6. CAUSES OF
PANCYTOPENI
A
HYPOCELLULAR
BONE MARROW
CELLULAR BONE
MARROW WITH
PRIMARY
MARROW
DISORDERS
CELLULAR BONE
MARROW WITH
SYSTEMIC
DISORDERS
7. HYPOCELLULAR BONE MARROW
CAUSES
1. APLASTIC ANEMIA
2. HYPOPLASTIC MYELODYSPLASTIC
SYNDROME
3. LYMPHOMA IN HYPOPLASTIC BONE
MARROW
4. CYTOTOXIC AGENTS AND
RADIOTHERAPY
VERY RARE- ACUTE LEUKEMIA IN
12. MOST COMMON CAUSES IN DEVELOPING
COUNTRY
1. Megaloblastic anemia
2. Infections
3. Hypersplenism
4. Aplastic anemia
5. Drug induced pancytopenia
6. Acute myeloid leukemia
15. SYMPTOMS OCCURENCE
Duration of symptoms MDS (long)
Severe Aplastic Anemia (short history)
Family history Congenital or Hereditary disease
Age of the patients MDS in Adult
Previous treatments/ Exposures Radiotherapy or Chemotherapy
MDS, AML
Drugs Toxic effect
Chronic alcohol abuse Hepatopathy
Pain crisis, black urine crisis Paroxysmal nocturnal haemoglobinuria
Bleeding, infections Estimation of the degree of pancytopenia.
Eventually additional hemostatic problems.
19. FOR ALL CASES :
1. PERIPHERAL BLOOD SMEAR
2. BONE MARROW ASPIRATION
AND TREPHINE BIOPSY
20. PERIPHERAL BLOOD SMEAR-
1. ANISOCYTOSIS AND POIKILOCYTOSIS.
2. WBC AND RBC PRECURSORS.
3. PLATELETS.
4. ABNORMAL INCREASED OR DECREASED
GRANULATION IN NEUTROPHILS.
5. HYPO/HYPERSEGMENTATION IN
NEUTROPHILS.
6. ESR
21. 1. ANISOCYTOSIS AND
POIKILOCYTOSIS-MODERATE
DEGREE IS COMMON
• Very marked Poikilocytosis- MYELOFIBROSIS
• Less degree- APLASTIC ANEMIA, MARROW
INFILTRATION BY LYMPHOMA/ MULTIPLE
MYELOMA.
• Conspicuous- METASTASIS BONE CARCINOMA
• Invariably absent- ACUTE LEUKEMIA
24. RBC INDICES
• RDW- Usually increased
• MCV- maybe increased or normal
• RETICULOCYTE COUNT- Define severity
and differentiate production vs. destruction.
25. 2. WBC AND RBC
PRECURSORS
• BLAST CELLS- MYELOFIBROSIS
SUBLEUKAEMIC LEUKEMIA
• METASTATIC CARCINOMA IN BONE
LESS CHARACTERISTIC: - PLASMACYTIC CELLS-MULTIPLE
MYELOMA
- IMMATURE LYMPHOCYTES- MARROW
INVOLVEMENT BY
LYMPHOMA
26.
27. WBC AND RBC PRECURSORS ARE NOT
TYPICAL OF APLASTIC ANEMIA.
SO THEIR PRESENCE IN PANCYTOPENIA
SUGGEST DIAGNOSIS OTHER THAN
APLASTIC ANEMIA.
31. 5. HYPOSEGMENTATION AND
HYPERSEGMENTATION IN
NEUTROPHILS-
• PELGER HUET LIKE CELLS- MDS
- SOME LEUKEMIAS
• HYPERSEGMENTATION- MEGALOBLASTIC
LEUKEMIA.
.
38. TEST RATIONALE
BONE X-RAYS Multiple myeloma, metastasis.
BLOOD CULTURE Infectious agent- Tuberculosis or virus.
