60% of women with menorrhagia, with reductions in menstrual blood loss (MBL) of the order of 30 to 40%. Clinical studies have shown that NSAIDs are more effective in women who have higher baseline MBL. A subset of women with menorrhagia have increased MBL related to overproduction of prostacyclin (PGI2) and increased local uterine vasodilatation, which may be targeted by NSAID therapy.

Among women with menorrhagia, those who produce higher baseline levels of PGI2 are more likely to have a better response to non-specific COX inhibition by NSAIDS than women who secrete lower levels. The variability and degree of response to NSAIDS observed in the literature may, at least in part, depend on the baseline levels of PGI2 production in women with menorrhagia. Other clinical factors such as age, weight, parity and dysmenorrhea may also predict a favourable response to NSAID therapy. The main objective of this study is to identify clinical predictors of response to NSAID therapy in women with menorrhagia. We will also determine if higher baseline levels of PGI2 in women with menorrhagia correlate with their clinical response to COX inhibition by NSAIDS.

Consecutive women between the ages of 18 and 40 with primary menorrhagia will be treated with an NSAID for two consecutive menstrual periods and the MBL will be recorded using the Pictorial Blood Assessment Chart (PBAC). Recruitment for this study will take place over 18 months. Potential clinical predictors of response to NSAIDS will be collected. Baseline levels of PGI2 urinary metabolites will be measured in all eligible women. Logistic regression will be used to assess various clinical variables and PGI2 as a predictor of significant response to NSAID therapy. A significant response will be defined as a >= 30% decrease in PBAC score. The average baseline PBAC score will be compared with an average of 2 post-treatment PBAC scores.

The results of this study should help clinicians identify women for whom NSAID therapy should be considered upfront to treat menorrhagia. Clinical indices including baseline PGI2 measurements could be a part of the initial clinical evaluation for menorrhagia and could help distinguish between women with menorrhagia who are likely to respond to treatment with NSAIDS and those who are not, in whom alternative therapies may be more beneficial. A similar treatment strategy could eventually be applied to women with menorrhagia related to bleeding disorders.

Bleeding disorders, menorrhagia and iron deficiency: An examination of quality of life

Dr. Ronald Barr
Department of Clinical Epidemiology and Biostatistics
Health Sciences centre – McMaster University, Hamilton, Ontario
First year funding

Co-investigators: Dr. David Lillicrap, Dr. Jean St-Louis, Dr. Christine Demers, Prof. Eleanor Pullenayegum

The Canadian Hemophilia Society has awarded Dr. Ronald Barr of McMaster University, and co-investigators at three other Canadian centres, a research grant to analyze data from a national survey of women and men with inherited bleeding disorders. The survey was undertaken because a pilot study had shown that women with the most common bleeding disorder, von Willebrand’s disease, had much poorer overall health than men with the same disease and about the same level of poor health as severe hemophiliacs who are infected with the AIDS virus. It was proposed that bleeding disorders in women, by causing heavy menstrual bleeding, lead to chronic iron deficiency, poor overall health and low educational achievement. All regional hemophilia centres in Canada supported the national survey that collected information and blood samples (to determine iron levels) from a total of 408 people. A questionnaire asked about 14 important aspects of overall health, highest level of education and use of iron supplements. Women in the survey answered a set of questions about their menstrual bleeding pattern. A state-of-the art measurement system was used to measure the overall health of each person. Statistical tests will show whether women with bleeding disorders have poorer health and lower educational achievement than comparison groups, such as men with similar bleeding disorders and whether these deficits are related to iron deficiency. Results from the study may justify a large randomized clinical trial of iron supplements to improve overall health and educational achievement in women with excessive menstrual blood loss associated with inherited bleeding dosorders. This study is important because iron supplements are inexpensive to make, easy to take, and could greatly improve the quality of life for millions of such women around the world.

Creating meaningful messages for individuals with mild hemophilia

JoAnn K. Nilson, PT
Physiotherapist
Saskatchewan Bleeding Disorders Program – Saskatoon, Saskatchewan
Second year funding

This multi-phased project brings individuals with mild hemophilia and physiotherapists together to create more meaningful educational materials specifically for people with mild hemophilia. The Canadian Physiotherapists in Hemophilia Care (CPHC) have serious concerns about gaps in patients’ understanding of mild hemophilia. Young adults with mild hemophilia are often seen in the emergency room days after a traumatic incident with an uncontrolled bleed which then takes weeks or months to totally resolve. These clinical experiences suggest that the educational materials and strategies currently in use, that target individuals with severe hemophilia, are not effective in providing information that facilitates those with mild hemophilia to seek care in a timely manner.

