What is sickle cell anemia / sickle cell disease?
Sickle cell anemia and sickle cell disease are recessive genetic disorders, in which the hemoglobin (the oxygen-transporting pigment in red blood cells) is abnormal. A person who is carrying one copy of this gene (heterozygous is) usually shows itself few signs or symptoms. However, if someone is homozygous for the gene (ie copies of received the defective gene from both parents) then this will usually be associated with symptoms of sickle cell disease.
Types and Terminology
"Sickle cell anemia" is the name of a specific form of sickle cell disease in which there is a homozygosity for the mutation that causes HbS. Sickle cell anemia is also called "HbSS", "sickle disease," or "hemoglobin S" (and all permutations thereof) mentioned.
These other forms of sickle cell disease are compound heterozygous States in which the person has, only one copy of the mutation that causes HbS and one copy of another abnormal haemoglobin allele.
The term "disease" is applied here because the abnormality causes a pathological image and to death and serious complications. Not all inherited variants of hemoglobin are harmful; a concept known as genetic polymorphism.
Mechanism
A sickle cell is an abnormally shaped red blood cell (erythrocyte), which is caused by a point mutation from glutamic acid to valine on the β-chain of the hemoglobin molecule. Normal hemoglobin contains four polypeptide chains, two of which α-polypeptide chains and two β-polypeptide chains. β-polypeptide chains each containing 146 amino acid residues of which sickle cell anemia, one at position 6 is replaced by valine. This results in place of the normal hemoglobin A (Adult), a form which is called hemoglobin S. This hemoglobin S spontaneously forms polymers that are insoluble as the oxygen pressure falls too far. This is the case in small capillaries (capillaries), where the oxygen concentration within (and outside) the red blood cell is low. On the spots where the hemoglobin are oxygen back off State, it crystallizes. This one can mimic using a sicklecelltest. While normally Hb that wouldn't do. As a result of this disorder get the red blood cells in which the polymerized HbS present a sickle-like shape and they are also much less smoothly. This causes the blood cells degrade faster or they sometimes spontaneously clump together or get stuck in small capillaries (capillaries), making blood circulation disorders, ischemia and eventually possibly necrosis of organs and tissues can arise (sickle cell crisis).
Symptoms of sickle cell anemia / sickle cell disease
Characteristic of the disease is chronic microcytic hemolytic anemia (anemia), episodes of painful botcrisen and the involvement of multiple organs. Sickle cell disease is also associated with an increased coagulation activation status. In addition, patients suffering from the disease, the tendency to the increase of infections, and they know a variety of other complications.
Carriers of the disease
The disease occurs mainly in ethnic groups from countries where malaria is prevalent. This means that the disease is more prevalent in black people or the descendants of black people, especially of West African origin, but also more common in people of Mediterranean origin, people from the Middle East and of Indian origin. The ones with the heterozygous mutation evolutionary seen a greater survival rate in malarious areas. This is because the malaria parasite, which is in a particular phase in red blood cells multiply, in blood cells with hemoglobin S can maintain less easily. There is therefore some time ago an investigation started by a couple of Dutch students who the defenses of Sickle cells against malaria parasites have recorded and analysed. It turned out to be a reaction of the malaria parasite on the solubility of the sickle cell disease-hemoglobin S. And so it is also difficult for the parasite to take as the hemoglobin to nutrient. According to research from 2011 Sickle cells are protected against malaria because the parasite has the more difficult in these cells actin of the cell to use for its own life cycle.
Under normal circumstances, comes the real sickle cell disease only in people who have inherited the abnormal gene from both parents. This is called homozygous form of the disease. In America, this for at the 1 on the 400 African-Americans. About 8% of African Americans is heterozygous for the disease, that is, they have received the foreign gene from only one parent. They are (usually) symptomless carriers of the disease, but can get symptoms if they also suffer from other serious illnesses.
Treatment of sickle cell disease and crisis
There is no cure for the disease, although some gene therapy as a potential cure manner is called in the future. Modern developments have made it possible that the average life (in the West) has increased to 46 years.
The anemia is treated with folic acid. Often, the disease can also be treated by taking Hydrea (hydroxyurea ie hydroxycarbamide), in order to promote production of non sikkelend hemoglobin and to reduce the risk of crises.
Sickle cell crises can be treated with:
- intravenous fluid administration
- heat
- pain management
- oxygen
- possibly antibiotics in (suspicion of) infections
- possibly blood transfusions at extremely low hemoglobin levels; often these people have already had more blood transfusions, however, leaving many antibodies against several blood antigens are made. This makes it difficult to find a good donor. There is also in frequent transfusions risk of iron overload.
- in severe, recurrent complaints can be considered a erythrocyte apheresis. The gesikkelde red blood cells are largely replaced by donor red cells, which also reduced the risk of iron overload is. The erythrocyte Apheresis can with a certain interval (weeks to months) are repeated.