Sickle Cell Disease (SCD) is a group of inherited hemoglobinopathies characterized by the presence of hemoglobin S (HbS) resulting from a point mutation in the β-globin gene (Glu6Val). Under deoxygenated conditions, HbS polymerizes, leading to red blood cell (RBC) deformation, chronic hemolysis, vaso-occlusion, and progressive organ damage.

The most severe genotype is sickle cell anemia (SCA, HbSS), in which an individual inherits two HbS alleles (homozygous state). Other clinically significant genotypes include HbSC and HbS/β-thalassemia.

SCD is inherited in an autosomal recessive pattern and manifests clinically after 6 months of age due to the decline in fetal hemoglobin (HbF).

Risk Factors

• Inheritance of HbS gene (parental carrier state)

• African, Middle Eastern, Mediterranean, and Indian ancestry

• Dehydration

• Infection

• Hypoxia

• Acidosis

• Cold exposure

• High altitude

• Surgery or anesthesia

• Pregnancy

Pathophysiology (Essential for Professional Reference)

• HbS polymerization under low oxygen tension

• RBC sickling → decreased deformability

• Vaso-occlusion → ischemia and infarction

• Chronic hemolysis → anemia, hyperbilirubinemia

• Nitric oxide depletion → endothelial dysfunction

• Functional asplenia → immunocompromise

Signs and Symptoms

Symptoms usually occur after 6 months of life.

Clinical manifestations are variable and may include:

Acute onset of unexplained illness including:

• Acute pain

• Anaemia

• Acute neurological symptoms

• Loss of vision

• Respiratory infections

• Hepatosplenomegaly

• Jaundice

• Swollen limbs

• Sepsis

Types of Crisis in SCD

1. Vaso-Occlusive Crisis (VOC)

• Most common

• Severe pain (back, limbs, abdomen, chest)

• Triggered by dehydration, infection, stress

• Diagnosis of exclusion (rule out osteomyelitis, appendicitis, etc.)

2. Hemolytic Crisis

• Sudden increase in hemolysis

• Jaundice

• Dark urine

• Falling hemoglobin

3. Sequestration Crisis

• Sudden splenic or hepatic enlargement

• Rapid fall in hematocrit

• Hypovolemic shock (especially in children)

4. Aplastic Crisis

• Bone marrow suppression (often Parvovirus B19)

• Severe anemia

• Reticulocytopenia

Medical Emergencies in SCD

Acute Chest Syndrome (ACS)

• Chest pain

• Fever

• Hypoxia

• Pulmonary infiltrates on chest X-ray

• Leading cause of mortality

Stroke

• Headache

• Focal neurological deficit

• Requires urgent exchange transfusion

Splenic Sequestration

• Rapid splenic enlargement

• Pallor

• Hypotension

Severe Infection

• Due to functional asplenia

• Encapsulated organisms (e.g., Streptococcus pneumoniae)

Diagnostic Criteria

Diagnosis requires demonstration of HbS:

• Hemoglobin electrophoresis (gold standard)

• High-performance liquid chromatography (HPLC)

• Isoelectric focusing (IEF)

Newborn screening programs are recommended where available.

Investigations

Screening Tests

• Sickling test

• Isoelectric focusing (electrophoretic separation)

Confirmatory Tests

• Sickle Scan

• Haemoglobin electrophoresis

• High Performance Liquid Chromatography (HPLC)

Other Ancillary laboratory investigations

• Full blood picture (FBP)

• Reticulocyte count

• Peripheral blood film

• Blood culture and sensitivity

• LDH

• Total and indirect bilirubin

• Liver profile

• Renal profile

• Point-of-care blood gases

• ECG

• mRDT

• Random blood glucose (RBG)

• Blood grouping and cross match

Imaging

• Chest X-ray (CXR)

• Echocardiography (ECHO)

• Ultrasound:

  • Abdominal ultrasound

  • Transcranial Doppler (TCD USS)

• CT scan head if stroke is suspected

Screening

• From the age of 10 years, screen annually for:

  • Renal disease (proteinuria by urine dipstick)

  • Retinopathy

• Annual screening for stroke risk by transcranial Doppler from age 2 years to 16 years

Pharmacological Treatment

A: Folic acid (PO) 5 mg every 24 hours.

Prophylaxis against Pneumococcal infection in patient with SCD

A: Phenoxymethyl penicillin (PO):

• 125 mg every 12 hours for children younger than 3 years

• 250 mg every 12 hours for children aged 3 years and above

Continue until 5 years of age in all children with SCA.

Immunisation against Pneumococcal infection in patient with SCD

A: Pneumococcal conjugate vaccine (PCV-13):

• From 2 months of age

• 3 doses given 8 weeks apart:

  • At 2 months

  • At 4 months

  • At 6 months

• Booster dose between 12–15 months

If the child has not previously received this vaccine, at least one dose should be given between 6–18 years.

PCV-13 and vaccine against Haemophilus influenzae are incorporated in the Tanzania EPI schedule.

