Anemia: Iron-deficiency (MICROCYTIC) PDF

**Anemia: Iron-deficiency (MICROCYTIC)** **Buttaro:** **Ch. 212, 214, 215, 218** **DESCRIPTION** Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss. Iron deficiency anemia (IDA) is characterized by decreased or absent iron stores, l...

**Anemia: Iron-deficiency (MICROCYTIC)** **Buttaro:** **Ch. 212, 214, 215, 218** **DESCRIPTION** Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss. Iron deficiency anemia (IDA) is characterized by decreased or absent iron stores, low serum iron concentration, low transferrin saturation, and low hemoglobin concentration or hematocrit value. The erythrocytes are [hypochromic and microcytic] and the iron binding capacity is increased. This type of anemia is most commonly associated with chronic blood loss. ---------------------------------------------------------------------- **Microcytosis: Red blood cells are smaller than average (\65 years - Frequent blood donations - Gastritis - Gastrointestinal or bariatric surgery - Heavy menstrual bleeding in women - Infancy, toddlerhood - Inflammatory bowel disease - Intravascular hemolysis - Low birthweight or preterm birth - Low socioeconomic status - Pregnancy **ASSESSMENT FINDINGS** - Angina in patients with coronary artery disease - Atrophic glossitis - Cold intolerance - Dry or rough skin - Exercise intolerance - Fatigue, malaise, headache, dyspnea on exertion, irritability, & mild decrease in exercise tolerance, tachycardia, brittle nails, pallor of the conjunctiva, mucus membranes, mail beds, & palmar creases. - Frequent infections - Inability to concentrate - Irritability to young children - Koilonychia (spoon-shaped, brittle nails) - Melena/hematochezia - Most are asymptomatic - Palpitations - Pica (craving for ice, starch, clay, etc.) - Pallor (best seen in conjunctivae) - Restless legs syndrome - Tinnitus - Vertigo **DIFFERENTIAL DIAGNOSES** - Anemia of chronic disease - Gastric or colonic carcinoma (especially in older adults) - GI bleeding (gastritis, peptic ulcer disease, varices) - Hypothyroidism - Lead toxicity - Renal failure - Sideroblastic anemia - Thalassemia trait Priority differentials include (1) blood loss (acute hemorrhage, hemolysis; chronic---GI/gynecologic causes), (2) bone marrow failure or disease, (3) malignancy, and (4) renal failure. **DIAGNOSTIC STUDIES** - Should begin with Complete blood count with RBC indices, [WBC differential], reticular count &[peripheral blood smear.] - Hemoglobin level \ - inability to adhere or intolerance of oral iron replacement - persistent IDA necessitating parenteral iron therapy - persistent microcytic anemia despite iron replacement and the exclusion of other conditions, such as acute or chronic inflammatory states. - Refer patients whose hemoglobin has not increased after 1 month of iron replacement - Refer all pregnant women with hemoglobin \ - **Beta thalassemia:** one or both beta-globin genes have mutations that lead to impaired production of beta-globin chains. Various presentations of disease classified by severity and clinical type: β-Thalassemia genes are located on chromosome 11; - **Silent carrier beta thalassemia:** asymptomatic - **Beta thalassemia trait (minor):** mild anemia with elevated HbA2, HbF or both. Can be mistaken for iron overload (Ovoid iron to prevent hepatoxicity). - **Intermedia:** less severe disease; normal lifespan but delayed puberty. May be mild to moderate and can lead to need for chronic transfusions later in life (third or fourth decade) - Beta thalassemia associated with beta chain structural variants - **Major (Cooley's anemia, homozygous beta thalassemia): **most severe form. Profound and lifelong dependence on transfusions; 85% mortality by age 5 years without treatment; if treated with chronic transfusions or stem cell transplant, may live into 40s or 60s - **Alpha thalassemia:** impaired production of alpha globin chains due to a mutation or deletion of one of the four alpha-globin genes. Various presentations of disease classified by severity and clinical type: - **Silent carrier alpha thalassemia/alpha thalassemia-2 trait: **this carrier state has no clinical significance. If two genes are affected, individuals are considered carriers and have mild anemia (α-thalassemia trait or α-thalassemia minor) - **Alpha thalassemia minor/alpha thalassemia-1 trait: **results in mild microcytic and hypochromic anemia; often mistaken for iron deficiency. People with hemoglobin H (α-thalassemia intermedia) disease have [three genes affected] and are moderately to severely anemic. - **Alpha thalassemia major: **this is the most severe form of alpha thalassemia. Leads to severe anemia during fetal development (hydrops fetalis). Usually incompatible with birth unless intrauterine transfusion can be performed. When all four genes are affected, the condition is called α-thalassemia major (hemoglobin hydrops fetalis) and most affected fetuses are born prematurely and stillborn or die shortly after birth. The individuals who survive will require lifelong transfusions and extensive medical care. - **Hemoglobin H disease (HbH):** can present as mild to moderately severe anemia **Type** **Severity** **Clinical Presentation** --------------------------------------------------------------------- ------------------ ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Beta Thalassemia** **Silent carrier** Asymptomatic No clinical significance **Beta thalassemia trait (minor)** Mild Mild anemia, elevated HbA2, HbF or both; can be mistaken for iron overload. each parent provides one gene to an offspring. An individual is considered a carrier if one gene is affected; this is known as β-thalassemia trait or minor **Beta thalassemia intermedia** Moderate Less severe; normal lifespan but delayed puberty; may need chronic transfusions later in life. When both genes are affected, the condition is