April 17th is World Haemophilia Day, an international campaign designed to honour the people and families coping with this rare condition and raise awareness of the disease. This year’s campaign focuses on “Access for All: Prevention of bleeds as the global standard of care” and ensuring that treatments are available globally. Clinical lab diagnostics can play an important role in achieving this goal.

Haemophilia is associated with uncontrollable bleeding due to insufficient clotting factors in the blood. Patients typically have low levels of Factor VIII (haemophilia A) or Factor IX (haemophilia B); severity of the condition increases as those levels decrease. Even minor injuries can be dangerous for people with haemophilia, and surgery can be extremely challenging. The condition can also cause spontaneous bleeding within joints, leading to chronic joint pain.

More than 200,000 people around the world are living with haemophilia. While it is a rare bleeding disorder, advocacy from the global haemophilia community has driven widespread awareness of the condition. As haemophilia is associated with an X-linked recessive variant, it is more common in males than females. Most people with haemophilia are born with it, but it can develop spontaneously in some cases.

With the recent launch of novel therapies for haemophilia, many efforts within the community have focused on expanding patient access to them. In addition, diagnostic laboratory tests—which are used to identify the condition, monitor response to treatment, match patients to emerging treatments, or assess genetic carrier status—are also powerful tools to complement the push to expand access to quality healthcare for all.

Diagnosing the disease and assessing carrier status

One of the biggest drivers of inequity in healthcare is the lack of uniform access to high-quality diagnostics, particularly in less well-resourced health systems. Until haemophilia patients receive that all-important initial diagnosis, they cannot receive the critical care they need to manage their conditions and lead safe, healthy lives.

Unfortunately, many patients are not diagnosed until they go through some kind of traumatic event with dangerous, out-of-control bleeding that alerts doctors to the possibility of haemophilia.

“The challenge lies in recognising and identifying individuals with haemophilia,” says Associate Professor Joyce Lam, Senior Consultant, Haemotology/Oncology Service, KK Women’s and Children’s Hospital in Singapore, who also leads the hospital’s haematology laboratory and blood bank. “Congenital bleeding disorders may not be among the top differential diagnoses of patients who present with bleeding symptoms, as these are considered rare conditions.”

“Education of healthcare providers to look out for these congenital bleeding conditions becomes very important,” she adds.  “Once they are identified, familial screening should be offered to identify other potential male patients and female carriers within the same family.”

The tests used to diagnose a congenital bleeding disorder such as haemophilia are fairly conventional; they are used consistently in labs around the world. From a standard complete blood count (CBC) test to a series of coagulation diagnostics such as PT, APTT, and fibrinogen, there are many tests used in routine screening for bleeding disorders such as haemophilia (see Haemophilia diagnostics and treatments: a brief introduction for a detailed overview of the diagnostic workflow).

All of those tests are typically considered routine screening tests for bleeding disorders. If those tests demonstrate that a patient’s blood is not clotting properly, follow-up tests may be deployed to identify the exact bleeding disorder. If haemophilia is diagnosed, further tests are performed to assess the severity of the condition. The tests will focus on specific levels of factor VIII and factor IX, classifying patients as having mild, moderate, or severe haemophilia.

Another area where diagnostic tools can make a difference in the haemophilia journey is in reproductive decisions. Genetic testing can be used to identify carriers of haemophilia—including women who may not even know their own risk of the condition—so they can make informed decisions regarding reproductive choices.

Treatment options and outcomes monitoring

After the initial diagnosis, the clinical laboratory continues to play an important role as physicians seek to monitor response to haemophilia treatments. Specific factor assays are used to monitor the response to current standard-of-care therapies that aim to replace the deficient clotting factor with plasma-derived factors or recombinant factor products. Continued monitoring over time is important to confirm continued effectiveness of therapy and to check for the development of inhibitors.

In both children and adults, replacement therapy is used prophylactically to prevent dangerous bleeds and preserve the health and function of joints. “With the proper management strategy involving regular replacement of clotting factor concentrates, physical training and use of protective equipment, many patients are able to lead physically active lives and participate in a number of sports, even at the competitive level,” says Associate Professor Lam.

These positive outcomes have been supported by an evolution in haemophilia treatment over the years. Novel treatments, including gene therapy, have come out in recent years, though they are not currently accessible in all countries (see Emerging haemophilia therapies highlight a need for quality diagnostics for a deeper discussion of the emerging treatment modalities). Still, there is a need to continue development of better treatments that would give patients even better outcomes, ideally eliminating the need for recurring replacement therapy.

Together with her team, Associate Professor Lam aims to improve the quality of care for haemophilia patients by collecting more data—another key role of clinical laboratories. “We are addressing the need to prospectively capture medical information and outcomes data for our cohort of patients with bleeding disorders on a national scale via a patient registry, so that we can better assess the quality of treatment strategies and continually improve the standards of care for our patients,” she says.

With careful monitoring and proper treatment, patients with haemophilia can lead a relatively normal and fulfilling life. Empowering patients through diagnostic testing and effective treatments is an achievable goal for clinical laboratory professionals and healthcare providers.