Is Genetic Testing the Future of Hemophilia Treatment?

An article at ASH Clinical News recently detailed some of the history of genetic testing for bleeding disorders like hemophilia or von Willebrand Disease. Although true genetic screening has only recently become possible after decades of technological advancement, the link between genetics and blood clotting factors has been observed for centuries.

About Bleeding Disorders

Bleeding disorders like hemophilia and von Willebrand Disease are characterized by a deficiency of clot-forming proteins in the blood. People with these conditions experience prolonged episodes of bleeding because their blood clots extremely ineffectively.

Although open wounds like lacerations or surgical incisions are of obvious concerns for such individuals, even strong blunt impacts can cause severe internal bleeding. Often the joints will also be affected, which can limit a patient’s mobility.

Increasing our Understanding

Even though our understanding of bleeding disorders is still growing, humans have been familiar with these diseases for centuries, if not millennia. A second-century Talmudic source suggests that Jews of the era were aware of such health conditions, and even had some understanding of their prevalence in certain families. A newborn Jewish boy was exempt from circumcision if two of his siblings had previously died from uncontrolled blood loss linked to the operation.

Centuries later, in 1803 (the early years of the Industrial Revolution), American physician John Conrad Otto formally presented his theory of family-linked bleeding disorders. Importantly, Otto also noted that these disorders were more likely to affect men than women – though the reason why wouldn’t be understood for many more decades. Later that century, Swiss researchers Friedrich Hopff and Johann Lukas Schönlein would become the first to call these uncontrolled bleeding disorders “hemophilia.”

With the discovery of chromosomes in the late 19th century and the advancement of the XY sex-determination system in 1905, scientists were finally able to establish why hemophilia was so much more common in men. Hemophilia is X-linked, meaning that mutations that lead to the condition are found on the X chromosome. Since men inherit only one X chromosome from their mothers, they only need to receive one mutated copy to develop the condition. Women have two X chromosomes – and since hemophilia genes are recessive, they must inherit two faulty X chromosomes to develop hemophilia. Women with just one hemophilia-positive X chromosome are so-called “carriers” of the disease and can still pass it to their offspring.

Genetic Testing: the Future of Treatment?

Of particular interest in recent medical literature is the development of increasingly reliable genetic tests that can assist in diagnosing health-threatening bleeding disorders. However, as these methods of testing evolve, our methodology must evolve in turn.

With new treatments comes new challenges. Scientists note that genetic screenings are expensive and resource-intensive, and aren’t practical options for general health screenings. Patients should only be referred for genetic testing once a concern for hemophilia has been established through the observation of other symptoms.  Additionally, some of these tests can yield false negatives or positives. In some patients, even extensive screening can fail to pinpoint a cause of their disorder – even though testing successfully identifies a disease-causing mutation in 98% of hemophilia A cases, and 99% of cases of hemophilia B.

Dr. Laura Swystun, a senior clinical scientist at the Canadian National Inherited Bleeding Disorder Genotyping Lab at Canada’s Queen’s University, noted that finding new ways to identify the cause of hemophilia in these 1-2% of patients is a growing concern for molecular scientists.

Work remains to be done to streamline and maximize the effectiveness of genetic testing for bleeding disorders. However, recent scientific advances have made hemophilia and related conditions more manageable and less mysterious than ever before – a trend likely to continue over the coming decades.

To what extent are scientific “discoveries” modified or refined versions of existing knowledge? How do you think ancient peoples’ familiarity with disease informs our own understanding of it now? Share your thoughts with Patient Worthy!

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