Sickle Cell Disease

Other Names

Hemoglobin SC disease (HbSC)

Hemoglobin SS disease (HbSS)

Sickle-Beta-Thalassemia (HbS/B0, HbS/B+)

Sickle Cell Anemia

Diagnosis Coding

D57.1, Sickle-cell disease without crisis

Disorder Category

A hemoglobin disorder

Screening

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)

Overview

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).

Incidence

Sickle cell disease affects about 100,000 persons in the United States. 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. About 1:365 African-American births and 1:16,300 Hispanic-American births in the United States are affected by sickle cell disease.

Inheritance

Autosomal recessive

Prenatal Testing

Genetic diagnosis by amniocentesis, CVS, or fetal blood sampling

Clinical Characteristics

Symptoms and symptom severity 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

Follow-up Testing after Positive Screen

Hemoglobin electrophoresis for hemoglobin separation, high-performance liquid chromatography, to confirm screening results. DNA testing to determine genotype.

Primary Care Management

Upon Notification of the + Screen

If the Diagnosis is Confirmed

  • Educate the family about the need for emergent care when the infant has a fever and the importance of ongoing hematology follow-up for long-term care.
  • Educate the family regarding the need to maintain 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 crisis.
  • 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.
  • See the Portal’s Sickle Cell Disease for more detail.

Specialty Care Collaboration

Upon diagnosis of sickle cell disease, the patient should be referred to a hematologist with expertise in managing SCD or a hemoglobinopathy center for management and prevention of complications. Comprehensive sickle cell care requires long-term follow-up care and access to multidisciplinary teams.

Resources

Information & Support

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

Hemoglobinopathies (UDOH)
Information about hemoglobinopathies; Utah Department of Health, Newborn Screening Program.

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.

Hemoglobinopathies (UDOH)
Information about hemoglobinopathies; Utah Department of Health, Newborn Screening Program.

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.

Sickle cell anemia: How our red blood cells evolved to fight malaria (HealthMatch)
This web resource discusses the evolutionary role of how sickle cells help fight malaria, with a discussion of emerging therapeutics and option to search for relevant drug trials.

Patient Education

What is Sickle Cell Disease? (GSLC)
A brief educational overview of single gene disorders that includes the genetics of sickle cell disease; Genetic Science Learning Center at the University of Utah.

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)

Genetics clinic services throughout the US can be found through the Genetics Clinic Services Search Engine (ACMG).

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