Nit mine

1. Approach to
Pancytopenia
Dr. Murtaza Kamal
MBBS, MD, DNB
Clinical Fellow (Pediatric Hemato-Oncology)
Rajiv Gandhi Cancer Institute & Research Center,Rohini, New Delhi
Dt: Feb 16,2017
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2. The terms…
• Cytopenia: Reduction in either of the cellular component
of blood
• Bicytopenia: Reduction in any of the 2 two cell lines of
blood
• Anemia + Thrombocytopenia- 77.5%
• Anemia + Leukopenia-17.3%
• Thrombocytopenia + Leukopenia-5.5%*
• *Neelam Verma et.al. Pediatric patients with bicytopenia/pancytopenia: Review of etiologies and clinicao-
hematological profile at a tertiary center. Indian Journal of Pathology and Microbiology;54(1), Jan-Mar 2011.
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3. The terms…(cont.)
• Pancytopenia: Reduction in all 3 cell lines of blood
The values of the 3 components being:
• Hb <13.5(M)/ 11.5(F) g/dl
• TLC< 4000/cu mm
• Platelets <1,50,000/ cu mm*
• *De Gruchy GC. Pancytopenia, aplastic anemia. De Gruchey’s clinical hematology in medical practice. 5th edition
• *Frank F. De Gruchey’s clinical hematology in medical practice. 5th edition. Blackwell:Berlin;2004:1199.
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4. It can occur due to:
• Bone marrow failure
• Marrow space occupying lesions
• Ineffective marrow production
• Peripheral destruction of hematopoietic cells
• Elizabeth P. et al. The differential diagnosis and bone marrow evaluation of new onset Pancytopenia. AM J Clin Pathol
2013;139:9-29. 4

5. Causes…
CAUSES OF
PANCYTOPENIA
INHERIT
ED
ACQUIR
ED 5

6. Inherited Causes…
Elizabeth P. et al. The differential diagnosis and bone marrow evaluation of new onset Pancytopenia. AM J Clin Pathol
2013;139:9-29.
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7. 7

8. Causes of childhood
pancytopenia
Category Condition B M Appearance
Aplastic anemia Idiopathic Hypocellular
Inherited BM failure
syndromes
Hypocellular
Drugs/Toxin associated Hypocellular
Megaloblastic Anemia Acquired Hypercellular
Congenital deficiency Hypercellular
Malignant infiltration ALL/AML Hyper/Hypocellular
MDS Hyper/Hypocellular
Hodgkin’s disease Infiltrated
Solid tumors Infiltrated
Histiocytic Syndromes Hypocellular with
hemophagocytosis
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9. Causes of childhood
pancytopenia (Cont.)
Category Condition B M Appearance
Non-malignant infiltration Storage disorders Infiltrated
Osteopetrosis Increased bony
trabeculae
Infection CMV, EBV, Parvovirus,
HHV-6, Hepatitis, HIV
Hypocellular(Pro-
erythroblasts in parvo-
virus)
Immune disorders SLE Hypercellular
Evan’s syndrome Hypercellular
Thymoma Hypocellular 9

10. Causes of childhood
pancytopenia (Cont.)
Category Condition B M Appearance
Acquired clonal bone
marrow failure disorder
PNH Variable
Metabolic Hypothermia Variable
Anorexia nervosa Hypocellular with fat
necrosis
Others Hypersplenism Hypercellular
*Bharat R Agarwal et al. Aplastic Anemia: Current Issues in Diagnosis and Management. Practical Pediatric Hematology.
2nd edition. Jaypee pg 58
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11. Common causes in Indian
Children*
Neelam Verma et al. Pediatric patients with bicytopenia/pancytopenia; Review of etiologies and clinico-hematological profile at a tertiary cente
Indian Journal of Pathology and Microbiology. 54(1), Jan-March 2011. PGI-Chandigarh
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12. Common causes in our
country(Cont…)*
Jain A et al. An etiological reappraisal of pancytopenia- Largest series reported to date from a single tertiary care teaching hospital
. BMC Hematology,13,10. 2013. Maharastra
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13. How to approach?
History Physical
Examination
Investigations
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14. Points to consider in history
• Age
• Sex
• Duration of symptoms
• Bone pains, fever, night sweats, malaise, weight loss
• Bleeding from any site
• Jaundice
• Joint pain, rash, photosensitivity
• Any radiation exposure
• Exposure to potentially toxic chemicals
• Treatment history including herbals and drug intake, blood
transfusions
• Dietary history
• Occupational exposure history
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15. Clinical Examination
• Anthropometry including stature
• Dysmorphic features
• Pallor, Jaundice, Lymphadenopathy, Edema
• Sings of CHF
• Stomatitis, cheilitis
• Nail dystrophy, leukoplakia, skin pigmentation
• Oral candidiatis, pharyngeal exudates
• Petechie, purpura, hyperpigmentation
• Sternal tenderness
• Gum hypertrophy
• Hepatosplenomegaly
• Joint swelling, sinuvitis 15

