1) Pancytopenia refers to decreases in all peripheral blood cell lines, specifically red blood cells, white blood cells, and platelets. Common causes include bone marrow infiltration, aplasia, or blood cell destruction. 2) Evaluation of pancytopenia involves a thorough history and physical exam focusing on symptoms, exposures, medications, and signs of organomegaly or lymphadenopathy. 3) Initial laboratory tests include a complete blood count, blood smear, and basic metabolic panel. Additional tests may include coagulation studies, blood cultures, serologies, and bone marrow examination based on specific clinical or laboratory findings.

1. Dr Bikal Lamichhane
1st year IM resident
Approach to pancytopenia

2. INTRODUCTION
 Pancytopenia refers to decreases in all peripheral blood lineages and is
considered to be present when all three cell lines are below the normal reference
range.
 Red blood cells – Hemoglobin <12 g/dL for non-pregnant women and <13 g/dL
for men
 White blood cells – nearly all cases of low white blood cells (leukopenia)
manifest as neutropenia.
Absolute neutrophil count (ANC) <1800/microL – Calculated as the total white
blood cells/microL x (percent [polymorphonuclear cells + bands] ÷ 100)
 Platelets – Platelet count <150,000/microL

3. MECHANISMS OF PANCYTOPENIA
Bone marrow infiltration/replacement
Bone marrow aplasia
Blood cell destruction or sequestration

7. Approach
 History:
 Time course and clinical severity – Prior laboratory results (when
available) and severity and duration of symptoms should be evaluated.
 Symptoms associated with cytopenias – Examples include:
•Recurrent, severe, or unusual infections that may be due to
leukopenia/neutropenia
•Fatigue, dyspnea, chest pain, hemodynamic instability, or claudication
due to anemia
•Bleeding or easy bruising due to thrombocytopenia or disseminated
intravascular coagulation

8.  Previous treatments –
for hematologic disorders, prior transfusions, hematinics (eg, vitamin B12,
folate, iron), or other treatments (eg, apheresis, plasma exchange).
 Other medical conditions – any comorbid medical condition or surgical
procedure can contribute to or exacerbate cytopenias.
 Problematic medications – Many medications (including prescription and over-
the-counter medications, health supplements, and home or folk remedies) may
cause or contribute to cytopenias.
 Personal and occupational exposures – Certain personal habits (eg, alcohol
consumption, diet), infection history (eg, HIV, viral hepatitides), exposure to toxic
agents at work or home (eg, organic solvents), and travel history (eg, exposure
to malaria, leishmania)

9.  Physical findings
 Rashes that may be related to drug reactions, rheumatologic
disorders, infections, and malignancies
 Oral lesions; as examples, thrush suggests immune compromise;
oral ulcers may be seen in diseases such as systemic lupus
erythematosus.
 Lymphadenopathy and/or splenomegaly.
 Jaundice and stigmata of liver disease

10.  Splenomegaly and/or liver disease .
 Liver disease/cirrhosis and portal hypertension
 Infections (eg, viral infections, malaria, leishmaniasis, endocarditis)
 Hematologic malignancies (eg, lymphomas, hairy cell leukemia, myeloproliferative
neoplasms)
 Extramedullary hematopoiesis (eg, associated with myelofibrosis or thalassemias)
 Congestion (eg, right sided congestive heart failure)
 Inflammation (eg, associated with rheumatoid arthritis [Felty syndrome] or other
autoimmune illness, endocarditis)
 Primary splenic disease (eg, hemorrhage, thrombosis)
 Storage diseases (eg, Gaucher disease)
 Hemophagocytic lymphohistiocytosis

11. Lymphadenopathy —
Potential disorders associated with lymphadenopathy and
pancytopenia include:-
●Hematologic malignancies (eg, lymphoma, leukemia)
●Autoimmune illnesses
●Infectious diseases

