Sickle Cell Disease

It is an autosomal co-dominant genetic blood disorder characterized by

red blood cells that assume an abnormal, rigid, sickle shape
Pathophysiology
• It is caused by point mutation in the B-globin chain of Hb, causing the
hydrophilic amino acid, Glutamic acid to be replaced with
hydrophobic amino acid Valine at the 6th Position.
• RBC typically live 90-120 days, but sickle cells only survice 10-20 days.
• The induction of sickling in susceptible erythrocytes requires
exposure to oxygen tensions of <40mmHg for 2-4 min. The De-
Oxygenation of HbS leads to polymerization of insoluble HbS strands.
• sickle hemoglobin(HbS), which polymerizes on deoxygenation, makes
the RBC more rigid, and causes structural damage to the RBC
membrane. This change leads to hemolytic anemia and contributes to
vaso-occlusion
OXY-STATE DEOXY-STATE
Pathophysiologic mechanisms causing
Morbidity
• Hemolysis:
• Sickled RBCs undergo both intravascular and extravascular hemolysis, which
leads to anemia, reticulocytosis, jaundice, gallstones, and occasional aplastic
crisis.

• Vaso-occlusion
• Intermittent and chronic vaso-occlusion result in both acute exacerbations
(e.g., painful crisis, stroke) and chronic disease manifestations (e.g.,
retinopathy, renal disease).
Clinical Features
Hematological
Hemolytic anemia Typical baseline hemoglobin levels are 6–9 g/dl in
SS disease.
Orthopedic
Osteonecrosis
Osteomyelitits.
Dactylitis Early onset is a marker of disease severity
Vascular
Leg ulcers
Clinical Features
Neurological Genitourinary
Pain crisis Chronic renal insufficiency
Stroke Priapism
Proliferative retinopathy Gastrointestinal
Chronic pain syndrome Cholelithiasis
Pulmonary Viral hepatitis from transfusion
Liver failure
Acute Chest Syndrome
Airway hyperreactivity
Restrictive lung disease
Clinical features in Infants
History
• Anemia
• It is chronic and hemolytic in nature and usually very well tolerated.
• While patients with an Hb level of 6-7 g/dL. Their tolerance for exercise and
exertion tends to be very limited.
• A serious complication is the aplastic crisis.
• Spleen Enlargement
• Occasionally, it undergoes a sudden very painful enlargement due to pooling
of large numbers of sickled cells.
• The nonfunctional spleen is a major contributor to the immune deficiency
that exists in these individuals.
Clinical Features in Infants
• hand-foot syndrome.
• This is a dactylitis presenting as painful swelling of the dorsum of the hand
and foot.

• Acute Chest Syndrome

• Consists of Chest pain, Tachypnea, Leukocytosis and Pulmonary Infiltrates
• This is a medical emergency and must be treated immediately
• It may lead to Acute Respiratory Distress Syndrome if not attended to
promptly so manage it Aggresively.
Factors That can Cause Sickle Cell Crisis
 Infections – Most common Cause of death in Children in SCD
 Low oxygen tension
 Concomitant medical conditions (e.g., sarcoidosis, diabetes mellitus,
herpes)
 Dehydration*
 Acidosis
 Extreme physical exercise
 Physical or psychologic stress
 Alcohol
 Pregnancy
 Cold weather
Investigations – Lab Studies
• FHG
• Anemia
• Leukocytosis - with a left shift raises suspicion for infection
• The platelet count is often elevated.
• PBF - sickle-shaped RBCs are found along with target cells.
• ABG – In Respiratory Distress
• LFT’s in patients with abdominal pain
• Type and cross-match in case transfusion is necessary.
• Urinalysis – Fever or signs of UTI (often have hematuria)3
• Hb electrophoresis- Differentiates individuals who are homozygous from
those who are heterozygous and other haemoglobinopathies.
Investigations – Imaging
• CXR
• initially be normal in patients with acute chest syndrome.
• Bone radiography
• Perform in patients with localized bone tenderness.
• Ultrasonography
• Use in patients with abdominal pain to rule out cholecystitis or an ectopic
pregnancy.
• Assess liver and spleen size.
• Head CT or MRI
• is used in cases of neurologic crisis.
Comprehensive Care of Sickle Cell Anemia
Patients
• Drug Prophylaxis
• Penicillin V - Allergy to penicillin, erythromycin may be substituted.
• Folic acid therapy – Due to anaplastic Crises leading to Folic Acid Deficiency
-
• Hydroxyurea increases fetal hemoglobin production, reduces the incidence of
pain episodes and acute chest syndromes in some patients who are severely
affected.
• Malarial prophylaxis – Mefloquine, Proguanil(Palludrine)
• Immunization
• pneumococcal vaccine
• Meningococcal vaccine
• The influenza virus vaccine
• Hepatitis A vaccine
• Good Nutrition
Acute Chest Syndrome - Evaluation &
Management
• Admit
• Analgesics –Pain Control / avoid Hypoventilation / Lung collapse
• Antibiotics - ACS linked to fat Embolism and Infections (Chlamydia species, Mycoplasma species,
and Streptococcus pneumoniae
• Ceftriaxone or Cefuroxime, Azithromycin, Vancomycin
• Correct fluid Deficit if Dehydrated. Consider Diuretics if Fluid Overload
• Bronchodilators if Wheezing/Reactive Airway Disease (RAD)
• Transfuse of Sa02 <95% or Hct <18
• Routine FHG
• Repeat CXR as needed
• Encourage Ambulation
• Chest Physio
• Transfuse of Sa02 <95% or Hct <18