sca

1. Dr shamsheer ali p t
moDerateD by:Dr.sheena
siCKle
Cell
anaemia

2.  I am the red of the blood responsible for
respiration;
 Deliver oxygen to tissues and return co2 to
lungs;
 influenced by factors ph, BPG, Cl in my
functions;
 disturbed in duties by structural abnormalities.

3.  Hb is tetrameric protein
 Consists of heme and globin .
HEME
 Red cell to blood
 Contains porphyrin molecule pp9 with fe at
centre
 4 pyrrole rings iron at centre .
 Iron binds with aa histidine of globin
 Also binds to o2.

4. globin :consist of two pairs of polypeptide chain.
(alpha & beta)
Abnormalities in these proteins leads to
hemoglobinopathies
Genes for hemoglobin production lies on
chromosome no 16 and 11 .
Chromosome 16 3 genes(zeta,alpha 1 n 2 ) ,chrom
11 5 genes(epsilon,2 gamma,delta genes,beta
genes )
 Molecular weight of Hb is 64000

5.  Hb A1- 97% of adult haemoglobin, consists of 2
alpha & 2 beta chains.
 Hb A2- Consists of 2 alpha & 2 delta chains.
 Hb F - 70 – 90% at birth, 25% by 1 month and
5% by 6months of age, consists of 2 alpha & 2
gamma chains.

6.  In the year 1904 cardiologist and professor of
medicine James B Herrick found peculiar elongated
cells in blood of a 20 years old dental student who
was suffering from anemia.
 Veron Mason in 1922 named SICKLE CELL
ANAEMIA.
 Linus Pauling in 1940 demonstrated that sickling
occurs as a result of abnormality in haemoglobin
molecule.
 Sickle cell disease is the first genetic disorder whose
molecular basis was known.
 June 19th
is celebrated as World Sickle Cell Day

8.  Sickle cell disease in Wayanad, Kerala: gene
frequencies and disease characteristics.
 Department of Pathology, Medical College,
Kerala, India.
 A large number of patients with sickle cell
anaemia are seen at the Medical College,
Calicut from among the tribals and Chetti
communities of the adjacent Wayanad district.
We carried out a population-based study of
gene frequencies and disease characteristics to
plan an appropriate intervention.

9. methoDs:
CliniCal examination anD haemoglobin
eleCtrophoresis were Done in 1016
subjeCts belonging to the tribal anD
Chetti Communities in wayanaD DistriCt,
by visiting hamlets anD sChools anD
evaluating everyone present at the
time of the visit.

10. results:
the gene frequenCy of haemoglobin s
rangeD from 0.019 in KattunayaKan to 0.196 in
wayanaDan Chettis. wayanaDan Chettis, Kurumas anD
aDiyas showeD a high number of homozygotes with the
olDest being 48 years. the survival of homozygotes is
longer than what is generally reCorDeD in other
states. the Disease was milD in 52.2% of Cases. painful
Crises were founD in 43.5% anD splenomegaly anD leg
ulCers in 4.3% eaCh. the mean haemoglobin f rate in
homozygotes was 25.9%. it was higher in CliniCally milD
Cases anD in those showing an absenCe of irreversible
siCKle Cells in the peripheral smear.

11. ConClusions:
the survival of patients with siCKle
Cell anaemia seems to be higher in Kerala as
CompareD to other states. it appears that
even small improvements in primary health
Care available to the population (as in
Kerala) are suffiCient to aChieve this effeCt.
integration of Disease Diagnosis anD
management into the alreaDy existing health
Care Delivery system may leaD to even
better survival anD quality of life

12. 1. HOMOZYGOUS AND HETEROZYGOUS SICKLE
CELL DISEASES.
2. HOMOZYGOUS means mutant gene inherrited from
both parents (HbSS) i.e sickle cell anemia
3. HETEROZYGOUS means (HbAS) only one gene is
affected other one is normal i.e sickle cell trait.
4. Sickle cell disease----sickle cell anemia +sickle cell traits
5. Haemoglobin C (HbSC)
6. Haemoglobin E (HbSE)
7. Haemoglobin S beta Thalasseamia-This is a mild form
of sickle disorder.

