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Nishant Rajendra Tiwari: Stepwise Approach to New-Onset Pancytopenia 
Nishant Rajendra Tiwari/X
Dec 11, 2025, 12:10

Nishant Rajendra Tiwari: Stepwise Approach to New-Onset Pancytopenia 

Nishant Rajendra Tiwari, Hematology-Oncology Fellow at OU Health Stephenson Cancer Center, posted on X:

”Stepwise Approach to New-Onset Pancytopenia
*Educational post – not medical advice.*

  1. Review baseline blood counts → Acute vs chronic?
  2. Evaluate for serious/critical conditions:
    – Acute leukemia? Other aggressive hematological malignancies? *(Peripheral smear, flow cytometry, bone marrow biopsy as indicated)*
    – Neutropenic fever? Treat per algorithm if present!
  3. Transfusions needed? Severe anemia or thrombocytopenia?
  4. Any signs of DIC or TLS? *(PT/aPTT, fibrinogen, LDH, uric acid, Phosphorus)*
  5. Medication review — always check latest literature for drug associations!
  6. Investigate secondary causes (clinically guided):
    – Nutritional: B12, folate, thiamine, copper, zinc
    – Viral: HIV, Hepatitis, CMV, EBV, HHV-6, VZV, Parvo B19, HSV1/2
    – Fungal: Disseminated histoplasmosis
    – Bacterial: Typhoid, brucellosis, TB
    – Parasitic: Leishmaniasis, malaria
    – Immune: SLE, RA, Evans syndrome
    – Endocrine: TSH, Free T4, AM cortisol, ACTH *(rule out panhypopituitarism)*
  7. Imaging? Look for lymphadenopathy, splenomegaly, liver cirrhosis, malignancy etc.
    – I try to get a CT chest/abdomen/pelvis with contrast if renal function allows!
  8. When to do bone marrow biopsy?
    – Suspected hematologic malignancy
    – Unrevealing workup
    – Planning growth factor therapy (G-CSF, TPO mimetics)
  9. Radiation? Heavy metals? Environmental toxins? Excess alcohol?
  10. Syndromic features of inherited bone marrow failure syndromes (IBMFS)?
    – Aplastic anemia morphology? Bone marrow exam clues?
    – Young patients or syndromic features? → Consider germline testing!
  11. Rare but notable causes (investigate as indicated):
    – PNH
    – Post-transplant LPD
    – Glycogen/lysosomal storage disorders
    – Primary HLH *(especially in kids)*
    – Sarcoidosis
    – Primary immunodeficiencies
  • Key Clinical Pearls:
    – Acute pancytopenia in a healthy adult = medical emergency → **always rule out acute leukemia**!
    – Microcytic anemia + pancytopenia? Think copper deficiency or severe malnutrition (B12/folate + iron deficiency!)
    – Secondary HLH is more common in adults than primary HLH.

This is a ‘framework’, not the full DDx — the differential is too vast for one tweet! Happy to hear any feedback for it’s improvement.”

Nishant Rajendra Tiwari

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