Loading...Sickle cell disease (SCD) is an inherited hemoglobinopathy with a mutation in the β-globin chain. Low oxygen tension results in sickling of the abnormal hemoglobin within the red blood cells, which presents as ischemia or hemolysis. As a chronic illness, patients depend on pain management. Disease management encompasses acute care, prevention, and screening for complications.
Table of Contents
Image: “Sickle Cell Anemia” Peripheral blood smear by Ed Uthman. License: CC BY 2.0
Epidemiology and Etiology
Epidemiology
- Most common in people of Sub-Saharan African, Mediterranean, and Middle Eastern heritage
- 1 in 500 inhabitants of Sub-Saharan Africa
- Equally present between males and females
Image: “Mode of Inheritance in Sickle Cell Disease” by the National Heart Lung and Blood Insitute (NIH). License: Public Domain
Etiology
- Autosomal recessive inheritance pattern
- Mutation in the β-globin gene
- HbS gene is a point mutation
- Chromosome 11, codon 6 – position 15.5 – adenine → thymine (GAG → GTG)
- Amino acid substitution at position 6; glutamic acid → valine
- Homozygous: two HbS genes → sickle cell disease (HbSS)
- Heterozygous: one HbS gene → sickle cell trait ( HbAS)
- Compound heterozygous: one HbS gene, one HbC gene (HbSC)
- HbC is a hemoglobinopathy where glutamic acid → lysine at the sixth position of the β-globin gene
Image: “Sickle Cell Disease. Point mutation” By Lecturio.
Video Gallery
Sickle Cell Anemia by Kevin Ahern, PhD
Sickle Cell Anemia: Etiology by Carlo Raj, MD
Pediatric Sickle Cell Disease by Brian Alverson, MD
Pathophysiology
- HbS is prone to polymerization with other hemoglobin molecules under conditions of low oxygen tension.
- Polymerization results in a rigid structure that distorts the membrane.
- Membrane damage results in calcium influx and efflux of potassium and water, which dehydrates the RBC giving it the characteristic sickle shape.
- Sickling is aggravated by:
- Infection
- Dehydration
- Hypoxia
- Fever
- Acidosis
- The fragile cell leads to hemolysis and vessel occlusion
- Hemoglobin released from hemolyzed cells readily binds to NO
- Depletion of NO results in vascular smooth muscle cell contraction and platelet aggregation
- There is a shortened half-life of the HbS containing RBCs to 12 days (average is 120 days)
- The sickle-shaped cell and shortened half-life renders immunity to malaria
Image: “Abnormal Hemoglobin results in Sickling” Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands. By The National Heart, Lung, and Blood Institute. License: Public Domain
Clinical manifestations
| Mechanism | Symptoms |
| Chronic hemolysis (intravascular/extravascular) |
|
| Vaso-occlusive crisis (infarction) | Fever plus any of the following:
|
| Acute pain crisis |
|
Video Gallery
Sickle Cell Anemia: Vaso-occlusive Crisis by Carlo Raj, MD
Diagnostics
- CBC
- ↓↓ Hb ( Hb <6)
- Normal MCV
- ↑↑ retic
- ↓ Hct
- ↓ ESR
- ↑ WBC
- ↑ bilirubin
- ↑ BUN, ↑ creatinine
- LFT -↑ AST/ALT
- Sickle Smear Prep: expose smear to sodium metabisulfite → low oxygen tension
- Best initial test
- Sickle cell
- Howell-Jolly bodies (patients with autosplenectomy)
- Cannot differentiate between HbAS and HbSS
- Hb electrophoresis
- Most accurate test
- No HbA
- HbS band (90%)
- HbA2 normal
- ↑↑ HbF (8%)
- In sickle cell trait: HbA is present, HbS is 45%
- Genetic screening
| Diagnostic tests useful in complications | ||
| Complication | Test | Findings |
| Acute chest syndrome | ECG | Myocardial infarction (STEMI/NSTEMI changes) |
| CXR | Pneumonia: consolidation | |
| Vaso-occlusive crisis | X-ray | Avascular necrosis (MRI most accurate) |
| Septic arthritis | Joint aspiration | Increased leukocyte
Salmonella-growth |
| Kidney | Urine-analysis | Hematuria
Proteinuria Casts |
| CNS | CT/MRI | Stroke (ischemic) |
| Cardiac | ECHO | Pulmonary hypertension
Systolic dysfunction |
Video Gallery
Sickle Cell Anemia: Hemoglobin Electrophoresis by Carlo Raj, MD
Treatment
- Genetic counseling
- HbAS: no treatment needed
- HbSS:
- Folic acid to compensate for high turn-over and folate deficiency
- Hydroxyurea:
- Enhances differentiation of stem cells to HbF
- Reduces polymerization
- Treating vaso-occlusive crisis
- Screening for complications
- Prevention of crisis: preventing infection, hypoxia, acidosis
| Management of HbSS | |
| Symptom | Management |
| Acute pain crisis |
|
| Acute splenic sequestration |
|
| Infections | Prevention:
|
| Priapism |
|
| Aplastic Anemia |
|
| Screening |
|
| Refractory | Hematopoietic stem cell transplant (HSCT) for:
|
Differential Diagnoses
- Hemolytic Anemia: encompasses anemia due to a shortened RBC half-life. Sickle cell disease is a form of hemolytic anemia. Other causes of hemolytic anemia must be considered as differential diagnoses.
- Thalassemia: An inherited deficiency in either the alpha (α) or beta (β) globin chain, resulting in hypochromic anemia. The presentation is mainly due to severe anemia, and the patient is transfusion dependent.
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