Anemia and Anti-Anemia Drugs Workshop Notes PDF

1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 MCHC: increased Reticulocyte count: increased (>3%) PBS Small RBCs without central pallor = spherocytes (MCV, MCH, and HCHC are normal) Characteristic, but not pathognomonic:...

1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 MCHC: increased Reticulocyte count: increased (>3%) PBS Small RBCs without central pallor = spherocytes (MCV, MCH, and HCHC are normal) Characteristic, but not pathognomonic: also seen in HS Polychromasia In severe cases: nucleated RBCs and Howell-Jolly bodies In severe cases: erythroid hyperplasia of the BM and normoblastic reaction Serum bilirubins: unconjugated hyperbilirubinemia Anemia-inducing plasmodia P. falciparum affects both young and old RBCs → severe anemia P. vivax affects only young RBCs → less severe anemia Mechanisms of P. falciparum-induced anemia Extravascular hemolysis: infected RBCs are recognized by splenic macrophages and removed from the circulation → Splenomegaly Diminished erythropoiesis: plasmodia → release of IFN-γ and TNF-⍺ → inhibition of erythropoietin response (anemia of inflammation) UR and LL: two infected with P. falciparum RBCs https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 46/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 RB concave w malaria ——- Moxon CA, Grau GE, Craig AG. Malaria: modification of the red blood cell and consequences in the human host. Br J Haematol. 2011 Sep;154(6):670-9. doi: 10.1111/j.1365-2141.2011.08755.x. Epub 2011 May 28. PMID: 21623767; PMCID: PMC3557659. Ring forms of P. falciparum in the RBCs https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 47/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Ed Uthman from Houston, TX, USA (https://commons.wikimedia.org/wiki/File:Plasmodium_falciparum,_peripheral_blood_(37093691502).jpg) , CC BY 2.0 (https://creativecommons.org/licenses/by/2.0) , via Wikimedia Commons A rare acquired genetic disorder that affects PIGA gene on X-chromosome (with possible lionization) and is manifested as persistent intravascular hemolysis Neither inherited nor congenital PIGA: phosphatidylinositol glycan complementation group A PIGA function: to catalyze the transfer of a glycosyl phosphatidyl inositol (GPI) to proteins that regulate (inhibit) complement activity PGI-linked proteins CD55: decay accelerating factor (DAF) CD59: membrane inhibitor of reactive lysis (MIRL) https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 48/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 1. Acquired mutation in PIGA gene on chromosome X Only a fraction of BM cells is affected 2. Inhibition of GPI-associated proteins (CD55 and CD59) 3. Inability to inhibit the alternative and classical pathways of complement activation (on RBC surface) 4. Persistent/chronic intravascular hemolysis In ≈¼ of patients, the hemolysis may be paroxysmal and nocturnal Hemoglobin- and hemosiderinuria → loss of iron → iron-deficiency The gold standard test for PNH Carried out on RBCs and granulocytes Diagnostic feature: a bimodal distribution of cells, with a discrete population that is CD59 and CD55 negative Staining patterns of red cells from a normal individual (A) and a patient (B) with paroxysmal nocturnal hemoglobinuria (PNH). About half of the red cells in the PNH patient are deficient in CD59. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 49/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 CBC RBC count: normal-to-reduced (mild-to-moderate-to-severe anemia) MCV: normal-to-increased (normocytic-to-macrocytic RBCs) With hemoglobin- and hemosiderinuria, and following iron deficiency, RBCs may turn to microcytic Reticulocyte count: markedly increased (3% —> 20%) PBS: not remarkable Bone marrow: erythroid hyperplasia Flow cytometry: see next two slides https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 50/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Erythrocytes (RBCs) and neutrophils (PMNs) from a healthy volunteer and a patient with PNH were analyzed by flow cytometry using anti-glycophorin A (top row, vertical axis) to identify RBCs and anti-CD11b (bottom row, vertical axis) to identify PMNs. GPI-AP expression was detected using a combination of anti-CD55 and anti-CD59 (top and bottom rows, horizontal axis). PNH cells are deficient in both CD55 and CD59 (upper left quadrant of each histogram). The percentage of GPI-AP–deficient (PNH) cells is shown for each sample Serum Tests for intravascular hemolysis Hemoglobinemia Unconjugated hyperbilirubinemia Low-to-absent haptoglobin Markedly elevated LDH Special tests for PNH Acidified serum (Ham) test A highly reliable but available only in a few laboratories Sucrose lysis test: not so good as acidified serum test Urine Hemoglobinuria Hemosiderinuria Ham Test Left tube: hemolysis —> PNH Right tube: control https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 51/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Nakamura, N., Sugawara, T., Shirato, Ki. et al. Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report. J Med Case Reports 5, 550 (2011). https://doi.org/10.1186/1752-1947-5-550 Anemia: pallor, dyspnea, palpitations, etc. Chronic hemolysis: jaundice, dark urine (hemoglobin- and hemosiderinuria) Episodic (paroxysmal) hemolysis when complement is activated by mild acidosis, e.g., respiratory acidosis during sleep (nocturnal) Complications Hemosiderinuria → loss of iron → iron-deficiency anemia Venous thrombosis Hepatic veins: Budd-Chiari syndrome Portal and mesenteric veins: intestinal infarct Cerebral veins and sinuses Pancytopenia AML and myelodysplastic syndrome Mechanical trauma to RBCs → intravascular hemolysis and formation of fragmented RBCs (schistocytes; syn.: helmet cells) Classification, causes, and mechanisms Macroangiopathic hemolysis: calcific aortic stenosis and prosthetic cardiac valves → turbulent blood flow and pressure gradient across the damaged valves Microangiopathic hemolytic anemia (MAHA): deposition of thrombi on the endothelial surface → direct injury to RBCs https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 52/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Disseminated intravascular coagulation (DIC) Hemolytic-uremic syndrome (HUS) Thrombotic thrombocytopenia purpura (TTP) Etc. Features of hemolytic anemia with intravascular hemolysis, similar to PNH Characteristic feature in PBS: schistocytes (syn.: helmet cells, triangular cells https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 53/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024  Click each section below to learn more about the types of macrocytic anemias. Macrocytes: RBCs with MCV > 100 fL Classification Megaloblastic anemia (megaloblasts: large erythroblasts) Vit B12 -deficiency anemia Folate (Vit B9) deficiency anemia Non-megaloblastic macrocytic anemias https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 54/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Alcohol-abuse macrocytic anemia Macrocytic anemia in chronic liver diseases https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 55/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Cobalamin and folate intersect in the methionine synthase reaction where 5-methyl-THF is able to donate its methyl group to homocysteine to form methionine with cobalamin in the form of MeCbl serving a cofactor in the transfer of the methyl group. In this way, THF is regenerated. Cbl, cobalamin; MeCbl, methylcobalamin; THF, tetrahydrofolate 1. Vit B12 - or folate deficiency 2. Deficient thymidine production 3. Inhibition of DNA synthesis 4. Delay in nuclear division and maturation with preserved maturation of cytoplasm in erythroid precursors 5. Nuclear-cytoplasmic asynchrony (cytoplasm > nucleus) with formation megaloblasts (large erythroblasts) 6. Ineffective erythropoiesis 7. Anemia; megaloblasts maturate to macro(ovalo)cytes Left: promegaloblast Right: basophilic megaloblast https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 56/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Central cluster 9 h - early polychromatophilic normoblast; 3h - late polychormatophilic normoblast with lobulated nucleus; 12 h - orthochromatic megaloblast (normoblast) https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 57/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 58/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Vit B12 -Deficiency Folate Deficiency Source Meat, eggs, and dairy products Stores last for 2-3 years Fresh fruits and vegetables Absorption site Ileum Jejunum Biochemical function Coenzymes in thymidine synthesis Cause for deficiency Vegetarian diet Excessive alcohol consumption Deficient absorption → pernicious anemia Chronic pancreatitis Ileal infection/resection Food overcooking Excessive alcohol consumption Pregnancy Clinical features Anemia Atrophic glossitis Subacute combined degeneration of the spinal cord Reversible cognitive deterioration Anemia Neural tube defects in utero https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 59/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Vit B 12 -Deficiency CBC and PBS Folate Deficiency Variable pancytopenia due to apoptosis of hematopoietic cells in the BM Macroovalocytes (normochromic) Hypersegmented neutrophils (≥5 segments) BM Hypercellular BM with erythroid hyperplasia and megaloblasts Giant metamyelocytes and bands Giant megakaryocytes Labs Increase