13.  Sickle cell anemia is a autosomal recessive
genetic disease that results from the
substitution of Valine from Glutamic acid in
position 6 of beta globin gene leading to
production of defective form of haemoglobin.
(Hb S)
 Hb S is a structurally defective haemoglobin.

14.  Hb s …sticky patches n receptors
 Deoxy hbs ..sticky patches n receptors
 Oxy hbs …only sticky patches n receptors
masked
 Deoxy hba ..only receptors no sticky patches
 So oxy hbs prevents sickling ..

15.  Deoxygenation leads to hydrophobic
interaction between adjacent Hb S molecules.
 Distortion of RBC into sickle form cells
 Rapid haemolysis
 Decreased elasticity of cell wall of RBC
 Decreased life span 10 – 20 days.
 Clogging of RBC in microcirculation.

18.  Vasooclusive crisis
 Haematological crisis
 Aplastic crisis
 Sequestration crisis
 Infectious crisis

19.  Often first manifestation of sca
 50% of children by 2 yrs of age
 Symmetrical or unilateral swelling of the hands
 Not to be confused with osteomyelitis as mgt
varies….

21.  Obstructed microcirculation leading to ischemic injury to
organ
1. Avascular necrosis
2. Acute chest syndrome
3. Acquired asplenia
4. Splenic sequestration
5. Hand foot syndrome
6. Papillary necrosis in kidneys
7. Hyposthenuria and enuresis
8. Cerebral infarction
9. Skin ulceration
10. Retinal hemorrhage and retinopathy
11. Priaprism

22.  seriously ill appearance
 hypotension sbp<70 @ 1 year of age,<70+2*age (in
year)
 Poor perfusion crt>4 seconds
 Temperature>40 c
 Wbc>30000/<500
 Platelet count <1 LAKH
 H/O PNEUMOCOCCAL SEPSIS
 Sever pain
 Dehydration
 Hb <5 gm

23.  Acute splenic sequestration, pooling of blood in
the engorged spleen
 Aplastic crisis – Seen in patients with parovrus B-
19 infection or folic acid deficiency leading to
decreased marrow
erythropoiesis..reticlopenia..dictum
 Anemia
 Pigmented gallstone
 Jaundice
 Delayed growth

24.  Infectious crisis is due to functional asplenia and
deficiency of opsonin of alternate compliment
pathway.. decreased level of serum
immunoglobulin M (IGM) increasing susceptibility
to infections.
 Haemophilius influenzae, streptococcus pneumoniae,
mycoplasma pneumoniae, salmonella typhimurium,
staphylococcus aureus, and escherichia coli are the
common causative microbes.
 Common infections include pneumonia,
bronchitis, pyelonephritis, cystitis, osteomyelitis,
meningitis, and sepsis

25.  Life threatening compli..
 Spleen becomes enlarged and engorged with
decline in hb,hypovolemia
 Etiology not known
 Parents to be taught to palpate spleen and seek
intervention at the earliest.

26.  Cardinal feature ..
 May involve chest ,abdomen and extremities
 Wonk baker Faces scale for pain
 Cause is due to decreased blood flow in
microvessels resulting in tissue ischemia

27. Phase Pain charcteristics Comfort measure
Baseline No vaso occl pain
,complicaton may be
present
No measures
Pre pain Prodrome of vasoocc
signs +..
INC FLUIDS
Pain start point First signs of vo Mild analg,fluids ,
Pain acc Mild to moderate Stronger
anal,rubbing,heat,
Peak pain exp High mod to severe Oral analg round d clck,
Pain decreas frm start
point
Decrease frm peak Caregivers console not
active
Steady pain decline Decr mre rapidly Wean frm iv analgesi
Pain resolution Tolerable pain
Normal
Oral analg

28.  Involuntary penile erection lasting for more than 30
min ..for an hour suggests priapism
 Ventral portion of glans of the penis is not involved
 Types
 Stuttering and refractory types
 Former self limiting,intermittent bouts
 Latter continuous for hour
 Rx is sitz bath for acute mgt
 Lasting >4 hrs then aspiration of blood from corpora
cavernosa followed by irrigation with epinephrine
 Etilefrine is safe drug for priapism prevention.

