pancytopenia clinical aproach

2. DR Mahammed Basiony

3.  normal adult marrow produces
170x109 RBC,
100x109 neutrophils
200x109 platelets
daily.

4. 10/1/2018 4
Pancytopenia
Definition
Reduction in the number of red cells,
white cells (neutrophils) and platelets in the
peripheral blood below the lower limits of the age.
Therefore it is combination of
(anemia, leucopenia and thrombocytopenia)
Hb<13.5 in ♂ & 11.5 in♀
Leucocyte count< 4000
Platelet count <150000

5. Severe pancytopenia
 Absolute neutrophil count < 500/cmm
 Platelet count < 20,000/cmm
 Corrected reticulocyte count < 1%.
Urgent full investigation in 1st 24-48 h

6. 10/1/2018 6
Normal 50-100000/mL
Normal ,5-1,5

7.  Bone marrow failure : aplastic
anemia either ( congenital or acquired)
 Bone marrow infiltration :
Acute leukemia
Lymphoma
Carcinoma
Myeloma
MDS
(non malignant infiltration (storage
disorder)
Causes

8.  Ineffective haematopoiesis
Megaloblastic anaemia
AIDS
 Peripheral pooling / destruction
Hypersplenism: portal hypertension ,
malaria , Myelofibrosis
SLE
Causes cont.

9. 1. Megaloblastic anemia
2. Infections
3. Hypersplenism
4. Aplastic anemia
5. Drug induced pancytopenia
6. Acute myeloid leukemia
Common causes in developing countries

10. Infections:
(HIV, tuberculosis, hepatitis viruses, EBV,
CMV)
Hypersplenism: causes
congestive splenomegaly
(cirrhosis, congestive heart failure),
malaria,leishmaniasis,thalassaemia and
Hodgkin’s disease
Most frequent haematologicmanifestation of SLE
normocytic and normochromicanaemia.
Leukopenia is also common and
almost always consists of lymphopenia
and not granulocytopenia.

11. history
• History and associated symptoms
Exam..
Inv1
Inv2
• General
• Systemic
• CBC with PBS, Reticulocyte count
• B12/Folate , LFT,Hepatic serology, Coagulation
profile, combs test, HIV .
• BM aspiration and biopsy
• Cytogenetics (if required)
Inv
3 • Special investigations to confirm the diagnosis

12. Clinical features
Related to
Pancytopenia
Or
Underlying
condition/disease
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13. Symptoms/Findings
Related to pancytopenia
Anaemia---- fatigue, shortness of breath,
dependent oedema
Neutropenia (fever, abscesses, rigors).
Thromboacytopenia mucocuteneous bleeding-
. Bruising.
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14. Symptoms/Findings
Related to the cause of
pancytopenia
eg:
Splenomegaly: Hypersplenism, lymphoma,
leukemia, myelofibrosis etc
Lymphadenopathy: Lymphoma , leukemia,SLE etc
Atrophic glossitis: Megaloblastic anaemia
Others
10/1/2018 14

15. History
 Duration of symptom
Long (MDS)
Short (aplastic anemia)
 History of transfusion
 History of hemoglobinurea
 Dietary history
 Exposure to
Radiation – Chemotherapy ( MDS , AML)
Drugs :
Anti cancer-anti thyroid-antibiotic(aplastic anemia)
Barbiturates , phenytoin ( B12, Folic acid)

16. History
 Age- inherited cause of bone marrow failure
 Jaundice (hepatitis viruses)
 Joint pain, rash,photosensitivity (lupus)
 Bonepains (acute leukemias)
 Night sweats (Hodgkins disease)
 malaise, weightloss (tuberculosis,malignancy)
 Joint Pain – (SLE)

17. General examination
A thorough physical exam is required
 Eye examination: retinal hemorrhage
leukemic infiltrations
Pallor (Anemia)
Jaundice (hepatitis-PNH-cirrhosis)
 Oral examination
Stomatitis or cheilitis (neutropenia , B12 deficiency)
Gingival hyperplasia (leukemia)
Oral candidiasis or pharyngeal exudate (neutropenia)

18.  Abdominal examination :organomegaly
lymphadenopathy
 skin examination : malar rash Petichae
purpura hypo or hyperpigmentation
 Musculoskelatal system :
short stature abnormal thumb
(fanconi anemia)
Synovitis/swelling (SLE)
Sternal tenderness (acute leukemia)
Signs of chronic liver disease.
General examination

19. Pancytopenia + Absent thumb
+Child

20.  Pancytopenia +Backpain+Hypercalcemia+
old age (multiple myeloma)
 Pancytopenia + Malar rash or GN+ = SLE
 pancytopenia + HSM = Leukemia
 Recurrent oral ulcers and chronic diarrhoea
may point towards HIV infection.
 Loss of height (multiple myeloma)