serum homocysteine Increased urine methylmalonic acid [deficient function of methylmalonyl coenzyme A (CoA) mutase] Reduced level of B12 in Vit B12 assay Increased serum homocysteine Normal urine methylmalonic acid Reduced folate level in folate assay https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 60/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 61/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Ed Uthman from Houston, TX, USA BY 2.0 (https://commons.wikimedia.org/wiki/File:Hypersegmented_Neutrophils_(36831145373).jpg) , CC (https://creativecommons.org/licenses/by/2.0) , via Wikimedia Commons Adults, >40 years of age Underlying condition: chronic autoimmune atrophic gastritis with impaired production of intrinsic factor (IF) Pathogenesis of gastritis: autoimmune damage of parietal cells; mechanisms CD4+T cells directed against H+/K+-ATPase Autoantibodies to the IF or IF-VitB12 complex Clinical features = Vit B12-deficiency anemia Clinical findings unique to PA Maldigestion due to chronic gastritis and achlorhydria Increased incidence of gastric cancer https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 62/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Pathogenesis: Cell-mediated (type IV) autohypersensitivity, cytotoxic T-cells, “autoantibodies”, Anti-H+-K+ ATPase, Anti-intrinsic factor (IF) antibody blocks binding to vitamin B12, anti-IF-B12 complex interferes with binding to ileal receptors Pathology: Chronic atrophic gastritis, thin flattened mucosa, loss of parietal cells (decreased IF, decreased HCl acid), Loss of chief cells, Lymphocyte and plasma cell infiltrate Effects: Increased risk of gastric cancer, achlorhydria, Loss of IF leads to failure of B12 absorption in terminal ileum which leads to abnormalities of proliferating cells throughout body, megaloblastic anemia and neurologic disease subacute combined degeneration of the spinal cord https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 63/80 1/19/24, 10:56 AM CoRus13 Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 (https://commons.wikimedia.org/wiki/File:Autoimmune_atrophic_gastritis_(H%26E),_high_mag.jpg) , CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) , via Wikimedia Commons https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 64/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 CoRus13 (https://commons.wikimedia.org/wiki/File:Autoimmune_atrophic_gastritis_(H%26E),_very_high_mag.jpg) , CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0) , via Wikimedia Commons Classification Anemia due to acute blood loss (posthemorrhagic anemia) Anemia due to chronic blood loss Chronic bleeding (e.g., peptic ulcer or colon cancer) → depletion of iron stores → diminished erythropoiesis → iron-deficiency anemia (covered above) CBC Hb: low HCT: low WBC count: high due to mobilization of granulocytes from the intravascular marginal pool https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 65/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Reticulocyte count (RC): → 10-15% after 5-7 days Platelet count: high due to BM production PBS First 3-4 days: normocytic normochromic RBCs (evacuated with the depot) After 5-7 days: polychromasia (reticulocytosis) https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 66/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024  AccessMedicine Chapter 33: Agents Used in Cytopenias; Hematopoietic Growth Factors. Basic & Clinical Pharmacology, 14e, by Katzung, Masters, & Trevor Practice questions on Canvas  https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 67/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Drugs and Drug Classes to Consider Antianemia Drugs Iron Preparations Oral Ferrous sulfate Iron Antidotes Vitamin B12 Preparations Folic Acid Preparations Deferoxamine Cyanocobalamin Folic acid Deferasirox Hydroxocobalamin Ferrous gluconate Ferrous fumarate Parenteral Iron dextran Ferric gluconate Iron sucrose Hematopoietic Growth Factors Erythropoiesis Stimulating Agents https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 68/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Drugs and Drug Classes to Consider Antianemia Drugs Iron Preparations Iron Antidotes Vitamin B12 Preparations Folic Acid Preparations Epoetin alfa Darbepoetin alfa 4  Deficit in the mass of circulating red blood cells. Anemia can be documented by measuring the concentration of hemoglobin in the blood or the hematocrit. Pharmacotherapy is dependent on the underlying cause of anemia: Iron deficiency Vitamin B12 deficiency Folic acid deficiency Renal failure Drug induced  Peripheral blood smear: microcytic and hypochromic red cells. Marked variation in size (anisocytosis) and shape. