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Sickle cell
anemia
Dr.Fedaa Shaher
Dr.Yasmeen Fayez
Hassan Qasim 19 year old Palestinian
male…a known case of sickle cell anemia
diagnosed at the age of 13 month at
Ajman hospital.
He received blood transfusion twice in
Ajman on diagnosis at 13 months & 19
months.
He was first seen Al Wasl Hospital at age 19
months on 1991, when he presented to
A\E because of jaundice & pallor of 6
months duration since then has been
followed up at the Dubai thalassemia
center.
Birth history:
Full term , NVD in Ajman hospital.
vaccination:
Pneumococcal vaccine in Nov 1991.
H.Influenza vaccine in May 1992.
HB vaccine 3rd dose in Jan 1993.
He has getting penicillin prophylaxis
regularly.
Family history:
Parents are 1st cousin. He is one of the 6
children.
Mother sickle cell trait.
Father sickle cell trait.
DNA study showed:
Beta globin gene analysis:
CD6 (GAG
GTG) \CD6 (GAG
Alpha gobin gene analysis:
αα\αα
GTG)
Patient was kept on regular blood
transfusion from April 1996.
Hassan used to have mild painful episode
once or twice per year.
On several occasions he had hemolytic
crises needed blood transfusion.
In Nov 1995 he developed stroke preceded
by febrile illness & manifested by left
sided hemi paresis, headache &
deterioration of his level of consciousness.
He was managed accordingly with blood
transfusion and parietal exchange
transfusion.
His condition improved & he was discharged
to be followed up in thalassemia center.
Since then he was put on regular blood
transfusion & regular chelating therapy with
desferal.
In April 1996 he developed an afebrile seizure
hence was put on Na valporate.
1st exchange transfusion was done on
23\4\2007 in Rashid hospital when he
presented to A\E with history of chest pain
& breathing difficulties.
Investigation
FBC on 4\11\08: WBC 8.1
RBC 2.95
HGB 9.9
MCV 101.9
MCH 33.6
RDW 25.8
PLT 97
Hb electrophoresis
On 21\10\08
HBA 36.4
HBF 9.6
HBS 50.4
HBA2 3.6
Haemoglobinopathy
Inherited disorders of hemoglobin structure
e.g. HbS, HbE, HbC,
or its production e.g. thalassemia
Globin fraction – 4 peptides
HbA – two alpha & two beta chains α2β2
HbF - two alpha & two gama chains α2γ2
HbA2 - two alpha & two sigma chains α2δ2
α chain – 141 amino acids
β chain – 146 amino acids
Sickle cell disease
Produces by replacement of
glutamic acid by valine at
position 6 of the β-chain
Symptoms
1-Anemia
Hb electrophoresis:
SS
no Hb A
only Hb S & Hb F
HbF
5 - 20% or more
the higher the level of Hb F, the
milder the disease
2-Episodes of pain
3-Hand-foot syndrome:
swollen hand & feet caused by sickle shaped
red cells blocking blood flow out of the
hand & feet.
4-Jaundice
6-Vision problems:
Some people with sickle cell anemia experience
vision problems. Tiny blood vessels that supply
your eyes may become plugged with sickle cells.
This can damage the retina.
5-Frequent infection
Infectious complications
Increased susceptibility to aggressive infections due
to loss of splenic function.
1-Strep. Pneumoniae – most common cause
2-H. Influenzae – second common
3-Meningitis – risk > 300 times that in gen pop.
4-Salmonella osteomyelitis – on infarcted bone
(Risk significantly reduced by vaccination and
prophylactic penicillin).
Other complications
Cerebrovascular events – TIA, stroke
Pulmonary hypertension
Cardiac complications: cardiomegaly & transfusion
iron overload.
Priapism: Abnormally persistent erection of the
penis in the absence of sexual desire occur in
persons with sickle cell anemia.
Renal complications: hematuria, papillary necrosis
& CRF.
Treatments and drugs
Antibiotics: Children with sickle cell anemia
usually begin taking the antibiotic penicillin when
they're about 2 months of age and continue until
they're 5 years old. Doing so helps prevent
infections, such as pneumonia, which can be
life-threatening to an infant or child with sickle
cell anemia. Antibiotics may also help adults with
sickle cell anemia fight certain infections
Pain-relieving medications:
To relieve pain during a sickle crisis.
