Sickle Cell Anemia

Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Hemoglobin SC disease (HbSC)
Hemoglobin SS disease (HbSS)
Sickle-Beta-Thalassemia (HbS/B0, HbS/B+)
Sickle Cell Anemia

ICD-10 Coding

D57.1, Sickle-cell disease without crisis

Disorder Category

Hemoglobin disorder

Screening

Abnormal Finding

F-S, F-S-C, or F-S-A pattern on newborn screening (most common genotypes) - other variants exist (F-S-Barts, F-S-E).

Tested By

Isoelectric focusing (IEF); high-pressure liquid chromatography (Utah newborn screen)

Description

In sickle cell disease, hemoglobin S (HbS) is an abnormal hemoglobin that results from a point mutation in the beta-globin gene on chromosome 11 that causes the substitution of a valine for glutamic acid as the sixth amino acid of the beta-globin chain. When inherited in the homozygous state (HbSS), or compound heterozygous with other beta-globin mutations (such as hemoglobin C or beta-thalassemia), states of deoxygenation, dehydration, acidosis, stress, and temperature changes cause hemoglobin S to polymerize, causing red blood cells to deform into a sickle shape. Red blood cell sickling causes anemia, premature RBC breakdown (hemolysis), intermittent episodes of microvascular occlusion, causing ischemic pain, acute and chronic organ dysfunction, and increased risk of infection. Many variant forms exist. Disease severity is affected by the genotype and modifiers of HbS polymerization (such as increased fetal hemoglobin levels).

Clinical Characteristics

Symptoms and symptom severity of sickle cell disease vary by individual and genotype. Symptom onset may occur in infancy or childhood, but usually after 4-months of life.
Symptoms may include:
  • Anemia
  • Jaundice
  • Pain (most likely due to ischemia from vaso-occlusion)
  • Auto-splenectomy - functional asplenia
  • Stroke
  • Increased susceptibility to infection, particularly with pneumococcus
  • Acute chest syndrome (associated with infection, surgery/general anesthesia, pulmonary infarction, or embolism)
  • Leg ulcers
  • Fatigue
  • Pneumonia
  • Splenic sequestration
  • Bone damage
  • Kidney damage
  • Aplastic crisis (associated with parvoviral infection)
  • Gallstones
  • Priapism
  • Bloody urine
  • Retinopathy
If not treated appropriately, patients may experience:
  • Acute complications of vaso-occlusive crisis, such as acute chest syndrome and stroke, and increased susceptibility to infections from asplenia may be life-threatening

Incidence

Sickle cell disease affects about 100,000 persons in the United States. [Hassell: 2010] The gene for Hb S is present in all racial and ethnic groups affecting males and females equally. However, it is more prevalent in people of African, Mediterranean, Middle Eastern, Southeast Asian, Caribbean, and Central and South American descent. The incidence in African Americans of sickle trait is 1:14, and sickle cell disease is 1:396. [Lorey: 1996]

Inheritance

Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and refer to Pediatric Hematology/Oncology (see UT providers [2]) for evaluation and ongoing collaborative and multidisciplinary management.
  • While awaiting subspecialist referral:
    • Initiate prophylactic penicillin (125 mg orally twice daily) prior to 2-months of age
    • Inform the family that they should seek immediate medical attention if the infant has a fever of 101°F (38.3°C) and inform the treating clinician of the SCD diagnosis

Confirming the Diagnosis

If the Diagnosis is Confirmed

  • For evaluation, ongoing collaborative management, and prevention of complications, consult Pediatric Hematology/Oncology (see UT providers [2]). Comprehensive sickle cell care requires long-term follow-up care and access to multidisciplinary teams.
  • Educate the family about the need for emergent care when the infant sickle cell has a fever and the importance of ongoing hematology follow-up for long-term care.
  • Educate the family regarding the need for current childhood immunizations, including additional immunizations for functional asplenia.
  • Prophylactic penicillin, red blood cell transfusions, hydroxyurea, folic acid supplements, and prevention of dehydration may be indicated for affected children.
  • Pain and symptom management are indicated for affected children in sickle cell crises.
  • Newer therapies, such as bone marrow transplant and gene therapy, may be considered for severely affected children after consultation with a specialist.
  • Assist in management, particularly with immunizations, developmental and educational interventions, and psychosocial assistance.

Resources

Information & Support

Related Portal Content
Sickle Cell Disease
Assessment and management information for the primary care clinician caring for the child with sickle cell disease.

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

Sickle Cell Disease (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Sickle Cell Anemia (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

For Parents and Patients

Sickle Cell Disease (MedlinePlus)
Overview of sickle cell disease plus links to many other relevant sources of information and support for patients and families; from the National Library of Medicine.

The Sickle Cell Information Center
Information for parents, providers, students, legislators, and the public; clinical guidelines, protocols, and PDA tools; educational presentations and materials; news; links to websites for kids; and links to many other resources and organizations; hosted by Grady Health System/Morehouse School of Medicine.

Sickle Cell Disease Association of America
The mission of this nonprofit is to improve the quality of health, life, and services for individuals, families, and communities affected by sickle cell disease and related conditions while promoting the search for a cure.

Tools

ACT Sheet for Sickle Cell Disease (HbSS Disease or HbS/Beta Zero Thalassemia) (ACMG)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithms for Sickle Cell Disease (Hb S) (ACMG)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.

Services for Patients & Families in Utah (UT)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Sickle Cell Disease (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

PubMed search for sickle cell disease and neonatal screening, last 2 years.

Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J.
Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.
JAMA. 2014;312(10):1033-48. PubMed abstract
Subscription required for full text.

American Society of Hematology.
American Society of Hematology Clinical Practice Guidelines on Sickle Cell Disease.
(2019) https://www.hematology.org/education/clinicians/guidelines-and-quality....

Authors & Reviewers

Initial publication: March 2007; last update/revision: April 2021
Current Authors and Reviewers:
Author: Jessica Meznarich, MD
Authoring history
2007: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Hassell KL.
Population estimates of sickle cell disease in the U.S.
Am J Prev Med. 2010;38(4 Suppl):S512-21. PubMed abstract

Lorey FW, Arnopp J, Cunningham GC.
Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state.
Genet Epidemiol. 1996;13(5):501-12. PubMed abstract