Sickle Cell Anaemia

Sickle Cell Anaemia

1. Definition
   Sickle Cell Anaemia is an inherited disorder in which a mutation of the β‑globin gene produces abnormal haemoglobin S; red cells assume a sickle shape, leading to chronic anaemia and episodic vaso‑occlusion. It is a major health problem in many tropical and subtropical populations.

2. Synonyms
   ‑ Sickle Cell Disease – the term used for the whole group of disorders that contain Hb S.
   ‑ Sickle Cell Disorder – another name often seen in clinical reports.

3. Causes / Etiology
   ‑ Point mutation (GAG → GTG) at codon 6 of the HBB gene replaces glutamic acid with valine, producing haemoglobin S.
   ‑ When two Hb S genes are inherited (homozygous) the disease manifests fully; a single gene (heterozygous) gives the trait.
   ‑ The mutation is autosomal recessive; carrier frequency is high in malaria‑endemic regions because heterozygotes have some protection against severe malaria.

4. Types / Classification

a) Sickle Cell Anaemia (SS) – homozygous Hb S; severe chronic anaemia, frequent crises, early organ damage.
b) Sickle Cell Trait (AS) – heterozygous; usually asymptomatic, but may have haematuria or splenic infarction under extreme stress.
c) Compound heterozygotes – Hb S combined with another abnormal haemoglobin (e.g., SC disease, Sβ⁺ thalassaemia, Sβ⁰ thalassaemia). Severity varies with the partner haemoglobin; SC disease often has milder anaemia but significant vaso‑occlusive complications.

Acute form refers to vaso‑occlusive pain crises, acute chest syndrome or splenic sequestration that develop over hours to days. Chronic form denotes the persistent haemolytic anaemia, organ dysfunction and growth failure that persist for months to years.

5. Pathophysiology / Pathology – step by step

‑ Under low oxygen tension Hb S polymerises, forcing the red cell into a rigid, crescent shape.
‑ Sickled cells lose flexibility, become trapped in the micro‑circulation, producing ischaemia and pain (vaso‑occlusive crisis).
‑ The abnormal cells are fragile and are destroyed prematurely in the spleen (extravascular haemolysis) and in the circulation (intravascular haemolysis), causing chronic anaemia and jaundice.
‑ Repeated sickling‑unsickling cycles damage the cell membrane, leading to increased adhesion to endothelium and further obstruction.
‑ Ongoing haemolysis releases free haemoglobin, which scavenges nitric oxide, contributing to endothelial dysfunction and pulmonary hypertension.

6. Clinical Features

General features – persistent anaemia (pallor, fatigue), jaundice from bilirubin, splenomegaly in early childhood, growth retardation.

Acute features – severe bone‑pain crises (often in the long bones, chest, back), fever, tachycardia, acute chest syndrome (cough, chest pain, hypoxia), splenic sequestration (rapid abdominal distension, shock), priapism in males.

Chronic features – chronic pain, leg ulcers, avascular necrosis of the hip, gallstones, renal papillary necrosis, retinopathy, pulmonary hypertension.

Each feature is important because it guides the urgency of treatment and the need for preventive measures.

7. Complications

Acute complications – vaso‑occlusive pain crisis, acute chest syndrome, splenic sequestration, stroke, priapism, infections (especially encapsulated bacteria). Prompt recognition reduces mortality.

Chronic complications – chronic haemolytic anaemia, iron overload from repeated transfusions, osteomyelitis, gallstone disease, renal dysfunction, leg ulcers, retinopathy, pulmonary hypertension. Preventive vaccination and iron chelation are essential to limit long‑term damage.

8. Investigations / Diagnosis

‑ Complete blood count – shows normocytic‑macrocytic anaemia, raised reticulocyte count.
‑ Peripheral smear – sickle‑shaped cells, target cells, Howell‑Jolly bodies after splenic loss.
‑ Haemoglobin electrophoresis or HPLC – quantifies Hb S (≥ 90 % in SS) and detects other haemoglobins.
‑ Solubility test – rapid screening for Hb S presence.
‑ Imaging – chest X‑ray for acute chest syndrome, MRI for avascular necrosis, trans‑cranial Doppler for stroke risk.