VITAMIN B12 AND FOLATE ASSAYS Megaloblastic anemia
ASPARTATEAMINOTRANSFERASE, ALANINE
AMINOTRANSFERASE, GAMMA GLUTAMYL
TRANSFERASE, BILIRUBIN
Evaluate hepatitis
BLOOD UREA NITROGEN, CREATININE Assess for Chronic Renal Failure
SEROLOGY For HIV, EBV, Hepatitis
HAM’S TEST Paroxysmal Nocturnal Haemoglubinuria
CHROMOSOMALBREAKAGE STUDIES Fanconi anemia
DNA ANTIBODY, LUPUS ERYTHEMATOSUS
CELL TEST
Systemic Lupus Erythematosus
39.
40.
41. PANCYTOPENIA AT INITIAL
EVALUATION
REFER PATIENT FOR URGENT EVALUATION
REPEAT CBC AND BLOOD SMEAR
BONE MARROW ASPIRATE ANDTREPHINE
BIOPSY
LFT,B12 AND FOLATE,COAGULATION
PROFILE,VIRAL ETIOLOGY,AUTOIMMUNE
BONE MARROW CYTOGENETICS BONE MARROW IMMUNOPHENOTYPING
PROFILE
70. CRITERIA FOR SEVERE APLASTIC ANEMIA
At least 2 of the following peripheral blood findings:
• Reticulocytes <1%, corrected for hematocrit
• Absolute neutrophil count <500/μL (0.5 × 109/L)
• Platelets <20,000/μL (20 × 109/L)
• AND
• Bone marrow biopsy with <25% normal cellularity
• OR
• Bone marrow biopsy with <50% normal cellularity in which less
• than 30% of the cells are hematopoietic
76. HISTORY
• A 20yr old male presents with sudden onset
malaise and fatigue with recurrent
abdominal pain.
• He also complains of dark color urine on
waking up.
82. PAROXYSMAL NOCTURNAL
HAEMOGLUBINURIA
• PNH arises as a result of nonmalignant clonal
expansion of one or more hematopoietic stem
cells that have acquired somatic mutation of the
X-chromosome gene PIGA
(phosphatidylinositol glycan class A)
83. “ Best Diagnostc
test of Paroxysmal
Nocturnal
Haemoglobinuria
is by FLOW
CYTOMETRY ”
85. HISTORY
• A 8yr old child comes with sudden onset fever
and fatigue.
• Also gives history of recurrent pneumonia.
• On examination- generalised lymphadenopathy
present.
100. SUBLEUKAEMIC LEUKEMIA
• MORE COMMON CAUSE OF
PANCYTOPENIA THEN APLASTIC
ANEMIA
• PROBLEM IN DIAGNOSIS- VERY
FEW OR NO BLAST CELLS IN BLOOD
FILM.
• DIAGNOSIS BY EXAMINATION OF
102. HISTORY
• A 70 yrs old male patient complains of
fever and weakness.
• He has history of recurrent infections.
• History of unprovoked bleeding from skin
and gums.
105. FURTHER WORK-UP
• BONE MARROW EXAMINATION- Ring sideroblasts seen
- Megakaryocytes with multiple nuclei.
106. MYELODYSPLASTIC SYNDROMES
• The myelodysplastic syndromes (MDS) are clonal
hematopoietic stem cell disorders characterized by
cytopenias with cellular marrow and a risk for
leukemic transformation.
• Features of dysplasia of hematopoietic cell lines with
impairment of proliferation and differentiation of these
cells.
• Hallmark – Ineffective hematopoiesis
107. WHO Classification
• Refractory Anemia (RA)
• Refractory Anemia with Ring Sideroblasts (RARS)
• Refractory cytopenia with multilineage dysplasia (RCMD)
• MDS associated with isolated del(5q)
• Childhood myelodysplastic syndrome
• Refractory anemia with excess blasts-1 (RAEB-1)
• Refractory anemia with excess blasts-2 (RAEB-2)
• Myelodysplastic syndrome, unclassified (MDS-U)
110. HISTORY
• A 40 yr old male presents with fever and cough.
• He also complains of fatigue and weakness.
