SICKLE CELL DISEASE

INTRODUCTION
Is the collective name given to hemoglobinopathies in
which HbS is inherited.
It is a point mutation in codon 6 of the -globin gene which
causes a change in the amino acid encoded from glutamine
to valine.
EPIDEMIOLOGY
Is most common in blacks and originate from tropical
Africa /Caribbean.
In UK up to 1 in 10 people of African /Caribbean descent
have SC trait & up to 1 in 60 have SCD.
 3 forms of SCD:
Sickle cell anemia (HbSS)
Homozygous for HbS, i.e. virtually all their Hb is HbS
No HbA because they have no normal -globin genes.
Sickle cell disease(HbSC)
Inherit HbS from one parent and HbC from the other
parent (HbC is formed as a result of a dierent point
mutation in -globin)
No HbA because they have no normal -globin genes.
Sickle -thalassemia
Inherit HbS from one parent and -thalassemia trait from
the other.
No normal -globin genes and most patients can make no
HbA and therefore have similar symptoms to those with
SCA.
SICKLE CELL TRAIT
Inheritance of HbS from one parent and a normal -globin
gene from the other parent, approximately 40% of the Hb
is HbS
 Do not have SCD but are carriers of HbS, so can transmit
HbS to their ospring.
Asymptomatic is only identified as a result of blood tests.
PATHOPHYSIOLOGY
Normally; the RBCs have a highly specific conformation
that allows efficient transport of O2; and also normally
RBCs interact with on another.
In SCD, in the presence of HbS, theres a conformational
change in the Hb tetramer especially in the deoxygenated
state and allows interaction with other HbS & forms rigid
polymers that gives the RBCs its characteristic sickled
shape, process termed sickling.
Other precipitating factors include; hypoxia, infection,
cold, dehydration, local or systemic hypoxia.
 With repeated episodes of sickling, red cells become
increasingly dehydrated, dense, and rigid.
Eventually, the most severely damaged cells are
converted to end-stage, non-deformable, irreversibly
sickled cells, which retain a sickle shape even when
fully oxygenated.
The severity of the hemolysis correlates with the
percentage of irreversibly sickled cells, which are
rapidly sequestered and removed by mononuclear
phagocytes (extravascular hemolysis).
Sickled red cells are also mechanically fragile, leading
to some intravascular hemolysis as well.
CLINICAL FEATURES
Sickle cell crisis
Acute vaso-occlusive crisis
- Dactylitis
Bone crisis
- Bone pain.
Abdominal crisis
- Sickle cell gardle syndrome
- Infarction of liver, spleen & lymph node resulting in
capsular stretching.
 Central nervous system crisis
- Convulsions, vertigo, meningeal signs & cerebral
infraction.
Pulmonary crisis
- Acute chest syndrome
Hepatic sequestration crisis
- Sudden onset of abdominal pain & splenomegaly,
sometimes associated with shock.
Priapism
Hematuria
ORGAN DYSFUNCTION IN SCD
Heart
Cardiomegaly
Myocardial dysfunction
Cor pulmonale
Lungs
Pulmonary fibrosis
CNS
Cortical atrophy
Dilatation of ventricles
 Permanent motor disabilities
Kidney
Papillary necrosis
Nephrotic syndrome
Renal infraction
Pyelonephritis
Renal medullary carcinoma.
Liver
Cholelithiasis
Bones
Dactylitis
Osteonecrosis of femoral & humeral head
Fish mouth vertebra
Hair on end appearance
Eyes
Retinopathy
Ears
Sensorineural hearing loss
INVESTIGATIONS
CBC
Hemoglobin is normal, except in those with coexisting
thalassemia trait who may be slightly anemic.
Mean cell volume and MCH are reduced in those with
coexisting thalassemia trait.
Blood Film
The blood film may be completely normal or may show
microcytosis or target cells. Sickle cells may be seen
characteristically. If a subject with sickle cell trait develops
iron deficiency, target cells are often prominent.
Hemoglobin electrophoresis
Hemoglobin S can be demonstrated by Hb electrophoresis
or in HPLC.
MANAGEMENT
Management of Crises
The mainstay of treatment of painful crisis is:
Analgesiastepwise from paracetamol to opioids
AntibioticsIV cephalosporins if infection suspected
HydrationIV uid as usually required.
Acute chest syndrome is responsible for 25% of death
in children with SCD. In addition to analgesia, hydration
and antibiotics, O2 is required. Top up blood transfusion for
significant anemia of 12 g below base level and exchange
transfusion may be life-saving. Red cell transfusion is usually
required for sequestration crisis.
 General Management
All patients with HBSS should receive oral penicillin V
and folate supplement and immunization against
Streptococcus pneumoniae.
Hydroxyurea: It increases HbF level and improves RBC
hydration which reduces frequency and painful chest crisis
and myelosuppression.
Transfusion: Every 34 weeks is indicated following
acute stroke.
Bone marrow/stem cell transplantation: This is
potentially curative.
COMPLICATIONS
Pulmonary hypertension secondary to ACS.
Impotence with recurrent episodes for priapism.
Seizures.
Renal failure
Leg ulcers
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