Each test confirms the diagnosis and helps monitor disease activity.

9. Differential Diagnosis

‑ Iron‑deficiency anaemia – microcytic picture, low ferritin; unlike sickle cell, no sickled cells.
‑ Thalassaemia major – similar severe anaemia but different electrophoretic pattern (elevated Hb F, absent Hb A).
‑ Autoimmune haemolytic anaemia – positive Coombs test, spherocytes rather than sickle cells.
‑ Acute vaso‑occlusive crisis may mimic appendicitis or osteomyelitis; careful clinical correlation and imaging differentiate them.

10. Management / Treatment

General management – maintain adequate hydration, avoid extreme temperatures, give analgesia promptly, and educate patients on early signs of crisis.

Modern medicine treatment – hydroxyurea to increase fetal haemoglobin and reduce crises; regular blood transfusion programmes for high‑risk patients; iron chelation (deferasirox, deferoxamine) when iron overload develops; prophylactic penicillin in early childhood and vaccination against pneumococcus, meningococcus and Haemophilus influenzae.

Diet and lifestyle advice – drink plenty of water (≥ 2 L/day) to keep blood less viscous; balanced diet rich in protein, folic acid and vitamin C to support erythropoiesis; avoid dehydration, high‑altitude exposure, and excessive physical exertion; quit smoking and limit alcohol because they increase vaso‑occlusion risk.

11. Homeopathic Therapeutics – 8 remedies (each with 7‑8 points)

12. Arnica montana
    ‑ Causation: trauma or bruising of bone and muscle.
    ‑ Characteristic symptoms: deep, throbbing pain that is worse on pressure.
    ‑ Modalities: pain increases when the part is touched or moved.
    ‑ Mental state: anxious, anticipates worsening.
    ‑ Thirst and appetite: increased thirst, normal appetite.
    ‑ Discharges: none specific.
    ‑ Physical generals: bruised appearance, soreness of muscles.
    ‑ Suitable constitution: patients who have suffered injury or have postoperative pain.
    ‑ Helps by reducing the inflammatory pain that follows a vaso‑occlusive episode.

13. Hypericum perforatum (commonly used)
    ‑ Causation: injuries to nerves or sharp, shooting pains.
    ‑ Characteristic symptoms: lancinating pain that radiates along a nerve pathway.
    ‑ Modalities: worse from slightest touch, better when the limb is at rest.
    ‑ Mental state: feeling of despair, often depressed.
    ‑ Thirst and appetite: decreased appetite, occasional thirst.
    ‑ Discharges: none.
    ‑ Physical generals: tingling, numbness, hypersensitivity.
    ‑ Suitable constitution: patients with nerve‑related pain after a crisis.
    ‑ Helps by relieving the neuropathic component of sickle‑cell pain.

14. Ruta graveolens
    ‑ Causation: strain or over‑use of tendons and joints.
    ‑ Characteristic symptoms: aching pain that is worse on movement.
    ‑ Modalities: pain aggravated by motion, better with rest.
    ‑ Mental state: irritable, impatient.
    ‑ Thirst and appetite: increased thirst, normal appetite.
    ‑ Discharges: none.
    ‑ Physical generals: stiffness of joints, feeling of “tightness”.
    ‑ Suitable constitution: patients with musculoskeletal soreness after repeated crises.
    ‑ Helps by easing joint stiffness that follows repeated sickling.

15. Gelsemium sempervirens
    ‑ Causation: exhaustion and weakness after prolonged illness.
    ‑ Characteristic symptoms: heaviness, weakness, and dull pain.
    ‑ Modalities: worse on mental exertion, better with warm drinks.
    ‑ Mental state: anticipatory anxiety, fear of worsening.
    ‑ Thirst and appetite: decreased thirst, reduced appetite.
    ‑ Discharges: none.
    ‑ Physical generals: trembling, muscle fatigue.
    ‑ Suitable constitution: patients who feel weak and listless after a crisis.
    ‑ Helps by restoring strength and reducing fatigue‑related pain.

