Hematopoietic Growth Factors Lecture PDF Flashcards
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Hemopoiesis definition
Production of formed elements of blood (erythrocytes, leukocytes, thrombocytes)
Red marrow location in children vs adults
Nearly all marrow in children is red, in adults it is confined to specific areas (skull, ribs and sternum, pelvis primarily) of bone, with yellow marrow replacing it in other locations (although it can convert back)
Hemocytoblast
Stem cells that form all elements of blood, also known as a pluripotential stem cell
Differentiation of stem cells occurs when they develop surface receptors for a specific 1 of 3 of these growth factor’s in which they are then committed for life to that line
- erythropoietin (transforms an uncommitted potential cell to a committed proerythroblast)
- thrombopoietin
- CSF’s
Erythrocyte differentiation pathway
Hemocytoblast Proerythroblast Erythroblast Reticulocyte (enters circulation) mature RBC
Erythrocyte homeostasis mechanism of action
- Drop in O2 content detected by receptors in kidney
- increases output of erythropietin by kidneys
- 3-4 days later, RBC rises and compensates for dropped O2 content
Polycythemia vera definition
Highly viscous blood, often due to RBC levels rising dangerously high to correct for hypoxemia from emphysema without any improvement being actually made at the oxygen content level
Major requirements for erythropoiesis to occur and what function do they serve(2)
- Iron (form hemoglobin)
- B12 and folic acid (proper cell division)
Iron metabolism and storage in the liver mechanism of action pathway
- Fe3+ is converted to Fe2+, or ingested Fe2+ sits in the gut
- Only Fe2+ can be absorbed by small intestine binding gastroferrin produced by stomach
- Dissociates from gastroferrin and binds transferrin to deliver to tissues of the body
- liver binds any excess iron to apoferrin, the iron storage complex becoming ferritin
- Ferritin releases stored Fe2+ converting itself back to apoferrin, iron goes into circulation as needed
3 differentiated types of WBC progenitors from the hemocytoblast
- B progenitors
- T progenitors
- granulocytes/macrophage colony forming units
When thrombopoietin binds to a hemocytoblast, what happens?
It becomes a megakaryoblast by replicating DNA without nuclear or cytoplasmic cytokinesis
How long to platelets survive in the circulation
5-9 days
Erythropoietic growth factors/erythropoiesis stimulating agents function
Allow the patient to see increase in RBC count in patients with CRF and cancer patients undergoing chemotherapy
Erythropoietic growth factors/erythropoiesis stimulating agents ADR’s (5)
- Hypertension is most significant
- Increased risk of DVT when used before elective surgery
- Can worsen some cancers
- cardiac arrest
- autoimmune pure red cell aplasia (PRCA)
Epoetin alfa (Epogen, procrit) class, therapeutic use,
- Erythropoietic growth factor
- can reverse anemia associated with CRF virtually eliminating need for transfusion
Erythropoietic growth factors/erythropoiesis stimulating agents including epoetin alfa (epogen, procrit) does NOT do these 3 things
- Improve quality of life
- decrease fatigue
- delay progression of renal deterioration
Procrit indications
- treats chemo induced anemia in patients with nonmyeloid malignancies reducing need for transfusions
- undergoing elective surgery when significant blood loss is expected
Zidovudine function and cross reactivity with procrit
Antiretroviral therapy for HIV/AIDS,
-Procrit is approved for patients infected with HIV to maintain or elevate erythrocyte counts reducing need for transfusions
Autoimmune pure red cell aplasia (PRCA) and treatment
Rare condition where treatment with epoeitin leads to a condition characterized by severe anemia and complete loss of erythrocyte precursor cells in bone marrow due to production of Abs directed against epoetin and native endogenous erythropoietin, which causes RBC production to cease, treatment consists of transfusions for survival
Risk evaluation and mitigation strategy (REMS) and its relation to erythropoiesis
Drugs are required to be described under this mandated by FDA, meaning all patients receiving ESA’s must receive a medication guide explaining benefits and risks
Epoetin alfa administration and 2 drugs of this class
Injection
-epogen and procrit
Darbepoeitin alfa (ARANESP) function
Long acting erythropoietin approved by FDA for treatment of anemia that has a slower clearance making half life 2-3x longer
Darbepoeitin alfa (ARANESP) ADR’s (3)
- Hypertension
- MI
- thrombosis
Filgrastim (neupogen) mechanism of action
Acts on cells of bone marrow to increase production of neutrophils using identical mechanism to G-CSF, and enhances phagocytic and cytotoxic actions of mature neutrophils
Filgrastim (neupogen) therapeutic uses (3)
- Approved to reduce risk of infections in patients undergoing myelosuppressive chemotherapy (many chemotherapuetics suppress bone marrow, this leads to increased infection)
- also used in bone marrow transplants and harvesting bone marrow
- treats severe chronic neutropenia
Filgrastim (neupogen) ADR’s (2)
- devoid of serious ADR’s
- bone pain
- leukocytosis
Filgrastim (neupogen) administration
Injection IV or SC
Filgrastim-sndz (Zarxio) characteristics
A filgrastim (neupogen) biosimilar, a highly similar product with no clinical meaningful difference, minor differences in clinically inactive components only
Pegfilgastrim (neulasta) characteristics
Long acting derivative of filgrastim (neupogen) that stimulates myeloid cells to increase neutrophil production, longer half life allows for treatment with one dose
Pegfilgastrim (neulasta) ADR
- devoid of serious ADR’s
- bone pain
Sargramostim (leukine, prokine) mechanism of action
Acts on cells in bone marrow to increase production of neutrophils, monocytes, macrophages and eosinophils by imitating a GM-CSF nearly identically
Sargramostim (leukine, prokine) therapeutic uses (3)
- Accelerated myeloid recovery in patients who have undergone bone marrow transplant after chemo
- treatment of failed bone marrow
- Given following induction chemotherapy in patients with myelogenous leukemia to accelerate neutrohpil recovery
Sargramostim (leukine, prokine) ADR’s (2)
- Acute reactions such as diarrhea, weakness, bone pain
- massive doses can cause pleural effusion
Oprelvekin (Neumega) mechanism of action
Nearly identical to interleukin 11, increasing platelet production
Oprelvekin (neumega) therapeutic use (1)
-Minimize thrombocytopenia
Oprelvekin (neumega) administration
SC injection
Oprelvekin (neumega) ADR’s (4)
- fluid retention
- cardiac arrhythmias
- severe allergic reactions
- conjunctival infection
- fluid retention
Romiplostim (Nplate) mechanism of action
Stimulates platelet production through acting as a thrombopoietin receptor agonist
Kostmann’s syndrome
A severe congenital neutropenia
Romiplostim (Nplate) ADR’s (3)
- arthalgias
- dizziness
- bleeding upon stopping medication