29.  CVS-Anemia and vasooclusive phenomena causing myocardial ischemia
and myocardial infarction, repeated blood transfusion leading to
restrictive cardiomyopathy.
 Pulmonary-Acute chest syndrome
 CNS-25% patient have TIA, strokes, cerebral hemorrhage,rpls reversible
post leuco encephalopathy syndrme.
 Excessive iron stores ..occurs in children receiving regular
transfusion..mri r2* liver , r2 heart . deferasirox
 Lung disease 2 nd most common
 Acs…radiodensity acute+fever+respi distress+pain in chest or back
abdomen
 Hepato biliary system-Gall stone recurrent abdominal pain,
autosplenectomy
 Urinary system- Haematuria, hyposthenurea and renal failure
 Ocular complication- Proliferative retinopathy, vitreous hemorrhage and
retinal detachment
 Orthopedic – Hand foot syndrome, avascular necrosis of hip,
osteomyelitis

35. 1. Young infants have recurrent edema of the dorsum of
hands and feet.
2. Infarction of cortex of long bones lead to prominent signs of
local inflammation.
3. Repeated infarction in the joints of large and small bones
lead to abnormal angled digits, malformed and frozen joints,
particularly at the knee and ankle.
4. Chronic leg ulcer is common in adolescent patients.
5. Abdominal examination may reveal splenomegaly if
sequestration is occurring otherwise the spleen is small in
size due to autoinfarction
6. Evidence of cholilethiasis is seen in patients as young as 3
years old.
7. By mid childhood most patients are underweight as
compared to children of their same age and height.

37. 1. There is a higher rate of spontaneous abortion. A
miscarriage may happen up to 25% of the time.
2. There is ahigher rate of babies not surviving to birth
or being stillborn. 8-10% .
3. Birth weight is lower than average.
4. Infection is more common in women with sickle cell
disease during pregnancy, especially bladder
infection.
5. Increased chance of PIH and preeclampsia
6. Increased incidence of PPH.

38.  Hb-6-8gm%
 Reticulocytes high
 Peripheral smear may show sickle cells
 Features of hyposplenism :Target cells and
Howell- Jolley bodies seen
 Sickling test with reducing agent Sodium
metabisulphide-na dithionite
 Hb electrophoresis
 High performance liquid chromatography(HPCL)
 WBC may be elevated
 Bilirubin may be elevated
 Urinary cast may be seen or trace of RBC in urine

39.  When subjected to electrophoresis in alkaline
medium sickle cell hb move towards anode
slow than does adult hb.
 Slow mobility of hbs is due to absence of –ve
charge caused by loss of glutamate.
 Incase sickle cell trait fast moving hba and slow
moving hba are seen.

40. 1. Oxygenation
2. Pain Management (NSAID, OPIODS)
3. Hydroxyurea15-20mg/kg daily upto 35
mg/kg/dose, Folic acid
4. Hydration
5. Blood Transfusion
6. Antibiotics (Penicillin group)
7. Steroids
8. Bone marrow transplantation
9. Gene therapy

41.  Blood transfusion is currently the most
effective and proven treatment for severe
anemia of SCD, it significantly reduces crisis.
 Blood transfusion reduces pain by increasing
the number of functioning RBC and by
increasing the oxygen caring capacity of blood

42.  Bone marrow transplant is the closest thing
possible to the cure of SCA.
 Helps in production of healthy RBC from
transplanted bone marrow
 The success rate is 90 – 95%

43.  Gene therapy is a relatively new idea of
inserting genes into the cells of an individual in
order to treat hereditary disease such as SCA,
in which a defective mutants alleles is replaced
with a functional one.
 Gene therapy would be the best cure for SCA
in future, as of now it is on it’s experimental
stage.

44.  Dialysis or kidney transplant for renal failure.
 Cholecystectomy for pigmented cholelitheasis.
 Hip replacement for avascular necrosis.
 Surgery for eye problem.
 Irrigation surgery for Priapism.
 Wound care for leg ulcer.

