Anemias: Hematologic Disorders (College of Pharmacy)

College of Pharmacy Fourth year. Clinical Pharmacy Hematologic Disorders Anemias Introduction 1-Anemia is a group of diseases characterized by a decrease in either hemoglobin (Hb) or the volume of red blood cells (RBCs), resulting in decreased oxygen-carrying capacity of blood. 2-The World Health Or...

College of Pharmacy Fourth year. Clinical Pharmacy Hematologic Disorders Anemias Introduction 1-Anemia is a group of diseases characterized by a decrease in either hemoglobin (Hb) or the volume of red blood cells (RBCs), resulting in decreased oxygen-carrying capacity of blood. 2-The World Health Organization defines anemia as Hb less than 13 g/dL in men or less than 12 g/dL in women. Pathophysiology 1-The functional classification of anemias is found in Fig. -1. Figure -1. Functional classification of anemia. 2- Morphologic classifications are based on cell size. A-Macrocytic cells are larger than normal and are associated with deficiencies of vitamin B12 or folic acid. B-Microcytic cells are smaller than normal and are associated with iron deficiency, whereas normocytic anemia may be associated with recent blood loss or chronic disease. 3-Iron-deficiency anemia (IDA), characterized by decreased levels of ferritin (most sensitive marker) and serum iron, and decreased transferrin saturation, can be caused by inadequate dietary intake, inadequate 1 gastrointestinal (GI) absorption, increased iron demand (eg, pregnancy), blood loss, and chronic diseases. 4-Vitamin B12– and folic acid–deficiency anemias, macrocytic in nature, can be caused by inadequate dietary intake, malabsorption syndromes, and inadequate utilization. A-Deficiency of intrinsic factor causes decreased absorption of vitamin B12 (ie, pernicious anemia). B-Folic acid–deficiency anemia can be caused by hyperutilization due to pregnancy, hemolytic anemia, malignancy, chronic inflammatory disorders, long-term dialysis, or growth spurt. C-Drugs can cause anemia by reducing absorption of folate (eg, phenytoin) or through folate antagonism (eg, methotrexate). 5-Anemia of inflammation (AI) is a newer term used to describe both anemia of chronic disease and anemia of critical illness. A-AI is an anemia that traditionally has been associated with malignant, infectious, or inflammatory processes, tissue injury, and conditions associated with release of proinflammatory cytokines. B-Serum iron is decreased but in contrast to IDA, the serum ferritin concentration is normal or increased. Clinical presentation 1-Acute-onset anemia is characterized by cardiorespiratory symptoms such as palpitations, angina, orthostatic light-headedness, and breathlessness. 2-Chronic anemia is characterized by weakness, fatigue, headache, orthopnea, dyspnea on exertion, vertigo, faintness, cold sensitivity, and pallor. 3-IDA is characterized by glossal pain, smooth tongue, reduced salivary flow, pica (compulsive eating of nonfood items), and pagophagia (compulsive eating of ice). 4-Neurologic effects (eg, numbness and paraesthesisas) of vitamin B12 deficiency may precede hematologic changes. Psychiatric findings, including irritability, depression, and memory impairment, may also occur with vitamin B12 deficiency. Anemia with folate deficiency is not associated with neurologic symptoms. Diagnosis 2 1-Rapid diagnosis is essential because anemia is often a sign of underlying pathology. Severity of symptoms does not always correlate with the degree of anemia. 2-Initial evaluation of anemia involves a complete blood cell count (CBC), reticulocyte index, and examination of the stool for occult blood. 3-The earliest and most sensitive laboratory change for IDA is decreased serum ferritin (storage iron). 4-In macrocytic anemias, mean corpuscular volume is usually elevated. Vitamin B12 and folate concentrations can be measured to differentiate between the two deficiency anemias. 5-In AI, serum iron is usually decreased, but, unlike IDA, serum ferritin is normal or increased. The peripheral smear reveals normocytic anemia. Treatment Goals of Treatment: The goals are to return hematologic parameters to normal, restore normal function and quality of life, and prevent long-term complications. Iron-deficiency anemia 1-Oral iron therapy with soluble ferrous iron salts, which are not enteric coated and not slow or sustained release, is recommended at a daily dosage of 150–200 mg elemental iron in two or three divided doses. 2-Iron is best absorbed from meat, fish, and poultry. Administer iron at least 1 hour before meals because food interferes with absorption, but administration with food may be needed to improve tolerability. 3-Consider parenteral iron for patients with iron malabsorption, intolerance of oral iron therapy, or nonadherence. 4-Iron dextran, sodium ferric gluconate, iron sucrose, ferumoxytol, and ferric carboxymaltose are available parenteral iron preparations with similar efficacy but different pharmacokinetics, bioavailability, and adverse effect profiles. Vitamin B12–deficiency anemia 1-Oral vitamin B12 supplementation is as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin B12 absorption pathway is independent of intrinsic factor. 3 2-Parenteral therapy acts more rapidly than oral therapy and is recommended if neurologic symptoms are present. Initiate daily oral cobalamin administration after symptoms resolve. 3-Continue vitamin B12 for life in patients with pernicious anemia. Folate-deficiency anemia 1-Oral folic acid, 1 mg daily for 4 months, is usually sufficient for treatment of folic acid–deficiency anemia, unless the etiology cannot be corrected. 2-If malabsorption is present, a dose of 1–5 mg daily may be necessary. Parenteral folic acid is available but rarely necessary. Anemia of inflammation 1-Treatment of AI is less specific than that of other anemias and should focus on correcting reversible causes. Reserve iron therapy for an established IDA; iron is not effective when inflammation is present. RBC transfusions are effective but should be limited to Hb of 7–8 g/dL. 2-Erythropoiesis-stimulating agents (ESAs) can be considered, but response can be impaired in patients with AI. Iron, cobalamin, and folic acid supplementation may improve response to ESA treatment. 3-Potential toxicities of exogenous ESA administration include increases in blood pressure, nausea, headache, fever, bone pain, and fatigue. Hb must be monitored during ESA therapy. An increase in Hb greater than 12 g/dL with treatment or a rise of greater than 1 g/dL every 2 weeks has been associated with increased mortality and cardiovascular events. 4-In patients with anemia of critical illness, parenteral iron is often used but is associated with a theoretical risk of infection. Anemia in pediatric populations 1-Infants aged 9–12 months: Administer ferrous sulfate 3–6 mg/kg/day (elemental iron) divided once or twice daily between meals for 4 weeks. Continue for two additional months in responders to replace storage iron pools. 2-The dose and schedule of vitamin B12 should be titrated according to clinical and laboratory response. The daily dose of folic acid is 1 mg. Evaluation of therapeutic outcomes 1-IDA: Positive response to oral iron therapy is characterized by an increase in Hb seen at 2 weeks. Hb should return to normal after 2 months; continue 4 iron therapy until iron stores are replenished and serum ferritin normalized (up to 12 months). 2-Megaloblastic anemia: Signs and symptoms usually improve within a few days after starting vitamin B12 or folic acid therapy. Reference Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 12 th Edition. 2023. 5