Anemia (PDF)

Definitions of Anemia Functional: - decrease in the oxygen carrying capacity of the blood. Operational: - reduction from the baseline value for the total number of RBCs, amount of circulating hemoglobin, and RBC mass for a particular patient. Conventional: - decrease in RBCs, Hb and Hct belo...

Definitions of Anemia Functional: - decrease in the oxygen carrying capacity of the blood. Operational: - reduction from the baseline value for the total number of RBCs, amount of circulating hemoglobin, and RBC mass for a particular patient. Conventional: - decrease in RBCs, Hb and Hct below the previously established reference values for healthy individuals of the same age, gender, and race and under similar environmental conditions.  Clinical Findings of Anemia 1. History 2. Physical examination 3. Signs and symptoms 4. Laboratory procedures History of patient Physical - Diet Examination - Bleeding history - Skin: pallor, jaundice, - Drug ingestion petechiae - Occupation - Eyes (hemorrhage) - Exposure to chemicals - Mouth (mucosal bleeding) - Travel - Sternal tenderness - Previous medication - Lymphadenopathy - Ethnic group - Cardiac murmurs - Family history of - Splenomegaly disease - Hepatomegaly - Hobbies - Vital signs - Neurologic symptoms  General Causes of Anemia 1. Decreased Red Blood Cell Production 2. Increased Red Blood Cell Destruction 3. Blood loss Anemia Due to Decreased Production of RBC 1. Iron Deficiency Anemia 2. Anemia due to Chronic Inflammation 3. Sideroblastic Anemia 4. Megaloblastic Anemia 5. Aplastic Anemia 6. Thalassemia 7. Anemia due to Chronic Renal Failure 8. Anemia due to Endocrine Disorder 9. Anemia due to Marrow Infiltration  Anemia caused by increased destruction of RBC A. Intracorpuscular Abnormality 1. Membrane Defect a. hereditary spherocytosis b. hereditary elliptocytosis c. hereditary pyropoikilocytosis d. hereditary stomatocytosis e. hereditary acanthocytosis f. hereditary Rh null disease 2. Enzyme deficiency a. G6PD deficiency b. Pyruvate kinase deficiency c. Porphyria 3. Paroxysmal Nocturnal Hemoglobinuria (PNH) 4. Globin abnormality a. Hemoglobinopathies (Hb SS, CC, SC) B. Extracorpuscular Abnormality 1. Mechanical a. Microangiopathic hemolytic anemia (MAHA) 1. thrombotic thrombocytopenic purpura 2. hemolytic uremic syndrome (HUS) b. Traumatic cardiac hemolytic anemia 2. Infection a. Hemolytic anemia 1. Malaria 2. Babesia 3. Bartonella 4. Ehrlichia 3. Chemical and Physical Agents - caused by drugs, toxins, burns 4. Antibody-mediated Anemia a. acquired hemolytic anemia Anemia due to blood loss 1. Acute post hemorrhagic anemia 2. Chronic post hemorrhagic anemia Laboratory Test for Anemia Assessment 1. CBC 2. Reticulocyte count 3. Peripheral smear 4. Bone marrow examination 5. Iron studies 6. Blood Chemistry (KFT, LFT) 7. Urinalysis 8. Fecalysis 9. Hematological special test procedures Morphological Classification of Anemia 1. Microcytic hypochromic anemia 2. Macrocytic normochromic anemia 3. Normocytic normochromic anemia MICROCYTIC HYPOCHROMIC ✓ decrease of all erythrocyte indices: MCV, MCH & MCHC ✓ found in: thalassemia & severe iron deficiency anemia Microcytic hypochromic anemia 1. Iron Deficiency Anemia Causes: a.Inadequate intake of iron - 1 mg of iron lost everyday b. Increased need of iron 1. infancy, childhood, adolescence 2. pregnancy c. Chronic blood loss 1. Heavy menstrual bleeding 2. GI bleeding from ulcers or tumors 3. Urinary tract with kidney stones 4. Iatrogenic cause IRON DEFICIENCY ANEMIA Blood Features: ↓ to normal retic ↓ serum iron ↓ serum ferritin ↑ total iron-binding capacity (TIBC) Microcytic