What causes symptoms of sickle cell disease and how are they managed?

From the Guidelines

Sickle cell disease symptoms are primarily caused by abnormal hemoglobin that leads to red blood cell sickling, resulting in blood vessel blockage, pain crises, and organ damage. The management of sickle cell disease involves both preventive care and acute treatment. Preventive measures include hydroxyurea, which increases fetal hemoglobin production and reduces sickling episodes, as well as regular hydration, pneumococcal and influenza vaccinations, and penicillin prophylaxis for children under 5 1.

Key Management Strategies

• Hydroxyurea (starting at 15-20 mg/kg/day) to increase fetal hemoglobin production and reduce sickling episodes
• Regular hydration (2-3 liters daily)
• Pneumococcal and influenza vaccinations
• Penicillin prophylaxis (penicillin V 125-250 mg twice daily) for children under 5

Acute pain crises are managed with aggressive hydration, oxygen supplementation when saturation falls below 95%, and pain control using NSAIDs like ibuprofen for mild pain or opioids like morphine for severe pain. Severe complications like acute chest syndrome require hospitalization, oxygen, antibiotics, and possibly blood transfusions, as outlined in the American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support 1.

Acute Complications Management

• Aggressive hydration for acute pain crises
• Oxygen supplementation when saturation falls below 95%
• Pain control with NSAIDs or opioids
• Hospitalization and specific treatments for acute chest syndrome, including antibiotics and possibly blood transfusions

Regular blood transfusions may be needed for stroke prevention in high-risk patients, often accompanied by iron chelation therapy to prevent iron overload. Newer treatments, such as voxelotor and crizanlizumab, offer additional management options for reducing sickling and vaso-occlusive crises. Bone marrow transplantation remains the only potential cure but carries significant risks and requires careful patient selection. The choice of treatment should always prioritize reducing morbidity, mortality, and improving quality of life, based on the most recent and highest quality evidence available.

From the FDA Drug Label

The mechanism of action of the amino acid L-glutamine in treating sickle cell disease (SCD) is not fully understood. Oxidative stress phenomena are involved in the pathophysiology of SCD. Sickle red blood cells (RBCs) are more susceptible to oxidative damage than normal RBCs, which may contribute to the chronic hemolysis and vaso-occlusive events associated with SCD

The symptoms of sickle cell disease are caused by oxidative stress and vaso-occlusive events associated with sickle red blood cells.

• Oxidative stress contributes to the chronic hemolysis
• Vaso-occlusive events are associated with sickle cell crises, which can lead to symptoms such as pain, chest syndrome, priapism, and splenic sequestration. Management of symptoms includes treatment with L-glutamine, which has been shown to reduce the number of sickle cell crises and hospitalizations due to sickle cell pain 2.

From the Research

Causes of Sickle Cell Disease Symptoms

• Sickle cell disease (SCD) is a hereditary blood disorder characterized by the production of abnormal hemoglobin molecules that cause red blood cells to take on a crescent or sickle shape 3.
• The primary cause of SCD is a mutation in the gene responsible for producing hemoglobin, the protein that carries oxygen in red blood cells 3.
• This mutation has abnormal hemoglobin called hemoglobin S, which causes red blood cells to become stiff and sticky, leading to various health complications 3.
• Patients with SCD may experience recurrent pain, fatigue, anemia, and increased infection susceptibility due to the abnormal shape of their red blood cells 3.

Management of Sickle Cell Disease Symptoms

• Treatment options for SCD focus on managing symptoms and preventing complications 3.
• Pain management with analgesics, hydration, and blood transfusions to improve oxygen delivery are common treatment approaches 3.
• Hydroxyurea, a medication that increases the production of fetal hemoglobin, is commonly used to reduce the frequency and severity of pain crises 3, 4, 5, 6, 7.
• Bone marrow or stem cell transplants can cure select individuals with severe SCD 3.
• Hydroxyurea has been shown to decrease the frequency of painful crises, hospitalizations, and blood transfusions in patients with SCD 4, 6, 7.
• The use of hydroxyurea in SCD has been associated with improved quality of life, reduced mortality, and decreased risk of life-threatening complications 5, 6, 7.