• On examination shows enlarged cervical lymph
nodes.
116. Granuloma in a trephine biopsy section of
bone marrow from a
patient with AIDS and disseminated
atypical mycobacterial infection. H&E
Bone marrow granuloma from a patient with
AIDS and disseminated Mycobacterium avium
intracellulare infection. The macrophages
contain many acid-fast bacillli. Ziehl–Neelsen
stain
118. HISTORY
• Mr. A 55yrs old male patient, a railway
worker, consulted his doctor for tiredness,
malaise and anorexia.
• He was found to be mildly jaundiced with
an enlarged irregular hepatomegaly and
considerable ascites.
121. FURTHER WORKUP
• SONOGRAPHY- Enlarged spleen
• BONE MARROW EXAMINATION-Normocellular
marrow with hematopoeisis
• HEPATITIS VIRUS STUDIES- Negative for A,
B and C.
122. HYPERSPLENISM
• Splenic hyperactivity with increased blood cell destruction.
Diagnostic criteria
1. Splenomegaly
2. Pancytopenia
3. Normal or hypercellular bone marrow
4. Reversibility by splenectomy
123. MYELOFIBROSIS
• Fibrosis of the bone marrow
• Etiology :
Due to dysregulated production PDGF and
TGF.
124. INVESTIGATIONS
• PERIPHERAL BLOOD SMEAR- Tear
drop cells.
• BONE MARROW ASPIRATION- Dry
tap
• BONE MARROW BIOPSY-Hypocellular
and fibrotic obliteration
of marrow space.
• JAK2 mutations present.
125.
126. HAEMOPHAGOCYTIC SYNDROME
• Also called Hemophagocytic lymphohistiocytosis
Clinical features
• Fever
• Hepatosplenomegaly
• Jaundice
• Lymphadenopathy
• Rash
133. Parvovirus B19-induced pure red cell aplasia. BM aspirate
smear - giant erythroblast with intranuclear viral inclusion,
resembling a large nucleolus, and the cytoplasm may be dark
blue and contain vacuoles. BM biopsy with early erythroid
precursors showing glassy• intranuclear inclusions ( lantern
135. METASTATIC SOLID TUMORS
TUMOURS METASTASIZING TO BONE
MARROW
Adults
• Breast
• Lung
• Prostate
• Kidney
• Thyroid
Children
• Neuroblastoma
• Ewing’s sarcoma
• Wilms’ tumor
• Retinoblastoma
• Rhabdomyosarcoma
• Germ cell tumor
136. DIAGNOSIS
1. Peripheral blood findings
• Anemia
2. Bone marrow aspiration & biopsy
• Cells not constituent to marrow.
• Myelofibrosis & Necrosis
• Special stains & IHC
137. 3. BIOCHEMICAL INVESTIGATIONS-
• Hypercalcemia
• Elevated Alkaline phosphatase
• Lactate dehydrogenase
• Parathyroid hormone related protein
• Specific tumor markers
138. Bone marrow biopsy
Metastasis from an adenocarcinoma. The
carcinoma cells are arranged in a well-defined
tubular pattern
Showing myelofibrosis and osteosclerosis
secondary to the metastatic tumor cells
from unidentified primary tumor
140. MAIN CAUSES OF MEDICAL ERRORS IN
HEMATOLOGICAL DIAGNOSTICS
• Incomplete information on the case
• Bad quality of the material- blood fils, aspirates,
biopsies, colorations.
• No integrated diagnosis- speak together.
• Confirmatory bias- to seek data that confirm a
favorite hypothesis and ti interpret even the low-relevance
data as being supportive of a
hypothesis.
144. REFERENCES
• Clinical Laboratory Hematology – Mckenzie.
• De Gruchy’s Clinical Haematology in Medical
Practice
• Dacie and Lewis Practical hematology
• Wintrobe’s Atlas of Clinical Haematology
• Atlas and Textbook of Hematology
145. “ LOOK CAREFULLY ,
YOUR PATIENTS AND
THEIR BLOOD FILMS ”
THANK YOU
