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Sickle cell disease (SCD) is an inherited disorder of hemoglobin, a protein present in red blood cells that helps carry oxygen efficiently to various parts of the body. In this article we will explore the causes, symptoms, diagnosis and treatments.
◉ What is sickle cell disease?
Sickle cell disease (SCD), also known as sickle cell anemia, is a genetic disorder characterized by abnormalities in hemoglobin. These abnormalities cause red blood cells to assume a crescent, sickle-like shape instead of the normal biconcave disk shape.
The abnormal shape of red blood cells makes them prone to easy breakage, clumping together, and blocking small blood vessels. This can lead to various complications such as vision problems, strokes, infertility, and episodes of extreme pain and inflammation.
SCD is a recessive hereditary disease; if you inherit a single gene, you are said to have the sickle cell trait. However, if you inherit two genes (one from each parent), you will have the disease.
There are treatments available to help individuals manage and live with sickle cell disease, preventing crises and infections, however, a stem cell transplant remains the only known cure.
◉ Causes et physiopathologie
Sickle cell disease is characterized by the presence of an abnormal hemoglobin called HbS, resulting from a mutation in the beta chain of the normal hemoglobin HbA, where glutamic acid at position 6 is replaced by valine.
- Sickle cell disease is the inheritance of 2 mutated genes (HbSS) and it is a severely aggressive form that reduces the life expectancy of the patient terribly.
- Sickle cell trait (SCT), however, is a milder form of the disease. It occurs in patients that inherit only a single gene, from one parent, while the other is healthy.
The disease can also occur when the individual inherits a hemoglobin S gene from one parent and another defective hemoglobin gene from the other parent. These defective genes may include:
- Hemoglobin SC disease (HbSC)
- Hemoglobin SD disease (HbSD)
- Hemoglobin SO-Arab (HbSO-Arab)
- Sickle beta thalassemia syndromes (HbS/βTh).
This deformity significantly decreases the main function of oxygen transfer successfully to different parts of the body, especially blood vessels with small diameters such as capillaries of the eyes, brain, and fingers as these red blood cells behave differently and start to adhere together forming clumps obstructing these blood vessels and causing ischemia.
◉ Symptoms and signs of sickle cell anemia
As mentioned earlier, sickle cell anemia is a disease that affects the function of red blood cells, leading to various symptoms. These symptoms typically manifest within the first six months of age. The presence of fetal hemoglobin (Hb F), which is produced at birth, masks the phenotypic expression of the disease during the initial months of life.
1. Vaso-occlusive crisis (painful crisis)
It's a severe pain affecting any organ system that occurs as a result of occlusion of blood vessels by sickle cells.
- Hand foot syndrome (sickle cell dactylitis)
- Severe abdominal pain.
- Pulmonary infarction and acute chest syndrome (ACS).
- Priapism (painful and irreducible prolonged erection)
2. Spleen sequestration and infarction
Splenic sequestration is manifested by acute spleen enlargement and abdominal pain, nausea, vomiting, lethargy, and irritability. These symptoms occur mostly in children between the ages of six months and three years.
It occurs due to the pooling of sickle cells in the spleen. If the patient develops recurrent episodes, it may progress to shock, and in such cases, splenectomy may be necessary to prevent further complications, including the risk of death.
3. Strokes
Sickled cells can obstruct blood flow to the brain, potentially leading to a stroke, particularly in the middle cerebral artery.
4. Hepatic sequestration
it's rapid liver enlargement with stretching of capsule causing pain in upper right quadrant of abdomen and jaundice.
5. Renal affection
Acute kidney injury, hematuria, urinary tract infection and pyelonephritis.
6. Aplastic crisis
Patient present with severe anemia, fatigue, shortness of breath, and may be syncope
7. Infections
patient with sickle cell anemia have high incidence to develop infection with streptococcus pneumoniae and hemophylus influenza.
8. Ocular manifestations
Blood vessels of eye may be occluded by sickle cells causing central retinal artery occlusion and orbital infractions.
9. Delayed growth and failure to thrive
Note: Individuals with the sickle cell trait typically do not exhibit symptoms, except under extreme conditions such as vigorous exercise, dehydration, and high altitudes.
◉ How is Sickle cell disease diagnosed?
In sickle cell anemia, the presentation of the disease varies from one case to another. Therefore, physicians must rely on a thorough clinical examination and investigation to reach the appropriate diagnosis.
Additionally, patients may undergo one or more of the following diagnostic tests, depending on their specific symptoms and conditions:
- Complete Blood Count (CBC): show low red blood cells count (RBCs), low hemoglobin(Hb), low hematocrit (Ht), normal mean corpuscular volume (MCV) as it's hemolytic anemia and high RDW.
- High reticulocyte count (reticulocytosis) due to hemolysis which causes bone marrow activation but in case of aplastic crisis reticulocytes will be low.
- Blood Film: show sickle cells (seen only in sickle cell anemia not in sickle cell trait) also we can find nucleated red blood cells, target cells and howell-jolly bodies which indicate hyposplenism.
- Increased indirect serum bilirubin, increased urobilinogen in urine and stool.
- The erythrocyte sedimentation rate (ESR) is typically low because red blood cells take a longer time to precipitate. However, it may increase during painful crises.
- Gel electrophoresis: this is the definitive method for diagnosis it will show Hemoglobin F (Hb F).
- Sickle cell screen test: this test done by adding sodium metabisulfite on blood sample. If patient has sickle cell anemia the oxygen tension will decrease causing blood cells to sickle due to presence of hemoglobin S.
◉ Treatment of sickle cell anemia
Sickle cell anemia is a disease that will continue with patient through his life so we should know that there's no definitive treatment for this disease and management of it aims to control and avoid pain crisis and preventing complications of it.
- Pain relievers: patient can administer NSAIDs for mild to moderate pain also Opioids is a good choice for patient with persistent severe pain.
- Treatment of sequestration crisis: Need rapid administration of intravenous fluids, pain control and simple or exchange blood transfusion. In patient with recurrent episodes of splenic sequestration or life threatening splenic crisis they should undergo splenectomy.
- Hydroxyurea: reduce the frequency of painful episodes. It helps RBCs to stay rounder and more flexible.
- Voxelotor: works by preventing red blood cells from becoming C-shaped and from breaking down too quickly.
- Blood transfusion: it increases oxygen carrying capacity of blood so decrease crisis of disease.
- Chelation therapy: if patient is transfusion dependent he need to take iron chelators to avoid iron overload chelator agent which can be taken is Desferasirox, Deferoxamine injection and Deferiprone.
- Bone marrow transplantation, the only cure for sickle cell disease.
- Vaccination: against H.influenza, pneumococci and meningeococci.
◉ Conclusion
In conclusion sickle cell anemia is a genetic disease that characterized by abnormal sickle cell accumulation in blood vessels that affect many organs as spleen, liver, kidney, brain, and hand and feet.
It is caused by A mutation in the hemoglobin gene replaces the amino acids valine and glutamate in the beta globin chain, leading to sickling of red blood cells.
Diagnosis of sickle cell anemia can be done prenatal or postnatal depending on family history and after birth depending on signs and symptoms that appear on patient.