Sickle Cell Disease: Classification, Pathogenesis, Clinical Features, Complications, Diagnosis, Prevention by Nurses Note

  Sickle Cell Disease

This is haemolytic anaemia resulting from the homozygous inheritance of a gene which causes an amino acid substitution in the haemoglobin molecule (beta-6 glutamate → valine) creating HbS due to point mutation.

It is common in black Africans and their worldwide descendants.

Classification of Sickle Cell Disease

1. Homozygote (SS)—sickle cell anaemia. 

2. Heterozygote (AS)—sickle cell trait (protects from falciparum malaria).

Symptomatic sickling occurs in homozygotes. Heterozygotes are asymptomatic and present with mild anaemia except in situations of hypoxia, anaesthesia when veno-occulsive events occur.

Factors Increasing Sickling

1. Low oxygen tension

2. Low pH

3. Increased 2, 3 diphosphoglycerate (2, 3 DPG)

4. Decreased RBC water content (increased serum osmolality)

5. Fever

6. Sluggish blood flow. 

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Pathogenesis of Sickle Cell Disease

In the deoxygenated state, the HbS molecules polymerize and causes sickling of RBCs. Sickle cells are rigid, and haemolyse, and block small vessels to cause infarction. Deoxygenated Hb align in parallel forming tactoids that distort the RBC into the classic sickle and oak leaf-shaped cells.

Clinical Features of Sickle Cell Disease

Anaemia (Hb 6-8 gm/dl), reticulocytosis (10-20%), jaundice, painful swelling of hands and feet, and splenomegaly in the early stages (later autosplenectomy occurs) can occur. Chronic ill-health, renal failure, bone necrosis, infections, leg ulcers can result.

Complications of Sickle Cell Disease

1. Thrombotic crisis/infarction crisis: Thrombosis occurs due to exposure to cold, dehydration, infection, ischaemia, fever, pregnancy, psychic stress, surgery, causing severe pain in the bones and other organs. It may simulate acute abdomen or pneumonia. Convulsions, focal neurological signs, priapism, hand foot syndrome (sickle dactylitis) proliferative retinopathy, leg and ankle ulcers, may also occur. Salmonella infection is common.

2. Aplastic crisis: This is usually due to parvovirus infection and is characterised by a low reticulocyte count.

3. Sequestration crisis: Due to RBC trapping, the spleen and liver enlarge. Anaemia becomes very severe which can be an acute manifestation and cause death in infants. Later, repeated infarction and fibrosis of spleen leads to ‘autosplenectomy’. Functional asplenia occurs much earlier (early childhood).

4. Haemolytic crisis: Rare.

5. Acute chest syndrome: Symptoms of chest pain, fever and cough with tachypnoea and arterial oxygen desaturation mimics pneumonia, pulmonary embolism or infarction. It is due to in situ sticking with the lung producing pain and dysfunction. Repeated episodes denote decreased survival.

Investigations of Sickle Cell Disease

1. Peripheral smear: Shows Howell-Jolly bodies due to autosplenectomy, target cells, nucleated RBCs, RBC fragments, occasional thrombocytosis and leukocytosis.

2. Hb electrophoresis at alkaline pH: HbS can be detected by starch or agargel electrophoresis.

3. “Sickle Prep” test: This is performed by depriving RBCs of oxygen using metabisulfite or dithionite compounds as reducing agents and placing a coverslip over a drop of blood on a glass side. The RBCs sickle in situ.

Sickling is less in the presence of other haemoglobins like HbA2, HbF.

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Prevention of Sickle Cell Disease

Antenatal tests are helpful for the diagnosis in the first and second trimester of pregnancy by using recombinant DNA technology. Amniocentesis, chorionic villous biopsy can be done as early as 7-10 weeks.

Management of Sickle Cell Disease

1. Infarction crisis: Analgesia (sustained release morphine) IV fluids (100-200 ml/hr)

2. Blood transfusion: If PCV or reticulocytes fall sharply, in CNS or lung complications or when Hb level is < 6 gm/dL, blood transfusion can be given. If Hb level is > 9 gm/dL give a partial exchange transfusion.

3. Treatment of infection by antibiotics.

4. Oxygen through nasal prongs at a rate of 3-4 litres/ minute to promote oxygenation at the pulmonary and arterial levels.

5. Treat complications

a. CNS complications—exchange transfusion

b. Acute splenic sequestration-exchange transfusion/splenectomy

c. Retinal lesions—exchange transfusion + long term ophthalmic follow-up laser/surgery

d. Priapism—if it fails to resolve in 24 hours, exchange transfusion is given

e. Aplastic crisis—RBC transfusion to maintain haematocrit in the range of 18-20%. It usually resolves in 7-10 days.

6. Antisickling agents

a. Hydroxyurea increases HbF to 14-15%

b. Butyrate compounds increases HbF by increasing number of erythroblasts expressing gamma-globin.

c. Decibitane can elevate HbF.

7. Folic acid 1 mg orally, daily.

8. Pneumovax in functional asplenia.

9. Bone marrow transplantation is under evaluation.

10. Monitor PCV, reticulocyte count, liver and spleen size.

11. Gene therapy is under investigation.

 Splenomegaly is rare in sickle cell disease after the age of 5 years. If splenomegaly is present after 5 years, think of concomitant thalassaemia.