• Clinical science

Sickle cell anemia

Abstract

Sickle cell syndromes are hereditary hemoglobinopathies. Homozygous sickle cell anemia (HbSS, autosomal recessive) is the most common variant of the sickle cell syndromes and occurs predominantly in individuals of African and East Mediterranean descent. Sickle cell trait occurs in heterozygous carriers (HbSA). Other rare variants of sickle cell syndrome occur in individuals with one HbS allele and one other allele (HbC or Hb-β thalassemia). A point mutation in the beta chain of hemoglobin leads to substitution of glutamic acid by valine, thus changing the structure (and properties) of hemoglobin. Abnormal hemoglobin polymerizes when deoxygenated, resulting in sickle-shaped erythrocytes, which cause vascular occlusion and ischemia. Sickle cell anemia manifests in early childhood with symptoms associated with vascular occlusion and hemolytic anemia. Infarctions in the spleen, kidneys, bone, CNS, and other organs are common and cause progressive loss of organ function and acute and chronic pain in affected parts of the body. Acute, painful vaso-occlusive crises are provoked by conditions associated with reduced oxygen tension. Neonatal screening for sickle cell anemia has been implemented across the U.S., allowing the diagnosis to be made before the first manifestation of the disease. In older children and adults, hemoglobin quantification tests are used to diagnose the condition. The cornerstones of treatment involve the management of painful vaso-occlusive crises, hemolytic anemia, and disease complications as well as prevention of infection. Allogeneic bone marrow transplantation is the only curative treatment option.

Epidemiology

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

Genetics

Hemoglobin composition in sickle cell disease

Hemoglobin Normal Sickle cell trait Sickle cell disease
HbA 95–98% 60% 0%
HbS 0% 40% 75–95%
HbF < 2% < 2% 5–25%

Pathomechanism

References:[1][3][4][5]

Clinical features

Sickle cell trait

Sickle cell disease and other forms of sickle cell syndrome

References:[6][7][1][8][9][10]

Diagnostics

Diagnosis

Disease monitoring

References:[7][1][11]

Treatment

Longterm management

Prevent infections

Prevent vaso-occlusive crises and manage anemia

Management of acute sickle cell crisis

  • Prompt and adequate supportive treatment
    • Hydration
    • Pain management with nonsteroidal anti-inflammatory agents and opioids
    • Thromboembolic prophylaxis
    • Nasal oxygen
    • Bed rest
  • Blood transfusions
    • Indications
    • Goal: maintain hematocrit > 30% or arterial saturation > 90%)
    • Iron chelation treatment may be required to treat iron overload due to continued transfusion
  • Exchange transfusions (erythrocytapheresis): automated removal of erythrocytes containing HbS and simultaneous replacement with HbS free erythrocytes
    • Indication: acute vaso-occlusive crisis (stroke, acute chest syndrome, acute multiorgan failure)
    • Advantages
      • Rapid effect!
      • Allows precise control of HbS levels and iron accumulation
    • Disadvantages
      • Expensive and equipment not readily available
      • Requires experienced practitioner

Curative therapy

References:[7][1][12][13][14]

Complications

Organ damage

Recurrent vascular occlusion and disseminated infarctions lead to progressive organ damage and loss of function. In homozygotes, this progress is associated with high morbidity and mortality. In heterozygotes, organ damage is very rare.

Organ system Complications
Spleen
Kidney
Skeletal
CNS
Male genitals
Lungs
Heart
Eye

As a result of repeated infarction of the spleen in sickle cell patients, the spleen is often atrophied rather than enlarged!References:[15][16][1][8][10][17]

We list the most important complications. The selection is not exhaustive.

Sickle cell disease and malaria

  • Individuals with sickle cell trait are less likely to develop severe forms of malaria and have reduced parasite prevalence.
  • The exact mechanism of malaria resistance is unknown; presumably, the plasmodia responsible for malaria are unable to multiply sufficiently within the erythrocytes and some studies suggest increased sickling in infected RBCs.

References:[18]