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Pancytopenia is the reduction in the number of:
RBCs
WBCs
PLATELETs
in the peripheral blood below the lower limits of the age adjusted normal range for the healthy people.
Combination of anemia , leukopenia and thrombocytopenia :
ANEMIA
RBCs < 13.5gm/dl(M)
<11.5 gm/dl (F)
LEUKOPENIA
WBCs < 4000/µl
THROMBOCYTOPENIA
PLATELETs < 150×103/µl
• DECREASED PRODUCTION OF BLOOD CELLS OR BONEMARROW FAILURE
• SYSTEM FAILURE
• DEFECTIVE HEMATOPOIETIC STEM CELLS
• DEFECTIVE WORKERS
• DEFICIENCY OF FACTORS STIMULATING HEMATOPOIESIS
• POWERCUT OFF
PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH PRIMARY BONE MARROW
DISEASE
HISTORY
CLINICAL EXAMINATION
COMPLETE BLOOD COUNT
PERIPHERAL SMEAR EXAMINATION
BONE MARROW ASPIRATION
BONE MARROW BIOPSY
OTHER SPECIFIC INVESTIGATIONS
MILD PANCYTOPENIA- SYMPTOMLESS detected incidentally on CBC is performed for another reason
DURATION OF SYMPTOMS H/O of TRANSFUSIONS H/O of HAEMOGLOBINURIA DIETARY H/O SOCIOECONOMIC STATUS WEIGHTLOSS, FEVER---MALIGNANCY JAUNDICE---HEP B & C INFECTIONS----T.B / MALARIA JOINT PAIN ----R.A BLOODLOSS EXPOSURE to DRUGS: anticancer/antibiotic/antiepileptic/
barbiturates/phenytoin/OCP (B12 & folate)CHEMICALS/RADIATION/INFECTION (APLASTIC)
Transient pancytopenia -chemotherapy and radiotherapy
Mild pancytopenia- non-specific viral illnesses Weight loss and/or anorexia are harbingers of
underlying infection
Thrombocytopenia symptom- Spontaneous mucosal bleeding
Anaemia- fatigue, shortness of breath, dependent oedema
Infection -secondary to neutropenia (fever, mucositis, abscesses, rigors).
Petechiae, and purpura with bruising (secondary to thrombocytopenia)
Lymphadenopathy(underlying Infection,IM, Lymphoproliferativedisorder and Malignancy)
Abdominal discomfort (Splenomegaly)
Widespread bone pain/loss of height (Myeloma,joint pain,SLE)
Weight loss (malignancy)
A standard battery of evaluation tests may include:
Reticulocyte Count
LiverFunctionTest
Hepatic Serology
Coagulation Profile,Bleeding Time, Fibrinogen & D-dimer
Serum Direct Antiglobulin Test
Serum B 12 & Folate level
Serum HIV & Nucleic Acid Testing
Anisocytosis & Poikilocytosis.
WBCs and RBCs Precursors
Platelets
Abnormal increased or decreased granulation in neutrophils
Hypo/Hypersegmentation in neutrophils
Examination of bone marrow is always indicated in cases of pancytopenia unless the cause is otherwise apperent(e.g established liver disease with PHTN)
B.M examination:ASPIRATE
TREPHINE BIOPSY
The differential diagnosis of pancytopenia may be broadly classified based on the BONE MARROW CELLULARITY.
Reduced cellularity indicates decreased production of blood cells whereas,
Increased cellularity indicates ineffective production or increased destruction or sequestration of blood cells.
Specifically bone marrow aspirate permits examination of:
CYTOLOGY : megaloblastic changes
dysplastic changes
abnormal cell infiltrates
hemophagocytosis and infection (e.gLeishman Donavan Bodies )
IMMUNOPHENOTYPING : acute & chronic leukemias,lymphoproliferative disorders
CYTOGENETICS : myelodysplasia, leukemias,lymphoproliferative disorders
PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH PRIMARY BONE MARROW
DISEASE
HYPOCEL LULAR MARROW
APLASTIC ANEMIA
HYPOPLASTICMYELODYSPLASTIC SYNDROME
FANCONI’S ANEMIA
POST CHEMOTHERAPY
DIAMOND SWACHMAN SYNDROME
TRANSFUSION ASSOCIATED GVHD
APLASTIC CRISIS IN HEMOLYTIC ANEMIA
Marrow fragments with increase in fat and scattered lymphocytes
Plasma cell
mast cell
Solitary megakaryocyte
Erythroidisland
Cellular area
Focal ares of cellularity
Decreased cellularity<30%
micromegakaryocyte
Clusters ..blast cells
Bmx..hypocellularmarrow .replacement of hemopoietic islands of fat resulting in pancytopenia.
