The reach of genetic testing spans across every aspect of clinical medicine – from the analysis of cellular mutations to the risk of inherited disease. This is no different in the case of diseases like hemophilia and other clotting disorders, but the role of traditional screening methodologies remains essential all the same. In a recent interview with ADVANCE, Margaret Ragni, MD, MPH, director of the Hemophilia Center of Western PA in the division of hematology and oncology, professor of medicine and ASH spokesperson, discussed the combination of molecular and traditional testing and the role of both in the diagnosis of hematologic disorders.
Traditionally, the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) have been the standard testing methods used in identifying, diagnosing and treating bleeding disorders, along with other, specific clotting factors for disorders like Von Wildebrands disease. These tests offer clinicians and pathologists a general picture in terms of whether there is a problem in clotting or not. Moving forward, the clinical laboratory industry is taking these tests, as well as genetic factors, into account to predict the severity of the disorders.
“Those are the basic screening tests – the PT and aPPT, which measure time to clot formation. There are also specific clotting factor levels that are measured to determine what is deficient. There are also more of what we call, ‘global assays.’ By ‘global,’ we mean they measure not just time to clot formation, but also [the] size and strength of [the] clot and [the] time to clot breakdown (i.e., a global view of the clot forming,)” said Ragni. “So, the global assays can provide rapid identification if clot formation or clot breakdown or clot strength are the problem. These global tests are not run in most coagulation labs – they’re in specialty labs.”
Additionally, genetic tests can help to determine any specific bleeding or clotting disorders that might be present, such as hemophilia or deep vein thrombosis (DVT), which are both genetic disorders. Genetic tests can assess whether a mutation is present in a gene encoding for deficient or dysfunctional clotting factors, such as factor VIII and IX in hemophilia or factor V Leiden in DVT. As such, the role of molecular diagnostics has been increasingly considered in determining risk in families with a history of bleeding or clotting disorders.
SEE ALSO: Personalized Medicine and the Lab
As each patient is physiologically unique, his or her respective diagnosis and treatment will vary depending on any number of factors, including their genetic makeup. For hemophilia, there are thousands of mutations that can cause the disease, so knowing whether a mutation is casual or just present with no effect is important. These genetic tests are continually being refined by testing in a large number of affected and unaffected individuals, in order to improve understanding of the tests and their application to individuals with bleeding or clotting disorders.
“One way that some of these genetic tests are definitely already being utilized is within a family in terms of family planning – in terms of trying to get an idea of the risk that parents will have an affected child,” continued Ragni.
While other disorders are sometimes treated via a more team-oriented approach to care, with multiple doctors and specialists contributing to a larger solution, bleeding disorders largely remain a one-on-one relationship between the affected patient and treating physician. Despite this, Ragni noted that there has been a substantial push in patient outreach to educate both patients and their families on the treatment and potential risks of bleeding disorders. As such, other healthcare professionals are being introduced incrementally to offer counseling and advice as appropriate.
“Certainly, for management of the individual patient, it’s a doctor one-on-one relationship. However, there is [a] large effort to make sure there are genetic counselors at each hemophilia center, so genetic options can be reviewed and patients can be educated,” explained Ragni. “In addition, the National Hemophilia Foundation holds an annual meeting, which includes not only physicians, geneticists, nurses, psychosocial counselors and other caregivers, but also patients and their families are invited.”
Looking towards the future, an emerging technique with the potential to impact screening and treatment for bleeding disorders incorporates the use of extended half-life (EHL) products. The current available EHL are “tagged” to IgG antibodies, which improves how long the drug is available to prevent a bleed. Thus, the patient can take [the] drug less frequently with the same outcome. Researchers are also looking into the role of pharmacokinetics, which is to say how a patient with respond to a drug – in addition to pharmacogenetics and pharmacogenomics.