either β-thalassemia intermedia, causing moderate anemia. If a pt develops abnormal facies, growth restriction, or pathologic fractures, they will require regular transfusions **Beta thalassemia associated with beta chain structural variants** Variable Depends on the specific variant **Beta thalassemia major (Cooley\'s anemia)** Severe Profound lifelong transfusion dependence; 85% mortality by age 5 without treatment; with treatment, may live into 40s or 60s. β-thalassemia major (Cooley anemia) with severe anemia. **Alpha Thalassemia** **Silent carrier/alpha thalassemia-2 trait** Asymptomatic No clinical significance **Alpha thalassemia minor/alpha thalassemia-1 trait** Mild Mild microcytic and hypochromic anemia; often mistaken for iron deficiency **Hemoglobin H disease (HbH)** Mild to Moderate Mild to moderately severe anemia **Alpha thalassemia major** Severe Severe anemia during fetal development (hydrops fetalis); usually incompatible with birth unless intrauterine transfusion is performed **ETIOLOGY** - Autosomal recessive, inherited **INCIDENCE** - Occurs throughout U.S. & Affects males and females equally. - 5% of world population has at least one thalassemia-variant allele - Historically found in malaria-endemic areas; may have evolved as a genetic mutation in response to malaria - **Alpha thalassemia** more common in people of Southeast Asian, Indian, Filipino, or Chinese descent - **Beta thalassemia** more common in people of Southeast Asian, Mediterranean, or African descent **RISK FACTORS** - Family history of thalassemia **ASSESSMENT FINDINGS** -------------------------------------------------------------------------------------------------------------- **Signs and symptoms vary depending on severity of the disease and the patient's age at time of diagnosis.** --------------------------------------------------------------------------------------------------------------   ---------------------------------------------------------------------------------------------------------------------------------------- **Thalassemia should be considered in any child who has hypochromic microcytic anemia that does not respond to iron supplementation.** ---------------------------------------------------------------------------------------------------------------------------------------- - **Beta thalassemia major** **(also known as Cooley anemia):** develop a severe, life-threatening anemia during their first year of life - Usually becomes symptomatic in the latter part of first 12 months of life: beta chains needed to pair with alpha chains to form hemoglobin - Developmental issues and decreased life expectancy. These patients require lifelong chronic transfusions to maintain adequate hemoglobin levels and iron chelation - physical changes of short stature - Children can be diagnosed as early as 3 months of age, with findings of severe anemia, pallor, jaundice, and enlarged spleen, liver, or heart. - Hemoglobin level 3-7 g/dL - Extreme pallor - Growth retardation: failure to thrive - Increased respiratory rate, Fatigue, shortness of breath - Splenomegaly/hepatomegaly - Pathologic fractures - **Severe bony changes:** ineffective erythroid production results in frontal bossing, prominent facial bones, or dental malocclusion - **Hypermetabolism:** ineffective erythropoiesis - Gout and kidney stones: hyperuricemia - Hemochromatosis: overproduction of iron or from transfusions - Metabolic symptoms: diabetes or thyroid disorders - Neuropathy/paralysis: common in patients with severe anemia who are not receiving transfusions - Cardiac complications: chronic heart failure, arrhythmias, cardiomyopathy - **Hemoglobin H (HbH):** - Hematologic abnormalities in newborn - Hepatosplenomegaly - Skeletal, developmental, and metabolic changes - **Alpha and beta thalassemia minor (trait):** - Asymptomatic - Mild anemia - **Alpha thalassemia major:** - Hydrops fetalis and hemoglobin Bart's; incompatible with life  A diagram of the body of a child Description automatically generated **DIFFERENTIAL DIAGNOSES** - Thalassemia major must be considered in young children who present with severe microcytic, hypochromic anemia, jaundice, and hepatosplenomegaly. - Iron deficiency anemia - hemoglobinopathies (Hb E)- Hemoglobin E is diagnosed by hemoglobin electrophoresis. - Storage diseases - Other microcytic, hypochromic anemias - Congenital dyserythropoietic anemia - Immune and nonimmune hydrops fetalis - Failure to correct the anemia with iron supplementation should then lead the provider to suspect thalassemia minor (or hemoglobin E disease if the individual is of Southeast Asian ancestry) **DIAGNOSTIC STUDIES** ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **CBC and peripheral blood smear results are usually sufficient to suspect the diagnosis. Hemoglobin (Hb) evaluation confirms the diagnosis in beta thalassemia, HbH disease, and HbE/beta thalassemia.** ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- - include a CBC with differential and reticulocyte count, serum iron studies, and hemoglobin electrophoresis. - Patients with thalassemia intermedia or major are diagnosed during the first few years of life, due to the severity of presentation. Severe forms of β-thalassemia can be associated with severe microcytosis and hypochromia, as well as anisocytosis and poikilocytosis - CBC, red cell indices - Iron studies - [Endocrine function test:] thyroid studies, parathyroid studies, and glucose tolerance testing - Hemoglobin electrophoresis: is used to determine hemoglobin composition of RBCs. - Chemistry panel, liver panel, ferritin level - Gene mapping - Electrocardiogram, echocardiogram - Liver biopsy or MRI to quantify iron overload - Bone density test - **Beta thalassemia major:** - Complete blood count (CBC) and differential including red blood cell (RBC) indices - Red blood cells: decreased - Hemoglobin: \