Hematopoietic Growth Factors Lecture PDF Flashcards

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1
Q

Hemopoiesis definition

A

Production of formed elements of blood (erythrocytes, leukocytes, thrombocytes)

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2
Q

Red marrow location in children vs adults

A

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)

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3
Q

Hemocytoblast

A

Stem cells that form all elements of blood, also known as a pluripotential stem cell

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4
Q

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

A
  • erythropoietin (transforms an uncommitted potential cell to a committed proerythroblast)
  • thrombopoietin
  • CSF’s
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5
Q

Erythrocyte differentiation pathway

A
Hemocytoblast
Proerythroblast
Erythroblast
Reticulocyte (enters circulation) 
mature RBC
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6
Q

Erythrocyte homeostasis mechanism of action

A
  • 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
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7
Q

Polycythemia vera definition

A

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

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8
Q

Major requirements for erythropoiesis to occur and what function do they serve(2)

A
  • Iron (form hemoglobin)

- B12 and folic acid (proper cell division)

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9
Q

Iron metabolism and storage in the liver mechanism of action pathway

A
  • 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
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10
Q

3 differentiated types of WBC progenitors from the hemocytoblast

A
  • B progenitors
  • T progenitors
  • granulocytes/macrophage colony forming units
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11
Q

When thrombopoietin binds to a hemocytoblast, what happens?

A

It becomes a megakaryoblast by replicating DNA without nuclear or cytoplasmic cytokinesis

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12
Q

How long to platelets survive in the circulation

A

5-9 days

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13
Q

Erythropoietic growth factors/erythropoiesis stimulating agents function

A

Allow the patient to see increase in RBC count in patients with CRF and cancer patients undergoing chemotherapy

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14
Q

Erythropoietic growth factors/erythropoiesis stimulating agents ADR’s (5)

A
  • 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)
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15
Q

Epoetin alfa (Epogen, procrit) class, therapeutic use,

A
  • Erythropoietic growth factor

- can reverse anemia associated with CRF virtually eliminating need for transfusion

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16
Q

Erythropoietic growth factors/erythropoiesis stimulating agents including epoetin alfa (epogen, procrit) does NOT do these 3 things

A
  • Improve quality of life
  • decrease fatigue
  • delay progression of renal deterioration
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17
Q

Procrit indications

A
  • treats chemo induced anemia in patients with nonmyeloid malignancies reducing need for transfusions
  • undergoing elective surgery when significant blood loss is expected
18
Q

Zidovudine function and cross reactivity with procrit

A

Antiretroviral therapy for HIV/AIDS,
-Procrit is approved for patients infected with HIV to maintain or elevate erythrocyte counts reducing need for transfusions

19
Q

Autoimmune pure red cell aplasia (PRCA) and treatment

A

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

20
Q

Risk evaluation and mitigation strategy (REMS) and its relation to erythropoiesis

A

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

21
Q

Epoetin alfa administration and 2 drugs of this class

A

Injection

-epogen and procrit

22
Q

Darbepoeitin alfa (ARANESP) function

A

Long acting erythropoietin approved by FDA for treatment of anemia that has a slower clearance making half life 2-3x longer

23
Q

Darbepoeitin alfa (ARANESP) ADR’s (3)

A
  • Hypertension
  • MI
  • thrombosis
24
Q

Filgrastim (neupogen) mechanism of action

A

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

25
Q

Filgrastim (neupogen) therapeutic uses (3)

A
  • 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
26
Q

Filgrastim (neupogen) ADR’s (2)

A
  • devoid of serious ADR’s
  • bone pain
  • leukocytosis
27
Q

Filgrastim (neupogen) administration

A

Injection IV or SC

28
Q

Filgrastim-sndz (Zarxio) characteristics

A

A filgrastim (neupogen) biosimilar, a highly similar product with no clinical meaningful difference, minor differences in clinically inactive components only

29
Q

Pegfilgastrim (neulasta) characteristics

A

Long acting derivative of filgrastim (neupogen) that stimulates myeloid cells to increase neutrophil production, longer half life allows for treatment with one dose

30
Q

Pegfilgastrim (neulasta) ADR

A
  • devoid of serious ADR’s

- bone pain

31
Q

Sargramostim (leukine, prokine) mechanism of action

A

Acts on cells in bone marrow to increase production of neutrophils, monocytes, macrophages and eosinophils by imitating a GM-CSF nearly identically

32
Q

Sargramostim (leukine, prokine) therapeutic uses (3)

A
  • 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
33
Q

Sargramostim (leukine, prokine) ADR’s (2)

A
  • Acute reactions such as diarrhea, weakness, bone pain

- massive doses can cause pleural effusion

34
Q

Oprelvekin (Neumega) mechanism of action

A

Nearly identical to interleukin 11, increasing platelet production

35
Q

Oprelvekin (neumega) therapeutic use (1)

A

-Minimize thrombocytopenia

36
Q

Oprelvekin (neumega) administration

A

SC injection

37
Q

Oprelvekin (neumega) ADR’s (4)

A
  • fluid retention
  • cardiac arrhythmias
  • severe allergic reactions
  • conjunctival infection
  • fluid retention
38
Q

Romiplostim (Nplate) mechanism of action

A

Stimulates platelet production through acting as a thrombopoietin receptor agonist

39
Q

Kostmann’s syndrome

A

A severe congenital neutropenia

40
Q

Romiplostim (Nplate) ADR’s (3)

A
  • arthalgias
  • dizziness
  • bleeding upon stopping medication