21. FINDINGS OCCURENCE
Lymphadenopathy
Lymphoma, Hodgkin lymphoma, also
viral----typically abscent in aplastic a
infection.
Splenomegaly Not found in MDS or Aplastic
anemia. Typical in
Myeloproliferative disorders,
sometimes in acute leukemia.
Hepatomegaly Myeloproliferative disorders,
Lymphoma
Mediastinal bulk Lymphoma,
Hodgkin’s disease
Bony tenderness
Multiple Myeloma,
Metastasis

22. A standard battery of evaluation tests include:
 COMPLETE BLOOD COUNT w indices
 PERIPHERAL SMEAR
 Reticulocyte Count
 LiverFunctionTest &Hepatic Serology
 Coagulation Profile,Bleeding Time, D-dimer
 (combs test)
 Serum B12 & Folate level
 Serum HIV . ANA.
bone marrow

23.  Anisocytosis & Poikilocytosis.
 WBCs and RBCs Precursors
 Platelets
 Increased or decreased granulation in
neutrophils
 Hypo/Hypersegmentation in neutrophils

24. MODERATE
DEGREE
COMMON
ANISOCYTOSIS & POIKILOCYTOsis
Verymarked Less degree ABSENT
MYELOFIBROSIS APLASTIC ANEMIA ACUTE LEUKEMIA
LYMPHOMA/
MULTIPLE MYELOMA

25. Myelofibrosis Multiple myeloma
Acute leukemias
Subleukemic leukemias
BLAST CELLS
PLASMACYTIC
CELLS
IMMATURE
LYMPHOCYTES
WBC AND RBC
PRECURSORS
Marrow involvement
by lymphoma
If present so not
Aplastic anemia

26. PLATELETS
NORMAL
PLATELETS
GIANT
PLATELETS
AplasticAnemia
MDS
Hypersplenism

27. NEUTROPHIL
SHAP
E
HYPERSEGMENTAL
MEGALOBLASTIC
ANEMIA
MDS
HYPOSEGMENTAL
CHRONIC LEUKEMIA
GRANULE
TOXIC GRANULE
INFECTION
HYPOGRANULAR
MDS

28. 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

29. BONE MARROW EXAMINATION
Specifically, bone marrow aspirate permits examination of:
•Cytology
Megaloblastic change,
Dysplastic changes,
Abnormal cell infiltrates
•Immunophenotyping : antigen or marker on cells surfaces e.g
(Leukemias, Lymphoproliferative disorders)
•Cytogenetics : structure of chromosome
•Myelodysplasia, Leukemias,
Lymphoproliferativedisorders

30. Bone marrow is diagnosic for :
Multiplemyeloma
Myelofibrosis
A leukemic leukemia
Aplastic anemia
Seideroblastic anemia

31. CELULARITY OF BONE MARROW
The differential diagnosis of pancytopenia are based on
cellularity of bone marrow:
Normocellular: 50-70% hematopoietic cells &30-50%fat
Hypocellular: excessive amount of fat cells
Hypercellular: 80-100% cells with little fat
Hypo ----indicates decreased production of blood cells
Hyper --indicates ineffective production or increased
destruction or sequestration of blood cell

32. HYPERCELLULAR

33. Causes of Hypocellular BM
1.Aplastic anemia (cong or aqui)
2.Hypoblastic MDS
3.Cytotoxic agents & radiotherapy

34. Causes of Hypercellular BM with
primary marrow disorders
1.Acute leukemia / lymphoma
2-Myelofibrosis
3- PNH
4- Mutiple myeloma
5. Mylodysblastic leukemia

35. Causes of Hypercellular BM with
systemic disorders
1.Hypersplenism
2- Megaloblastic anemia
3- Infection (T.B ,kala azar, brucellosis)
4- Overwhelming infections
5- SLE, Sjogren’s
6- Sarcoidosis
7- Storage disease- Gaucher, Niemann-
pick

36. Pancytopenia +markedly
Hypocellular scattered mature
lymphocytes
aplastic anemia

37. Pancytopenia + Hypercellular
BM
Infiltration by RS cells HL

38. Pancytopenia + Hypercellular
B.M + old age
MDS

39. Pancytopenia + Hypercellular
marrow
Infiltration with malignant cells (Metastasis)

40. SPECIFIC INVESTIGATIONS

41. TEST RATIONALE
BONE X-RAYS
immunoelectrophoresis
, metastasis
Multiple myeloma
ANA test Systemic Lupus Erythematous
BLOOD CULTURE Infectious agent- Tuberculosis or virus
VITAMIN B12 AND FOLATEASSAYS Megaloblastic anemia
LFT Evaluate hepatitis
KFT Assess for Chronic RenalFailure
SEROLOGY HIV, EBV, Hepatitis
Flow cytomertry Paroxysmal Nocturnal Haemoglobunuria
CHROMOSOMAL
BREAKAGE STUDIES
Fanconi anemia

42. pancytopenia
Retic count or