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 69/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Route of administration: Oral Absorption: Approx. 25% of orally administered iron is absorbed Ferrous (Fe2+) salts are the most efficiently absorbed Gastric acid and ascorbic acid increases the absorption Mechanism of action: Corrects anemia by supplementing iron in the body to facilitate hemoglobin formation Route of administration: Iron dextran: IM and IV Ferric gluconate: IV Iron Sucrose: IV https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 70/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Mechanism of action: Increase iron; replaces iron found hemoglobin, myoglobin and enzymes. Clinical use: Treatment of iron-deficiency anemia in patients with chronic anemia who cannot be maintained with oral iron. This includes patients with chronic kidney disease undergoing hemodialysis in conjunction with supplemental erythropoietin therapy. Also used for patients with various post-gastrectomy conditions, inflammatory bowel diseases, malabsorption syndromes, etc. Treatment of iron-deficiency anemia in patients who are unable to tolerate or absorb oral iron. Clinical use: Prevention and treatment of iron-deficiency anemia (hypochromic, microcytic anemia). Oral iron preparations are preferred in most cases if absorption for gastrointestinal tract is normal. Oral treatment may require 3 – 6 months to replenish body stores Adverse effects: Constipation, dark stools, nausea, stomach cramps and vomiting Acute iron toxicity (overdose): gastrointestinal bleeding, vomiting, abdominal pain andbloody diarrhea followed by very low blood pressure and difficulty breathing. Seen most commonly in young children who accidentally ingest iron tablets. Drug Interactions: Medications which reduce gastric acid can reduce iron absorption Calcium containing foods and beverages may also impair iron absorption Adverse effect: https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 71/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Allergic or infusion reactions may occur with IV administration, including urticaria, bronchospasm, and anaphylaxis (test dose required) Headache, light-headedness, muscle cramps, nausea and diarrhea Brown discoloration of skin by IM inj (overlying the injection site) (Z- track technique to avoid it)  Seen most commonly in young children who accidentally ingest iron tablets - as few as 10 tablets of common iron preparations can be lethal in young children (tablets should be stored in child-proof containers) Necrotizing gastroenteritis, vomiting, abdominal cramps, bloody diarrhea, shock, lethargy, dyspnea, metabolic acidosis, coma and death Treatment Whole bowel irrigation – to flush out unabsorbed pills Deferoxamine – iron-chelating agent, binds and increases the excretion of iron Activated charcoal, a highly effective adsorbent for most toxins, does not bind iron and thus is ineffective Supportive therapy for GI bleeding, metabolic acidosis, and shock Most commonly seen in patients with inherited hemochromatosis and patients who receive many red cell transfusions over a long period of time (e.g. individuals with β-thalassemia). Excess iron is deposited in the heart, liver, pancreas, and other organs, leading to organ failure and death. Chronic iron overload can be treated with oral Deferasirox or parenteral Deferoxamine. Chronic iron overload in the absence of anemia is most efficiently treated with intermittent phlebotomy. One unit of blood can be removed every week until the excess iron is removed. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 72/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Route of administration: Deferasirox – Oral Deferoxamine – IV, IM and SubQ Mechanism of action: Binds to Fe3+ (ferric) ions to a form a complex, which is then excreted in urine (deferoxamine) or feces and bile (deferasirox). Clinical uses: Deferasirox – treatment of chronic iron overload Deferoxamine – treatment of acute iron overload and chronic iron overload. Adverse effects: Deferasirox – acute renal failure, hepatic failure and gastrointestinal hemorrhage, which may be fatal. Deferoxamine – infusion reaction (skin, flushing, urticaria and shock)  https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 73/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Serves as a cofactor for several biochemical reactions https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 74/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Synthetic forms of vitamin B12 Route of administration: IM and SubQ Oral – not recommended due to poor absorption. May be used if parenteral therapy is refused or poorly tolerated. Mechanism of action: Supplement