45. 1. Genetic counseling
2. Pre implantation genetic diagnosis
3. High perfomance liquid chromatography to
detect hb phenotype. In new born ..
4. Perenatal testing -amniocentesis (16 – 18 wks)
and chorius villus sampling ( 9 -10 wks)

46. 1. Regular health check up & good hydration.
2. Vaccination for pneumonia, meningitis, influenza,
and hepatitis
3. Preventing infection – daily dose of penicillin
4. Preventing strokes – Transcranial doppler
ultrasound every 3 months.
5. Preventing eye damage – Fundus examination
every 3 months.
6. Avoid alcohol, smoking, cold climate, high
altitude exposure.
THERE ARE 4 MILLION SICKLE CELL DISEASED
PATIENTS WORLDWIDE

47.  Malaria caused by plasmodium falciparum .
 The parasite spends part of its cycle in
erythrocytes.so lysis interupts cycle
 Mp increases acidity of erythrocytes which in
turn cause increased sickling to 40 % frm nrml
2%.therefore entry of mp cause incresased
sickling and lysis
 Concn of pottasium is low in sickle cells
unfavourable for mp to survey

49.  Hb Gower 1-Confined to embryonic stage,
consists of 2 alpha & 2 epsilon chains.
 Hb Gower 2-Consists of 2 alpha & 2 zeta
chains.
 Hb Portland- Found in trace in neonates and
intrauterine life.
 Hb –Brat’s –Found in small amount in cord
blood of neonates with thalasseamia.

50.  New concepts in the field of priapism research
suggest that priapism often results from altered
vascular homeostatic actions in the penis and is
associated with deficient erection control
mechanisms on a molecular level.
 A leading proposal in this regard is the
notion of aberrant signaling of the
endothelium-derived nitric oxide and PDE5
signal transduction pathway in the penis.

51.  Additionally, dysfunctional regulatory control
of signal transduction systems which interact
with this pathway such as adenosine and
RhoA/Rho-kinase may contribute to the
development of priapism.Recent investigations
of opiorphins also demonstrate a role in
regulating corporal smooth muscle tone and
thereby dysregulation of erection physiology in
priapism. These advances have paved the way
for understanding this disorder as having a
molecular pathogenesis.

52.  The Human Genome Project has provided
valuable insight and extensive
research advances in the understanding of the
human genome and sickle cell disease.

53.  A 3.5-year-old girl from race of Arab reffered to Shafa Hospital with
severe anemia, thrombocytopenia, leucocytosis and elevated ESR and
LDH. Her parents assigned fever, cough, pallor, weakness and
tachypnea from six day ago (Figure 1).
 Fig. 1
 Chest x ray.
 Past medical history and familial history of the patient was negative.
On physical examination, she had fever with temperature of 39.5°C,
severe pallor, pulse rate of 110 per minute, respiratory rate of 32 per
minute and blood pressure of 90/60 mmHg. On abdominal
examination, she had hepatosplenomegaly. Rales and rhonchi were in
both lung fields on respiratory examination while the other systemic
examination was essentially normal. Initial laboratory investigations
demonstrated hemoglobin of 4.5 gm/dL, white cell count of
19,000/mm(3) (55% neutrophils, 45% lymphocyte), platelet count of
70,000/mm(3) and an erythrocyte sedimentation rate of 45 mm/hour.
Renal function tests and urinalysis were normal. A chest radiograph
revealed bilateral haziness. For decline of malignancy, bone marrow
aspiration was done and discussed reactive bone marrow due to
infection.
 ootnotes

54.  After one day a dactylitis was present in hands
of the patient (Figure 2).
 Fig. 2
 Dactylitis.
 In follow up of Hb electrophoresis, Hb s was 80%, Hb F: 18%, and
Hb A2: 2%. Finally in peripheral blood smear, sickling of RBC was
detected and the patient was diagnosed with sickle cell anemia
and acute splenic sequestration crisis which was associated with
acute chest syndrome treated with wide spectrum antibiotic
(cefotaxim and erythromycin) and transfusion exchange (Figure
3). The patient was discharged with stable clinical state after 8
days.
 F

55.  Fig. 3
 Prepheral blood smears with sickle cell.
 The clinical presentation of our patient is rare
and unusual for initial presentation of sickle
cell anemia. Also association between acute
chest syndrome and splenic sequestration is
unusual.
 Go to:

56.  Nelson 19th
edition
 Biochemistry U satyanarayanan
 William’s hematology
 www.pubmed.com.

57. THANKs…