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Research Projects Funded in 2008

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.