The purpose of this study is to consult young adults with mild hemophilia, parents of children or adolescents with mild hemophilia and PTs from across Canada in order to identify appropriate communication strategies to be used in educational material about health and healthcare specifically for people with mild hemophilia. In Phase 1 we will focus on the lived experiences of young adults with mild hemophilia from four locations in Canada. Through semi-structured interviews, we will learn about participants’ internal ‘processes’ and choices that they make in accessing medical care after injury, learn about messages, information and knowledge that participants feel would motivate them to seek care in a timely manner. During Phase 2, the knowledge gained in Phase 1 will be used to guide a group of PTs from across Canada. They will identify educational strategies that are grounded both in the experiences and attitudes of individuals with mild hemophilia and in the realities of the health care system. In Phase 3, these strategies will be further refined during focus groups of young adults and PTs and parents of children with mild hemophilia and PTs in both French and English. This phase will also include written or telephone consultation with young adults with mild hemophilia who live in rural settings. Participants from each phase will be invited to continue their involvement in the project through written or verbal feedback after each phase.

This research will help to develop a model that demonstrates a viable way of integrating the perspectives and knowledge of patients and health care professionals in order to create the most meaningful, client centered, realistic educational strategies specifically for persons with mild hemophilia.

The prevalence of symptomatic pediatric VWD

Dr. Paula James, FRCPC
Assistant Professor
Queen’s University – Kingston, Ontario
First year funding

Von Willebrand disease (VWD) is an inherited bleeding disorder that causes bleeding from mucous membranes (ie: nosebleeds, bleeding gums and heavy menstrual periods) and easy bruising. Diagnosing the condition can be very difficult, particularly in children. Although bruises and nosebleeds are common among children with VWD, very young children may not have had a chance to manifest other characteristic bleeding symptoms, such as heavy menstrual periods or bleeding after surgery. To compound this, it is often difficult for patients to recognize whether certain symptoms are normal or abnormal and most of the attempts to address this by creating standardized bleeding questionnaires have been focused on the adult population.

In the current study, we propose to address the issue of the symptomatic prevalence of VWD in children by investigating children who have symptoms of bleeding or bruising for VWD. Additionally, we propose to validate a commonly used (modified) adult bleeding questionnaire in children during the course of this study. We will accomplish this by screening between 10,000 and 15,000 children attending a pediatric outpatient centre for bleeding or bruising symptoms. Those that report a problem with bleeding or bruising symptoms will be further evaluated using a bleeding questionnaire. Children with positive bleeding scores will then be investigated with VWF laboratory studies. The bleeding questionnaire will also be administered to a group of ~300 normal children to allow for the validation of the questionnaire. This study will be carried out by investigators who have recently completed a complementary study, performed primarily on adults, evaluating the prevalence of VWD at the level of primary care.

Non-steroidal anti-inflammatory drugs and menorrhagia revisited

Dr. Rochelle Winikoff, FRCP
Staff hematologist
CHU Sainte-Justine – Montreal, Quebec
First year funding

Menorrhagia is a common clinical problem to which there is no standard medical treatment approach. It is estimated that about 30% of women complain of menorrhagia and it is the main presenting complaint in women referred to gynecologists. Non-steroidal anti-inflammatory drugs (NSAIDS), which non-specifically inhibit cyclooxygenase (COX), are effective in approximately 50 to 60% of women with menorrhagia, with reductions in menstrual blood loss (MBL) of the order of 30 to 40%. Clinical studies have shown that NSAIDs are more effective in women who have higher baseline MBL. A subset of women with menorrhagia have increased MBL related to overproduction of prostacyclin (PGI2) and increased local uterine vasodilatation, which may be targeted by NSAID therapy. 

Among women with menorrhagia, those who produce higher baseline levels of PGI2 are more likely to have a better response to non-specific COX inhibition by NSAIDS than women who secrete lower levels. The variability and degree of response to NSAIDS observed in the literature may, at least in part, depend on the baseline levels of PGI2 production in women with menorrhagia. Other clinical factors such as age, weight, parity and dysmenorrhea may also predict a favourable response to NSAID therapy. The main objective of this study is to identify clinical predictors of response to NSAID therapy in women with menorrhagia. We will also determine if higher baseline levels of PGI2 in women with menorrhagia correlate with their clinical response to COX inhibition by NSAIDS.

