Sickle cell anemia

Test

Provide the most accurate diagnosis but usually reserved for prenatal diagnosis or those with more difficult-to-diagnose genotypes.

Often used for confirming an abnormality found by hemoglobin studies. May be used in place of hemoglobin studies in some screening programs. Considered to be more reliable than hemoglobin isoelectric focusing (Hb IEF).

If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, for example the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[17]​American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication]. https://web.archive.org/web/20230326143738/https://www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics/

Test

Although not a definitive diagnostic test, IEF is commonly used to determine the presence of the sickle cell gene.[25]Centers for disease control and prevention (CDC). Hemoglobinopathies: current practices for screening, confirmation and follow-up. Dec 2015 [internet publication]. https://www.cdc.gov/ncbddd/sicklecell/documents/nbs_hemoglobinopathy-testing_122015.pdf

Can also be used to determine the percentage of HbS in a blood sample. This is particularly helpful in guiding and monitoring treatment - for example, to determine how effective simple or exchange transfusion has been to decrease the patient's level of sickled hemoglobin.

All newborn screening is performed using Hb IEF or high-performance liquid chromatography (HPLC) fractionation.

Do not repeat hemoglobin electrophoresis in patients who have a prior result, unless the results of interventional therapies or hemoglobin levels are being monitored.[18]​American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication]​. https://web.archive.org/web/20230316185857/https://www.choosingwisely.org/societies/american-society-for-clinical-pathology

Test

In older children and adults, cellulose acetate electrophoresis at an alkaline pH is most commonly used to determine hemoglobin subtype. Diagnosis can be confirmed using an alternative method.

Do not repeat hemoglobin electrophoresis in patients who have a prior result, unless the results of interventional therapies or hemoglobin levels are being monitored.[18]​American Society for Clinical Pathology. Thirty five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication]​. https://web.archive.org/web/20230316185857/https://www.choosingwisely.org/societies/american-society-for-clinical-pathology

Test

When abnormal hemoglobin is identified, DNA-based assays or HPLC are used to confirm the diagnosis and further identify the genotype. These tests also allow the distinction between heterozygotes and homozygotes.

If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, for example the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[17]​American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication]. https://web.archive.org/web/20230326143738/https://www.choosingwisely.org/societies/american-college-of-medical-genetics-and-genomics/

Test

May be used for initial screening in older children and adults, but cannot distinguish between sickle cell trait (heterozygotes) and sickle cell disease (homozygotes).

Not recommended for infants under 6 months because the high proportion of fetal hemoglobin in relation to adult sickle cell hemoglobin in a newborn's blood may affect the results.

A normal result excludes sickle cell disease in patients older than 6 months without symptoms or signs of severe anemia or very high fetal hemoglobin levels.

Test

Helps rule out additional causes of anemia but requires expert interpretation and cannot be used to determine whether patient is in vaso-occlusive crisis.[Figure caption and citation for the preceding image starts]: Red cells in sickle cell diseaseFrom the personal collection of Sophie Lanzkron, MD; used with permission [Citation ends].

Evaluation of the type and an estimate of the number of white blood cells, red blood cells, and platelets is made to assess if they are normal in morphology and number. Sickle-shaped cells, Howell-Jolly bodies, presence of nucleated red blood cells, and cell fragments can be seen on the blood smear. Oat cells and target cells can be seen in HbSC disease.

Test

Used in testing older children and adults to evaluate number and quality of red blood cells, hemoglobin content, and white blood cell count. Useful in establishing a baseline for ongoing evaluation. Widely available, inexpensive, and provides rapid results, but it is not diagnostic.

Patients can present with vaso-occlusive pain and not have any change from baseline in their hemoglobin or reticulocyte count.

White blood cell count can occasionally be overestimated if the count is not corrected for the presence of nucleated red cells, which are often present.

In patients with very low reticulocyte counts <1%, parvovirus infection should be strongly considered.

Test

Helps distinguish hemolytic anemia from iron-deficiency anemia. Patients that have been transfused in the past will have elevated results.

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Pulse oximetry monitoring is important as early drops in oxygen saturations can suggest the beginning of acute chest syndrome.

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Used to confirm the presence of bone infarction. Most bone infarctions are diagnosed clinically by symptoms (bone pain) and signs (e.g., absence of fever).[Figure caption and citation for the preceding image starts]: Avascular necrosis of the femoral head in patient with heterozygous (hemoglobin SC) sickle cell anemiaFrom: Davies SC, Oni L. BMJ. 1997 Sep 13;315(7109):656-60 [Citation ends].

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Bacterial cultures (using blood, sputum, urine, stool, and/or pus) should be obtained in patients with fever and/or those who appear toxic.

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Performed if the patient has respiratory symptoms, fever, or chest pain.[Figure caption and citation for the preceding image starts]: Chest x-ray in acute chest syndromeFrom: Davies SC, Oni L. BMJ. 1997 Sep 13;315(7109):656-60 [Citation ends].