Sickle Cell Anemia

What is Sickle Cell Anemia?

Sickle cell Anemia is a blood disorder that affects hemoglobin, protein that found in red blood cell that helps carry oxygen throughout the body. It characterized by red blood cell that assume an abnormal, rigid, sickle shape. Sickling decreases the cells’ flexibility and results in their restricted movement through blood vessels, depriving downstream tissues of oxygen. The disease is chronic and lifelong: individuals are most often well, but their lives are punctuated by periodic painful attacks and a risk of various other complications. Life expectancy is shortened, with older studies reporting an average life expectancy of 42 and 48 years for males and females, respectively.

Genetic Abnormality of Sickle Cell Anemia

The allele responsible for sickle-cell anemia is autosomal recessive and can be found on the short arm of chromosome 11. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the disease and a 1-in-2 chance of their child just being a carrier.

This disease will not affect by either X gene or Y gene because it can be found on the short arm of chromosome 11.

The symptoms

1. Vaso-occlusive crisis

The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischemia, pain, and organ damage. The frequency, severity, and duration of these crises vary considerably.

2. Aplastic crises

Aplastic crises are acute worsening of the patient’s baseline anemia producing pallor, tachycardia, and fatigue. This crisis is triggered by parvovirus B19, which directly affects erythropoiesis (production of red blood cells). Parvovirus infection nearly completely prevents red blood cell production for 2-3 days. In normal individuals this is of little consequence but the shortened red cell life of sickle-cell patient’s results in an abrupt, life-threatening situation. Reticulocyte counts drop dramatically during the disease and the rapid turnover of red cells leads to the drop in hemoglobin. Most patients can be managed supportively; some need blood transfusion.

3. Splenic sequestration crises

Splenic sequestration crises are acute, painful enlargements of the spleen. The abdomen becomes bloated and very hard. Management is supportive, sometimes with blood transfusion.

4. Hemolytic crises

Hemolytic crises are acute accelerated drop in hemoglobin level. The red blood cells break down at a faster rate. This is particularly common in patients with co-existent G6PD deficiency. Management is supportive, sometimes with blood transfusion.

Complications

1. Stroke can result from a progressive vascular narrowing of blood vessels, preventing oxygen from reaching the brain. 2. Decreased immune reactions due to hyposplenism (malfunctioning of the spleen). 3. Priapism and infarction of the penis. 4. During pregnancy, intrauterine growth retardation, spontaneous abortion and pre-eclampsia are the possibilities. 6. Chronic pain: even in the absence of acute vaso-occlusive pain, many patients have chronic pain that is not reported^{. 7.} Pulmonary hypertension (increased pressure on the pulmonary artery), leading to strain on the right ventricle and a risk of heart failure; typical symptoms are shortness of breath, decreased exercise tolerance and episodes of syncope.

Treatments

1. Painful (vaso-occlusive) crises

Most people with sickle-cell disease have intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises, however, vary tremendously. Painful crises are treated symptomatically with analgesics; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manages on NSAIDs (such as diclofenac or naproxen). For more severe crises most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. Diphenhydramine is also an effective agent that is frequently prescribed by doctors in order to help control any itching associated with the use of opioids.

2. Folic acid and penicillin

Children born with sickle cell disease will undergo close observation by the pediatrician and will require management by a hematologist to assure they remain healthy. These patients will take folic acid 1mg daily for life. From the age of birth to 5 years of age they will also have to take penicillin daily, due to the immature immune system which makes them more prone to early childhood illnesses.

3. Acute chest crises

Management is similar to vaso-occlusive crises with the addition of antibiotics (usually a quinolone or macrolide, since wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome), oxygen supplementation for hypoxia, and close observation. Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple blood transfusion or exchange transfusion is indicated. The latter involves the exchange of a significant portion of the patient’s red cell mass for normal red cells, which decreases the percent hemoglobin S in the patient’s blood. Blood transfusion not a routine and automatic occurrence in these cases due to iron overload (hemosiderosis)

4. Hydroxyurea

The first approved drug for the causative treatment of sickle-cell anemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al) and shown to possibly increase survival time in a study in 2003 (Steinberg et al). This is achieved, in part, by reactivating fetal hemoglobin production in place of the hemoglobin S that causes sickle-cell anemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but this risk has been shown to be either absent or very small and it is likely that the benefits outweigh the risks.

5. Bone marrow transplants

Bone marrow transplants have proven to be effective in children

Sickle cell and malaria

Malaria is a disease caused by protozoan parasites, normally affected people of region in sub-Saharan Africa. People with sickle cell trait would survive from dying from anemia and malaria as well. This is because, in sickle cell trait, the alleles Hbs defend the body by sacrificing itself upon in contact with parasitic protozoa. Parasites reduce the oxygen tension within the erythrocytes to very low levels. The deformation of sickle cell as abnormal and target them for destruction by phagocytes. In the end, the normal blood cell would remain as it is for destruction by phagocytes. In the end, the normal blood cell would remain as it is.