SICKLE CELL DISEASE
Prepared by: Halah O.Hassan
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
CLINICAL FEATURES & MANAGEMENT:
The typial 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.
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
*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
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 :
1) Adequate hydration .
2) 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 )
3) Good oxygen supply.
4) Control of fever.
5) Specific treatment of the precipitating cause ( as
6) Blood transfusion in severe acute crises.
7) For leg ulcers:bed rest, leg elevation, dressing, gentle
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.
Supportive care must be given including red cell
transfusion until bone marrow output is restored to normal .
If pancytopenia is present platelet transfusion with
protection against infection is needed.
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.
• 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).
• Adequate hydration .
• 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
• It is a myelosuppresive drug arrest the development of
mature erythroid precursors, resulting in recruitment of
earlier erythroid progenitors with a greater capacity for
• It may have a direct effect on Reprograming of globin
synthesis by early progenitors.
• It increase the intravascular & intaerythrocytic NO
• its maximum dose is 25 mg/kg /day
OTHER THERAPUTIC INTERVENTIONS:
iron chelation therapy if repeated blood transfusion is
Antiplatelet therapy to decrease platelet aggregation.
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
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,
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
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
recently, the use of lentiviral vector derived from HIV
genome allow more efficient transduction of human cells