16. Signs & Symptoms
Neelam Verma et al. Pediatric patients with bicytopenia/pancytopenia; Review of etiologies and clinico-hematological profile at a tertiary
center. Indian Journal of Pathology and Microbiology. 54(1), Jan-March 2011. PGI-Chandigarh
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17. Lab Evaluation:
1. CBC WITH
PERIPHERAL BLOOD SMEAR
2. BONE MARROW ASPIRATION
AND BIOPSY
3. SPECIFIC INVESTIGATIONS 17

18. PERIPHERAL BLOOD SMEAR
Anisocytosis and poikilocytosis
WBC and RBC precursors
Platelets
Granulation in neutrophils (Abnormally
increased/decreased)
Neutrophils(Hypo/Hypersegmentation)
ESR
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19. 1. Anisocytosis & Poikilocytosis
MODERATE DEGREE IS COMMON
Very marked Poikilocytosis: MYELOFIBROSIS
Less degree: APLASTIC ANEMIA,
MARROW INFILTRATION BY
LYMPHOMA/MULTIPLE MYELOMA
Invariably absent: ACUTE LEUKEMIA 19

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21. RBC INDICES
• RDW: Usually increased
• MCV: Can be increased or normal
• RETICULOCYTE COUNT- Define severity and
differentiate production vs. destruction
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22. 2. WBC AND RBC PRECURSORS
Blast cells: Myelofibrosis
Acute leukemias
Subleukemic leukemias
Plasmacytic cells: Multiple myeloma
Immature lymphocytes: Marrow
involvement by lymphoma
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23. WBC AND RBC PRECURSORS ARE
NOT TYPICAL OF APLASTIC
ANEMIA
SO THEIR PRESENCE IN
PANCYTOPENIA SUGGEST
DIAGNOSIS OTHER THAN
APLASTIC ANEMIA
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24. RBC INCLUSIONS:
HOWEL JOLLY BODIES
• Basophilic nuclear
remnants (clusters of
DNA) in RBCs
• Megaloblastic anemia
• MDS
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25. 3. Platelets
• Normal Platelets: Aplastic Anemia
• Giant Platelets: MDS
Hypersplenism
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26. 4. ABNORMAL GRANULATION IN
NEUTROPHILS
• Toxic granules: Infections
• Hypo granular neutrophils: MDS
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27. 5. HYPO/HYPERSEGMENTATION
IN NEUTROPHILS
• Hyper segmented Neutrophils: Megaloblastic Anemia
• Pelger Huet like cells: MDS,
Chronic leukemias,
Folate and B12 deficiency.
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28. HYPERSEGM
ENTATION
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29. 6. ESR
• Increased in : Infections
Multiple myeloma
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30. BONE MARROW EXAMINATION
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31. Bone Marrow Examination
Almost always indicated in cases of pancytopenia unless
cause is apparent
Both aspiration and biopsy are indicated
Specifically, bone marrow aspirate permits examination of:
• Cytology (megaloblastic change, dysplastic changes,
abnormal cell infiltrates)
• Immunophenotyping : antigen or marker on cells
surfaces e.g ( leukemias, lymphoproliferative disorders)
• Cytogenetics : structure of chromosome
(myelodysplasia, leukemias, lymphoproliferative
disorders)
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32. Cellularity of Bone Marrow
The differential diagnosis of pancytopenia are based on
cellularity of bone marrow :
Hypocellular: excessive amount of fat cells
Normocellular: 50-70% hematopoietic cells & 30-50% fat
Hypercellular: 80-100% cells with little fat
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33. HYPERCELLULAR
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34. Bone Marrow Examination findings
Features Seen in
CELLULARITY HYPERCELLULAR: Megaloblastic anemia, Hyperslenism
DRY TAP: Myelofibrosis
HYPOPLASTIC: Myelodysplastic syndromes
ERYTHROPOIESIS DYSPLASTIC: MDS, some AML
INCREASED: Hemolysis
MYELOPOIESIS DYSPLASTIC: Myelodysplastic syndrome
Mophologically normal: Myeloproliferating disorders
BLASTS Myelodysplastic disorders, Acute Leukemias
MEGAKARYOPOIESIS DYSPLASTIC: Myelodysplastic disorder
OTHER CELLS Reedsternberg cell: Hodgkin cell
Bacteria, Fungus, Parasite, Viruses, LD bodies 34

35. SPECIFIC
INVESTIGATIONS
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36. TEST RATIONALE
BONE X-RAYS Multiple myeloma, metastasis
BLOOD CULTURE Infectious agent- Tuberculosis or virus
VITAMIN B12 AND FOLATE ASSAYS Megaloblastic anemia
LFT Evaluate hepatitis
KFT Assess for Chronic Renal Failure
SEROLOGY HIV, EBV, Hepatitis
HAM’S TEST Paroxysmal Nocturnal Haemoglubinuria
CHROMOSOMAL BREAKAGE
STUDIES
Fanconi anemia
ANA test Systemic Lupus Erythematosus
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37. Thanks for your
Attention
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