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McMaster researchers develop test for rare bleeding disorder


Researchers at McMaster University have developed the first assessment tool of its kind for evaluating risks faced by Canadians suffering from a rare and often fatal bleeding disorder.

Their detailed bleeding questionnaire helps discriminate between patients - often in the same family - affected by a puzzling and rare condition known as Quebec Platelet Disorder (QPD) and those who are not.

The new tool for detecting different symptoms and complications was developed in the laboratory of hematologist Dr. Catherine Hayward, an associate professor in the departments of pathology and molecular medicine and medicine in the Michael G. DeGroote School of Medicine of McMaster’s Faculty of Health Sciences. The Transfusion Medicine Research Team at McMaster, headed by Nancy Heddle, helped develop the tool. Before Hayward began her research, Quebec families with this bleeding disorder didn’t know what was causing their illness—or even what they suffered from.

Bleeding disorders tend to run in families and can be particularly difficult to detect. Normally, when a person bleeds, blood clots stop the bleeding. The clotting process (coagulation) requires both blood cells (platelets) and proteins (clotting factors). In bleeding disorders, blood platelets are not working as they should or there are too few platelets, or clotting factors, which cause bleeding to continue for longer than normal.

Gold standard tests are available to determine risks in diseases such as heart attacks and strokes but there has never been gold standards for rare bleeding disorders, such as QPD. Although this specific disorder appears to affect a few families in Quebec, this tool is a step forward to developing a better way to assess bleeding problems in many other conditions.

The McMaster researchers developed a detailed bleeding history questionnaire based on interviews with physicians and focus groups of patients who suffered a broad spectrum of bleeding disorders, and applied this with a “gold standard” laboratory test her group developed for the QPD. "It is touching that what patients told us to ask about proved to be valuable clues to helpful bleeding symptoms," said Dr. Hayward.

The researchers gave the questionnaire to 127 relatives in two families with QPD who ranged in age from one year to 89 years. Their average age was 34.

They found those with QPD had a much higher likelihood of bleeding that led to lifestyle changes, bruises that spread or became as large, or larger, than an orange, bleeding in joints and bleeding that lasted longer than 24 hours. The study has established the consequences of inheriting the QPD - a disease that transforms platelets from “clot formers” into “clot busters.” “This is going to be very helpful to doctors trying to sort out if a patient with bleeding has the QPD,” said Dr. Hayward.

Dr. James N. George of the University of Oklahoma Health Sciences Centre commented in the journal Blood that the study by McMaster scientists has important lessons for hematologists who investigate and manage patients with bleeding disorders by providing new insights into this condition. "The use of quantitative measures of bleeding symptoms will allow for greater understanding of the interactions of multiple common inherited traits on the risks for excessive bleeding," he said.

Fifteen years ago, Dr. Hayward made scientific history when she discovered a previously unknown protein called multimerin 1, one of the largest proteins in the human body. This discovery led her to study bleeding problems experienced by QPD families and how platelets support blood clotting.

Earlier this month, Samira B. Jeimy, a graduate student in Hayward’s McMaster research laboratory, presented a study that was chosen from among more than 5,700 abstracts submissions for delivery at the American Society of Hematology’s annual meeting in San Diego. The society’s annual meeting is the premier hematology meeting in the world and attended by more than 20,000 scientists.
Jeimy’s study centred on the molecular interactions between the platelet protein multimerin 1 and the blood clot accelerator factor V. She found that factor V and multimerin 1 bind in a unique way, without blocking clot formation. Ultimately, the advance may lead to new tests and treatments for diseases with too little, or too much, blood clot formation, such as heart attacks and strokes.

Jeimy is enrolled in the medical sciences graduate program at McMaster and holds a master’s studentship award from the Heart and Stroke Foundation of Ontario. Her research was supported by a Canadian Institutes of Health Research (CIHR) grant, and by Dr. Hayward’s Heart and Stroke Foundation Career Investigator Award and Canada Research Chair. The study was done in collaboration with world experts on factor V - Dr. William Kane, Duke University, United States; Dr. Bjorn Dahlback, Lund University, Sweden; and Dr. Gerry Nicolaes, Maastricht University, Netherlands.

Veronica McGuire | EurekAlert!
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