vitamin B12 (cobalamin); coenzyme for various enzymatic reactions necessary for the synthesis of nucleic acids and proteins. Learn more about the advantages and disadvantages of oral and intramuscular (IM) vitamin B12 (https://www-uptodatehttps://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 75/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 com.rossuniversity.idm.oclc.org/contents/image? imageKey=HEME%2F142051&topicKey=HEME%2F7154&search=advantages%20and%20 disadvantages%20of%20oral%20and%20IM%20vitamin%20b12&rank=1~150&source=see _link) . Clinical Use: Treatment of vitamin B12 deficiency due to: Pernicious anemia (inadequate secretion of intrinsic factor) After partial or total gastrectomy (to mitigate loss of intrinsic factor synthesis) Deficiency due to dietary deficiency or malabsorption and inadequate utilization of vitamin B12 during neoplastic (cancer) treatment. Increased requirement due to pregnancy, hemorrhage, thyrotoxicosis, malignancy, and liver or kidney disease. Route of administration: Folic acid – oral (preferred), IM, IV and SubQ Mechanism of action: Folic acid – supplementation of folic acid required for enzymatic reactions necessary for nucleic acid synthesis. Clinical uses: Treatment of megaloblastic anemia due to folate deficiency. Supplementation to prevent neural tube defects in developing fetus.  All blood cells, including the cells of the immune system are derived from pluripotent hematopoietic stem cells. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 76/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 The type of mature cell that develops is determined by exposure of progenitor cells to specific growth factors. A recombinant form of the growth factor erythropoietin (EPO) is used to treat some types of anemia. Epoetin alfa is recombinant human erythropoietin Darbepoetin alfa is a modified form of erythropoietin with a greater half-life Pharmacokinetics https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 77/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 Route of administration: IV and SubQ Pharmacodynamics Mechanism of action: Epoetin alfa and Darbepoetin alfa induce erythropoiesis by interacting with erythropoietin receptors on red cell progenitors and stimulating differentiation and proliferation. Induces the release of reticulocytes from the bone marrow to the bloodstream. This results in an increase in hematocrit and hemoglobin levels. FDA. (n.d.). FDA approves first oral treatment for anemia caused by chronic kidney disease for adults on dialysis. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-anemia-caused-chronic-kidney-diseaseadults-dialysis Title: FDA Approves First Oral Treatment for Anemia Caused by Chronic Kidney Disease for Adults on Dialysis The U.S. Food and Drug Administration approved Jesduvroq tablets (daprodustat) as the first oral treatment for anemia (decreased number of red blood cells) caused by chronic kidney disease for adults who have been receiving dialysis for at least four months. Jesduvroq is not approved for patients who are not on dialysis. Other FDA-approved treatments for this condition are injected into the blood or under the skin. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 78/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024  Microcytic anemia usually occurs as a result of B12 deficiency.  True  False  Check  1. Microcytic anemia usually occurs as a result of B12 deficiency. True False (answer) 2. __________ salts/compounds are more efficiently absorbed when given orally. Ferrous (Fe2+) Ferric (Fe33+) 3. Which iron preparation can be administered both IM and IV? Ferrous gluconate Ferrous sulphate Iron Sucrose Iron Dextran (answer) 4. Deferasirox is used to manage persons who present with acute iron overload. True False (answer) 5. Cyanocobalamin may be used to manage persons who have vitamin B12 deficiency. True (answer) False 6. Megaloblastic anemia may occur if someone has folic acid defiency. https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 79/80 1/19/24, 10:56 AM Week 1: Fusion Session | Workshop: Anemia and Antianemia Drugs: Hemtlgy Onclgy Infectn Imm - January 2024 True (answer) False 7. Persons who have anemia due to chemotherapy or due to zidovudine used for management of HIV may best be treatment with ferrous sulphate compounds. True False (answer)  Quiz | Anemia and Antianemia Drugs (https://rossmed.instructure.com/courses/3318/quizzes/19377)  Dr. Michael Yakubovskyy Email: [email protected] (mailto:[email protected]) Dr. Natalie Mayers-Ames Email: [email protected] (mailto:[email protected]) https://rossmed.instructure.com/courses/3318/pages/week-1-fusion-session-%7C-workshop-anemia-and-antianemia-drugs 80/80