Pathology
Haematology
Question 109 of 180
Regarding sickle cell disease, which of the following statements is CORRECT:
Answer:
Hand-foot syndrome in children caused by infarction of metaphyses of small bones is frequently the first presentation of the disease. The condition is inherited as an autosomal recessive trait. The spleen has usually infarcted by adulthood. Aplastic crisis usual follows infection with B19 parvovirus. Splenic sequestration results in thrombocytopaenia.Sickle Cell Disease
Pathology / Haematology / Anaemia
Last Updated: 24th April 2019
Sickle cell disease is a group of haemoglobin disorders resulting from the inheritance of the sickle β-globin gene. Homozygous sickle cell anaemia (Hb SS) is the most common severe syndrome. The carrier state is widespread, found in up to 30% of West African people, maintained at this level due to the protection against falciparum malaria that is afforded by the carrier state. The mutant gene also occurs in other parts of the world where malaria is present e.g. the Middle East, Far East and Indian subcontinent.
Pathophysiology
- Point mutation in the β-globin gene results in substitution of valine for glutamic acid in the sixth position of the β-globin chain, Hb S is formed
- Hb S is insoluble in its deoxygenated state; the insoluble chains crystallise in red cells causing sickling and vascular occlusion
Clinical Features
Features of sickle cell disease include:
- Anaemia (symptoms are usually mild because the O2 dissociation curve of Hb S is shifted to the right)
- Vaso-occlusive crisis
- Sickling causes blockage of small vessels
- Common precipitants are infection, dehydration, acidosis and deoxygenation
- Abdominal pain is caused by infarction affecting abdominal organs
- Bone pain may occur in the back, pelvis, ribs and long bones
- Infarction may affect the central nervous system, lungs, spleen or kidneys
- Hand-foot syndrome in children caused by infarction of metaphyses of small bones is frequently the first presentation of the disease
- Acute sickle chest syndrome is the most common cause of death in adults and children (dyspnoea, falling arterial PO2, chest pain, pulmonary infiltrates on CXR)
- Visceral sequestration crisis
- Sickling with pooling of red cells in the liver, spleen or lungs
- Aplastic crisis
- Usually following infection with B19 parvovirus
- Temporary arrest of erythropoiesis, rapidly causing severe anaemia requiring transfusion
- Increased susceptibility to infection
- Splenic function is reduced because infarction leads to hyposplenism
- Pneumococcal infections may lead to pneumonia and meningitis
- Infarction of intestinal mucosa predisposes to Salmonella infection and osteomyelitis
- Other clinical features:
- Pigment gallstones with cholecystitis
- Chronic leg ulcers
- Avascular necrosis of the femoral and humeral heads or other bones
- Cardiomyopathy
- Pulmonary hypertension
- Proliferative retinopathy
- Priapism
- Renal papillary necrosis
- Stroke
Laboratory Findings
- The haemoglobin is usually 60 - 90 g/L
- Sickle cells and target cells occur in the blood
- Features of splenic atrophy may be present (e.g. Howell-Jolly bodies)
- Screening tests for sickling are positive when the blood is deoxygenated
- Haemoglobin electrophoresis demonstrates abnormal Hb
Management
- Prophylactic - avoid factors known to precipitate crises
- Folic acid
- Good general nutrition and hygiene
- Pneumococcal, Haemophilus and meningococcal vaccination and regular oral penicillin
- Crises - treat with rest, warmth, rehydration, analgesia and antibiotics as required; transfusion with blood products if symptomatic; exchange transfusion may be needed particularly if there is neurological damage, a visceral sequestration crisis or repeated painful crises
- Special care taken in pregnancy or with anaesthesia
- Transfusions - sometimes given repeatedly as prophylaxis to patients having frequent crises or who have had major organ damage
- Hydroxycarbamide - can increase Hb F levels and improve the clinical course of children or adults
- Stem cell transplantation - can cure the disease, with 80% disease free
- New potential drugs to enhance Hb F synthesis or to increase the solubility of Hb S
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