Case of an 8-year-old boy with a hypocellular bone marrow, dispersed erythropoiesis and mainly immature granulocyte precursors. Megakaryocytesare present in normal numbers. This patient later developed pancytopenia.
rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature. After cystic fibrosis (CF), it is the second most common cause of exocrine pancreatic insufficiency in children.
Bms…marked erythroidhyperplasia with normoblastic reaction.
Increased reticulocytecount
microspherocytes
polychromatophils
PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH PRIMARY BONE MARROW
DISEASE
CELLULAR MARROW WITH DEFICIENCY AND SYSTEMIC DISEASE
Vit B 12 & Folic Acid deficiency
HYPERSPLENISM
TUBERCULOSIS , BRUCELLOSIS,KALA AZAR
METASTATIC SOLID TUMORS
ALCOHOLISM
STORAGE DISEASE:
GAUCHER’SNIEMAN PICK’S DISEASE
HIV
Tear drop cell
Moderate degree of anisopoikilocytosis
Hypersegmentedmacropolycytes
Hypersegmented neutrophil
Howell jolly bodies in RBCs
Basophilic stippling cabots ring
Severlybasophilic RBC
HJ bodies in late megaloblast
Basophilic stippling
Fragmentation of late megaloblasts
Irregular nuclei
Giant megaloblast biopsy
Erythroidhyperplasia.linear nucleoli.
Frequent mitosis
Megakaryocyte demonstrate abnormal open nuclear chromatin and complex nuclear lobular hypersegmentation.
SPLENIC INFARCTS: 2820 gm .massively enlarged due to extramedullaryhematopoiesis secondary to myelofibrosis.
CH.MYELOID.LEUKEMIA POLYCYTHEMIA VERA
Massivesplenomegaly due to extramedullary haematopoiesisoccuring in setting of advanced marrow fibrosis.3020 gm.
Enlarged spleen with greatly expanded red pulp stemming from neoplastic haematopoiesis,2630 gm.
Tuberculosis
Malaria
Kala azar
Typhoid
Brucellosis
Cirrosis of liver
Haemolytic anemias
Myeloproliferative disorders
CELLULAR AMRROW WITH DEFICIENCY AND SYSTEMIC DISEASE
Vit B 12 & Folic Acid deficiency
HYPERSPLENISM
TUBERCULOSIS
METASTATIC SOLID TUMORS
ALCOHOLISM
STORAGE DISEASE:
GAUCHER’SNIEMAN PICK’S DISEASE
HIV
Parvo virus B19
Bmx..collection of neutrophils
Area of necrosis surrounded by epitheloid cells.
Three large cells with high n/c ratio.Nuclei show prominent nucleoli and cytoplasm is vacuolated
Bma. Clusters of metastatic malignant cells .hyperchromatic nulei and prominent nulcleoli.
Bmx .clusters of metastatic cells with dense fibrosis
Naked megakaryocytes
Diminised hemopoieticelements
Gelatinous marrow transformation
BMA.CYTOPLASMIC PROTRUSIONS …DOGS EARS
GIANT PROERYTHOBLAST
PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH PRIMARY BONE MARROW
DISEASE
Primary Marrow disease with cellular marrowMYELODYSPLASTIC SYNDROME
MYELOFIBROSIS
PAROXYSMAL NOCTURNAL HEMOGLOBINUREA
HEMOPHAGOCYTICSYNDROME
MARROW NECROSIS
MYELOPTHISIS
ACUTE LEUKEMIA WITH LOW RETICULOCYTE COUNT
PANCYTOPENIA WITH MACROCYTOSIS
Megaloblastoid nucleated red cell
Blast with high n/c ratio
Giant hypogranular platelets
Hypocellular marrow..bma
BMA.Auer rodsAbnormal myeloid precursors
Refractory anemia with excess blasts
BMA.MICROMEGAKARYOCYTE
.BMA .Bi/tri nucleate megakaryocyte
BX.BLASTS
CD 34 ..BLASTS.IHC
TEAR DROP RBC
Neutrophilscore alk. Phs. Score increases
Bx.cellularand fibrotic area
Bx.sclerosisand dec. cellularity
Thick reticulinfibers
Urine,pearl stain. hemosiderin
Bma.plateletphagocytosisby marrow macrophages.