12.  Aids to the diagnosis of an underlying cause of lymphadenopathy in the setting
of pancytopenia include:-
●Imaging (eg, CT scan, ultrasound, or PET scan to define the extent of
lymphadenopathy, and as a possible adjunct to biopsy).
●Lymph node biopsy (including morphology, flow cytometry, molecular studies).
●Flow cytometry of peripheral blood and/or lymph node specimen (eg, to evaluate
hematologic malignancies).
●Serologic studies for infectious or autoimmune illnesses.
●Bone marrow aspirate and biopsy may be required if other studies are non-
diagnostic

13. Constitutional symptoms —
 unexplained fevers, soaking sweats, and weight loss.
 Possible causes of pancytopenia associated with
constitutional symptoms include:
●Infections (viral illness, miliary tuberculosis, fungal infection,
endocarditis)
●Hemophagocytic lymphohistiocytosis (HLH)
●Hematologic malignancies (eg, lymphoma, leukemia)
●Autoimmune illnesses

14.  Metabolic abnormalities —
 Certain metabolic disorders (eg, hypercalcemia, tumor lysis
syndrome, renal failure, hyperuricemia) may be associated
with diseases that also cause pancytopenia, including multiple
myeloma, leukemia, and lymphoma

15. Laboratory studies
 Complete blood count (CBC), with white blood cell differential count and red
blood cell indices
 Peripheral blood smear
 Reticulocyte count: An absolute reticulocyte count <20,000 indicates a marked
decrease in red blood cell production and suggests a hypoproliferative condition.

 Prothrombin time (PT) and partial thromboplastin time (PTT). Coagulopathies in
the setting of pancytopenia generally require prompt evaluation and referral.
 Serum chemistry tests, including electrolytes, renal and liver function tests,
lactate dehydrogenase, calcium, and uric acid.
 Blood type and screen

16. Specific clinical scenarios
 Coagulopathy —
 The finding of elevated prothrombin time (PT) and/or partial thromboplastin time
(PTT) in the setting of pancytopenia may suggest microangiopathic hemolytic
anemia (MAHA).
 This requires urgent examination of the peripheral blood smear for the presence
of schistocytes with thrombocytopenia.

17.  Abnormal cells on blood smear
 Circulating blasts associated with various leukemias; eg, acute
leukemias, hairy cell leukemia, or other hematologic malignancies.
 Dysplastic leukocytes, including pseudo-Pelger-Huët cells or reduced
neutrophil cytoplasmic granules in myelodysplastic syndromes.

 Immature myeloid cells, such as promyelocytes, myelocytes, and
metamyelocytes that may reflect an underlying myeloproliferative
neoplasm (MPN), such as primary myelofibrosis.
 Leukoerythroblastic findings, including nucleated red blood cells
associated with myelofibrosis or other MPNs

18.  Confirmation of the nature of such abnormal cells will require
further specialized testing including:-
●Bone marrow aspirate and biopsy.
●Flow cytometry of peripheral blood and/or bone marrow.
●Cytogenetic testing (fluorescent in situ hybridization [FISH] or
karyotype) of bone marrow or peripheral blood.
●Molecular studies (eg, mutation analysis, gene expression profiling

19. Bone Marrrow Examination Finding

20. Non-malignant cells
 Hypersegmented neutrophils in association with ovalomacrocytes
suggest a megaloblastic disorder.
 Atypical lymphocytes can be seen following viral infections such as
infectious mononucleosis, and may be associated with pancytopenia due
to bone marrow suppression, hypersplenism.
 Leukoerythroblastic appearance of the blood smear, with RBC teardrops,
nucleated RBCs, and microangiopathic hemolytic anemia (MAHA), may
be associated bone marrow infiltration caused by myelofibrosis or
metastatic cancer.
 Schistocytes or other evidence of MAHA may reflect disseminated
intravascular coagulation, due to sepsis, acute promyelocytic leukemia,
or other causes

21. SPECIFIC INVESTIGATIONS
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