By Diana grib - Own work, CC BY-SA 4.0, Wikimedia
OVERVIEW OF SICKLE CELL DISEASE
The red blood cells in the body contain the molecules called haemoglobin which help to transport oxygen to the tissues. The normal hemoglobin in an adult is hemoglobin A and for the fetus, there is a fetal hemoglobin called hemoglobin F.
However, there are abnormal hemoglobin which includes Haemoglobin S, hemoglobin C, hemoglobin O Arab, hemoglobin D Punjab, etc. Of all these, the commonest abnormal hemoglobin in our environment is hemoglobin S which is characterized by the sickling phenomenon.
According to the American Society of Haematology;
Approximately 70,000 to 100,000 Americans have sickle cell disease, the most common form of an inherited blood disorder.
When a child inherits Hb A from both parents, the child's genotype is said to be AA, when he inherits Hb A from one parent and Hb S from another parent, the genotype is AS. Those with AS have the sickling trait in their blood but they do not have the sickle cell disease. It is only when the child inherits the Hb S from both parents that the child is said to have sickle cell disease and the genotype is SS which is referred to as sickle cell anemia.
So, sickle cell disease occurs when an individual inherits 2 abnormal hemoglobins of which one must be the hemoglobin S. At the molecular level, Hb S results when there is a point mutation during hemoglobin synthesis. This mutation causes the substitution of the water-soluble amino acid (glutamic acid) of Hb A with a fat-soluble amino acid (valine) at the position 6. This results in the formation of Hb S.
By The National Heart, Lung, and Blood Institute (NHLBI), Public Domain, Wikimedia
Due to the presence of valine in the Hb S amino acid chain which is not water-soluble, the Hb S becomes insoluble in the plasma and crystallizes out to form a sickle-shaped red blood cell.
These sickle-shaped red blood cells are rigid and cannot meander through the capillaries as normal red blood cells do. In addition to that, they also have a lesser life span as they are easily broken down. These form the basic pathophysiologies of sickle cell crises.
SICKLE CELL CRISES
There are broadly two types of sickle cell crises which are the Vaso Occlusive Crises and the Acute Anaemic Crises. Understanding the pathophysiology of sickle cell described above helps us to understand how these crises occur and how to prevent them.
VASO OCCLUSIVE CRISES (VOC)
Normal red blood cells are flexible and can change their shape to pass through the capillaries and narrow spaces within the circulation.
In Vaso Occlusive Crises, the rigid sickle red blood cells find it difficult to pass through the narrow spaces. This makes them to block and occlude those spaces which compromise the blood flow. This shortage of blood flow to the affected tissues causes pain due to ischemia. This pain especially in the limbs, chest, abdomen, and back is the hallmark of the presentation of vaso occlusive crises.
The patients come in complaining of pain in their hands, legs, chest, stomach, etc. The pain can be very severe to make the patient very restless. There may also be associated fever.
For these patients, our first line of treatment is usually to hyperhydrate the patient orally or intravenously depending on the severity, then give drugs to stop the pain and treat underlying causes, most times, infections.
By Kep17 - Own work, CC BY-SA 4.0, Wikimedia
ACUTE ANAEMIC CRISES
The second pathophysiology of sickle cell crises I described above is the fact that these sickle red blood cells are easily broken down and they don't stay up to the normal life span of normal red blood cells (about 120 days).
This breakdown of red blood cells leads to low levels of hemoglobin in the body, but some of them live well with this according to their steady stay.
However, at some points, the breakdown of red blood cells becomes too rapid that the hemoglobin level goes so low as to throw the patient into an anaemic crisis. The patient presents with pallor, weakness, low blood level, enlarged spleen, etc.
There are subdivisions of acute anaemic crises. These include;
Hyper hemolytic crises where there is a rapid breakdown of the red blood cells leading to severe anemia. An aplastic crisis where there is a failure of the bone marrow to synthesize enough red blood cells. Sequestration crises where the spleen traps a large quantity of blood that there is very little left in circulation. Megaloblastic crises due to folate deficiency and also iron deficiency crises.
All these forms of crises lead to severe anemia and most times, the patient will need an urgent blood transfusion to survive it.
PRECIPITANTS OF SICKLE CELL CRISES
Many persons with sickle cell live without any crises. However, some factors are known to precipitate crises in these individuals. These factors include Infections, Dehydration, Fever, exposure to too much cold or too much heat, and emotional stress.
MAINTAINING A STEADY STATE
A steady state is a state of no crises in individuals living with sickle cell disease. Many have been able to achieve this steady state and live well without any complications. However, some others go off their steady-state and run into crises. So, a vital aspect of living with sickle cell disease is learning how to maintain this steady state.
To maintain a steady state, we must identify the factors that precipitate crises and avoid them.
The chief among these factors is infection. This is because the attachment of those sickle red blood cells to the endothelium causes inflammation which mobilizes the white blood cells to release cytokines and reactive oxygen species which causes further damage. Therefore, a stage of elevated white blood cells in the body during infections is very harmful.
So, children with sickle cell anemia should receive adequate prophylaxis against infections like penicillin prophylaxis, antimalarial, adequate immunization, and vaccination against pneumococcal organisms. There should also be adequate hygiene, a clean environment, and safe drinking water to prevent infections. Other illnesses which come up should be immediately diagnosed and promptly treated.
Adequate hydration: Dehydration is also a major precipitant of crises. Therefore, they must stay well hydrated at all times by taking enough water and avoiding water loss. They must also protect themselves from harsh weather conditions like extreme cold or heat. Folate supplementation also helps to prevent folate deficiency.
By Iid Muiz - Own work, CC BY-SA 4.0, Wikimedia
There is also a great need for adequate counseling and health education. The patient and patient relatives as well as the caregivers must be well informed of the disease, the causes, the pattern of inheritance, the complications, and how to avoid them. The available treatment options like stem cell transplant, gene therapy, etc should also be discussed with them and allow them to make an informed decision.
Early diagnosis is very important. The diagnosis of sickle cell disease can even be made prenatally within the first trimester of the pregnancy. The earlier the diagnosis, the better. A proper follow-up will help to detect any problem early and address it immediately. Those who are followed up early tend to do better.
Finally, the ultimate prevention of sickle cell disease lies in the ability of couples to know their genotype and make the right decision. According to the Mendelian pattern of inheritance, a marriage between two individuals with sickle cell traits stands a 50% probability of giving birth to offspring with the Sickle cell trait and a 25% probability of giving birth to offspring with the sickle cell disease.
So, couples should be adequately counseled before marriage. Individuals with AS should not marry another individual with AS. This is the only surest way to a sickle cell-free future.
Last year, I met a guy who had an unplanned pregnancy with his girlfriend. They never knew their genotype. After the delivery of the baby, they discovered that the baby was SS. They did the genotype of the guy and the lady and both were AS. I felt sad for the ordeals the innocent child will pass through due to the mistake of the parents.
So, to avoid things like this, every partner in an intimate relationship should at least know their genotype. So that in case of any unplanned occurrence, an innocent child won't be made to suffer.
This awareness must continue in rural villages where people start producing children without the necessary laboratory tests to check for compatibility. The problems of sickle cell disease are enormous and no child should be made to pass through it.
Thanks for reading.
For references and further reading, please check the resources below.