hypochromic type Anisocytosis/Poikilocytosis Decrease in OFI  Smooth tongue and koilonychia in iron deficiency. Top panel: Iron deficiency can result in a painless, smooth, shiny, and reddened tongue Bottom panel: Koilonychia, a condition also referred to as “spoon-shaped nails,” is associated with iron deficiency in which the fingernails are thin, brittle, and concave with raised edges. Iron deficiency blood films. Top panel: This peripheral blood film demonstrates severe iron deficiency with microcytosis, hypochromasia, and multiple morphologic changes: pencil cells, target cells, teardrops, and rare fragments. Early iron deficiency may be normocytic with no significant morphologic changes. Microcytic hypochromic anemia 2. Sideroblastic anemia - develop when the incorporation of iron into heme is blocked. 2 Types: a. Hereditary Sideroblastic Anemia - due to a congenital enzyme defect delta amino-levulinic acid synthetase or heme synthetase b. Primary Acquired Sideroblastic Anemia -due to somatic mutation of the erythroid progenitor cells that cause either defects in heme synthesis or defects in DNA synthesis Sideroblastic anemia Primary is genetic Secondary caused by: ▪ Certain therapeutic drugs ▪ Chronic transfusion (Aplastic) ▪ Alcoholism and food fads ▪ Use of iron utensils & iron in water Diagnostic lab finding is ringed sideroblasts in the bone marrow and Pappenheimer bodies in peripheral blood Sideroblastic anemia. Peripheral blood film of dual population and sideroblastic anemia. Normocytic cells are present, along with a minor population of microcytic, hypochromic erythrocytes possessing a thin rim of cytoplasm. Occasional teardrop cells are visible. Pappenheimer bodies, target cells, and basophilic stippling occur in some cases. Sideroblastic anemia. Numerous ringed sideroblasts are seen in this marrow aspirate smear stained for iron. They are normoblasts with ≥10 iron- containing granules in the cytoplasm encircling at least one-third of the nucleus. Often, focusing up and down on the cell will more clearly demonstrate the iron-containing granules. Lead Poisoning Lead interferes with iron storage in the mitochondria Lead damages the activity of enzymes used for heme synthesis (basophilic stippling) Top panel: Gums in lead poisoning. Lead lines are shown in gums of this patient suffering from lead poisoning. Bottom panel: Peripheral blood film demonstrating coarse basophilic stippling. Normocytic or microcytic anemia may be present. Porphyria Rare disease caused by accumulation of porphyrins in developing RBC’s Characterized by dermal photosensitivity and rash caused by the sun. The original werewolf was probably a person with erythropoietic prophyria Microcytic hypochromic anemia 3. Anemia due to chronic inflammation - anemia associated with systemic diseases: a. arthritis b. tuberculosis c. HIV d. malignancies - leukemia, lymphoma, myeloma Microcytic hypochromic anemia 4. Thalassemia -inherited disorders caused by genetic alterations that reduce or preclude the synthesis of the globin chains of hemoglobin tetramer. -predominant in Mediterranean, African and Asian ancestry. Microcytic hypochromic anemia Laboratory Iron Anemia due to Sideroblastic Thalassemia Test Deficiency Chronic anemia Anemia Inflammation Reticulocyte count ↓ N ↓ ↑ Serum ferritin ↓ ↑ ↑ N Serum iron ↓ ↓ ↑ N Transferrin ↓ ↓ ↑ N Saturation TIBC ↑ ↓ ↓ N FEP/ZPP ↑ ↑ ↑ N Prussian Blue ↑ reaction (BM iron  Types of Thalassemia 1. Beta (β) Thalassemia 2. Alpha (α) Thalassemia 3. Hereditary Persistence of Hb F (HPHF) 4. Hemoglobin Lepore 5. Hemoglobinopathy + Thalassemia a. Hemoglobin