16. Lac caninum (milk of the dog)
    ‑ Causation: inflammatory swelling of glands or joints.
    ‑ Characteristic symptoms: painful, swollen area that feels hot.
    ‑ Modalities: worse from pressure, better from cool compresses.
    ‑ Mental state: weepy, wants to be left alone.
    ‑ Thirst and appetite: increased appetite, normal thirst.
    ‑ Discharges: milky or creamy secretions if glands are involved.
    ‑ Physical generals: localized edema, tenderness.
    ‑ Suitable constitution: patients with swollen joints during a crisis.
    ‑ Helps by diminishing inflammatory swelling and pain.

17. Myrica cerifera (wax myrtle)
    ‑ Causation: skin irritation and burning after sweating.
    ‑ Characteristic symptoms: itching, burning, and stinging sensations.
    ‑ Modalities: worse from heat, better from cool air.
    ‑ Mental state: restless, unable to stay still.
    ‑ Thirst and appetite: increased thirst, normal appetite.
    ‑ Discharges: watery, clear skin exudate.
    ‑ Physical generals: erythematous rash, especially on limbs.
    ‑ Suitable constitution: patients who develop skin itching during feverish crises.
    ‑ Helps by soothing the pruritic skin eruptions that may accompany haemolysis.

18. Natrum muriaticum
    ‑ Causation: emotional upset or loss, often after a traumatic event.
    ‑ Characteristic symptoms: dry, cracked skin, especially on the face.
    ‑ Modalities: worse from exposure to sun or sea‑water, better from fresh air.
    ‑ Mental state: reserved, often weeping in private.
    ‑ Thirst and appetite: increased thirst for cold water, reduced appetite.
    ‑ Discharges: salty, thin nasal discharge.
    ‑ Physical generals: headache, feeling of “dryness” throughout.
    ‑ Suitable constitution: patients who are emotionally sensitive and develop pain crises after stress.
    ‑ Helps by addressing the emotional trigger that can precipitate vaso‑occlusion.

19. Ustilago maydis (corn smut)
    ‑ Causation: chronic skin eruptions with itching.
    ‑ Characteristic symptoms: intense itching with burning, especially at night.
    ‑ Modalities: worse from cold, better from warmth.
    ‑ Mental state: irritable, impatient for relief.
    ‑ Thirst and appetite: decreased appetite, occasional thirst.
    ‑ Discharges: watery, sometimes serous exudate from lesions.
    ‑ Physical generals: papular rash, sometimes crusted.
    ‑ Suitable constitution: patients who develop nocturnal itching during haemolytic episodes.
    ‑ Helps by calming the persistent itching that can disturb sleep and worsen fatigue.

20. Prognosis
    The outlook depends on the frequency of crises, the presence of organ damage and the effectiveness of disease‑modifying therapy. With early diagnosis, regular hydroxyurea, vaccination and iron‑chelation, many patients now survive into middle age with a reasonable quality of life; however, severe chronic complications still shorten life expectancy in untreated individuals.

21. Prevention
    ‑ Genetic counselling for at‑risk couples to inform about carrier status and options for prenatal diagnosis.
    ‑ Universal newborn screening to start prophylactic penicillin and vaccination promptly.
    ‑ Patient education to avoid known triggers (dehydration, extreme temperatures, high altitude) and to seek early treatment for fever or pain.
    These measures markedly reduce mortality and the burden of severe crises.

22. Diet
    Recommended foods – high‑protein sources (lean meat, legumes) to support erythropoiesis, leafy greens for folic acid, vitamin C‑rich fruits to improve iron absorption, and adequate fluids (water, oral rehydration solutions).

Avoided foods – excessive simple sugars and salty snacks that can promote dehydration and increase blood viscosity; iron‑rich supplements unless iron deficiency is proven, because iron overload from transfusions is a greater risk.