MIDTERM 06 - Hematopoietic Agents Flashcards
Refers to a connective tissue that consists of blood plasma plus formed elements
Blood
Refers to the fluid part of the blood
Plasma
Refers to plasma without clotting factors
Serum
Type of blood cell that carries oxygen
Erythrocytes (RBCs)
Type of blood cell that has a role in immunity
Leukocytes (WBCs)
Type of blood cell involves in blood clotting
Thrombocytes (Platelets)
Refers to the process of blood cell production; occurs mainly in the red bone marrow after birth
Hematopoiesis
Refers to the process of making red blood cells (erythrocytes)
Erythropoiesis
Refers to the process of making white blood cells (leukocytes)
Myelopoiesis
Refers to the process of making platelets (thrombocytes)
Thrombopoiesis
Growth factor of erythropoiesis
Erythropoietin
2 growth factors of myelopoiesis (GG)
GM-CSF, G-CSF
2 growth factors of thrombopoiesis (IT)
IL-11, Thrombopoietin
Decreased RBC count (Examples of hematopoietic disorders)
Anemia
Decreased WBC count (Examples of hematopoietic disorders)
Leukopenia
Decreased platelet count (Examples of hematopoietic disorders)
Thrombocytopenia
Increased RBC count (Examples of hematopoietic disorders)
Polycythemia
Increased WBC count (Examples of hematopoietic disorders)
Leukocytosis
Increased platelet count (Examples of hematopoietic disorders)
Thrombocytosis
A group of diseases characterized by a decrease in hemoglobin or red blood cells, resulting in the decreased oxygen-carrying capacity of the blood
Anemia
Amount of Hb per volume of whole blood (Laboratory evaluation)
Hemoglobin (Hb)
Actual volume of RBCs in a unit volume of whole blood (in %) (Laboratory evaluation)
Hematocrit (Hct)
The actual count of RBCs per unit of blood (Laboratory evaluation)
RBC count
Average volume of RBCs (Laboratory evaluation)
Mean corpuscular volume
Average amount of Hb in an RBC (Laboratory evaluation)
Mean corpuscular Hb
Concentration of Hb in a volume of RBCs (Laboratory evaluation)
Mean corpuscular Hb concentration
An indirect assessment of new RBC production (Laboratory evaluation)
Reticulocyte production index (RPI)
Variability of RBC size (Laboratory evaluation)
RBC distribution width (RDW)
Best indicator of iron deficiency or overload; used to estimate total body iron stores (Laboratory evaluation)
Serum ferritin
Test used to diagnose pernicious anemia (Laboratory evaluation)
Schilling test
Test for hemolytic anemia (Laboratory evaluation)
Coombs test
Most common cause of chronic anemia
Iron
Fe2+ in heme from __________ sources are less abundant but better absorbed
Animal
Free Fe3+ in __________ sources are more abundant but less absorbed
Plant
____________ to __________ mg of dietary elemental Fe is required per day
10-15
10-15% or __________ to __________ mg/day of Fe is absorbed
1-2
Absorption of dietary iron occurs in the __________ and __________ (DP)
Duodenum, Proximal jejunum
Fe2+ heme is absorbed on the apical surface via __________
Heme carrier protein (HCP)
Free Fe3+ is absorbed in the apical surface via __________ and enhanced by vitamin C
DMT-1
Combination of Fe3+ combines with apotransferrin, to form and circulate as __________, which is involved in the transport of iron
Transferrin (Tf)
Cellular uptake of iron involves the binding of transferrin-bound Fe3+ to __________ on erythroblasts and other iron-requiring cells
Transferrin receptors (TfR)
Binding of Fe3+ to apoferritin forms __________, which is involved in the storage of iron
Ferritin
In iron overload, ferritin is stored as __________, which is a form of degraded ferritin complexed with additional iron that cannot be readily mobilized
Hemosiderin
Exit of Fe2+ from heme degradation in macrophages is via __________ (involved in iron recycling)
Ferroportin
Oxidization of Fe2+ to Fe3+ is done by _________, which is Cu-containing
Ceruloplasmin
Recycled iron meets approximately __________% of daily need
90
Excretion of iron is no more than __________ mg daily
1
Excretion of iron is through __________ or _________; trace amounts of iron are also excreted in bile, urine, and sweat (DB)
Defecation, Bleeding
Regulation of iron metabolism is done by __________, which is produced in the liver
Hepcidin
Condition where plasma iron levels are reduced
Hypoferremia
The most common nutritional deficiency in developing and developed countries (Types of anemia)
Iron-deficiency anemia
Anemia characterized by smaller than normal RBCs due to less hemoglobin; type of iron deficiency anemia
Microcytic hypochromic anemia
Corrects IDA as rapidly and completely as parenteral FE if absorption is normal; taken before meals (Treatment for iron-deficiency anemia)
Oral iron therapy
Oral iron therapy contains __________ ion, which is the most efficiently absorbed iron ion
Fe2+
___________ to __________ mg of elemental Fe/day is taken to correct iron deficiency most rapidly
200-400
