Sickle cell anemia is an increasingly serious problem, says scientist

In an interview with Agência FAPESP, Sara Olalla Saad, of Unicamp's Hematology and Hemotherapy Center, affirms that the disease has been neglected and explains why it is urgent to develop new treatments and study means of prevention.

By Fábio de Castro

Agência FAPESP – Sickle cell anemia is a hereditary disease that causes blood cell malformations and complications in practically all of the body’s organs, and is prevalent among individuals of African descent. In Brazil, the prevalence is one in every 1,000 people on average. In Bahia, where the contingent of Afro-Brazilians is greater, the disease affects one in every 650 live births.

The disease is congenital and worsens continuously over time, reducing the patient’s life expectancy to an average of 40 years. Over time, treatment becomes more and more difficult. Adults present with chronic lesions in all organs and acute pain caused by the occlusion of blood vessels, in addition to neurological sequelae and other deadly degenerative changes.

For 30 years, Professor Sara Olalla Saad of Universidade Estadual de Campinas’ (Unicamp) Hematology and Hemotherapy Department has been dedicated to studying the disease and applying this knowledge to the treatment of patients.

In 1992, an international group of researchers published studies that demonstrated the benefits of hydroxyurea in reducing patient suffering. Since then, the Unicamp group has begun to utilize the drug, which was only approved in Brazil 10 years ago.

Pioneerism, coupled with research and clinical practice, led the group to publish many studies with international impact. At present, the scientists are conducting a cohort study with 114 patients aged 14 to 55. The patients are followed continuously in an effort to understand the disease and test new therapies.

Saad, who directs the National Science and Technology Center (INCT) for Blood, participated in the Regional Symposium on Translational Medicine, held at FAPESP’s headquarters to celebrate the 60th anniversary of the National Scientific and Technological Development Council.

In an interview with Agência FAPESP, Saad commented on the course of research on sickle cell anemia and emphasized that the social conditions of patients, coupled with neurological sequelae, contribute to the disease. Despite its high incidence and gravity, sickle cell disease is largely neglected by public health policy.  

Agência FAPESP – Hydroxyurea has been utilized to treat sickle cell anemic patients for more than 20 years. What do we still need to learn about this drug?
Sara Olalla Saad – Although we have been utilizing hydroxyurea for a long time, we still don’t know if the drug can be used upon birth. That is the main focus of recent studies. Generally, to begin treatment, the doctors wait for an indication, such as acute chest syndrome or a sequence of crises. But when a patient reaches adulthood, the sequelae are much more severe and the quality of life is terrible. We want pediatricians to begin treatment early, either with hydroxyurea or with a bone marrow transplant.

Agência FAPESP – How do you evaluate the impact of the disease on a patient’s quality of life?
Sara Olalla Saad – We consider diabetes, for example, a grave disease because of the sequelae it can cause. But sickle cell anemia is much more grave because all of the patient’s organs have lesions. The malformed blood cells have difficulty crossing capillaries, which can clog, causing necrosis, cell death and intense pain crises.  It is common for ulcers to appear on legs, retina to detach, and priapism, strokes, heart attacks, kidney failure and lung collapse to occur. All bones are compromised, causing pain in articulations. And the disease is a one-way street, because as time passes, it only worsens. When these individuals reach 40, the situation is desperate.

Agência FAPESP – What is the objective of the cohort studies that are being conducted by your group?
Sara Olalla Saad – We have investigated all of the chronic complications that occur, and we managed to intervene in each of them. We have kidney markers that today are used worldwide, and when it comes to hearts, we use echocardiograms to determine if it is time to administer transfusions. But for several chronic complications, we do not have many details on the parameters that should be controlled. In this cohort, we also study the best medical practices to define how we can take care of these patients and prevent and retard sequelae, in addition to promoting greater survival.

Agência FAPESP – You have expressed concern over the increase in the number of people with sickle cell anemia. Is this happening because patients are living longer?
Sara Olalla Saad – Yes. That is occurring. As we make interventions, they live longer. But this does not guarantee their quality of life, which is very poor. Some decades ago, survival was a maximum of 30 years. Today, the average age of our patients is 40 years old. We have increased lifespan, but they have sequelae. We want to take advantage of advanced methods to test some options using in vitro or in animal models. Due to advances such as optical tweezers, we can do this, even working with a small cohort of patients without the need for lengthy studies. With this resource, we can test the use of diverse medicines and rapidly observe how these tools modify the dynamics of cells. We have not managed to observe chronic complications because it takes 20 years for that. Therefore, we need parameters that can be studied rapidly.

Agência FAPESP – There is controversy surrounding the use of transplants as an alternative because chemotherapy must be used in patients that do not have cancers. What’s your opinion?
Sara Olalla Saad – I am in favor of transplants, and I recently asked for a transplant for a patient of mine. I told him that if he got the transplant he ran the risk of dying in 10 days, but he preferred to die because he had many sequelae and severe bone aches. He is very well now. I have a patient on the waiting list who is 19. The boy has many vascular-occlusion crises. We are fearful of doing transplants in adult patients because they are full of sequelae, and for chemotherapy, it is ideal if patients do not have lesioned organs. But studies have shown that the results of transplants are excellent.

Agência FAPESP – Treatment with hydroxyurea and transplants are the main alternatives? Are there many limitations?
Sara Olalla Saad – There are some limitations. Some patients do not respond to hydroxyurea. Also, not everyone can find a donor for transplants. Furthermore, we have to work with other drugs that improve not only inflammation, but occlusion as well, because of the neurological sequelae caused by the disease. Treating only vascular occlusion will not resolve it because it also causes inflammation that can lead to neuronal death, causing neurological sequelae. We don’t know yet if hydroxyurea alone will prevent this problem. As we will have an increasing number of patients, we need to invest in other drugs with a composition that can be used with hydroxyurea and thalidomide, which is an anti-inflammatory and immunosuppressive. I hope that some nitric oxide and magnesium donors can be used in vascular occlusion crises to alleviate a patient’s pain. I think all of these alternatives could have good results.

Agência FAPESP – Can you say that sickle cell anemia has been neglected throughout history?
Sara Olalla Saad – Yes, certainly. Just look at the story of hydroxyurea. In 1992, there was already evidence that the drug was effective in humans, and yet we couldn’t get it approved. The Ministry of Health published a decree for the usage of hydroxyurea, which included an absurd list of side effects and a consent term for those patients who do not wish to use it. But we have used the drug for 10 years, and these side effects never occurred. Any medicine could have many side effects, but they could be rare, while the sequelae of the disease are absolutely real.

Agência FAPESP – Why was there so much resistance to adopting the drug?
Sara Olalla Saad – I don’t know. I didn’t understand why. But I think that the negligence could be linked to the fact that these patients are very poorly mobilized. They are needy, very poor, and several are of African descent and have a grave, chronic illness with severe neurological sequelae. They are excluded from society in all its forms.