Sickle Cell Disease (SCD)


Sickle cell disease (SCD) is an inherited blood disorder in which the red blood cells have a sickled, elongated shape and become stiff and sticky. Normal red blood cells are round and flexible, with a lifespan of up to 120 days in the body. Sickle cells are destroyed within 10 to 20 days, especially in the spleen, which filters inflexible or oddly shaped red cells from the blood.1,2 

The premature death of abnormal red blood cells causes chronic anemia, which impedes the efficient transportation of oxygen throughout the body. The ongoing destruction of sickle cells in the spleen may also damage the spleen, increasing the risk for infection. Additionally, the sickle cells block blood vessels, obstructing blood flow to the tissues. Vascular obstruction leads to episodes of pain and even stroke.1,2 

Risk Factors for Inheriting SCD

Genetically, the biggest risk factor for inheriting SCD is a family history of the disease. When each parent has 2 copies of the sickle cell gene, they both have sickle cell disease, and each of their children will have the disease. When each parent has one sickle cell gene (ie, sickle cell trait [SCT]) and one normal gene, each child has a 25% chance of having SCD, a 50% chance of having SCT and a 25% chance that each child will carry no mutant alleles and so will not be a carrier and will not have the condition. If only one parent has SCD, each child will inherit one sickle cell gene from that parent and will have SCT.2-4   

The prevalence of SCD is increased in individuals belonging to specific ethnic groups—persons of African, Middle Eastern, Indian, Mediterranean, Asian, or Hispanic-American (Central and South America) ancestry. It is estimated that 1 in 12 Americans of African descent carry at least one sickle cell gene.3 

Risk Factors for Sickling and Painful Crises

Multiple factors may increase the number of sickle cells in the body, causing a painful crisis. Factors that induce plasma hypertonicity or acidosis accelerate the sickling process. These include local tissue hypoxia, environmental exposure to heat or cold, fatigue, psychological stressors, and dehydration secondary to infection, viral illness, vomiting, or nausea.5

Risk Factors for Vaso-occlusive Crises

Exposure to cold results in vasospasm. Because it is difficult for elongated, stiff sickle cells to travel through constricted blood vessels, the likelihood of vessel obstruction is increased. Infection, dehydration, hypoxia, emotional stress, pregnancy, alcohol intoxication, and acidosis also precipitate blood vessel occlusion. Excessive exercise or exertion, when accompanied by dehydration, hypovolemia, and exposure to environmental heat, may also contribute to both sickling and vaso-occlusive crises.5

Individuals with SCD are at risk for the development of cognitive impairment, ischemic or hemorrhagic stroke, spinal cord injury (SCI), and vasculopathy, all of which can be diagnosed with transcranial Doppler ultrasonography. The factors that increase the risk for these problems in patients with SCD include severe acute and chronic anemia, acute chest syndrome, reticulocytosis, and low oxygen saturation. Regular blood transfusions may decrease, but not eliminate, the risk for neurological complications such as stroke and SCI in children with SCD.6 

Risk Factors for Aplastic Crises

Aplastic crisis in SCD is characterized by a rapid drop in the hemoglobin level accompanied by a paucity or absence of reticulocytes. A severe deficiency of reticulocytes indicates failure of the bone marrow to respond to an increased rate of red blood cell turnover.7 

Folic acid deficiency, parvovirus B19 infection, and the ingestion of bone marrow toxins such as phenylbutazone are all known risk factors for aplastic crises.5

Risk Factors for Acute Chest Syndrome

Individuals with SCD are more likely to experience acute chest syndrome if they have asthma, infection, fat embolism, or a history of pain episodes.5

Risk Factors for Osteonecrosis

Recurrent vaso-occlusive episodes and acute chest syndrome are risk factors for osteonecrosis, which in turn causes multifocal degenerative joint disease. Osteonecrosis affects approximately 30% of individuals with SCD.8 Additional risk factors for osteonecrosis, specifically of the femoral head, among individuals with SCD include older age, male gender, high body mass index, leukopenia, and hemoglobin SS disease with concomitant alpha-thalassemia trait.8

Risk Factors for Early Mortality in Sickle Cell Anemia

In individuals who are homozygous for sickle hemoglobin (HbSS), risk factors for early death include acute chest syndrome, renal failure, seizures, baseline white blood cell count above 15,000/mm3, and low level of fetal hemoglobin.9 

According to an investigative study, 18% of deaths due to SCD were the result of acute organ failure, primarily renal failure. Organ failure was not the cause of death in 33% of cases; these deaths occurred during an acute sickling crisis in which 78% of the individuals had pain, acute chest syndrome, or both; the other 22% had a fatal stroke.9

References

  1. What is sickle cell disease? Centers for Disease Control and Prevention. Accessed November 20, 2021.
  2. Sickle cell disease. Johns Hopkins Medicine. Accessed November 20, 2021.
  3. Sickle cell disease. American Society of Hematology. Accessed November 20, 2021.
  4. Sickle cell inheritance. Be the Spark. Accessed November 20, 2021.
  5. Maakaron JE. Sickle cell disease: practice essentials, background, genetics. Medscape. Updated November 2, 2021. Accessed November 20, 2021.
  6. Hirtz D, Kirkham FJ. Sickle cell disease and stroke. Pediatr Neurol. 2019;95:34-41. doi:10.1016/j.pediatrneurol.2019.02.018
  7. Aplastic crisis – an overview. ScienceDirect Topics. Accessed November 20, 2021. 
  8. Adesina OO, Neumayr LD. Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management. Hematology Am Soc Hematol Educ Program. 2019;2019(1):351-358. doi:10.1182/hematology.2019000038
  9. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330(23):1639-1644. doi:10.1056/NEJM199406093302303

Reviewed by Harshi Dhingra, MD, on 11/22/2021.

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