Oral iron therapy is continued for ___________ to __________ months after correction of iron deficiency
3-6
Reserved for patients who are unable to tolerate or absorb oral Fe (Treatment for iron-deficiency anemia)
Parenteral iron therapy
Parenteral iron therapy contain __________ ion
Fe3+
Ferric hydroxide core and a carbohydrate shell; used for IDA in patients with intolerance to oral iron (Types of parenteral iron therapy)
Ferric carboxymaltose
Iron strongly bound to a chemically modified isomaltooligosaccharides; used for IDA in patients with intolerance to oral iron (Treatment for iron-deficiency anemia) (IF)
Iron isomaltoside/Ferric derisomaltose
Characterized by necrotizing gastroenteritis with vomiting, abdominal pain, and bloody diarrhea (Types of iron toxicity)
Acute iron toxicity
2 treatments for acute iron toxicity (WD)
Whole bowel irrigation, Deferoxamine (IV)
Excess iron is deposited in the heart, liver, pancreas, and other organs; can lead to organ failure and death (Types of iron toxicity)
Chronic toxicity (Hemochromatosis)
Treatment for chronic iron toxicity (hemochromatosis)
Phlebotomy weekly
Reserved for individuals who have symptoms of anemia and require immediate intervention (Treatment for iron-deficiency anemia)
RBC transfusion
Anemia caused by abnormal DNA metabolism resulting from vitamin B12 or folate deficiency (Types of anemia)
Megaloblastic anemia
Megaloblastic anemia is a form of __________, which is characterized by abnormally large RBCs despite a normal amount of hemoglobin
Macrocytic normochromic anemia
Vitamin whose source is microbial synthesis; is not synthesized by animals or plants
Vitamin B12
Vitamin whose chief dietary source is meat (especially liver), eggs, and dairy products
Vitamin B12
Bonded to 5’-carbon of 5’-deoxyadenosine (Active forms of vitamin B12)
5’-deoxyadenosylcobalamin
Bonded to carbon of a methyl group (Active forms of vitamin B12)
Methylcobalamin
Occurs equally through buccal, duodenal, and ileal mucosa; rapid but extremely inefficient (Types of vitamin B12 absorption)
Passive absorption
Occurs through the distal ileum; efficient for small oral doses of cobalamin (Types of vitamin B12 absorption)
Active absorption
Active vitamin B12 absorption is mediated by gastric __________ produced by parietal cells
Intrinsic factor (IF)
Vitamin B12 is primarily stored in the __________
Liver
The total vitamin B12 storage pool is __________ to __________ mcg
3000-5000
__________ is a megaloblastic, macrocytic anemia associated with mild or moderate leukopenia or thrombocytopenia (Types of megaloblastic anemia)
Vitamin B12 deficiency anemia
It would take around __________ years for all stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if B12 absorption were stopped
5
Due to pernicious anemia and inadequate gastric acid (Etiology of vitamin B12 deficiency anemia)
Malabsorption syndromes
Is rare; occurs in strict vegans, chronic alcoholics, and elderly who have tea and toast diet (Etiology of vitamin B12 deficiency anemia)
Inadequate intake
Bonded to a cyanide group (Treatment for vitamin B12 deficiency anemia)
Cyanocobalamin (PO, IV)
Bonded to hydroxyl group; is more protein-bound and has longer half life (Treatment for vitamin B12 deficiency anemia)
Hydroxocobalamin (PO, IV)
Vitamin required for biochemical reactions that provide precursors for synthesis of amino acids, purines, and DNA
Folic acid (Pteroylglutamic acid)
Vitamin whose dietary source is yeast, liver, kidney, and green vegetables
Folic acid
Absorption of folic acid is complete in the __________
Proximal jejunum
Recommended amount of dietary folate per day
500-700 mcg
Amount of folic acid absorbed per day
50-200 mcg/day
Folic acid is stored in the ___________ and other tissues
Liver
Folic acid is eliminated in the __________ and __________ (US)
Urine, Stool
Folic acid is destroyed by __________
Catabolism
__________ is an anemia that can develop within 1-6 months due to low body stores of folic acid and high daily requirements (Types of megaloblastic anemia)
Folic acid deficiency anemia
Junk food, alcoholics, food faddists, the impoverished, chronically ill, and demented (Etiology of folic acid deficiency anemia)
Inadequate intake
Malabsorption syndromes (Etiology of folic acid deficiency anemia)
Decreased absorption
Increased rate of cell division, hemolytic anemia, myelofibrosis, malignancy, chronic inflammatory disorders, long-term dialysis, burn patients, and growth spurts (Etiology of folic acid deficiency anemia)
Increased folate requirements
Use of DNA synthesis inhibitors, folate antagonists, and alcohol (Etiology of folic acid deficiency anemia)
Drugs
Treatment for folic acid deficiency anemia
Folate (PO)
Anemia of chronic disease and anemia of critical illness; traditionally associated with malignant, infectious, or inflammatory conditions (Types of anemia)
