Pancytopenia¶

Matthew Lu

Background¶

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

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)