DREPANOCYTOSIS AND PANMYELOPHTISIS AKA SICKLE CELL ANEMIA

1. Drepanocytosis &
Panmyelophthisis
J Darshan Ranganath

2. DREPANOCYTOSIS
• Also known as sickle cell anaemia
• Characterised by the presence of Hbs which
imparts sickle shape to the RBCs during reduced
oxygen tension
• Autosomal Recessive

4. GEOGRAPHICAL DISTRIBUTION

5. • Sickle cell anaemia –SS one gene each from both
the parents
• Sickle cell trait- heterozygous state-AS-one gene
from one parent is for HbS while other gene is
for HbA
• Sickle cell disease- refers to all diseases in which
atleast one gene is of HbS which maybe in
combination with normal or abnormal gene eg.
Thalassemia,HbE,HbC,etc..

6. GENETICS – PUNNETT SQUARE

7. Hemoglobin S (Hb S) is the result
of a single base pair change,
thymine for adenine, at the 6th
codon of the β-globin gene.
This change encodes valine instead
of glutamine in the 6th position in
the β-globin molecule

8. PATHOGENESIS

9. CLINICAL FEATURES
• Age of onset – 3 months to 1 year of life
(<3 months- HbF protects RBCs)
• Growth and development – reduced height
& weight , delayed puberty
• Bony Abnormalities – Hand food syndrome ,
Cod fish spine, Osteomyelitis due to
staphylococcus, salmonella
• Spleen- initially enlarges but after 5-6 years of
age autosplenectomy

10. SICKLE DACTYLITIS
SALMONELLA TYPHIMURIUM
OSTEOMYELITIS

11. • Infections-
pneumonia,meningitis,osteomyelitis
• Cardiopulmonary system-
Acute chest syndrome (fever,chest
pain,^WBC,pulmonary infiltrates) , Atypical
Pneumonia,Cardiomegaly,Anaemia
• Hepatobiliary system: Jaundice,
Hepatomegaly,Gall Stones
• Genitourinary-Renal Papillary
Necrosis,Priapism
• Eye- Sickle retinopathy(salmon patch
haemorrhages n sea fans)
• CNS- stroke
• Leg ulcers

12. ACUTE CHEST SYNDROME
LOWER BULBAR
CONJUNCIVA -
SEQUESTRSTIONS

13. CRISES
• SICKLING CRISIS
• HAEMOLYTIC CRISIS
• APLASTIC CRISIS
• SEQUESTRATION CRISIS

14. INVESTIGATIONS
• HAEMATOLOGICAL FINDINGS
Anaemia,WBC- TLC shift to left,Platelets ^
Peripheral smear – Anisopoikilocytosis,Sickle
cells,Target cells,Ovalocytes,Howell Jolly bodies
if autosplenectomy has taken place
Reticulocytosis,low
haptoglobulin,^urobilinogen,low ESR
Marrow- Hypercellular with erythroid hyperplasia
demonstrating normoblastic reaction

15. DIAGNOSTIC TESTS
• Sickling test- adding reducing agent like 2%
sodium metabisulphite
• Hb electrophoresis – Hb S is a slow moving Hb
• HPLC
• Hb F estimation
• Family studies
• Hb S solubility

16. PRINCIPLES OF TREATMENT
• Folic acid
• Patient education – awareness about
precipitating factors about crisis
• Hydroxy urea- reduces the incidence of sickling
and elevates Hb F
• Blood transfusions
• Treating infections

17. PREVENTION
• Chorionic villous sampling at 10-12 weeks
gestational age

19. PANMYELOPTHISIS
• Synonymous with Aplastic Anaemia
• Aplastic anemia is a clinical syndrome
manifested as a deficiency of red cells,
neutrophils, monocytes, and platelets in the
blood, and fatty replacement of the marrow with
a near absence of hematopoietic precursor cells

20. NORMAL MARROW APLASTIC MARROW

21. BONE MARROW IS THE BLOOD
FACTORY!
• MAY BE EXPOSED TO DAMAGE OR FAILURE

22. CAUSES

23. HEREDITARY
• Fanconi’s anaemia
• Dyskeratosis congenita
• Dubowitz syndrome
• Seckel syndrome
• Reticular dysgenesis
• Shwachman Diamond
• WT syndrome

24. DRUGS
• Antibiotics-
Chloramphenicol,cotrimoxazole,nitrofuratoin
• Antiinflammatory-
Phenybutazone,Indomethacin,Diclofenac
• Antithyroid-Carbimazole,Methimazole,Methyl
thiouracil
• Psychotropic-Phenothiazine
• Anticonvulsant-Phenytoin
• DMARD-Gold salts,d-penicillamine
• Cytotoxic drugs-
Vincristine,Adriamycin,methotrexate

25. TOXINS
• Benzene
• Commercial solvents
• Aresenic
• Ionizing radiation
VIRUS
• Epstein-Barr virus
• Non-A, non-B, non-C, non-D, non-E, and non-
G hepatitis virus
• Human immunodeficiency virus

26. AUTOIMMUNE/CONNECTIVE TISSUE
DISORDERS
• Eosinophilic fasciitis
• Immune thyroid disease (Graves disease,
Hashimoto thyroiditis)
• Rheumatoid arthritis
• Systemic lupus erythematosus

27. PATHOGENESIS
• Stem cell defect
Environmental
factors
• Activated T cells
of CD8 type
hampering stem
cell proliferation
Immune
mechanism

28. CLINICAL FEATURES
LOW
RBC
fatigue
Shortness
of breath
Chest pain
pallor
Coldness in
feet/hands
dizziness

29. Low
WBC
fever
infection
Low
Platelets
Easy
brusing
Prolonged
bleeding

30. HAEMATOLOGIAL FINDINGS
• PANCYTOPENIA – paucity in WBC, RBC,
platelets,decreased Hb,PCV
• RETICULOCYTOPENIA
• BONE MARROW ASPIRATE – marked
hypocellularity(replaced by fat), paucity of
erythroid,myeloid and megakaryocytic
precursors
• BONE MARROW TREPHINE BIOPSY

31. MARROW SMEAR APLASTIC BIOPSY

32. PRINCIPLES OF TREATMENT
• SUPPORTIVE
- packed red cells for anaemia
- platelets for thrombocytopenia
- G-CSF/GM CSF to raise neutrophil count
- Antibiotics prophylactically

33. ATTEMPTS TO RESTORE MARROW
ACTIVITY
• IMMUNOSUPPRESIVE THERAPY –
Antilymphocytic
globulin,Cyclosporin,Antithymocyte globulin
• ANDROGENS/ANABOLIC STEROIDS
• ALLOGENIC BONE MARROW
TRANSPLANTATION