Pancytopenia is a reduction in red blood cells, white blood cells, and platelets caused by decreased bone marrow production or destruction of blood cells. Evaluation of pancytopenia involves examining the complete blood count, peripheral smear, and bone marrow aspiration and biopsy to determine if the cause is aplasia, deficiencies, infections, infiltrative disorders, or primary bone marrow diseases like myelodysplastic syndrome. Management depends on the underlying etiology based on history, examination, and specific diagnostic tests.

1. Dr ABHIJEET BARUA
MD PGT [PATH]
MEDICAL COLLEGE AND
HOSPITAL KOLKATA

2.  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.

3.  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

7. • DECREASED PRODUCTION OF BLOOD CELLS OR
BONEMARROW FAILURE
• SYSTEM FAILURE
• DEFECTIVE HEMATOPOIETIC STEM CELLS
• DEFECTIVE WORKERS
• DEFICIENCY OF FACTORS STIMULATING
HEMATOPOIESIS
• POWERCUT OFF

8. PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH
PRIMARY BONE MARROW
DISEASE

9.  HISTORY
 CLINICAL EXAMINATION
 COMPLETE BLOOD COUNT
 PERIPHERAL SMEAR EXAMINATION
 BONE MARROW ASPIRATION
 BONE MARROW BIOPSY
 OTHER SPECIFIC INVESTIGATIONS

10.  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)

11.  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).

12.  Petechiae, and purpura with bruising
(secondary to thrombocytopenia)
 Lymphadenopathy
(underlying Infection,IM, Lymphoproliferative
disorder and Malignancy)
 Abdominal discomfort
(Splenomegaly)
 Widespread bone pain/loss of height
(Myeloma,joint pain,SLE)
 Weight loss (malignancy)

13. 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

14.  COMPLETE BLOOD COUNT
(preferably automated)
 PERIPHERAL SMEAR

15.  Anisocytosis & Poikilocytosis.
 WBCs and RBCs Precursors
 Platelets
 Abnormal increased or decreased granulation
in neutrophils
 Hypo/Hypersegmentation in neutrophils

16.  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

17.  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.

18. 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

19. PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH
PRIMARY BONE MARROW
DISEASE

20. HYPOCEL LULAR
MARROW
APLASTIC ANEMIA
HYPOPLASTIC
MYELODYSPLASTIC
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
Erythroid
island
Cellular
area
Focal ares of cellularity
Decreased
cellularity<30%
micromegakaryocyte
Clusters ..blast
cells
Bmx..hypocellular
marrow .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. Megakaryocytes
are 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 erythroid
hyperplasia with
normoblastic reaction.
Increased reticulocyte
count
microspherocytes
polychromatophils

22. PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH
PRIMARY BONE MARROW
DISEASE

23. 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’S
NIEMAN PICK’S DISEASE
HIV

24. Tear drop cell
Moderate degree of
anisopoikilocytosis
Hypersegmented
macropolycytes
Hypersegmente
d neutrophil
Howell jolly
bodies in RBCs
Basophilic
stippling cabots ring
Severly
basophilic RBC

25. Marked erythroid
hyperplaia(M;E::1:5)
Early megaloblast:seive like nuclear chromatin

26. HJ bodies in
late
megaloblast
Basophilic
stippling
Fragmentation of
late megaloblasts
Irregular
nuclei
Giant
megaloblast biopsy
Erythroid
hyperplasia.
linear nucleoli.
Frequent
mitosis

27.  Megakaryocyte demonstrate abnormal open
nuclear chromatin and complex nuclear lobular
hypersegmentation.

28. SPLENIC INFARCTS: 2820 gm .massively enlarged due to extramedullary
hematopoiesis secondary to myelofibrosis.

29. CH.MYELOID.LEUKEMIA POLYCYTHEMIA VERA
Massivesplenomegaly due to
extramedullary haematopoiesis
occuring in setting of advanced marrow
fibrosis.3020 gm.
Enlarged spleen with greatly expanded
red pulp stemming from neoplastic
haematopoiesis,2630 gm.

30.  Tuberculosis
 Malaria
 Kala azar
 Typhoid
 Brucellosis
 Cirrosis of liver
 Haemolytic anemias
 Myeloproliferative disorders

31. CELLULAR AMRROW WITH DEFICIENCY AND SYSTEMIC
DISEASE
Vit B 12 & Folic Acid deficiency
HYPERSPLENISM
TUBERCULOSIS
METASTATIC SOLID TUMORS
ALCOHOLISM
STORAGE DISEASE:
GAUCHER’S
NIEMAN 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 hemopoietic
elements
Gelatinous marrow
transformation
BMA.CYTOPLASMIC
PROTRUSIONS
…DOGS EARS
GIANT PROERYTHOBLAST

32. PANCYTOPENIAHYPOCELLULAR
MARROW
CELLULAR MARROW WITH
DEFICIENCY AND SYSTEMIC DISEASES
CELLULAR MARROW WITH
PRIMARY BONE MARROW
DISEASE

33. Primary Marrow disease
with cellular marrow
MYELODYSPLASTIC
SYNDROME
MYELOFIBROSIS
PAROXYSMAL NOCTURNAL
HEMOGLOBINUREA
HEMOPHAGOCYTIC
SYNDROME
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 rods
Abnormal
myeloid
precursors
Refractory anemia with excess blasts
BMA.MICROMEGAKARYO
CYTE
.BMA .Bi/tri
nucleate
megakaryocyte
BX.BLASTS
CD 34
..BLASTS.IHC
TEAR DROP
RBC
Neutrophil
score alk. Phs.
Score increases
Bx.cellular
and fibrotic
area
Bx.sclerosis
and dec.
cellularity
Thick
reticulin
fibers
Urine,pearl stain.
hemosiderin
Bma.platelet
phagocytosis
by 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.

34. • DECREASED PRODUCTION OF BLOOD CELLS OR
BONEMARROW FAILURE
• SYSTEM FAILURE
• DEFECTIVE HAEMATOPOIETIC STEM CELLS
• DEFECTIVE WORKERS
• DEFICIENCY OF FACTORS STIMULATING
HAEMATOPOIESIS
• POWERCUT OFF

35. IMMUNE MEDIATED
DESTRUCTION
NON IMMUNE MEDIATED
SEQUESTRATION AT PERIPHERY

36. Immune-mediated
destruction
Non-immune-mediated
sequestration in the periphery
Drug-induced
Autoimmune pancytopenia
(Evans' syndrome)
Liver disease with PHTN,
Hypersplenism
Myeloproliferative disorders

37.  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

38.  Leucopenia(mostly mature~80%)
:AplasticAnemia
 Neutrophils present in increase number with
toxic granules, shift to left
:Infections
 Basophilic stippling , hypersegmented
neutrophils
:Megaloblastic anemia
 Blasts
:Subleukemic Leukemia

39.  Normal count
: rules out Aplastic anemia
 Giant platelets
: MDS/ Hypersplenism

40.  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

41.  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.

42.  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

43.  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.

45. 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)
Inv
3 •Special investigations to confirm the diagnosis