S: Pneumococcal polysaccharide vaccine (PPSV-23):

• At 2 years of age

• Repeated every 5 years for life

Table 3.2: Analgesia for General Pain Relief

If unable to take orally:

• Paracetamol (IV) 1 g every 6–8 hours

• Morphine 0.1 mg/kg every 8–12 hours

If morphine is not available, tramadol may be used.

B: Tramadol (PO) 50–100 mg every 6 hours as needed.

Hydration

Encourage oral fluids first whenever possible.

Give IV fluids, preferably normal saline, if the patient:

• Is unable to drink adequately

• Has severe pain

• Has abdominal symptoms

• Divide the total daily volume by 24 hours to obtain the hourly fluid rate.

Indications for Use of Hydroxyurea

All Children

• All children older than 9 months with proven SCD

Adolescents and Adults

• Recurrent vaso-occlusive crises (3 or more severe episodes requiring admission in the last 12 months)

• Severe and/or recurrent acute chest syndrome (ACS) (2 or more episodes in a lifetime)

• Severe symptomatic chronic anaemia interfering with daily activities or quality of life

• Where chronic transfusion therapy is not feasible as an alternative for prevention of new or recurrent stroke

• Silent infarcts

• Stroke

• Abnormal TCD (199 cm/sec)

• Recurrent priapism

• Chronic kidney disease on erythropoietin to improve anaemia

Principle of Dosage Initiation and Monitoring

S: Hydroxyurea (PO) 15 mg/kg/day every 24 hours.

• Use 5–10 mg/kg/day in patients with chronic kidney disease.

S: Hydroxyurea (PO) 20 mg/kg/day as the starting dose for infants and children.

• Increase dose by 2.5–5 mg/kg/day every 3 months.

• Maximum tolerated dose (MTD) should not exceed 30 mg/kg/day.

Blood Work Monitoring

• Bi-monthly FBP and reticulocyte count for 1 month

• Then monthly for 3 months

• Then every 3 months if blood counts remain stable

Every 6 months:

• HbF percentage analysis

• Liver function tests

• Serum creatinine

• Urea

• Weigh the patient every 3 months and adjust dosage accordingly.

Threshold for Dose Reduction

• Neutrophil ANC <1.5 × 10⁹/L

• Reticulocyte count <80 × 10¹²/L

• Platelet count <80 × 10⁹/L

• Hb <6 g/dL

If Haematologic Toxicity Occurs

• Discontinue hydroxyurea until blood counts recover, usually within 1–2 weeks.

• Reinitiate hydroxyurea at a dose 2.5 mg/kg/day lower than the previous dose to achieve the maximum tolerable therapeutic dose.

• Perform FBP according to the initiation schedule.

Notes

• Clinical response to hydroxyurea may take 3–6 months.

• A 6-month trial on MTD is required before considering discontinuation due to treatment failure.

• Hydroxyurea should be stopped at least 3 months prior to conception in both males and females.

• Hydroxyurea should be discontinued in:

  • Pregnant women

  • Breastfeeding women

Blood Transfusion in SCA

Simple (Top-Up) Blood Transfusion

Indicated in:

• Symptomatic anaemia

• Haemoglobin drop >2 g/dL below steady-state value

Exchange Blood Transfusion

Aim:

• Reduce HbS to 30%

Indications

• Cerebrovascular accidents (CVAs)

• Acute chest syndrome (ACS)

• Prior to major surgery

• Multi-organ failure including systemic marrow fat embolism (SMFE)

• Multiple pregnancies

• Prevention of recurrent stroke

Relative Indications for Exchange Blood Transfusion

• Intractable or very frequent severe crises

• Major priapism unresponsive to other therapy

Note

• Blood transfusion is not routinely indicated in steady-state SCD simply because haemoglobin is below 8–10 g/dL, as the cardiovascular system adapts to chronic anaemia.

• Packed red cell transfusion is preferred to minimize the risk of fluid overload.

Prevention

• Newborn screening

• Genetic counseling

• Carrier screening

• Routine vaccinations

• Stroke screening (TCD)

• Renal and ophthalmologic screening

• Early hydroxyurea initiation

• Education on hydration and infection prevention

Complications

• Stroke

• Pulmonary hypertension

• Chronic kidney disease

• Avascular necrosis

• Leg ulcers

• Retinopathy

• Gallstones

• Iron overload (transfusion-related)

Prognosis

With comprehensive care (vaccination, hydroxyurea, stroke prevention), life expectancy has significantly improved into adulthood. However, morbidity remains high without appropriate management.

Note

Prescribing of Medicines with Regard to Level of Service Provision and Professional Expertise

Similar to previous editions, the NEMLIT will be used with regard to levels of care. Additionally, a new categorization of prescribing medicines with regards to expertise has been introduced to facilitate reimbursement of medicines by the NHIF. In summary, stocking and prescribing of medicines as per level of care will be: tertiary hospitals (A, B, C, D & S); Regional Referral Hospitals (A, B, C & D); District Hospitals (A, B & C); Health Centers (A & B) and dispensaries (A). Additional category reflects professional expertise; regardless of level of care: Specialists (A, B, C, D & S); Medical Officers (A, B, C & D); Assistant Medical Officer (A, B & C); Clinical Officers (A & B) and Assistant Clinical Officers (A).