Physical Rehabilitation in Sickle Cell Anemia

Sickle cell anemia (SCA) is one of the most neglected diseases worldwide, according to the World Health Organization. In the adult population with SCA, the systemic effects of the disease, such as respiratory and peripheral muscle dysfunction, cause a decrease in quality of life. As a consequence, there is a concern about functional rehabilitation, since the aging of this population is already a reality in our environment. Thus, the objective of this project is to evaluate the effects of functional rehabilitation on quality of life in adult patients over 18 years of SCA. In this longitudinal intervention study, patients will be submitted to a three-month rehabilitation program. Before and after the intervention, patients will be submitted to the following assessments: spirometry; quality of life questionnaire - Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36); functional scale of joint integrity - Lower Extremity Functional Scale (LEFS); fatigue assessment scale - Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); physical activity assessment questionnaire - International Physical Activity Questionaire (IPAQ); peripheral muscle assessment (handgrip and isometric dynamometry of the quadriceps muscle); and 6-minute walk test (6MWT). The protocol will consist of warm-up and cool-down exercises, muscle strengthening and endurance exercises, aerobic training, balance training and proprioception. Thus, it is expected that patients with sickle cell anemia will benefit significantly, with a consequent improvement in musculoskeletal function, pain and health-related quality of life.

Over the past 40 years, Public Health measures have led to an impressive decline in infant mortality related to sickle cell disease (SCA) and, thus, modified its evolution. Sickle cell disease went from a life-threatening disease in childhood in the 1970s to a chronic disease of adults today. In Brazil, the median age of cases that evolved to death was 26.5 years in Bahia, 31.5 years in Rio de Janeiro and 30 years in São Paulo. In a study carried out in Minas Gerais, the average age at the time of death was 33.5 years considering only adults; this was higher in the female gender (46.5 years) and the majority occurred as a result of acute events.

Osteoarticular and muscle involvement is common in adults with sickle cell disease and has high morbidity. Since bone microcirculation is a place where sickling of red blood cells is common, there is a tendency for thrombosis, infarction and necrosis. The osteoarticular lesion is characterized mainly by osteonecrosis, osteomyelitis and arthritis, with frequent involvement of the hip and shoulder bones and the vertebral bodies.

Bone changes in SCA can be grouped into two main forms: those associated with ischemic events and those associated with bone marrow hyperplasia due to chronic anemia. The pathogenesis of microvascular occlusion, the key event of vaso-occlusive crises, is complex and involves the activation of leukocytes, platelets and endothelial cells, in addition to hemoglobin S containing red blood cells. These events can occur in almost any organ, but are particularly common in the bone marrow, possibly because of its hypercellularity, leading to a decrease in blood flow and regional hypoxia. There is also evidence of a possible association between changes in calcium metabolism and the occurrence of osteoporosis in people with sickle cell disease.

Regarding muscle disease, some studies have shown a decrease in both muscle strength and endurance in individuals with sickle cell disease. General amyotrophy results from repeated episodes of vasoocclusion and ischemia of the muscles, sometimes silent or subclinical, which occur in sickle cell anemia and are known to induce dysfunction and, eventually, skeletal muscle necrosis. Sickle cells and oxidative stress can cause microvascular obstruction and damage peripheral muscles in patients with SCA. Consequently, there are marked changes in skeletal muscle structure, with rarefaction of microvessels and decreased capillary tortuosity.

The main cause of emergency care for people with SCA is painful osteoarticular crises, which are observed in about 70% of cases, while the most frequent complications that require hospitalization in these individuals are the vaso-occlusive crisis and osteomyelitis. Other bone complications in acute SCA are stress fractures, orbital compression, vertebral collapse and spinal necrosis.

Osteonecrosis is a frequent complication in SCA, manifesting through painful and debilitating findings, and 50% of patients with the disease have evidence of complications after the age of 30. Spinal bone injury has been attributed to areas of bone infarction that can reach the central portions of the vertebral plateau and, as a consequence, lead to overgrowth of the adjacent portions and central depression of the plateau. Vaso-occlusive seizures mainly affect long bones, but they can also occur in the vertebrae and ribs and cause complications of respiratory function. Osteonecrosis of the femoral head has an incidence of 4.5 cases per 100 patients/year, often being bilateral. These vaso-occlusive crises are caused by obstructions in the microcirculation and are favored by some factors, such as prolonged immobilization, physical exercise, sudden changes in temperature, fever and dehydration.

Muscle weakness may be the result of the pathophysiology of SCA, in which patients have frequent vaso-occlusive crises due to the polymerization process of the hemoglobin S, which promotes greater adhesion of these cells to the vascular endothelium and can induce ischemia, inflammation and oxidative stress . It is known that oxidative stress can damage the peripheral muscles, causing damage to the performance of these muscles. The systemic damage caused by SCA can also lead to a more sedentary lifestyle, which, in turn, can result in an overall loss of muscle strength with a consequent reduction in functional capacity.

SCA is a chronic disease in which a cure is not yet possible and supportive treatment is prolonged, with palliative care being basically provided. Quality of life then appears as an essential challenge to be reached by patients, family members and health professionals. According to the World Health Organization, quality of life refers to the individual's perception of their position in life, in the context of the culture and value system in which they live, and in relation to their goals, expectations, standards and concerns. In addition, there is the concept of "health-related quality of life", which assesses the impact of health on the individual's ability to live fully. Thus, the health/disease process of people with SCA is governed by hereditary, biological and environmental factors and also suffers interference from the social environment, gender, race/ethnicity and class inequalities, which consequently compromise the factors considered acquired.

In patients with SCA, physical, emotional and social changes cause losses in quality of life. These changes result from the various complications that can arise over the natural course of the disease, in addition to the decrease in the life expectancy of the individual. SCA causes limitations in the lives of patients, with pain and several hospitalizations, most likely, responsible for the physical and emotional destabilization of patients.

Eligibility Criteria:
Inclusion Criteria:

* Patients with sickle cell anemia, of both sexes, aged ≥ 18 years.
* Patients who have clinical stability and are eligible for the treatment protocol.

Exclusion Criteria:

* Presence of comorbidities not related to sickle cell anemia.
* Patients with inability to perform the six-minute walk test.
* Patients who have cognitive impairment that impairs their inclusion in the study.
* Abandonment of treatment during the application of the protocol.
* Uncontrolled hypertension or use of psychotropic drugs.
* Any significant limitations due to osteoarthropathy.
* Have had any orthopedic surgery in the previous year.