TREATMENT OF

SICKLE CELL
DISEASEPrepared by:
Andrew Silungwe
Sickle cell disease:
▶ A type of structural haemoglobinopathy.
▶ Defined as inherited chronic hemolytic anemia
resulting
from point mutation affecting one base in the gene
coding for amino acids of the globin chain.
▶ Substitution of thymine for adenine at position 6 of
glutamic acid DNA codon resulting in substitution
of valine for glutamate.
▶ This structural changes lead to polymerization of
HB, redudes deformability of RBC and sickling of
the red cells.
 Characteristics of sickle cells
RBCS SICKLED CELLS
■ 30-40 day life span
■ 120 day life span
■ Hb has normal oxygen ■ Hb has decreased

carrying capacity oxygen carrying

■ 12-14 g/dl
capacity
of
■ 6-9 g/dl of
Hb
Hb
 Sign & symptoms
• excessive fatigue or irritability, from anemia
• bedwetting, from associated kidney problems
• jaundice, which is yellowing of the eyes and skin
• swelling and pain in hands and feet
• frequent infections
• pain in the chest, back, arms, or legs
 Other Clinical Manifestations
■ CNS
➢ Hemorrhage

➢ Paralysis

❑ CVS

➢ CHF

➢ Heart rate increased

 Cont…
■ Pulmonary
➢ Atelectasis
➢

➢ Pneumonia
➢ Pulmonary hypertension
❑ Resp. rate increased
GIT
➢ Acute hepatomegaly
➢ Spleenomegaly
■ GU
Cont…
➢ Hematuria
➢ Diuresis
■ Musculoskeletal
➢ Painful swelling of hands & feet
■ Ophthalmology
➢ Blindness
➢ Retinopathy
■ Dermatology
➢ Ulcers of hand &feet
 Diagnostic test
•Blood counts can reveal an abnormal Hb level
in the range of 6 to 8 grams per deciliter.
•Blood films may show RBCs that appear as
irregularly contracted cells.
•Sickle solubility tests look for the presence of
Hb S.
Hb electrophoresis
Hb electrophoresis is always needed to
confirm the diagnosis of sickle cell disease. It
measures the different types of hemoglobin
CLINICAL FEATURES &
MANAGEMENT:
▶ The typical course of sickle cell anemia is characterized
by the presense of chronic haemolysis & anemia
(usually well tolerated anemia) interrupted by Crises.
▶ Hb S has a low affinity to O2, so the oxygen is
rapidly delivered to tissues,so symptoms of aemia are
better tolerated with little or no tissue hypoxia
▶ The clinical course, presentation and complications of
patient with sickle cell disease will determine the type
of treatment to be implicated.
TREATMENT:
1 The usual clinical course of the disease
in which both extra & intravascular hemolysis present
with anemia (well tolerated) can be treated with:-
A) a daily dose of 5 mg folic acid to over come folate
loss due to continuous RBC break down.
B) Preventive measures :avoidance of conditions that
may cause or increase RBC sickling & precipitate
any crises which include:
*febrile illness (infections):require the use of
proper antibiotic ,antipyretic to relief fever
(salicylate to be avoided to decrease acid load),
good hydration
*avoidance of cold exposure( cause vasoconstriction
with subsequent hypoxia and sickling).

*avoidance of sudden transition to higher altitude

(cause in O2 tention).

*prophylactic penicillin to prevent pneumococcal

infection

*pnemococal vaccination especialy for

splenectomized children with SCD.
2-Crises & their treatment:( 4 types of crises )
A) Vaso- oclusive crises:
The most common clinical manifestation, results from
occlusion of micro vasculature by adherent normal &
sickled RBCs ,WBCs ,platelets and inflammatory
cytokines. Characterized by pain in chest, back,
extremities and abdominal pain (can affect any organ).