Consecutive women between the ages of 18 and 40 with primary menorrhagia will be treated with an NSAID for two consecutive menstrual periods and the MBL will be recorded using the Pictorial Blood Assessment Chart (PBAC). Recruitment for this study will take place over 18 months. Potential clinical predictors of response to NSAIDS will be collected. Baseline levels of PGI2 urinary metabolites will be measured in all eligible women. Logistic regression will be used to assess various clinical variables and PGI2 as a predictor of significant response to NSAID therapy. A significant response will be defined as a >= 30% decrease in PBAC score. The average baseline PBAC score will be compared with an average of 2 post-treatment PBAC scores.

The results of this study should help clinicians identify women for whom NSAID therapy should be considered upfront to treat menorrhagia. Clinical indices including baseline PGI2 measurements could be a part of the initial clinical evaluation for menorrhagia and could help distinguish between women with menorrhagia who are likely to respond to treatment with NSAIDS and those who are not, in whom alternative therapies may be more beneficial. A similar treatment strategy could eventually be applied to women with menorrhagia related to bleeding disorders

Haemostatic Changes during Pregnancy in Healthy Women and Women with Inherited Bleeding Disorders Presenting with Menorrhagia

Dr. Christine Demers
2nd year funding
Centre Hospitalier Universitaire Affilié de Québec

Inherited bleeding disorders are associated with a wide spectrum of clinical symptoms depending on the type and the severity of the disease. During pregnancy, the risk of bleeding is generally low in affected women, because the levels of many of the coagulation factors naturally rise over the course of a pregnancy. However, the risk of bleeding can be significant at delivery and after the pregnancy (during the post-partum period), because these levels once again fall to the baseline. In fact, it has been demonstrated that the risk of postpartum hemorrhage is increased to 10 to 25% in women with bleeding disorders compared to less than 1% in the general population. Management is difficult, in part, because there is a lack of information concerning variation of the coagulation factors during pregnancy both in normal women and in women with bleeding disorders.

In this study we are planning to recruit 2 groups of women: 20 normal and 25 with an inherited bleeding disorder. The first objective of this study is to evaluate how the levels of coagulation factors vary over the course of pregnancy in both groups, and also to determine the rate with which these coagulation factors return to the baseline after delivery. Coagulation factors will be measured 3 times during pregnancy, at delivery and 4 times in the 4 weeks postpartum. We will try to co-ordinate this blood testing, whenever possible, with the regular testing of pregnancy

Post-partum bleeding is very difficult to assess and at the present time there is no way of objectively measuring it. However, there is a graphical chart that has been extensively evaluated in women with heavy periods. The second objective of the study is to evaluate if a modified version of the chart is a useful tool to measure post partum bleeding. All women will complete the pictorial chart during the 4 weeks postpartum.

With this study, we hope that a better understanding of coagulation during and after pregnancy will result in a better management of pregnancy for women affected with an inherited bleeding disorders.

Investigation of Clotting Factor Activity Heterogeneity in Severe Hemophilia A

Dr. Man-Chiu Poon and Gary D. Sinclair
2nd year funding
University of Calgary
Calgary, Alberta

Persons with severe hemophilia (clotting factor activity below 1%) tend to bleed frequently and spontaneously into joints, leading to disabling arthritis. The current standard of treatment is regular, preventative factor concentrate infusion. This p6rimary prophylaxis started at an early age improves quality of life but the treatment is intensive; representing a burden to those with hemophilia and their families. It is also expensive. Often, a device is implanted to facilitate infusion and this may be complicated by infection and thrombosis.

Among severely affected individuals, approximately 10-15% have milder than expected bleeding symptoms. It is important to identify these persons so that their treatment can be customized, avoiding unnecessary infusion. We believe that some severe persons have factor VIII in their blood, but below the 1% detectable by routine laboratory methods. Furthermore, in the ongoing Canadian Prophylaxis trial (Dr. Victor Blanchette), some severely affected need only once or twice weekly FVIII infusion – the FVIII levels would be below 1% for a period before the next infusion and yet appear protective.

