Dr ABHIJEET BARUA

MD PGT [PATH]MEDICAL COLLEGE AND

HOSPITAL KOLKATA

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

COMPLETE BLOOD COUNT (preferably automated)

PERIPHERAL SMEAR

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

Marked erythroidhyperplaia(M;E::1:5)

Early megaloblast:seive like nuclear chromatin

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 AT PERIPHERY

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

Normal count

: rules out Aplastic anemia

Giant platelets

: MDS/ Hypersplenism

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