Hydroxyurea:
This prescription drug, normally used to treat cancer, may
be helpful for adults with severe disease. When taken
daily, it reduces the frequency of painful crises and may
reduce the need for blood transfusions. It seems to work
by stimulating production of fetal hemoglobin that helps
prevent the formation of sickle cells.
There is some concern about the possibility that long-term
use of this drug may cause tumors or leukemia in certain
people
Blood transfusions.
Supplemental oxygen.
Exchange transfusion.
Bone marrow transplant.
BMT for Sickle Cell Disease
The first BMT for sickle cell disease was
reported in 1984. The patient had both
sickle cell anemia and acute leukemia.
Subsequently, a handful of other patients
who had both sickle cell disease and
another blood disorder underwent
successful BMTs, and it was observed that
their sickle cell disease was eliminated.
Three large clinical trials--one in Belgium,
another in France and a third in the US-have reported results of BMT for 116
patients with sickle cell disease.
Of the 116 patients, 91 (78 %) were alive
and disease-free 2 to 4 years following
BMT.
An additional 16 were alive, but had
rejected the donor marrow or cord blood
(graft rejection), and continued to have
symptoms of sickle cell disease.
Neurological problems such as bleeding in
the brain developed in about 25% of
patients following BMT.
Patients who had experienced a stroke prior
to BMT developed neurological
complications more often than those who
had not.
Who's a Good Candidate ?
it is difficult to predict how the disease will
progress in each individual. Some patients
with sickle cell disease have few
symptoms for many years. Others
experience repeated episodes of extreme
pain, lung problems and/or other organ
damage.
The unpredictable course of the disease has made it
difficult to determine the best time to offer BMT to
patients. Most patients with sickle cell disease survive
the first 10 years of their life without major
complications.
While BMT can cure patients with sickle cell disease, some
will die as a result of the treatment and some survivors
will have long-term problems that affect their quality of
life to varying degrees.
BMT considered only for children younger
than 16 who have:
1-Severe sickle cell disease complications,
including repeat strokes, episodes of acute
chest syndrome, and painful events.
2-An available donor (a healthy brother or
sister who has matching bone marrow).
3-No significant damage to major organs.
About 1% of people with sickle cell disease
meet the criteria for bone marrow
transplant.
Description : Chemotherapy agent that allows –
sickled shaped blood cells to assume
the shape and characteristics of fetal
hemoglobin by becoming larger and
less adherent, thus allowing travel
through the blood vessels to occur
easier.
Shown to reduce frequency
of painful crises and to
reduce need for blood
transfusions in patients
with recurrent
moderate-to-severe
painful crises episodes
Drug Category :- Cytoreductive agent
Adult Dose :15-20 mg/kg/d PO qd
initially; may
increase by 5
mg/kg/d q12wk until
maximum tolerated
dose achieved; not to
exceed 35 mg/kg/d
Pediatric Dose :Not established; data
suggest to
administer as in
adults
Contraindications :Patients who have a sensitivity to
hydroxyurea
Interactions :Coadministration with fluorouracil can
increase neurotoxicity; coadministration
with didanosine or stavudine may cause
fatal pancreatitis and hepatotoxicity;
immunization with live-virus vaccine may
cause severe or fatal infection in
immunocompromised patient
Precautions :
Monitor blood count q2wk and
adjust dose accordingly (ie,
disconatinue if hematologic toxicity
occurs, then resume after recovery
by reducing dose associated with
hematologic toxicity by 2.5
mg/kg/d .
hematologic toxicity :
is defined as
neutrophils <2000/mL,
platelets <80,000/mL,
hemoglobin<4.5 g/dL,
reticulocytes <80,000/mL (if Hbg
<9 g/dL);
caution with renal impairment,
. may cause renal tubular
dysfunction
Transfusion In Sickle Cell
(Controversy!)
Used correctly : transfusion can
prevent organ damage and the lives
of sickle cell disease patients.
