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Approach to pancytopenia
This document provides an overview of pancytopenia, including definitions, common causes, clinical evaluation, and diagnostic approach. Pancytopenia is defined as a reduction in all three blood cell lines. The evaluation involves obtaining a complete blood count with peripheral smear, bone marrow aspiration and biopsy, and specific tests depending on findings. The bone marrow examination can help differentiate causes based on cellularity and features seen in erythropoiesis, myelopoiesis, megakaryopoiesis and other cell types. Common causes include bone marrow failure, infiltrative disorders, infections, immune disorders and nutritional deficiencies. A thorough history, examination and systematic evaluation of the bone marrow are required to identify the underlying cause of pancy
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Introduction to the presentation on Pancytopenia, delivered by Dr. Murtaza Kamal, specializing in Pediatric Hemato-Oncology.
Definitions of cytopenia, bicytopenia, and pancytopenia, along with critical thresholds for blood components.
The causes of pancytopenia including bone marrow failure, space-occupying lesions, and various inherited or acquired conditions.
Overview of common causes of pancytopenia among Indian children and a review of a significant study on this topic.
Strategies for approaching a diagnosis, including history taking, physical examination findings, and clinical signs.
Essential laboratory tests for diagnosing pancytopenia, including CBC, bone marrow aspiration, and examination of blood cells.
Importance of bone marrow examination, cellularity, and findings indicative of various conditions related to pancytopenia.
Additional specific tests needed for further evaluation of suspected causes of pancytopenia.
Concluding slide thanking the audience for their attention during the presentation.
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Approach to pancytopenia
- 1. Approach to Pancytopenia Dr. MurtazaKamal MBBS, MD, DNB Clinical Fellow (Pediatric Hemato-Oncology) Rajiv Gandhi Cancer Institute & Research Center,Rohini, New Delhi Dt: Feb 16,2017 1
- 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. 2
- 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. 3
- 4. It can occurdue 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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- 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. 6
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- 8. Causes of childhood pancytopenia CategoryCondition 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 8
- 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 10
- 11. Common causes inIndian 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 11
- 12. Common causes inour 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 12
- 13. How to approach? HistoryPhysical Examination Investigations 13
- 14. Points to considerin 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 14
- 15. Clinical Examination • Anthropometryincluding 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 NeelamVerma 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
- 17. Lab Evaluation: 1. CBCWITH PERIPHERAL BLOOD SMEAR 2. BONE MARROW ASPIRATION AND BIOPSY 3. SPECIFIC INVESTIGATIONS 17
- 18. PERIPHERAL BLOOD SMEAR Anisocytosisand poikilocytosis WBC and RBC precursors Platelets Granulation in neutrophils (Abnormally increased/decreased) Neutrophils(Hypo/Hypersegmentation) ESR 18
- 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 21
- 22. 2. WBC ANDRBC PRECURSORS Blast cells: Myelofibrosis Acute leukemias Subleukemic leukemias Plasmacytic cells: Multiple myeloma Immature lymphocytes: Marrow involvement by lymphoma 22
- 23. WBC AND RBCPRECURSORS ARE NOT TYPICAL OF APLASTIC ANEMIA SO THEIR PRESENCE IN PANCYTOPENIA SUGGEST DIAGNOSIS OTHER THAN APLASTIC ANEMIA 23
- 24. RBC INCLUSIONS: HOWEL JOLLYBODIES • Basophilic nuclear remnants (clusters of DNA) in RBCs • Megaloblastic anemia • MDS 24
- 25. 3. Platelets • NormalPlatelets: Aplastic Anemia • Giant Platelets: MDS Hypersplenism 25
- 26. 4. ABNORMAL GRANULATIONIN NEUTROPHILS • Toxic granules: Infections • Hypo granular neutrophils: MDS 26
- 27. 5. HYPO/HYPERSEGMENTATION IN NEUTROPHILS •Hyper segmented Neutrophils: Megaloblastic Anemia • Pelger Huet like cells: MDS, Chronic leukemias, Folate and B12 deficiency. 27
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- 29. 6. ESR • Increasedin : Infections Multiple myeloma 29
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- 31. Bone Marrow Examination Almostalways 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) 31
- 32. Cellularity of BoneMarrow 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 32
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- 34. Bone Marrow Examinationfindings 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
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- 36. TEST RATIONALE BONE X-RAYSMultiple 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 36
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