The focus of this research is to develop a sensitive assay to accurately measure circulating factor VIII levels between 0 and 1%, based on measurement of the activity of the enzyme, thrombin, that develops in proportion to the level of FVIII activity present. Three aspects of hemophilia treatment will then be investigated with participation from clinics across Canada. First, we will measure FVIII activity on 200 severe hemophilia A persons at a time when they have not been treated for 5 days or more (or at diagnosis) to determine if their “baseline” FVIII levels have a bearing on when they had their first spontaneous joint bleeding. We will take into account whether the affected individuals have inherited other mutations thought to promote clotting despite very low FVIII activity. Secondly, for patients in the Canadian Dose Escalation Prophylaxis study (Dr. Blanchette), we will measure the plasma FVIII level prior to their next FVIII injection. This may help discover the minimal FVIII level that will protect against bleeding and hence determine the frequency of FVIII infusions. Lastly, we will investigate (with Dr. Carcao) if the baseline FVIII level of severe hemophilia A persons can be related to how much FVIII is recovered after an injection, and how quickly the recovered FVIII disappears.

In conclusion, this study will assess the minimum level of FVIII below 1% that is still protective to help customize treatment for individuals with severe hemophilia.

Creating Meaningful Messages for Individuals with Mild Hemophilia Through Consultaion: Integrating Grounded Theory and Action Research

JoAnn Nilson, Physiotherapist
1st year funding
Saskatoon, SK

This multi-phased project brings individuals with mild hemophilia and physiotherapists together to create more meaningful educational materials specifically for people with mild hemophilia. The Canadian Physiotherapists in Hemophilia Care (CPHC) have serious concerns about gaps in patients’ understanding of mild hemophilia. Young adults with mild hemophilia are often seen in the emergency room days after a traumatic incident with an uncontrolled bleed which then takes weeks or months to totally resolve. These clinical experiences suggest that the educational materials and strategies currently in use, that target individuals with severe hemophilia, are not effective in providing information that facilitates those with mild hemophilia to seek care in a timely manner.

The purpose of this study is to consult young adults with mild hemophilia, parents of children or adolescents with mild hemophilia and PTs from across Canada in order to identify appropriate communication strategies to be used in educational material about health and healthcare specifically for people with mild hemophilia. In Phase 1 we will focus on the lived experiences of young adults with mild hemophilia from four locations in Canada. Through semi-structured interviews, we will learn about participants’ internal ‘processes’ and choices that they make in accessing medical care after injury, learn about messages, information and knowledge that participants feel would motivate them to seek care in a timely manner. During Phase 2, the knowledge gained in Phase 1 will be used to guide a group of PTs from across Canada . They will identify educational strategies that are grounded both in the experiences and attitudes of individuals with mild hemophilia and in the realities of the health care system. In Phase 3, these strategies will be further refined during focus groups of young adults and PTs and parents of children with mild hemophilia and PTs in both French and English. This phase will also include written or telephone consultation with young adults with mild hemophilia who live in rural settings. Participants from each phase will be invited to continue their involvement in the project through written or verbal feedback after each phase.

This research will help to develop a model that demonstrates a viable way of integrating the perspectives and knowledge of patients and health care professionals in order to create the most meaningful, client centered, realistic educational strategies specifically for persons with mild hemophilia.

Haemostatic Changes during Pregnancy in Healthy Women and Women with Inherited Bleeding Disorders Presenting with Menorrhagia

Dr. Christine Demers
1st year funding
Centre Hospitalier Universitaire Affilié de Québec

Inherited bleeding disorders are associated with a wide spectrum of clinical symptoms depending on the type and the severity of the disease. During pregnancy, the risk of bleeding is generally low in affected women, because the levels of many of the coagulation factors naturally rise over the course of a pregnancy. However, the risk of bleeding can be significant at delivery and after the pregnancy (during the post-partum period), because these levels once again fall to the baseline. In fact, it has been demonstrated that the risk of postpartum hemorrhage is increased to 10 to 25% in women with bleeding disorders compared to less than 1% in the general population. Management is difficult, in part, because there is a lack of information concerning variation of the coagulation factors during pregnancy both in normal women and in women with bleeding disorders.

In this study we are planning to recruit 2 groups of women: 20 normal and 25 with an inherited bleeding disorder. The first objective of this study is to evaluate how the levels of coagulation factors vary over the course of pregnancy in both groups, and also to determine the rate with which these coagulation factors return to the baseline after delivery. Coagulation factors will be measured 3 times during pregnancy, at delivery and 4 times in the 4 weeks postpartum. We will try to co-ordinate this blood testing, whenever possible, with the regular testing of pregnancy

Post-partum bleeding is very difficult to assess and at the present time there is no way of objectively measuring it. However, there is a graphical chart that has been extensively evaluated in women with heavy periods. The second objective of the study is to evaluate if a modified version of the chart is a useful tool to measure post partum bleeding. All women will complete the pictorial chart during the 4 weeks postpartum.

