Pancytopenia and Bicytopenia

Jamila Mammadova

Background

  • Pancytopenia is a decrease in all peripheral blood lineages (RBC, WBC, PLT).
  • Many causes of pancytopenia can cause bicytopenia (decrease in any two cell lines), so the workup is similar

 

Framework for differential

Mechanism

Causes

Example(s)
Bone marrow failure and suppression Infiltrative Malignancies (leukemia, lymphoma, myeloma, metastatic solid tumors), amyloidosis, fibrosis (myelofibrosis) , hemochromatosis
Myelodysplastic and hematologic syndromes Can be primary MDS or secondary (chemo, radiation), PNH
Drug induced Antibiotics (chloramphenicol, linezolid, bactrim), antivirals (gancyclovir, zidovudine, ribavirin), immunosuppressants (AZA, MMF, MTX), antiepileptics (valproate, carbamazepine, phenytoin), antithyroid (PTU, methimazole), NSAIDs, chemotherapies
Infection Sepsis, HIV, CMV, EBV, Parvovirus, HBV, HCV, TB, histo, tick-borne
Toxicity Radiation, benzene exposure, arsenic (may be irreversible), EtOH
Autoimmune SLE, RA/Felty syndrome, sarcoidosis, autoimmune subtype of aplastic anemia, Evan’s syndrome
Nutritional deficiency Vitamin B12, folate, copper (primary vs secondary to zinc toxicity), anorexia nervosa, malabsorptive diseases (i.e. Crohn’s)
Other Hemophagocytic syndromes Hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS)
Consumption DIC (sepsis or acute PML)
Splenomegaly Congestion (portal HTN), malignancies, EBV, autoimmune disorders

Evaluation 

  • HPI: B-symptoms, fatigue, dyspnea, infections, bleeding/bruising, timing of symptoms
  • Review medications (refer to the table above)
  • PMHx: autoimmune disease (SLE, RA, scleroderma), radiation, gastric surgery, malabsorption (e.g. celiac, Crohn’s), liver disease, malignancy, transplant , immunosuppression
  • Social Hx: EtOH use, malnutrition, occupational exposures, travels, hiking, exposures to fungal infections, TB, leishmaniasis, or ticks
  • Exam: look for lymphadenopathy, hepatosplenomegaly, neuropathy, rashes, petechiae, mucosal bleed, stigmata of liver disease, cachexia, oral lesions
  • CBC w/ diff, peripheral smear, IPF, reticulocyte count
  • TMA/DIC labs: haptoglobin, LDH, LFTs, PT/PTT, fibrinogen, D-dimer, peripheral smear (for schistocytes), retics (will be high), renal function
  • Infectious work-up (as clinically indicated):
    • Viral serologies: HIV, HBV, HCV, EBV, CMV, parvovirus
    • Sepsis: blood cultures, urine culture, sputum cultures
    • Fungal work-up: 1,3-Beta-D-Glucan, aspergillus galactomannan, urine blasto Ag, urine and serum histo Ag, crypto Ag
    • Tick-borne: RMSF, Ehrlichia, Anaplasma
    • Leptospirosis
    • TB and/or NTM: AFB, interferon-gamma release assay
  • Autoimmune work-up (as clinically indicated): ESR, CRP, ANA w/ reflex, C3/C4, RF, APL antibodies
  • Nutritional studies: B12, folate, copper, zinc, Fe
  • Abdominal U/S to look for splenomegaly (or review recent imaging)
  • HLH: ESR, CRP, ferritin, triglycerides, soluble IL-2R
  • Consider flow cyt, bone marrow biopsy, cytogenetics, and FISH (c/s heme at this stage)

Management 

  • Get type and screen and blood products transfusion consent if low counts or evidence of bleeding
  • Hold DVT prophylaxis, avoid NSAIDs and ASA for platelet<50K
  • Identifying the cause of pancytopenia is the biggest part of management (then find respective management tips in the handbook)
  • Emergencies that may require urgent evaluation, management, or hospitalization - can’t miss
    • Neutropenia (ANC < 1000, or severe when ANC < 500) with fever or other evidence of infection
    • Symptomatic anemia (cardiac symptoms like chest pain, SoB, HDUS, worsening CHF)
    • Platelets < 10k or < 50k with bleeding
    • Abnormal blood smear (schistocytes or blasts): suspect DIC, TMA
    • HLH (unexplained fever, hepatomegaly, lymphadenopathy, neurologic symptoms, very high ferritin, abnormal LFTs, coagulopathy)
    • When pancytopenia is slow, progressive over time, or acute without any other precipitating factors and a specific etiology is in mind (e.g. leukemia 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 will often not yield results that will change clinical management (most likely will show an aplastic marrow)
  • Supportive treatments to consider:
  • Transfusions as indicated
  • Consult heme for pharmacologic support options:
    • G-CSF (Filgrastim) for neutropenia
    • Erythropoietin stimulating agents for certain anemias
    • TPO receptor agonists (Elthrombopag, Romiplostim) for certain thrombocytopenias
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