Anemia of inflammation (AI)
3 treatments for anemia of inflammation (AI) (IRE)
Iron, RBC transfusion, Erythropoietin
A 34 to 39-kDa glycoprotein hormone produced by the kidneys; usually given with Fe
Erythropoietin
Produced in a mammalian cell expression system; given 3x a week (Types of recombinant erythropoietin)
Epoetin alfa (rHuEPO)
More heavily glycosylated; given weekly (Types of recombinant erythropoietin)
Darbepoetin alfa
Isoform of erythropoietin; given every 2 weeks or monthly (Types of recombinant erythropoietin)
Methyoxy polyethylene glycol-epoetin beta
Hormone used in anemia in CKD, HIV-infected patients treated with zidovudine, and cancer patients treated with myelosuppressive cancer chemotherapy
Erythropoietin
___________’s adverse effects include hypertension and thrombotic complications
Erythropoietin
___________ can be used as a performance-enhancing drug and in “blood doping”
Erythropoietin
Caused by impaired Hb synthesis and accumulation of iron in the perinuclear mitochondria of erythroid precursors (ringed sideroblasts) (Types of anemias)
Sideroblastic anemia
Treatment for sideroblastic anemia
50 mg pyridoxine PO qd
Treated with cupric sulfate PO (Types of anemia)
Copper deficiency anemia
Treatment for copper deficiency anemia
Cupric sulfate (PO)
A hypoproliferative anemia treated with riboflavin (Types of anemia)
Riboflavin deficiency anemia
Riboflavin deficiency anemia is treated with __________
Riboflavin
Condition characterized by abnormally few neutrophils in the blood
Neutropenia
Growth factors that bind to JAK/STAT receptors on myeloid progenitor cells
Myeloid growth factors
Stimulates proliferation and differentiation of progenitors committed to the neutrophil lineage (Myeloid growth factors)
G-CSF
Has broader biologic actions; stimulates proliferation and differentiation of early and late granulocytic progenitor cells (Myeloid growth factors)
GM-CSF
Includes filgrastim, Tbo-filgrastim, pegfilgrastim, and lenograstim (Recombinant myeloid growth factors)
G-CSF (IV, SC)
Includes sargramostim (Recombinant myeloid growth factors)
GM-CSF (IV, SC)
Produced in a bacterial expression system (G-CSF - recombinant myeloid growth factors)
Filgrastim
Similar to filgrastim with minor structural differences and equivalent activity (G-CSF - recombinant myeloid growth factors)
Tbo-filgrastim
Filgrastim covalent conjugated to polyethylene glycol; has longer half-life (G-CSF - recombinant myeloid growth factors)
Pegfilgrastim
Glycosylated recombinant G-CSF (G-CSF - recombinant myeloid growth factors)
Lenograstim
Produced in a yeast expression system (GM-CSF - recombinant myeloid growth factors)
Sargramostim
__________ are used for neutropenia, stem cell/bone marrow transplantation, and mobilization of peripheral blood progenitor cells (PBPCs)
Myeloid growth factors
G-CSF is __________ tolerated than GM-CSF
Better
A rare but serious complication for PBSC mobilization
Splenic rupture
Condition that involves low platelet count in the blood
Thrombocytopenia
Includes romiplostim and eltrombopag (Megakaryocyte growth factors)
Thrombopoietin
Includes oprelvekin (Megakaryocyte growth factors)
IL-11
Has high affinity binding to the human MpI receptor (Thrombopoietin - megakaryocyte growth factors)
Romiplostim
Binds to the transmembrane domain of the MpI receptor (Thrombopoietin - megakaryocyte growth factors)
Eltrombopag
Binds to cytokine receptors to stimulate the growth of multiple lymphoid and myeloid cells (IL-11 - megakaryocyte growth factors)
Oprelvekin
Produced by fibroblasts and stromal cells in the bone marrow (Recombinant megakaryocyte growth factors)
IL-11
Thrombopoietin against peptide covalently linked to antibody fragments to extend t1/2; t1/2 is 3-4 days (Thrombopoietin - recombinant megakaryocyte growth factors)
Romiplostim (SC)
Small nonpeptide thrombopoietin agonist molecule; t1/2 is 26-35 hours (Thrombopoietin - recombinant megakaryocyte growth factors)
Eltrombopag (PO)
Produced by expression of E. coli; t1/2 is 7-8 hours (IL-11 - recombinant megakaryocyte growth factors)
Oprelvekin (Recombinant IL-11, SC)
Used for idiopathic thrombocytopenic purpura (Thrombopoietin - megakaryocyte growth factors)
Romiplostim
Used for idiopathic thrombocytopenic purpura and thrombocytopenia in patients with hepatitis C (Thrombopoietin - megakaryocyte growth factors)
Eltrombopag
Used for nonmyeloid malignancies (IL-11 - megakaryocyte growth factors)
Oprelvekin
Causes increased blast count and risk of progression to acute myeloid leukemia (Thrombopoietin - megakaryocyte growth factors)
Romiplostim
Is potentially hepatotoxic (Thrombopoietin - megakaryocyte growth factors)
Eltrombopag
Causes fatigue, headache, and dizziness (IL-11 - megakaryocyte growth factors)
Oprelvekin