With this study, we hope that a better understanding of coagulation during and after pregnancy will result in a better management of pregnancy for women affected with an inherited bleeding disorders.

Investigation of Clotting Factor Activity Heterogeneity in Severe Hemophilia A

Dr. Man-Chiu Poon and Gary D. Sinclair
1st year funding
University of Calgary
Calgary, Alberta

Persons with severe hemophilia (clotting factor activity below 1%) tend to bleed frequently and spontaneously into joints, leading to disabling arthritis. The current standard of treatment is regular, preventative factor concentrate infusion. This p6rimary prophylaxis started at an early age improves quality of life but the treatment is intensive; representing a burden to those with hemophilia and their families. It is also expensive. Often, a device is implanted to facilitate infusion and this may be complicated by infection and thrombosis.

Among severely affected individuals, approximately 10-15% have milder than expected bleeding symptoms. It is important to identify these persons so that their treatment can be customized, avoiding unnecessary infusion. We believe that some severe persons have factor VIII in their blood, but below the 1% detectable by routine laboratory methods. Furthermore, in the ongoing Canadian Prophylaxis trial (Dr. Victor Blanchette), some severely affected need only once or twice weekly FVIII infusion – the FVIII levels would be below 1% for a period before the next infusion and yet appear protective.

The focus of this research is to develop a sensitive assay to accurately measure circulating factor VIII levels between 0 and 1%, based on measurement of the activity of the enzyme, thrombin, that develops in proportion to the level of FVIII activity present. Three aspects of hemophilia treatment will then be investigated with participation from clinics across Canada. First, we will measure FVIII activity on 200 severe hemophilia A persons at a time when they have not been treated for 5 days or more (or at diagnosis) to determine if their “baseline” FVIII levels have a bearing on when they had their first spontaneous joint bleeding. We will take into account whether the affected individuals have inherited other mutations thought to promote clotting despite very low FVIII activity. Secondly, for patients in the Canadian Dose Escalation Prophylaxis study (Dr. Blanchette), we will measure the plasma FVIII level prior to their next FVIII injection. This may help discover the minimal FVIII level that will protect against bleeding and hence determine the frequency of FVIII infusions. Lastly, we will investigate (with Dr. Carcao) if the baseline FVIII level of severe hemophilia A persons can be related to how much FVIII is recovered after an injection, and how quickly the recovered FVIII disappears.

In conclusion, this study will assess the minimum level of FVIII below 1% that is still protective to help customize treatment for individuals with severe hemophilia.

The Role of Vitamin C in Bleeding Disorders

Dr. Alex Levin
2nd year funding
The Hospital for Sick Children
Toronto, Ontario

Vitamin C plays a critical role in preventing bleeding by keeping blood vessel walls sturdy. There are currently no normal values for children. Establishing normal ranges is important to serve as a basis for future research trying to understand why some children bleed more than others especially if they have other bleeding tendencies. Perhaps low vitamin C levels play a role. Prior attempts to measure vitamin C levels have been unreliable due to testing methods which were affected by diet, time of day and other factors. We will measure vitamin C levels from a type of blood cell called lymphocytes. Lymphocyte levels of vitamin C are more accurate and less subject to daily fluctuation. We have developed a High Performance Liquid Chromatography (HPLC) method for measuring lymphocyte vitamin C levels. Pilot testing using 50 samples showed that the test works very well. We will get specimens of blood from patients who are already getting a blood count test for other reasons. No extra blood or needle sticks need to be taken. Patients will be identified from Departments and Divisions at The Hospital for Sick Children who have patients who are likely not to suffer from conditions that influence vitamin C levels and who do not have a bleeding disorder. Parents will answer a brief questionnaire designed to identify dietary habits which might be affecting vitamin C levels.

After establishing normal age and gender related values for vitamin C (ascorbic acid) in healthy children, we will apply to begin researching the possible role of unrecognized vitamin C deficiency in bleeding disorders and eye (retina) haemorrhage. We will measure vitamin C levels in children with bleeding disorders such as haemophilia, von Willebrand disease, and idiopathic thrombocytopaenic purpura, comparing those children who have prominent bleeding problems to those who do not. Likewise, we will examine vitamin C levels in victims of Shaken Baby syndrome and accidental head injury with and without retinal hemorrhages. Lastly we will examine the effects of routine childhood immunization on vitamin C lymphocyte levels.

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