Sickle Cell Trait

Excerpt

Sickle cell trait is a genetic condition that results when an individual inherits a gene for normal hemoglobin (A) and a gene for sickle hemoglobin (S) that results in the genotype (AS). Conversely, sickle cell disease occurs when an individual inherits 2 abnormal sickle genes (SS). There are different types of sickle cell disease, including hemoglobin SS (HbSS), hemoglobin SC (Hb SC), and hemoglobin S beta-thalassemia. These hemoglobin types cause a vaso-occlusive crisis; however, HbSS is the most common and severe type. HbSC results when an individual inherits HbS from 1 parent and HbC from the other. Hb C is caused by a switch from glutamic acid to lysine. HbS beta-thalassemia is a rare mutation that occurs when an individual inherits beta-thalassemia hemoglobin from 1 parent and HbS from the other. However, a vaso-occlusive crisis does not occur just because sickling hemoglobin is present; vaso-occlusion occurs due to multiple events, including deformed red blood cells, increased red blood cell fragility, and increased cation permeability and stickiness.

Sickle cell disease, a significant public health issue, was first described by James B Herrick in 1910, and almost 4 decades later, Linus Pauling and his colleagues concluded that a genetic disorder caused sickle cell disease. Sickle cell disease results in lifelong debilitation and early mortality due to chronic anemia and organ damage, leading to poor quality of life. Sickle cell trait, on the other hand, is relatively benign because patients do not have vaso-occlusive crises as individuals with sickle cell disease do; they have a better quality of life, and mortality is the same as the rest of the general population. Due to the sickle cell trait's nature, it generally has no severe clinical implications. However, there have been reports of adverse conditions due to the patient's trait status. Patients with sickle cell trait can have the same presentation as sickle cell anemia if exposed to conditions that favor sickling, including severe hypoxia, dehydration, increased sympathetic outflow, hypothermia, hyperthermia, high 2,3-DPG levels, or released inflammatory cells. Pain characteristic of SCT is typically described as cramping, weakness, and a dull ache that occurs within minutes of activity due to reduced blood to the muscles, unlike heat stroke. An athlete with SCT with these symptoms should be treated as a sickling exacerbation until this diagnosis can be excluded. Other symptoms of sickling include upper left quadrant abdominal or chest pain, chest tightness, and shortness of breath.

Sickle cell trait is generally diagnosed through screening tests followed by confirmatory testing or genetic analysis. Since the Sickle Cell Anemia Act was established in 1972, there has been increased screening for sickle cell trait and disease. Furthermore, each state in the US now offers universal newborn screening before discharge from the hospital. Hemoglobin electrophoresis is used to confirm the diagnosis after a positive screening test. Treatment is only indicated to reverse conditions causing sickling (eg, dehydration or hypoxia) or comorbid medical conditions associated with the SCT. Clinicians need to recognize the complications associated with sickle cell trait so that prompt management can be started once patients present with symptoms (eg, hematuria or papillary necrosis).