Hematopoietic Growth Factors

On this page

Erythropoiesis-Stimulating Agents - Red Cell Rally

ESAs mimic endogenous erythropoietin (EPO).

  • Agents: Epoetin alfa, Darbepoetin alfa (longer-acting), Methoxy PEG-epoetin beta.
  • MOA: Activate JAK-STAT pathway on erythroid precursors; increase RBC production.
  • Pharmacokinetics: IV/SC.
    FeatureEpoetin AlfaDarbepoetin Alfa
    Half-life (IV)4-13 hrs~21 hrs (longer)
    GlycosylationStandardIncreased sialic acid
  • Clinical Uses:
    • Anemia of CKD (target Hb 10-12 g/dL)
    • Chemo-induced anemia (non-myeloid)
    • Zidovudine-induced anemia (HIV)
    • Anemia in MDS
    • Reduce allogeneic transfusions (surgery).
  • Adverse Effects:
    • Hypertension (most common)
    • Thrombotic events (MI, stroke, VTE): Risk if Hb > 11-12 g/dL or rises > 1 g/dL/2 wks.
    • PRCA (antibody-mediated)
    • Seizures
    • Potential tumor progression
    • 📌 Mnemonic: EPO causes HHH - Hypertension, Hypercoagulability, Hyperviscosity.
  • Cautions/CI:
    • Uncontrolled hypertension, known hypersensitivity, history of PRCA.
    • Caution: cancer patients not receiving chemotherapy.
  • Monitoring: Monitor: Hb (target 10-12 g/dL, avoid rise > 1 g/dL/2 wks), iron, BP.

⭐ Darbepoetin alfa's significantly longer half-life compared to epoetin alfa is due to its increased sialic acid content from additional glycosylation sites.

Erythropoiesis regulation by EPO and growth factors

Myeloid Growth Factors - Neutrophil Ninjas

Stimulate myeloid progenitor proliferation & differentiation.

  • G-CSF (Granulocyte Colony-Stimulating Factor)

    • Agents: Filgrastim, Pegfilgrastim (long-acting), Lenograstim.
    • MOA: ↑ Neutrophil lineage. 📌 G-CSF for Granulocytes.
    • Clinical Uses:
      • Chemotherapy-induced neutropenia (prophylaxis & treatment, esp. ANC < 500/µL).
      • Bone Marrow Transplant (BMT): PBSC mobilization, accelerates post-transplant neutrophil recovery.
      • Aplastic anemia, congenital neutropenias, Myelodysplastic Syndromes (MDS).
    • Adverse Effects:
      • Bone pain (common), flu-like symptoms, splenic rupture (rare), ARDS.

    ⭐ Pegfilgrastim, a pegylated G-CSF, has a prolonged half-life due to reduced renal clearance, allowing for once-per-chemotherapy-cycle dosing.

  • GM-CSF (Granulocyte-Macrophage CSF)

    • Agents: Sargramostim, Molgramostim.
    • MOA: Broader: ↑ neutrophils, eosinophils, monocytes, macrophages. 📌 GM-CSF for Granulocytes & Macrophages.
    • Clinical Uses:
      • Chemotherapy-induced neutropenia.
      • BMT (post-transplant recovery, engraftment failure).
      • Aplastic anemia.
    • Adverse Effects:
      • Fever, myalgia, arthralgia, rash, capillary leak syndrome, effusions, first-dose reaction (hypotension, dyspnea).

Myelopoiesis pathway with G-CSF and GM-CSF action

Thrombopoietic Growth Factors - Platelet Promoters

  • TPO Receptor Agonists (TPO-RAs):
    • Agents & PK:
      • Romiplostim (SC).
      • Eltrombopag (Oral; chelation with $Ca^{2+}$ - take empty stomach/low-$Ca^{2+}$ meal).
      • Avatrombopag (Oral), Lusutrombopag (Oral).
    • MOA: Mimic TPO → stimulate megakaryopoiesis → ↑ platelet production.
    • Uses:
      • Chronic ITP (target platelets > 50,000/µL).
      • Thrombocytopenia in CLD (pre-procedure).
      • Severe aplastic anemia (Eltrombopag).
    • AEs: Headache, arthralgia, myalgia, marrow reticulin fibrosis (monitor), thromboembolism. Rebound thrombocytopenia (on discontinuation).
      • Eltrombopag: Hepatotoxicity (monitor LFTs).

⭐ Eltrombopag is an oral, non-peptide TPO receptor agonist that must be taken on an empty stomach or with a low-calcium meal to avoid chelation with polyvalent cations.

  • Interleukin-11 (IL-11):
    • Agent & PK: Oprelvekin (SC) - less used.
    • MOA: Stimulates various hematopoietic cells, including megakaryocyte progenitors.
    • Uses: Prevention of severe thrombocytopenia post-myelosuppressive chemo (non-myeloid malignancies).
    • AEs: Fluid retention (edema, dyspnea), atrial arrhythmias (tachycardia, fibrillation), fatigue, headache. 📌 Oprelvekin (IL-11) makes you 'swell-even'.

High‑Yield Points - ⚡ Biggest Takeaways

  • Erythropoietin (EPO) & Darbepoetin alfa stimulate RBCs; treat anemia of CKD.
  • G-CSF (Filgrastim, Pegfilgrastim) boosts neutrophils; for chemotherapy-induced neutropenia.
  • GM-CSF (Sargramostim) stimulates myeloid lineages; used in aplastic anemia, BMT.
  • TPO agonists (Romiplostim, Eltrombopag)platelets; treat ITP.
  • EPO adverse effects: hypertension, thrombosis, pure red cell aplasia (PRCA).
  • Oprelvekin (IL-11)platelets; side effects (fluid retention) limit use.
  • Monitor hemoglobin with EPO; target <12 g/dL to avoid thrombosis.

Practice Questions: Hematopoietic Growth Factors

Test your understanding with these related questions

Drug inhibiting granulocyte migration is:-

1 of 5

Flashcards: Hematopoietic Growth Factors

1/10

Ruxolitinib is used to treat chronic myeloproliferative disorders that have _____ mutations including myelofibrosis and polycythemia vera

TAP TO REVEAL ANSWER

Ruxolitinib is used to treat chronic myeloproliferative disorders that have _____ mutations including myelofibrosis and polycythemia vera

JAK2

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial