Sickle Cell Disease (SCD)


Sickle cell disease (SCD) comprises a group of inherited blood disorders in which alterations in the structure of hemoglobin result in the sickling and early death of red blood cells. The result is inefficient transportation of oxygen to the tissues. The abnormally shaped red cells also obstruct small blood vessels, causing pain and sometimes stroke.1

Genetic Testing

In the United States, newborn screening via DNA analysis for the early detection, monitoring, and prompt treatment of SCD is mandatory.2 A prenatal diagnosis of SCD can be obtained early via chorionic villus sampling or later, between weeks 14 and 16, through amniotic fluid testing.2,3 Before pregnancy, women may undergo genetic carrier testing and genetic counseling so that they understand the risks of passing SCD along to their children.3 The identification of less common variants of SCD may require specialized DNA sequencing.3

Blood Tests

Blood tests are part of the preliminary evaluation for SCD. Common hematologic abnormalities in patients with SCD include elevated levels of platelets, leukocytes (primarily neutrophils; cell count between 12,000 and 20,000/mm3), and often reticulocytes. Laboratory tests also show decreases in the hemoglobin level (5-9 g/dL), hematocrit (17%-29%), and erythrocyte sedimentation rate.4 

Peripheral blood smears reveal the characteristic elongation and sickling of red blood cells. The patient may be asplenic if red blood cells with Howell-Jolly bodies (nuclear remnants) are present.4

Although they are not diagnostic, the hemoglobin S (HbS) solubility test and sodium metabisulfite test may identify HbS in children older than 6 months. The tests do not differentiate between those with SCD and those with sickle cell trait (SCT).3

In hemoglobin electrophoresis, an electric current is used to identify and measure the different types of hemoglobin in the blood. The presence of abnormal hemoglobin (HbS, HbC, or HbE) may indicate sickle cell disease or anemia.5 

In addition to hemoglobin electrophoresis, other tests used to evaluate for a hemoglobinopathy include isoelectric focusing, hemoglobin fractionation by high-pressure liquid chromatography (HPLC), mass spectrometry, and capillary zone electrophoresis.3

Iron studies measuring the body’s ability to store and use iron can detect either iron deficiency anemia or iron overload in patients who require multiple blood transfusions.3

Children younger than 5 years of age with fever should undergo urinalysis, blood cultures, liver function tests, and a complete blood cell (CBC) count, including a differential and reticulocyte count. A significant drop in the hemoglobin level of more than 2 g/dL suggests a hematologic crisis, which may require a blood transfusion. Before a transfusion, a blood type and crossmatch test is required to ensure that the donor blood is compatible with the patient’s blood.6 

Although the leukocyte level is usually elevated in individuals with SCD, major elevation to above 20,000/mm3 indicates possible infection. A decrease in the leukocyte level is associated with a possible parvovirus infection. Numerous factors influence the reticulocyte count, an indicator of bone marrow responsiveness. The reticulocyte count in splenic sequestration is normal. Aplastic crisis and hyperhemolytic crisis cause low and high reticulocyte counts, respectively.6 

Additional Testing

Other potentially useful laboratory tests include serum electrolyte, serum creatinine, and blood urea nitrogen measurements; a lactic dehydrogenase assay; and a haptoglobin assay. Although the 2 assays are not mandatory, increased LDH and decreased haptoglobin can indicate the presence of hemolysis.7

Urinalysis in a patient with SCD commonly reveals hematuria and isosthenuria but may also identify a urinary tract infection that requires treatment.7

In individuals without a diagnosis, a sickling test can confirm the presence of an abnormal beta-globin gene. In individuals with a diagnosis, arterial blood gas measurements indicate the severity of a respiratory crisis. Additionally, an elevated level of secretory phospholipase A2, an enzyme that metabolizes triglycerides by removing fatty acids, is a clinical biomarker of acute chest syndrome during a pain crisis.7

Chest radiography may assist in diagnosing SCD in patients experiencing acute respiratory distress. Plain radiography may help in the evaluation of bone infarction, osteonecrosis, and advanced osteomyelitis.8 

Magnetic resonance imaging (MRI) may detect avascular necrosis, marrow hyperplasia, early signs of osteonecrosis, osteomyelitis, bony infarction, and cerebral infarction in patients with SCD.9 

Computed tomography (CT) is used to rule out renal medullary carcinoma in patients with SCD who present with hematuria. CT may also be helpful in detecting subtle changes of osteonecrosis in patients who cannot undergo MRI.9

Nuclear medicine is a cost-effective way to detect the initial stages of osteonecrosis (technetium 99m bone scanning) and osteomyelitis (indium 111 white blood cell scanning).10 

Transcranial Doppler ultrasonography (TCD) may be used to analyze blood flow velocity within the circle of Willis. Children with SCD whose blood flow velocity is relatively high are at increased risk for stroke. Children in whom sickle cell anemia (HbSS) or sickle-beta zero thalassemia has been diagnosed between the ages of 2 and 16 years should be screened with TCD annually if the results continue to be normal, every 4 months if the results are marginal, and within 2 to 4 weeks if the results are abnormal.11 

Abdominal ultrasonography can be performed to measure the size of the liver and spleen and to detect cholecystitis, cholelithiasis, nephrolithiasis, ectopic pregnancy, and papillary necrosis in the kidneys.12 

Echocardiography can rule out left ventricular diastolic dysfunction, which correlates with premature death in patients with SCD. It also identifies tricuspid regurgitation and pulmonary hypertension in these patients. Patients with SCD who have respiratory problems should undergo echocardiography. The ability of echocardiography to detect early-stage high-output heart failure is limited when a patient is evaluated at rest; therefore, low-level invasive exercise testing is recommended when heart failure is suspected in a patient with SCD whose echocardiographic results are inconclusive.13

References

  1. What is sickle cell disease? Centers for Disease Control. Accessed November 19, 2021.
  2. Maakaron JE. Sickle cell disease workup. Approach considerations.  Medscape. Updated November 2021. Accessed November 19, 2021.
  3. Sickle cell tests. Testing.com. Last modified November 9, 2021. Accessed November 19, 2021.
  4. Maakaron JE. Sickle cell disease workup. Baseline blood study abnormalities. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  5. Hemoglobin electrophoresis. Medline Plus. Accessed November 19, 2021. 
  6. Maakaron JE. Sickle cell disease workup. Laboratory studies in the ill child. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  7. Maakaron JE. Sickle cell disease workup. Additional tests. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  8. Maakaron JE. Sickle cell disease workup. Radiography. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  9. Maakaron JE. Sickle cell disease workup. Magnetic resonance imaging. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  10. Maakaron JE. Sickle cell disease workup. Nuclear medicine scans. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  11. Maakaron JE. Sickle cell disease workup. Transcranial Doppler ultrasonography. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  12. Maakaron JE. Sickle cell disease workup. Abdominal ultrasonography. Medscape. Updated November 2, 2021. Accessed November 19, 2021.
  13. Maakaron JE. Sickle cell disease workup. Echocardiography. Medscape. Updated November 2, 2021. Accessed November 19, 2021. 

Reviewed by Kyle Habet, MD, on 11/30/2021.

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