Understanding the Pathophysiology of Sickle Cell Anemia in Nigeria

Sickle cell anemia or Sickle Cell Disease (SCD) is a blood disorder that is passed on from parents which leads to the abnormal haemoglobin molecules making the red blood cells rigid, sticky and sickle-shaped. Sickle cell disease (SCD) is one of the highest burden diseases in Nigeria, hence the importance of understanding pathophysiology of the disease for patients, families and healthcare professionals.

Pathophysiology of Sickle Cell Anemia

The pathophysiology of sickle cell anemia:

Mutation of gene

• Restriction site mutation, 11 β -globin gene.

• A glutamic acid residue in the 6 position of the 8 globin protein has been substituted by a valine residue.

• They don’t make “normal, adult” hemoglobin.

Hemoglobin Polymerization 

• Upon oxygen unloading, a long and rigid rod comprising many HbS molecules forms.

• This makes red blood cells to be bent or to have a sickle-shape.

Red Blood Cell Sickling

Sickled RBCs are:

• Hard and less flexible

• Susceptible to hemolysis (breaking up prematurely)

• Have a shorter life span (~10–20 days compared to 120 days for healthy RBCs)

Vaso-occlusion

Sickled cells:

• Become trapped in small capillaries

• Cause blockages in blood vessels

• Cause tissue ischemia, pain and organ damage

Hemolysis and Anemia 

Progressive destruction of sickle cells results in:

• Hemolytic anemia levels

• Hyperbilirubinemia 

• Gallstones 

Inflammation 

Blocked blood flow and cell damage cause:

• Inflammatory chemicals

• Endothelial activation and damage

• More adhesion of leukocytes and sickled cells to blood vessel walls

Complications of Sickle Cell Disease

Include:

• Pain Crises

• Severe Anemia

• Increased Risk of Infections

• Acute Chest Syndrome

• Stroke

• Organ Damage

• Delayed Growth and Puberty

• Vision Problems

• Leg Ulcers

• Gallstones

• Priapism in Men

• Pregnancy Complications

• Mental and Emotional Challenges

Treatments for Sickle Cell Disease

Medications

Hydroxyurea:

• The mechanism of pain diminishing is increasing fetal hemoglobin induced by hydroxyurea.   

Blood Transfusions

•  Patients with high risk receive are given regular blood transfusions to avoid risk of stroke, severe anemia and organ damage.

Pain Management

• Treatment for pain involves fluids, oxygen, medications, and support.

Infection Prevention

Patients often receive:

• Vaccinations

• Antibiotics

• Nutritional support

• Folic acid supplements

Gene Therapy

A new therapy is currently being developed in which a normal gene is introduced into a person's cells to replace the faulty one that is the cause of sickle cell disease. 

Bone Marrow Transplant

Bone Marrow Transplant is the most effective and successful cure for sickle cell disease.

In this procedure:

• The diseased marrow is destroyed and replaced with healthy stem cells.

• Healthy donor cells produce normal red blood cells.

• With time, the patient may be able to avoid sickle cell crises and many disease complications.

Generally, the highest results are achieved in:

• Children and youth

• A matched sibling donor 

• Patients with not so severe organ damage.

Recent studies, and clinical reports, show that today's transplants methods have greatly enhanced survival and cure rates.

Conclusion

The understanding of the pathophysiology of sickle cell anemia in Nigeria explains the fact that the disease may involve more than just the red blood cells and may give rise to complications other than anemia. The mutation that is present in the underlying gene causes the production of HbS, which has a tendency to polymerise when it is deoxygenated. This results in red-cell sickle, vaso-occlusion, chronic haemolysis, inflammation and subsequent organ damage. Comprehensive follow-up and preventive care, coupled with timely diagnosis and disease-modifying treatments, are crucial. Advanced and complicated disease may require specialist haematologist input for Nigerian patients in order to determine the best course of action to be taken.