4. Congenital haemolytic anemias – sickle cell disease and thalassemia

Sickle cell disease

Definition

• Sickle cell anemia is an inherited disorder of the globin chains that causes hemolysis and chronic organ damage!
• Homozygous sickle cell anaemia (Hb SS) is the most common severe syndrome while the doubly heterozygote conditions of Hb S/C and Hb S/βthal also cause sickling disease

Etiology

• Sickle cell mutation occurs when negatively charged glutamine is replaced by a neutral valine at the sixth position of the beta-globin chain.
• Inherited in an autosomal codominant fashion
• Leads to faulty hemoglobin protein, called hemoglobin S
• Changes flexible red blood cells into rigid, sickle-shaped cells. These sickle cells can block blood flow, and result in pain and organ damage

Factors that can cause sickling

• Low affinity of HbS to oxygen
• Physiologically high 2,3-diphosphoglycerate
• Increased sphingokinase-1 activity
• Increased expression of xanthine dehydrogenase, xanthine oxidase
• Decreased expression of NADPH oxidase

Pathophysiology

• Sickle cell anemia is characterized by two major components: Hemolysis and vaso-occlusive crises (VOC)
• HbS molecule can convert into rigid, elongated polymers when in deoxygenated state
• As a result, these abnormal shaped cells can block vessels causing vaso-occlusive crisis!

Symptoms

• Symptoms of anaemia are often mild

Vaso-occlusive subphenotype

• Higher HCT
• Sporadic and unpredictable
• Infarcts cause severe pain in the bones (hips, shoulders and vertebrae)
• Splenic sequestration

Aplastic crises

• Due to infection with parvovirus or from deficiency of folate
• Sudden fall in Hb
• Rise in reticulocytes

Diagnosis

• Lab workup:
• Hb- lowered
• Sickle cells and target cells seen in the peripheral blood
• Positive screening test (when blood is deoxygenated)
• Hb electrophoresis

Treatment

• Prophylactic – avoid those factors known to precipitate crises
• Dehydration, anoxia, infections, stasis of the circulation and cooling of the skin surface.
• Daily folic acid
• Good general nutrition and hygiene
• Pneumococcal, Haemophilus and meningococcal vaccination
• Stem cell transplantation
• Hydroxycarbamide
• Transfusions
• In case of crises- treat by rest, warmth, rehydration by oral fluids or IV saline (3L/24hr)
• Analgesia should be given (paracetamol, NSAIDs, opiates)
• Blood transfusion in cases of severe anemia