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PRESENTED BY-DR.BISWAJEETA SAHA(1ST YR PGT)
 MODERATOR-DR.S.RAMAN,KIMS,BHUBANESWAR
DEFINITION

 Combination of anemia, leucopenia and thrombocytopenia

 Hb<9g/dl

 TLC<4000/cmm

 TPC<1.5 lacs/cmm
ETIOLOGY
Hypocellular marrow        Cellular marrow with       Primary marrow disease
                           def/syst diseases          with cellular marrow

•Aplastic anemia           •Vit B12 and folic acid    •Aleukemic leukemia
•Hypoplastic MDS           deficiency                 •Hairy cell leukemia
•Post chemotherapy         •Hypersplenism             •MDS
•Fanconi’s anemia          •Kala azar                 •Marrow necrosis
•Diamond-Shwachman         •SLE,sjogrens              •Myelofibrosis
syndrome                   syndrome,sarcoidosis       •PNH
•Transfusion associated    •Tuberculosis,brucelosis   •HPS
GVHD                       •Metastatic solid tumors
•Aplastic crisis in        •Alcoholism
hemolytic anemia           •Storage diseases
•Drugs
•Infections
Peripheral smear
 RBC-
 Normocytic normochromic with few macrocytes,no anisopoikilocytosis,no
  nRBCs,reticulocytopenia----aplastic anemia
 Macroovalocytes,howel jolly bodies-megaloblastic anemia
 Tear drop cells,howel jolly bodies,basophilic stippling--MDS
 nRBCs,sickle cells-aplastic crisis in sickle cell anemia


 WBC-
 Leucopenia,mostly mature lymphocytyes(80-90%)---aplastic anemia
 Neutrophils present in increased number,with toxic granules,shift to left—
  infections
 Basophilic stippling,hypersegmented neutrophils—megaloblastic anemia
 If blasts present—subleukemic leukemia
 Hypogranular neutrophils,pseudo pelger heut anomaly--MDS


 PLATELETS-
 Normal TPC rules out aplastic anemia
 Giant platelets—MDS /hypersplenism
History taking
 Duration of symptoms
 How many blood transfusions,intervals between transfusions
 h/o hemoglobinuria
 Dietary history
 Socio economic status
 Exposure to
     Drugs, especially antineoplastic, antibiotics (chloramphenicol,
      sulphonamides),anti epileptics and antithyroid drugs (Aplastic)
    barbiturates, phenytoin, and oral contraceptives (B12)
 Exposure to radiation (Aplastic)
 Chemical exposure
    Benzene & insecticides (Aplastic)
 Infections
    Viruses (viral hepatitis,EBV, parvovirus, and HIV. (Aplastic)
 Weight loss , fever (malignancy, inflammatory)
 Jaundice (Hep B & C)
 Evidence of bleeding
 Infections
    TB, Malaria
 Joint pains
    SLE
General physical examination

 Eye examination
 Retinal hemorhage
 Leukemic infiltration
 Jaundiced sclera(PNH,hepatitis,cirrhosis)
 Epiphora(dyskeratosis congenita)


 Oral examination
 Oral petechaie
 Stomatitis/chelitis
 Gingivial hyperplasia
 Oral candidiasis
 Cardiovascular examination
                                       Musculoskelatal system
 Tachycardia,edema,CCF               Short stature
                                      Synovitis
 Respiratory system                  Abnormal thumb
 Clubbing
 Tachypnoea


 Abdominal examination
 Hepatomegaly
 Lymphadenopathy
 Splenomegaly


 Skin examination
 Malar rash
 Purpura
 Reticular pigmentation,dysplastic
  nails(dyskeratosis congenita)
 Hypopigmented areas
 hyperpigmentation
Bone marrow examination
Almost almost always indicated in cases of pancytopenia unless the cause is
  apparent.
 Both aspiration and biopsy required
 Sample for cytogenetics and immunophenotyping,culture and serological
  studies

