approach to pancytopenia
TRANSCRIPT
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Approach to Pancytopenia
Dr. Murtaza KamalMBBS, MD, DNBClinical Fellow (Pediatric Hemato-Oncology)Rajiv Gandhi Cancer Institute & Research Center,Rohini, New DelhiDt: Feb 16,2017
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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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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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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
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Causes…
CAUSES OF
PANCYTOPENIA
INHERITED
ACQUIRED 5
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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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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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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 Hypocellular9
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Causes of childhood pancytopenia (Cont.)
Category Condition B M AppearanceAcquired 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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Common causes in Indian Children*
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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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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How to approach?
History Physical Examination Investigations
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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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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
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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 16
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Lab Evaluation:
1. CBC WITH PERIPHERAL BLOOD SMEAR
2. BONE MARROW ASPIRATION AND BIOPSY
3. SPECIFIC INVESTIGATIONS 17
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PERIPHERAL BLOOD SMEAR
Anisocytosis and poikilocytosisWBC and RBC precursorsPlateletsGranulation in neutrophils (Abnormally
increased/decreased)Neutrophils(Hypo/Hypersegmentation)ESR
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1. Anisocytosis & Poikilocytosis
MODERATE DEGREE IS COMMON
Very marked Poikilocytosis: MYELOFIBROSIS
Less degree: APLASTIC ANEMIA, MARROW INFILTRATION BY LYMPHOMA/MULTIPLE MYELOMA
Invariably absent: ACUTE LEUKEMIA19
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RBC INDICES
• RDW: Usually increased• MCV: Can be increased or normal• RETICULOCYTE COUNT- Define severity and
differentiate production vs. destruction
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2. WBC AND RBC PRECURSORS
Blast cells: MyelofibrosisAcute leukemiasSubleukemic leukemias
Plasmacytic cells: Multiple myeloma
Immature lymphocytes: Marrow involvement by lymphoma
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WBC AND RBC PRECURSORS ARE NOT TYPICAL OF APLASTIC
ANEMIA
SO THEIR PRESENCE IN PANCYTOPENIA SUGGEST DIAGNOSIS OTHER THAN
APLASTIC ANEMIA 23
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RBC INCLUSIONS:HOWEL JOLLY BODIES
• Basophilic nuclear remnants (clusters of DNA) in RBCs• Megaloblastic anemia• MDS
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3. Platelets
• Normal Platelets: Aplastic Anemia
• Giant Platelets: MDS Hypersplenism
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4. ABNORMAL GRANULATION IN NEUTROPHILS
• Toxic granules: Infections
• Hypo granular neutrophils: MDS
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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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HYPERSEGMENTATION
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6. ESR
• Increased in : InfectionsMultiple myeloma
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BONE MARROW EXAMINATION
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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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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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HYPERCELLULAR
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Bone Marrow Examination findings
Features Seen inCELLULARITY HYPERCELLULAR: Megaloblastic anemia, Hyperslenism
DRY TAP: MyelofibrosisHYPOPLASTIC: Myelodysplastic syndromes
ERYTHROPOIESIS DYSPLASTIC: MDS, some AMLINCREASED: Hemolysis
MYELOPOIESIS DYSPLASTIC: Myelodysplastic syndromeMophologically normal: Myeloproliferating disorders
BLASTS Myelodysplastic disorders, Acute LeukemiasMEGAKARYOPOIESIS DYSPLASTIC: Myelodysplastic disorderOTHER CELLS Reedsternberg cell: Hodgkin cell
Bacteria, Fungus, Parasite, Viruses, LD bodies34
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SPECIFIC INVESTIGATIONS
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TEST RATIONALEBONE 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 Erythematosus36
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Thanks for your Attention
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