This document discusses several blood disorders including pancytopenia, aplastic anemia, myelodysplastic syndrome, sideroblastic anemia, and iron overload. Pancytopenia is a low blood cell count affecting red blood cells, white blood cells, and platelets. Aplastic anemia is a bone marrow failure syndrome causing pancytopenia. Myelodysplastic syndrome is a group of disorders where the bone marrow does not make enough healthy blood cells, which can progress to acute leukemia. Sideroblastic anemia and iron overload are also discussed in regards to their causes, presentations, and treatments.
2. Learning objectives
• ✓ To identify pancytopenia
• ✓ To recognize the clinical manifestations
• ✓ To list treatment lines of aplastic anaemia
• ✓ To differentiate MDS from AA
• ✓ To define sideroblastic anemia
• ✓ To appraise complications and prevention of iron overload
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4. Aplastic anemia
•Syndrome of BM failure
• HSC disorder (cytotoxic CD8+ T cells)
•pancytopenia & reticulocytopenia
• All cells are normal looking
• No abnormal cells seen
• with hypocellular bone marrow
• replaced by fat cells
• result in deficient production of all the blood cells
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5. CLINICALLY:
•At least 2 findings:
•Hb <100 g/l
•Neutrophil count <1.5x10^9/l
•Platelet <100 x10^9/l
•Hypocellular BM <25%
•With no abnormal cell in blood or BM
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6. Types
I. Inherited AA (constitutional):
less common, progressive, risk of AML
• Fanconi anemia,
• Dyskeratosis congenita
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7. • Fanconi anemia is an autosomal recessive inherited disorder
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8. Types
II. Acquired AA
1) Idiopathic;
primary;
common(65%)
2) Acquired
secondary;
•Possible cause?????
1. drugs: unproven yet,
after 2-3 months
I. Antibiotics
II. Anti-malarial
III. Anti-inflammatory
IV. Anti rheumatic
V. Anti-epileptic
VI. Anti-thyroid
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10. Incidence: idiopathic AA
•2-5/million per year in west
•5 times > east Asia
•All age group
•Biphasic age;1st at10-25yrs, 2nd>60yr
•Equal for both sex
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11. Clinical presentation
Blood cell reduced in number but normal
function
•Usually well at presentation
•Bleeding tendency
•(skin, gum,vaginal,CNS)
•Anemia
•Infection (fever, sepsis)
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13. Investigations
•Confirm diagnosis
•Find reversible cause
1.CBC; Pancytopenia,
Macrocytosis.
Reticulocytopenia
NO abnormal cells
NO dysplastic
features.
NO blast cell
2. BM biopsy ; hypocellular
marrow , increased fat
spaces
• virology, serology
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14. Definition of severity
Guide for treatment & prognosis
Severe AA; any 2 of
• neutrophils<500 cells(0.5x10^9/l)
• Platelets <20 000 (20x10^9/l)
• Reticulocyte< 20 000 (20x10^9/l)
Very severe AA;
• neutrophils <200 cells(0.2x10^9/l)
Non severe AA
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15. Differential diagnosis
•Pancytopenia with
bone marrow
failure:
1.Hypoplastic acute leukemia
2.Hairy cell leukemia
3.Myelofibrosis
4.BM metastasis
5.PNH
•Pancytopenia with
active cellular
marrow:
1.Hypersplenism
2.Megaloblastic anemia.
3.MDS
4.Auto immune disease (SLE)
5.Sepsis ,miliary TB
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16. Treatment
•Supportive : immediately
•Accelerate BM: long term
Initial supportive measure
1. Discontinue potential agent
2. Transfusion packed RBC. ( Hb 8-10g/dl),
leucocyte depleted, Iron overload >20-25 units
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17. Treatment
3.Avoidance &control bleeding
• if plat.<20 000/mm, or at bleeding.
• Antifibrinolytics (tranexamic acid)
• oral hygiene, soft brushing, norethisterone, no
NSAID or trauma, IM injection.
4. Prevention of infection
5. Treatment of neutropenic fever
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18. Accelerate BM activity
1. Allogenic stem cell transplantation-SCT
• severe or very severe AA, <30 yrs ,before multiple
transfusion
• HLA identical donors
75%-90% cure.
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19. Accelerate BM activity
2. Immunosuppressive therapy;
• if not eligible for SCT:
• Severe or very severe AA ( > 30 yrs & no donor)
• Non severe AA ,transfusion dependant
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20. Immunosuppressive therapy
• Combination of
•Antithymocyte globulin-ATG
immunosuppressive against cytotoxic T cells
•Cyclosporin
Inhibitors of T lymphocyte effect & productionIL-2,γ IFN
• Response 80%
• Anti CD 52 (Alemtuzumab)
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21. • Androgens &anabolic
steroids (in Fanconi’s
anemia)
Oxymethalon, danazole
• growth factors
• Eltrombopag :
thrombomimetic stimulates
platelet production
• G-CSF
• Iron chelating therapy
Prognosis
• Death 50% in 1 yr
(infection ,bleeding)
• progress to PNH,MDS,
acute leukemia (25-40%)
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22. Myelodysplastic syndrome MDS
•common cause of pancytopenia in elderly
•group of acquired clonal HSC disorders
characterized by
• Progressive BM failure with Dysplastic changes
• Resulting in cytopenias or pancytopenia
With defective function
• ineffective hematopoiesis (Increasing apoptosis )
• risk of development of AML (pre leukemia).
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23. Myelodysplastic syndrome MDS
Presentation:
Elderly Median age 60-65
like AA but
• splenomegaly, skin inflitration
• DDx
• Pancytopenia; AA,PNH, MF,AML
• Dysplasia; megal.anemia, alcohol
Death: marrow failure
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PSEUDO PELGER HUET CELLS
25. Iron overload
•Excess amount of total body iron
A. Excessive iron absorption; hereditary
hemochromatosis, ineffective erythropoiesis,
chronic liver diseases
B. Frequent blood transfusion;
C. Increased iron intake;
D. Combination
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28. Investigations
o Anemia +Reticulocytopenia
o Pappenheimer bodies
o Features of iron overload:
• high S.iron,
• low TIBC ,
• saturation >50%,
• high S.ferritin
o Increased marrow iron stores &ring sideorblast
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31. Diagnosis of iron overload
1. Evidences of iron overload
Very high serum ferittin and others
2. Evidences of iron tissue deposition
Liver MRI or biopsy: iron index
Cardiac MRI
BM
3. Evidences of tissue damage by iron
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32. Chelating therapy
• Desfrrioxamine B;
not absorbed orally, short half live,
IV,SC. infusion 12 hrs /night for 5
nights/week
SE; pain, necrosis, deafness, tinnitus, optic
neuritis, growth defect, infection
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33. Chelating therapy
•Deferiprone; oral , effective for tissue iron, cardiac
protection
• Deferasirox; new, oral, long life 16 hrs.
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34. Prognosis
•Early diagnosis & treatment before onset of
cirrhosis, to achieve normal life expectancy &
avoid hepatoma, DCMP
•Death; HF, arrhythmia
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