Interleukin-11 acts through a specific cell surface cytokine receptor to stimulate the growth of multiple lymphoid and myeloid cells. It acts synergistically with other growth factors to stimulate the growth of primitive megakaryocytic progenitors and, most importantly, increases the number of peripheral platelets and neutrophils.
Romiplostim has high affinity for the human Mpl receptor. Eltrombopag interacts with the transmembrane domain of the Mpl receptor. Both drugs induce signaling through the Mpl receptor pathway and cause a dose-dependent increase in platelet count. Romiplostim is administered once weekly by subcutaneous injection. Eltrombopag is an oral drug. For both drugs, peak platelet count responses are observed in approximately 2 weeks.
Interleukin-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experience severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 mcg/kg daily. It is started 6–24 hours after completion of chemotherapy and continued for 14–21 days or until the platelet count passes the nadir and rises to more than 50,000 cells/μL.
In patients with chronic immune thrombocytopenia who failed to respond adequately to previous treatment with steroids, immunoglobulins, or splenectomy, romiplostim and eltrombopag significantly increase platelet count in most patients. Both drugs are used at the minimal dose required to maintain platelet counts of greater than 50,000 cells/μL.
The most common adverse effects of IL-11 are fatigue, headache, dizziness, and cardiovascular effects. The cardiovascular effects include anemia (due to hemodilution), dyspnea (due to fluid accumulation in the lungs), and transient atrial arrhythmias. Hypokalemia also has been seen in some patients. All of these adverse effects appear to be reversible.
Eltrombopag is potentially hepatotoxic and liver function must be monitored, particularly when used in patients with hepatitis C. Portal vein thrombosis also has been reported with eltrombopag and romiplostim in the setting of chronic liver disease. In patients with myelodysplastic syndromes, romiplostim increases the blast count and risk of progression to acute myeloid leukemia. Marrow fibrosis has been observed with thrombopoietin agonists but is generally reversible when the drug is discontinued. Rebound thrombocytopenia has been observed following discontinuation of TPO agonists.
Ferrous gluconate and ferrous fumarate: Oral iron preparations
Iron dextran, iron sucrose complex, sodium ferric gluconate complex, ferric carboxymaltose, and ferumoxytol: Parenteral preparations can cause pain, hypersensitivity reactions
Required for biosynthesis of heme and heme-containing proteins, including hemoglobin and myoglobin Adequate supplies required for normal heme synthesis
Iron deficiency, which manifests as preparation Complicated endogenous system for absorbing, storing, and transporting iron • Toxicity: Acute overdose results in necrotizing gastroenteritis, abdominal pain, bloody diarrhea, shock, lethargy, and hemochromatosis, with damage to the heart, liver, pancreas, and other organs