IN THE ASPIRATE:
 Empty particles,markedly hypocellular,only scattered mature lymphocytes and
   sometimes plasma cells in excess---aplastic anemia
 Sometimes pockets of cellularity with widespread hypocellularity—evolving
   phase of aplastic anemia
 Hypocellular BM with Blasts(>20%)----hypoplastic leukemia
 Hypocellular BM with Dysplastic megakaryocytes—hypoplastic MDS
 Scattered proerythroblasts with large nuclear inclusions in hypocellular BM—
   parvo virus
In hypercellular BM


  Erythroid hyperplasia with megablastosis—megaloblastic anemia

  Trilineage dysplasia with ringed sideroblasts on perl stain—MDS

  Infiltration by RS cells—HL

  Infiltration with malignant cells—metastasis

  In PNH and fanconis anemia—early stage will show hypercellular normal
    appearing marrow
Specific testing pinpoints diagnosis in following
conditions

  Fanconis anemia: diepoxybutane (DEB) test for chromosomal breakage in
   peripheral blood lymphocyte
  Lymphoproliferative disorders:immunophenotyping,cytogenetics,lymph node
   biopsy
  PNH:peripheral blood immunophenotyping for deficiency of
     phosphatidylinositol glycan linked molecules on peripheral blood cells(cd 16,cd
     55,cd 59),HAMs test
    CMV:serum IgM,IgG
    EBV:serum monospot,viral capsid antigen(VCA),Epstein barr nuclear
     antibody(EBNA)
    Leishmaniasis:blood and bone marrow culture,ELISA
    Serum PSA:prostatic ca
pancytopenia


                                       History,examination,CBC,retic
                                       count,serum iron/TIBC




                                         Blast,hypo   Unexplained       No specific    Hypersegmented
Palpable spleen      Sepsis/bleeding                                                   PMNs,marked
with increased retic                     granular     splenomegal       finding
                                         PMNs         y/M                              anisopoikilocytosis
                                                      protein/meta
                                                      stasis
                                                                                             Trial of B12 and folic acid

                                                                               No response                 response



                                                                       Acid hemolysis test

Hypersplenism/m
alaria/leishmanias
is

                                                                        HIV antibody


                             Bone marrow aspiration and biopsy
CBC AND PS




•LFT                 •PNH and IBMFS       •Bone marrow
•B12/Folate levels   investigations       biopsy and
•Coagulation                              aspirate
profile
•Viral serology
•Autoimmune
profile


                           Bonemarrow        Blood/bm
                           cytogenetics      immunophen
                                             otyping
THANK YOU

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Investigations of pancytopenia

