Pancytopenia

Background

• Combination of anemia (<120-130), neutropenia (<1.8), and platelet (<150)

Clinical Manifestations

• Increased infections, from leukopenia
• Bleeding, from thrombocytopenia
• Angina and other hypoxemic symptoms, from anemia

Differential Diagnosis

• See also aplastic anemia
• Congenital causes (chronic pancytopenia)
  • Telomere diseases: dyskeratosis congenita (early hair graying, pulmonary fibrosis, cirrhosis)
  • Fanconi anemia (short statue, café-au-lait spots, skeletal abnormalities, urogenital abnormalities)
  • GATA2 deficiency (persistent or unusual infections)
  • CTLA4 deficiency (intestinal disease, adenopathy, infections, autoimmune disorders)
  • Schwachman-Diamond syndrome (skeletal abnormalities, exocrine pancreatic dysfunction)
  • Wiskott-Aldrich syndrome (eczema, recurrent infections, low IgM, elevated IgA/E)
• Medication-induced
  • Immunosuppressants, chemotherapy, radiation
  • Antiseizure: carbamazepine, levetiracetam, phenytoin, phenobarbital, valproate
  • Gout: allopurinol, colchicine
  • Antibiotics: coadministration of TMP-SMX and methotrexate, albendazole, chloramphenicol, cidofovir, dapsone, foscarnet, ganciclovir, linezolid, quinine, sulfonamides, zidovudine
  • NSAIDs: aspirin, diclofenac, ibuprofen, indomethacin, phenylbutazone, salicylates, sulindac
  • Anti-thyroid: methimazole, propylthiouracil
  • Cardiovascular: aspirin, amiodarone, captopril, lisinopril, nifedipine, quinidine, ticlopidine
  • Diuretics: acetazolamide, furosemide, thiazides
  • GI: cimetidine, nizatidine
  • Psychiatric: bupropion, lithium, valproate
  • Exposures: benzene, MDMA, glue, pesticides, radiation, organic solvents
• Decreased production
  • Infection
    • Viral
      • Epstein-Barr virus: chronic active EBV and primary infection that results in hemophagocytic lymphohistiocytosis
      • Parvovirus B19: usually transient, but can also cause pure red cell aplasia
      • Cytomegalovirus, if immunocompromised
      • Hepatitis A virus
      • Human immunodeficiency virus
      • Dengue virus
    • Bacterial
      • Mycobacterium tuberculosis, in the context of disseminated disease
      • Leptospira
      • Brucella
      • Bartonella henselae and Bartonella quintana, causing bacillary angiomatosis involving liver and spleen
      • Mycoplasma pneumoniae, associated with fulminant infection and the presence of cold agglutinin disease
      • Ehrlichia chaffeensis, causing hemophagocytic lymphohistiocytosis
    • Fungal
      • Pneumocystis jirovecii, from bone marrow necrosis
    • Parasitic
      • Visceral leishmaniasis
  • Malignancy
    • Hematologic malignancy
    • Solid organ malignancy
      • Metastases
  • Other
    • Sarcoidosis
    • Amyloidosis
  • Nutritional
    • Vitamin B12 deficiency
    • May be from underlying severe caloric restriction, eating disorder, bariatric surgery, malabsorption, or alcohol use
• Increased destruction with decreased production: autoimmune disorders, PNH, hematologic malignancies, HLH, sepsis
• Increased destruction (hemolysis with increased reticulocytes): Evan syndrome, thrombotic microangiopathy, DIC
• Sequestration (splenomegaly): portal hypertension, cirrhosis, infections, autoimmune disorders, myeloproliferative neoplasm, leukemia, lymphoma, storage diseases

Investigations

• Initial investigations:
  • Review prior CBCs to determine chronicity
  • CBC with differential and reticulocyte count
  • Peripheral blood film
    • Leukoerythroblastic reaction: BM infiltration and sepsis
    • Blasts: AML or ALL
    • Pelger-Huet anomaly or dysplasia: MDS
    • Megaloblastic: B12 or folate deficiency
    • Atypical lymphocytes: viral (such as EBV)
    • Schistocytes: DIC, sepsis, TMA
  • Lytes/creatinine, uric acid, LDH
  • Liver panel
  • Coags
  • Iron studies
  • ESR/CRP
• Consider the following, based on initial workup:
  • Copper, zinc, B12/MMA, folate
  • HLH workup
  • Infectious workup
  • Haptoglobin
  • HIV, EBV, CMV, HBV, HCV, HHV6, parvovirus
  • ANA, ENA
  • DIC panel
• Then consider the following, based on initial workup:
  • Flow cytometry
  • Tuberculosis or fungal workup
  • US/CT/MRI/PET-CT
  • Bone marrow aspirate and biopsy