S- Thalassemia b. Hemoglobin C-Thalassemia c. Hemoglobin E-Thalassemia  Types of Thalassemia 1. Beta (β) Thalassemia Other names Description a. Thalassemia minor Heterezygous thalassemia - results when one of the 2 genes that produce beta globin is defective Cooley’s trait - usually presents a Rietti-Greppi-Micheli disease mild,asymptomatic anemia b. Intermediate Thalassemia Intermedia -more severe anemia than minor β-thalassemia β-thalassemia but do not require regular transfusion - occasional transfusions but do not require them on a regular basis. c. Thalassemia major Homozygous thalassemia -decrease or complete lack of beta globin production Cooley’s anemia -most severe form and transfusion Mediterranean anemia dependent anemia Target cell anemia  Types of Thalassemia 2. Alpha (α) Thalassemia Description Hemoglobin Present a. Silent Carrier - deletion of one α globin birth: 1%-2% Hb Bart’s (- α/ α α) gene, leaving 3 functional α adult: normal Hb A, Hb globin genes Bart b. α Thalassemia Trait - deletion of two α globin birth: 2%-10% Hb Bart’s homozygous (- α/- α) gene adult: normal Hb A heterozygous(--/ α α) c. Hemoglobin H Disease - caused by the presence of birth: 10%-40% Hb Bart’s (--/- α) only one gene producing α replaced by Hb H 30-50% chains. remainder: Hb F, HbA₂, Hb Bart’s and Hb A adult: 70% Hb A d. Hydrops Fetalis -results in the absence of all birth: 80%-90% Hb Bart’s (--/--) α chains synthesis 5%-20% Hb Portland - incompatible with life trace of Hb H  Types of Thalassemia 3. Hereditary Persistence of Hb F (HPHF) - thalassemia with increased levels of fetal hemoglobin - partial or total suppression of beta and delta chains and HB F increased to compensate 4. Hemoglobin Lepore - a rare class of thalassemia caused by crossing over of beta and delta genes 5. Hemoglobinopathy + Thalassemia a. Hemoglobin S- Thalassemia - is a double heterozygous abnormality - the abnormal genes for Hb S and thalassemia are co-inherited Types: 1. Hb S-α-thalassemia 2. Hb SS-α-thalassemia 3. Hb S-β-thalassemia  Types of Thalassemia b. Hemoglobin C-Thalassemia - β thalassemia with inherited Hb C c. Hemoglobin E-Thalassemia - co-inherited of Hemoglobin E and β thalassemia that results to a marked reduction of β chain production. Laboratory Findings of Thalassemia 1. CBC ↓Hb and Hct ↑RBC count ↓RBC indices (MCV and MCHC) ↑RDW 2. Peripheral Smear - microcytic hypochromic - exhibits anisocytosis and poikilocytosis (target cells and elliptocytes) - presence of NRBC - polychromasia and basophilic stippling Laboratory Findings of Thalassemia 3. Increased Reticulocyte count 4. Bone marrow examination - shows hypercellular with extreme erythroid hyperplasia 5. Decreased OFT 6. Supravital stain -shows Hb H inclusions 7. Electrophoresis - differentiates hemoglobin variants Laboratory Findings of Thalassemia 8. Mass Spectrophotometry - assess the difference in mass of the globin chains - detects single amino acid substitutions in the globin chains 9. DNA analysis - identify globin gene mutations a. PCR b. Signal Amplification System 10. Increased Indirect Bilirubin Macrocytic normochromic anemia 1. Megaloblastic anemia -disorder in the DNA synthesis of RBC -the maturation of nucleus is delayed relative to that of cytoplasm 2 Types: a. Pernicious anemia - Vitamin B₁₂ (cobalamin)deficiency b. Folic Acid Deficiency - nutritional megaloblastic anemia Effects of Vitamin B12 and Folate Deficiency  Vitamin B12 :  Neurologic symptoms:  Memory loss  Numbness  Tingling in toes and fingers  Impairment of walking by loss of vibratory sense.Vit Macrocytic normochromic anemia Causes of Megaloblastic