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: Allergic bronchopulmonary aspergillosis, 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