Kruse - Anemia and Hematopoietic Growth Factors Flashcards
Iron is absorbed as Fe__ state.
Iron is transported and stored in Fe___ state
- Absorbed: Fe2+ (ferrous) – ORAL
- Transported/Stored: Fe3+ (ferric); with transferrin – PARENTERAL
Increased erythropoiesis is associated with an increase in number of ___-receptors on developing erythroid cells.
Transferrin
Iron store depletion and iron deficiency anemia are associated with an increased concentration of serum ___.
Transferrin
Iron is stored as ___.
ferritin
In what states can iron be administered orally?
Administer as FERROUS salt (Fe2+): ferrous sulfate, ferrous gluconate, ferrous fumarate
How should oral iron be administered (taken with…?)
water or juice on an empty stomach; may be admin with food to prevent irritation.
Adverse effects of oral iron therapy.
N, epigastric pain, black stools, abdominal cramps, constipation, diarrhea (dose related; reduced if taken with or immediately after meals).
Parenteral iron therapy is reserved for what type of pateints?
People unable to tolerate/absorb oral iron or with chronic anemia that can’t be maintained with oral iron (CRD, IBD, SI resection)
Parenteral iron administration bypasses what regulatory mechanisms - beneficial why?
Bypasses iron storage regulatory mechanisms of the intestine – can deliver more iron than can can safely be stored.
Name the three forms of parenteral iron is USA.
- Iron dextran - (IV>IM), adverse effects - HA/fever/arthralgia/ N/V/back pain, flushing BRONCHOSPASM, ANAPHYLAXIS
- Sodium ferric gluconate complex
- Iron-Sucrose Complex
What age is acute iron toxicity seen in? Symptoms?
Young children - see vomiting, abdominal pain, bloody diarrhea –> shock, lethargy, dyspnea –> metabolic acidosis, coma, death
Treatment of acute iron toxicity.
Whole bowel irrigation and parenteral deferoxamine.
Signs and symptoms of Chronic Iron Toxicity.
Deposits onto heart, liver, pancreas, etc = organ death.
Treatment for Chronic Iron Toxicity.
Intermittent phlebotomy.
Oral iron chelator deferasirox.
Two forms of active Vitamin B12 in humans + form of administration.
Cyanocobalamin and hydroxocobalamin - parenteral
Most common clinical manifestation of B12 deficiency
Megaloblastic, macrocytic anemia.
Describe the neurologic syndrome associated with B12.
Begins with paresthesias in peripheral nerves/weakness –> COT to spasticity, ataxia.
-homocysteine
Richest dietary sources of folic acid.
Yeast, kidney, liver, green veggies.
What is the clinical manifestation of folic acid deficiency?
Megaloblastic anemia.
How does presentation of folic acid deficiency v. B12 deficency differ.
Both have megaloblastic anemia, but B12 has neuro syndrome and Folic Acid deficiency does not.
Name four drugs that can cause folic acid deficiency.
- Inhibitors of DHFR: MTX, Trimethoprim, Pyrimethamine
- Phenytoin (long term)
In what scenarios does EPO rise to induce erythropoiesis?
Anemia, hypoxemia, (kidney disease, marrow damage, iron deficiency, vitamin deficiency).
Two erythrocyte-stimulating agents
Epoetin alpha and darbepoetin alpha
Results of inducing erythropoiesis -
inc reticulocyte count (10 days), rise in Hct/Hb (2-6 weeks)
Clincal scenarios when Erythropoiesis-Stimulating Agents are used.
Anemia (secondary to CKD or due to primary bone marrow disorders), AIDS, MM, MDS, MPD, etc).
Banned in professional athletes.
Toxicity of ESAs
HTN, thrombotic complications (due to increase in blood)
Function of myeloid growth factors
Enhance function of mature granulocytes and monocytes.
Name two Granulocyte Colony-Stimulating Factors (G-CSF)
Filgrastim (recombinant human G-CSF) and pegfilgrastin (longer 1/2 life, administer less frequent)
(plerixafor)
When is plerixafor used?
when patients respond suboptimally to G-CSF alone.
Use: filgrastim + plerixafor = inc. CD34+
Function - to increase HSC from marrow to PB
Function of G-CSF
Stimulates proliferation and differentiation of progenitors already committed to the neutrophil lineage - activates phagocytic activity of mature neutrophils.
Name a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Sargramostim
How does GM-CSF differ from G-CSF.
GM-CSF’s primary effect is to stimulate myelopoiesis (broader then G-CSF) - erythroid/megakaryocyte progenitors, mature neutrophil function, T-cell proliferation with IL-2
Tx for cancer chemo-induced ***neutropenia
G-CSF accelerates neutrophil recovery
Toxicity of Filgrastim and pegfilgrastim
bone pain
Toxicity of GM-CSF
fever, malaise, arthralgia, myalgia, capillary leak syndrome (would see peripheral edema and pleural/pericardial effusion)
What class of growth factor should be given for patients with thrombocytopenia?
Megakaryocyte growth factor.
Name the two megakaryocyte growth factors.
Oprelvekin (IL-11) and Romiplostim (recombinant thrombopoietin)
Clinical use for oprelvekin
Secondary prevention of thrombocytopenia in people receiving cytotoxic/myelosuppressive chemotherapy for NONmyeloid cancers - reduced # of platelet transfusions.
Clinical use for romiplostim
Used to treat thrombocytopenia in people with chronic immune (idiopathic) thrombocytopenia purpura.
(ITP)
AE of oprelvekin v. romplostim
- Oprelvekin - HA, dizziness, fatigue, CV, hypOk (all reversible)
- Romiplostim - mild HA
MOA of oprelvekin
Activates surface cytokine receptors to stimulate growth of lymphoid/myeloid cells. Stimulate primitive megakaryocyte progenitors = inc. peripheral platelet and neutrophils.
MOA of romiplostim
activates Mpl TPO receptor to cause dose dependent increase in platelet count.
