David Gómez-Almaguer M.D. FACP
Head Hematology Service. Hospital Universitario, UANL, Monterrey, México, Chair of Council International Society of Hematology
One of the most common bleeding inherited disorders is haemophilia. Haemophilia A occurs in around one in 5,000 male births and haemophilia B is one in 25,000 live male births.
Haemophilia A and B are clinically similar. Both are X-linked recessive disorders, occurring by mutations in the gene for blood clotting factors.
The severity of bleeding varies in direct relation to factor activity or level in circulating in plasma. More than half of patients with haemophilia are considered severe, as they have factor levels of less than 1% of normal.
These patients have a severe bleeding condition, suffering from frequent soft tissue and musculoskeletal affection.
The importance of factor replacement
Without proper factor replacement, patients will develop repeated episodes of intra-articular bleeding, which causes severe and progressive arthropathy.
Eventually many patients will present with deformity, loss of joint function and may be permanently disabled.
Many years ago, the administration of fresh or frozen plasma and cryoprecipitates was the only way to treat these patients.
There are several impressive advances in the field of haemophilia treatment. But the questions regarding cost remain.
It is important to understand that, in many low-middle income countries, these blood derived products are still the only way to treat haemophilia patients.
In more developed countries, FVIII or FIX concentrates are employed and therefore considered the gold standard.
Currently, the ideal strategy for clotting factor administration is prophylaxis. In this setting, FVIII or FIX concentrates are regularly infused with the goal of maintaining the factor level above 1%.
It is important to start in early childhood in order to avoid complications, as this strategy prevents arthropathy and allows patients with haemophilia to obtain a near-normal life expectancy with a good quality of life.
Prophylaxis in haemophilia is not an easy task since frequent IV administration of factor concentrates is needed.
Usually, the infusion must be done two to three times a week and this is burdensome, demanding and highly expensive.
New advances in haematological care
In the International Society of Hematology (ISH), we have considered that there are three recent important advances in the field:
- The long half-life concentrates of FVIII and FIX. These new, different synthetic formulations that have been modified could be administered once weekly for haemophilia A and even once bi-weekly in patients with haemophilia B.
- The development of a new antibody: Emicizumab facilitates the change of FX to its active form improving haemostasis. It has been suggested that this improvement is equal to a plasma FVIII level around 15%. It is active even in the presence of inhibitors and could be delivered by subcutaneous administration.
- Finally, the development of gene therapy. There is new scientific evidence that this kind of permanent therapy could work, resulting in improvement of bleeding. Several studies in this area are moving forward.
Of course, there are still some obstacles, but it is expected that curative gene therapy is going to be soon among us.
There are several impressive advances in the field of haemophilia treatment. But the questions regarding cost remain. We must remember that 80% of the population live in the low and middle-income countries.
We will have to find the way to bring these new advances to everyone in the world. ISH is ready to help.
1 Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis vs episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J MED. 2007; 357:535-544 | 2 Lambert T, Benson G, Dolan G et al. Practical aspects of extended half life products for the treatment of hemophilia. Ther Adv Hematol, 2018; 9:295-308 | 3Nathwani AC. Gene therapy for hemophilia. Hematology ASH Education Program 2019. 1-8.