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Matthew Lu


  • Pancytopenia is a decrease in all peripheral blood lineages (RBC, WBC, PLT). Many causes of pancytopenia can also cause bicytopenia, so bicytopenia is often worked up in a similar manner

Framework for differential

  • Impaired production
    • Bone marrow infiltration/replacement
    • Hematologic malignancies (Acute leukemias, lymphoma, etc.), metastatic solid tumors, myelofibrosis, MDS
    • Infections: TB, NTM, Fungal
    • Bone marrow suppression/aplasia
    • Vitamin/nutritional deficiencies: B12, folate, copper (can be caused by zinc toxicity)
    • Aplastic anemia (AA)
    • Infection: HIV, hepatitis, parvovirus B19, EBV, CMV, tick-borne
    • Medications (see below)
    • Toxins: ethanol
    • Sepsis
  • Peripheral destruction
    • TMA syndromes: TTP, HUS,
    • Autoimmune hemolytic
    • Evan’s syndrome (idiopathic or secondary)
    • Autoimmune disorders: SLE
    • Myelo- or lymphoproliferative disorders: CLL, CML, multicentric Castleman’s
    • Infection: EBV, CMV, HIV, hep B, hep C
  • Sequestration (splenomegaly)
  • Combined process: PNH (associated with AA), SLE, malignancies, HLH, Crohn’s, infections


  • HPI: B-symptoms, fatigue, dyspnea, infections, bleeding/bruising
  • Medications
    • NSAIDs, anti-epileptics, chemotherapy, antimicrobials/antivirals (Bactrim, valganciclovir, linezolid, RIPE therapy), immunosuppression (MMF, azathioprine, tacrolimus), anti-gout (allopurinol, colchicine), anti-thyroid (methimazole)
  • PMHx: autoimmune disease (SLE, RA, Scleroderma), radiation, gastric surgery, malabsorption (e.g. celiac, Crohn’s), liver disease, malignancy, transplant
  • Social Hx: EtOH use, malnutrition, occupational exposures, exposures to TB, leishmaniasis, or ticks
  • Exam: lymphadenopathy, hepatosplenomegaly, neuropathy, rashes, petechiae, stigmata of liver disease, cachexia, oral lesions
  • Diagnostic studies
    • CBC w/ diff, peripheral smear, IPF, reticulocyte count
    • TMA/DIC labs: PT/PTT/Fibrinogen, CMP, LDH, haptoglobin, smear
    • Viral studies: hepatitis B/C, EBV, CMV, HIV, parvovirus B19
    • Infectious work up (as clinically indicated): non-invasive fungal, Quant-gold/AFB, Anaplasma/Erhlichia PCR, RMSF
    • Nutritional studies: B12, folate, copper, zinc, iron
    • Abdominal ultrasound (for splenomegaly)
    • HLH (as clinically indicated): ESR/CRP, ferritin, triglycerides, soluble IL-2R, biopsy (liver or bone marrow)
    • Autoimmune (as clinically indicated): ANA w/ reflex, C3/C4, ESR/CRP
    • Can consider: flow cytometry, bone marrow biopsy, cytogenetics and FISH (typically driven by hematology recs)


  • Emergencies that may require urgent evaluation, management, or hospitalization
    • Febrile neutropenia (ANC < 500), symptomatic anemia (cardiac symptoms), platelets < 10k or < 50k with bleeding, abnormal blood smear (schistocytes or blasts)
  • When pancytopenia is slow, progressive over time, or acute without any other precipitating factors and a specific etiology is in mind (e.g. HLH or marrow infiltrating infection), consult hematology for consideration of bone marrow syndromes and/or bone marrow biopsy
  • Note: Bone marrow biopsy for acquired pancytopenia in the hospital setting often will not yield results that will change clinical management (I.e. most likely will just show an aplastic marrow)