  • 1. PRESENTED BY-DR.BISWAJEETA SAHA(1ST YR PGT) MODERATOR-DR.S.RAMAN,KIMS,BHUBANESWAR
  • 2. DEFINITION  Combination of anemia, leucopenia and thrombocytopenia  Hb<9g/dl  TLC<4000/cmm  TPC<1.5 lacs/cmm
  • 3. ETIOLOGY Hypocellular marrow Cellular marrow with Primary marrow disease def/syst diseases with cellular marrow •Aplastic anemia •Vit B12 and folic acid •Aleukemic leukemia •Hypoplastic MDS deficiency •Hairy cell leukemia •Post chemotherapy •Hypersplenism •MDS •Fanconi’s anemia •Kala azar •Marrow necrosis •Diamond-Shwachman •SLE,sjogrens •Myelofibrosis syndrome syndrome,sarcoidosis •PNH •Transfusion associated •Tuberculosis,brucelosis •HPS GVHD •Metastatic solid tumors •Aplastic crisis in •Alcoholism hemolytic anemia •Storage diseases •Drugs •Infections
  • 4. Peripheral smear  RBC-  Normocytic normochromic with few macrocytes,no anisopoikilocytosis,no nRBCs,reticulocytopenia----aplastic anemia  Macroovalocytes,howel jolly bodies-megaloblastic anemia  Tear drop cells,howel jolly bodies,basophilic stippling--MDS  nRBCs,sickle cells-aplastic crisis in sickle cell anemia  WBC-  Leucopenia,mostly mature lymphocytyes(80-90%)---aplastic anemia  Neutrophils present in increased number,with toxic granules,shift to left— infections  Basophilic stippling,hypersegmented neutrophils—megaloblastic anemia  If blasts present—subleukemic leukemia  Hypogranular neutrophils,pseudo pelger heut anomaly--MDS  PLATELETS-  Normal TPC rules out aplastic anemia  Giant platelets—MDS /hypersplenism
  • 5. History taking  Duration of symptoms  How many blood transfusions,intervals between transfusions  h/o hemoglobinuria  Dietary history  Socio economic status  Exposure to  Drugs, especially antineoplastic, antibiotics (chloramphenicol, sulphonamides),anti epileptics and antithyroid drugs (Aplastic)  barbiturates, phenytoin, and oral contraceptives (B12)  Exposure to radiation (Aplastic)  Chemical exposure  Benzene & insecticides (Aplastic)  Infections  Viruses (viral hepatitis,EBV, parvovirus, and HIV. (Aplastic)
  • 6.  Weight loss , fever (malignancy, inflammatory)  Jaundice (Hep B & C)  Evidence of bleeding  Infections  TB, Malaria  Joint pains  SLE
  • 7. General physical examination  Eye examination  Retinal hemorhage  Leukemic infiltration  Jaundiced sclera(PNH,hepatitis,cirrhosis)  Epiphora(dyskeratosis congenita)  Oral examination  Oral petechaie  Stomatitis/chelitis  Gingivial hyperplasia  Oral candidiasis
  • 8.  Cardiovascular examination  Musculoskelatal system  Tachycardia,edema,CCF Short stature Synovitis  Respiratory system Abnormal thumb  Clubbing  Tachypnoea  Abdominal examination  Hepatomegaly  Lymphadenopathy  Splenomegaly  Skin examination  Malar rash  Purpura  Reticular pigmentation,dysplastic nails(dyskeratosis congenita)  Hypopigmented areas  hyperpigmentation
  • 9. Bone marrow examination Almost almost always indicated in cases of pancytopenia unless the cause is apparent.  Both aspiration and biopsy required  Sample for cytogenetics and immunophenotyping,culture and serological studies IN THE ASPIRATE:  Empty particles,markedly hypocellular,only scattered mature lymphocytes and sometimes plasma cells in excess---aplastic anemia  Sometimes pockets of cellularity with widespread hypocellularity—evolving phase of aplastic anemia  Hypocellular BM with Blasts(>20%)----hypoplastic leukemia  Hypocellular BM with Dysplastic megakaryocytes—hypoplastic MDS  Scattered proerythroblasts with large nuclear inclusions in hypocellular BM— parvo virus
  • 10. In hypercellular BM  Erythroid hyperplasia with megablastosis—megaloblastic anemia  Trilineage dysplasia with ringed sideroblasts on perl stain—MDS  Infiltration by RS cells—HL  Infiltration with malignant cells—metastasis  In PNH and fanconis anemia—early stage will show hypercellular normal appearing marrow
  • 11. Specific testing pinpoints diagnosis in following conditions  Fanconis anemia: diepoxybutane (DEB) test for chromosomal breakage in peripheral blood lymphocyte  Lymphoproliferative disorders:immunophenotyping,cytogenetics,lymph node biopsy  PNH:peripheral blood immunophenotyping for deficiency of phosphatidylinositol glycan linked molecules on peripheral blood cells(cd 16,cd 55,cd 59),HAMs test  CMV:serum IgM,IgG  EBV:serum monospot,viral capsid antigen(VCA),Epstein barr nuclear antibody(EBNA)  Leishmaniasis:blood and bone marrow culture,ELISA  Serum PSA:prostatic ca
  • 12. pancytopenia History,examination,CBC,retic count,serum iron/TIBC Blast,hypo Unexplained No specific Hypersegmented Palpable spleen Sepsis/bleeding PMNs,marked with increased retic granular splenomegal finding PMNs y/M anisopoikilocytosis protein/meta stasis Trial of B12 and folic acid No response response Acid hemolysis test Hypersplenism/m alaria/leishmanias is HIV antibody Bone marrow aspiration and biopsy
  • 13. CBC AND PS •LFT •PNH and IBMFS •Bone marrow •B12/Folate levels investigations biopsy and •Coagulation aspirate profile •Viral serology •Autoimmune profile Bonemarrow Blood/bm cytogenetics immunophen otyping