Used unwisely : transfusion
therapy can result in serious
complications.
Transfusion In Sickle Cell
Simple transfusion :
give blood.
Partial exchange transfusion :
Remove blood and give blood.
Erythrocytapheresis :
use apheresis to maximize
blood exchange.
When to use each method?
Transfusion In Sickle Cell
In severely anemic patients, simple
transfusions should be used.
- Acute splenic sequestration.
- Transient red cell aplasia.
- Hyperhemolysis (infection, acute
chest syndrome, malaria).
- If the patient is stable and the
reticulocyte count high,
transfusions can (and should)
be deferred.
Transfusion in Sickle Cell
…In general, patients should be
transfused if there is sufficient
physiological derangement to result
heart failure, dyspnea,
hypotension, or marked fatigue.
…Tends to occur during an acute
illness or when hemoglobin falls
under 5 g/dL.
in
Transfusion in Sickle Cell
(exchange transfusion)
An exchange transfusion is a medical
treatment in which apharesis is used to
remove one person's red blood cells or
platelets and replace them with
tranfused blood products
exchange transfusion is used in the treatment
of a number of diseases, including:
Transfusion in Sickle Cell
(exchange transfusion)
Except in severe anemia, exchange transfusion
offers many benefits and is our first choice.
Phenotypically matched, leukodepleted packed
cell are the blood product of choice.
A posttransfusion hematocrit of 36 percent or less
is recommended.
Avoid hyperviscosity, which is dangerous to sickle
cell patients.
Transfusion in Sickle Cell
(exchange transfusion)
Exchange transfusion :
…Bleed one unit (500 ml), infuse
500 ml of saline
…Bleed a second unit and infuse
two units.
…Repeat. If the patient has a
large blood mass, do it
again.
Transfusion in Sickle Cell
(exchange transfusion)
... A comprehensive transfusion protocol should include
accurate records of the patient’s red cell phenotype,
alloimmunization units rechistory, number of eived,
serial Hb S percentages, and results of monitoring for
diseinfectious ases and iron overload.
…Transfusions are used to raise the oxygen-carrying
capacity of blood and decrease the proportion of sickle
red cells.
Transfusion in Sickle Cell
(exchange transfusion)
Transfusions usually fall into two
categories :
…episodic, acute transfusions to
stabilize or reverse complications.
…long-term, prophylactic transfusions
to prevent future complications.
Transfusion in Sickle Cell
(exchange transfusion)
… episodic, acute transfusions to stabilize or
reverse complications.
-Limited studies have shown that aggressive
transfusion (get Hgb S < 30%) may
help in sudden severe illness.
-May be useful before general anesthesia.
Transfusion in Sickle Cell
(chronic transfusion therapy)
Stroke
Chronic debilitating pain
Pulmonary hypertension
Setting of renal failure and heart failure
Transfusion in Sickle Cell
(chronic transfusion therapy)
Controversial uses :
..Prior to contrast media exposure
..Sub-clinical neurological damage
..Priapism
..Ulcers
..Pregnancy
Erythrocytapheresis thus has the
advantage of controlling iron
accumulation in patients with
sickle cell disease who undergo
long-term transfusion, and the
ability to achieve adequate Hb
and HbS concentrations without
exceeding the normal
concentration.
This precision is achieved because
the computer in the pheresis
machine is able to use various
physiologic parameters such as
height, weight, and Hb level to
compute expected amount of
packed RBCs required to obtain a
specific hemoglobin level.
Further, erythrocytapheresis
requires the least amount of
time when compared to
using similar blood volumes
on patients receiving simple
blood transfusions.
Although erythrocytapheresis is more
expensive than simple transfusion, if
the cost of chelation and organ damage
due to iron overload is considered,
erythrocytapheresis without
chelation costs less than simple
transfusion programs.
Central venous access devices
can safely be used for
long-term
erythrocytapheresis in
patients with sickle cell
disease with a low rate of
complications.
Transfusion in Sickle Cell
Inappropriate uses of transfusion:
..Chronic steady-state anemia
..Uncomplicated pain episodes
..Infection
..Minor surgery
..Uncomplicated pregnancies
..Aseptoic necrosis
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