Bmx. Extensive phagocytosis.
Myelophthisis is a form of bone marrow failure that results from the destruction of bone marrow precursor cells and their stroma, which nurture these cells to maturation and differentiation.
• DECREASED PRODUCTION OF BLOOD CELLS OR BONEMARROW FAILURE
• SYSTEM FAILURE
• DEFECTIVE HAEMATOPOIETIC STEM CELLS
• DEFECTIVE WORKERS
• DEFICIENCY OF FACTORS STIMULATING HAEMATOPOIESIS
• POWERCUT OFF
Immune-mediated destruction
Non-immune-mediated sequestration in the periphery
Drug-induced
Autoimmune pancytopenia(Evans' syndrome)
Liver disease with PHTN,
Hypersplenism
Myeloproliferative disorders
Normocytic/normochromic with few macrocytes
: APLASTIC Anemia
Macroovalocytes with Howell Jolly bodies
: MEGALOBLASTIC Anemia
Tear drop cells with, Howell jolly bodies & basophillic stippling
: Myelodysplastic syndrome
Nucleated RBC, sickle cells
:Aplastic crisis in HemolyticAnemia
Leucopenia(mostly mature~80%) :AplasticAnemia
Neutrophils present in increase number with toxic granules, shift to left
:Infections
Basophilic stippling , hypersegmentedneutrophils
:Megaloblastic anemia
Blasts
:Subleukemic Leukemia
Empty particles, markedly hypocellular, only scattered mature lymphocytes and sometimes exess plasma cells : Aplastic anemia
Pockets of cellularity with widespread hypocellularity: Evolving AA
Hypocellular with BM blasts (<20 %): Hypoplastic MDS
Scattered proerythroblasts with large nuclear inclusion in hypocellular BM : PARVOVIRUS
Erythroid hyperplasia with megaloblastosis: Megaloblastic anemia
Trilineage dysplasia with ringed sideroblast on pearlm stain :MDS
Infiltration by RS cell : HL
Infiltration by malignant cell : metastasis
In PNH & FA : early stage which show hypercellular normal appearing marrow.
Childhood- Viral infection, Aplastic anemia, Acute Leukemia
Adults- Megaloblastic anaemia, Aplastic anemia, Acute Leukemia Infections
Elderly- Megaloblastic anemia, Leukemia (Myeloid & Lymphoid), MDS, Hypersplenism and Carcinoma
Fanconi's anaemia: diepoxybutane (DEB) test for chromosomal breakage in peripheral blood lymphocytes
Lymphoproliferative disorders: immunophenotyping, cytogenetics, lymph node biopsy
Multiple myeloma: immunoelectrophoresis
PNH: peripheral blood immunophenotyping for deficiency of phosphatidylinositol-glycan-linked molecules on peripheral blood cells (e.g., CD16, CD55, CD59)
CMV infection: serum IgM and IgG
Epstein-Barr: serum monospot, viral capsid antigen (VCA), and Epstein-Barr nuclear antibody (EBNA)
Leishmaniasis and other rare infections: blood and bone marrow culture, serum ELISA
Rare genetic and metabolic disease: leukocyte glucocerebrosides
Serum PSA in suspect cases of prostatic malignancy.
history• History and associated symptoms
Exam..
• General
• Systemic
Inv1
• CBC with PBS, Reticulocyte count
• B12/Folate , LFT,Hepatic serology, Coagulation profile, directAntiglobulin test, HIV & nucleic acid testing
Inv2• BM aspiration and biopsy
• Cytogenetics (if required)Inv3 • Special investigations to confirm the diagnosis
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