Hand-Foot syndrome :painful dactylitis caused by

infarction of small bones.Could be the first
manifestation in children.
Acute chest syndrome:chest pain, dyspnea, tachypnea,
fever and hypoxia

Leg ulcers:occlusion of small blood vessles in the legs

will cause tissue ischemia with future ulcerations

Hepatobiliary:occlusion of hepatic sinosoids ,

further impairment of liver function & cholilithiasis
Treated with :
Adequate hydration - Administer
fluids IV or orally at 1 to 1.5 times the maintenance
requirement. Consider an infectious etiology and initiate
empiric therapy if indicated.
1) Pain control is vital in the management ,
( acetaminophen, NSAID, opioids-morphin 0.1-
0.15 mg/kg, hydromorphon 0.015-0.02 mg/kg I.V )
What of pethidine?
3) Good oxygen supply.
4) Control of fever.
5) Specific treatment of the precipitating cause
( as infection).
 B) Aplastic crises :
Acute sever drop in Hb level due to sessation of red
cell production from B.M. in the face of ongoig
haemolysis.
Mostly caused by parvo virus B19 infection affecting
erythroid progenitors. Although pancytopenia may
occur.

Treatment :
Supportive care must be given including red cell
transfusion until bone marrow output is restored to normal
.
If pancytopenia is present platelet transfusion
 C) Sequestration crises :
Sudden massive pooling of RBCs mainly in the spleen
resulting in hypovolemic shock with circulatory
collapse (mainly in children).
Patient present with rapidly enlarging spleen ,
pallor , abdominal pain, hypoxia and shock.
** It may occur in liver also.
Treatment :
• Oxygenation
• Red cell transfusion or exchange transfusion.
• Splenectomy may be performed if high frequency of
this crises is present.
 D) Hyperhaemolytic crises :
Episodes of accelerated haemolysis occur in patients
with Hx of repeated blood transfusion that cause
alloimmunization (decrease Hb level- reticulocytosis-
hyperbilirubinemia- increase LDH).

Treatment:
• Adequate hydration .
• Oxygenation.
• Blood transfusion.
• High dose of folic acid (5mg /
day)
 NEW APPROACHES TO THERAPY:
a) Activation of Hb F SYNTHESIS:( Hydroxyurea)
a cytotoxic drug with no effect on DNA methylation ,
increase Hb F synthesis in patient with severe sickle
cell anemia.
• It is a myelosuppresive drug arrest the development
of mature erythroid precursors, resulting in
recruitment of earlier erythroid progenitors with a
greater capacity for Hb synthesis.
• It may have a direct effect on Reprograming of
globin synthesis by early progenitors.
• It increase the intravascular & intaerythrocytic NO
• The starting dose is 15 mg/kg as a single daily dose
• its maximum dose is 25 mg/kg /day
OTHER THERAPUTIC INTERVENTIONS:
▶ iron chelation therapy if repeated blood
transfusion is needed.(deferiprone, deferoxamine)
▶ Antiplatelet therapy to decrease platelet aggregation.
▶ Intravenous immunoglobulin
▶ neutrophil antiselectin
▶ red cell antiselectin
The last two interventions are to dedrease aggregation
& adhesion of RBCS & WBCS
b) Anti-sickling agents:
Poloxamer- nonionic copolymer emulsifying agent that
counteract the tendency of sickled cell to adhere to
endothelium by reducing yhe interaction red cells and
fibrenogene

c) Reduction of red cell haemoglobin concentration:

Long-acting antidiuretic hormone desmopressin, salt
restriction & water loading.all cause sufficient
hyponatremia and osmotic swelling of RBCs to reduce
the MCHC by 2-3 gm/dl
Complications: fluctuating Na level, poor
compliance, neurological manefistations
d) Bone marrow(stem cell) transplantation:
 Provide a definitive cure of SCD but with higher rate
of morbidity & mortality
 A donor must be HLA- identical sibling to the
recipient
 Pre-transplantation conditioning regimin
includes: busulfan or cyclophosphamide with or
without antithymocyte globulin.
Source of stem cells are:peripheral blood, bone
marrow, cord blood of a new born.
 The transplanted stem cells are administered
intravenously to the recipient to be engrafted in
the hemopoietic tissue space.
e) Gene therapy:
 Provide a potential cure for sickle cell disease but
there are current concerns about random genomic
insertion that must be resolved.
 previously, gene transfer to stem cells has
alimited progress
 recently, the use of lentiviral vector derived from HIV
genome allow more efficient transduction of human
cells
THANK YOU