Anemia - dietary deficiency 1. Inadequate intake sources of folic acid - leafy green vegetables, dried beans, liver, beef and some fruits sources of Vitamin B₁₂ - meat, eggs and dairy products 2. Increased need - during pregnancy, lactation and growth 3. Impaired absorption in the intestine 4. Impaired use due to drugs such as antiepileptic drugs 5. Excessive loss during renal dialysis Macrocytic normochromic anemia Laboratory Findings of Megaloblastic Anemia: 1. CBC a. Pancytopenia b. Hb and Hct: decreased c. MCV: increased (>120 fL) d. MCH and RDW: increased e. MCHC: normal 2. Decreased in absolute reticulocyte count Macrocytic normochromic anemia Laboratory findings of Megaloblastic anemia: 3. Peripheral smear a. oval macrocytes/megalocytes b. poikilocytosis - dacryocytes, fragments, microspherocytes c. NRBCs d. Howell-Jolly bodies e. Basophilic stippling f. Cabot rings 4. Hypersegmented neutrophil(5 or more lobes) Macrocytic normochromic anemia Laboratory findings of Megaloblastic anemia: 5. Chemistry Analysis decreased serum Folate level decreased serum Vitamin B₁₂ level increased Homocysteine – Folate def. increased Methylmalonic acid – B12 def. increased LDH increased total and indirect bilirubin 6. Schilling Test - used to distinguish malabsorption of vitamin B12 from other causes of malabsorption - uses oral dose of radioactive vitamin B12 Macrocytic normocytic anemia 2. Non-megaloblastic anemia - anemia caused by conditions such as a. alocholism b. chronic liver disease Normocytic normochromic anemia A. Extrinsic Hemolytic Anemia 1. Antibody Mediated Anemia 2. Mechanical 3. Chemical and Physical Agents 4. Infection Normocytic normochromic anemia 1. Antibody Mediated Anemia Classifications: 1. Autoimmune Hemolytic Anemia 2. Drug-Induced Immune Hemolytic Anemia 3. Alloimune Hemolytic Anemia 1. Autoimmune Hemolytic Anemia - characterized by premature RBC destruction caused by autoantibodies that bind the RBC surface. Types of Autoimmune Hemolytic Anemia a. Warm-Reactive Autoimmune Hemolytic Anemia b. Cold-Reactive Autoimmune Hemolytic Anemia c. Paroxysmal Cold Hemoglobinuria (PCH) a. Warm-Reactive Autoimmune Hemolytic Anemia - responsible for approximately 70% of Immune hemolytic cases - mediated by antibody with maximum binding affinity at 37°C b. Cold-Reactive Autoimmune Hemolytic Anemia - mediated by antibody with maximum binding affinity at 4°C or below 32°C c. Paroxysmal Cold Hemoglobinuria (PCH) - a rare acute form of cold-generated hemolysis - hemolysis occurs when blood is warmed after previous exposure to chilling - caused by an antibody (Donath-Landsteiner antibody) present in the plasma Characteristics of Autoimmune Hemolytic Anemia Warm-Reactive Cold Reactive PCH Type of Ig IgG IgM IgG Maximum Temp. 37°C 4°C 4°C Reactivity Complement variable yes yes activation Type of Hemolysis Extravascular Intra/Extravascular Intravascular Autoantibody Rh complex Anti-I Anti-P Specificity Anti-i Treatment Corticosteroids Avoidance of cold Avoidance of cold Splenectomy Plasmapheresis Corticosteroids Normocytic normochromic anemia 2. Drug-Induced Immune Hemolytic Anemia - self-limiting, but severe even fatal following the administration of drug that can cause immune hemolytic anemia Examples of Drugs: a. Penicillin b. Stibophen c. Alpha methyldopa Normocytic normochromic anemia 3. Alloimune Hemolytic Anemia - usually occurs in newborns following the transplacental passage of maternal anti-fetal red cells antibody. 2 Causes: 1. Erythroblastosis fetalis - Isoimmune HDN due to Rh incompatibility 2. Isoimmune HDN due to ABO incompatibility  To be continued…