Classification & Lab Assessment of Anemias PDF

Classification & Laboratory Assessment of Anemias Mary Rose M. Apuyan, RMT, DTA, MSMLS ( c) College of Medical Technology Philippine College of Health Sciences, Inc. Anemia Present if the hemoglobin concentration of the red blood cells (RBCs) or the packed cell volume of RBCs (hematocrit)...

Classification & Laboratory Assessment of Anemias Mary Rose M. Apuyan, RMT, DTA, MSMLS ( c) College of Medical Technology Philippine College of Health Sciences, Inc. Anemia Present if the hemoglobin concentration of the red blood cells (RBCs) or the packed cell volume of RBCs (hematocrit) is below the lower limit of the 95% reference interval for the individual’s age, gender, and geographical location. 2 Anemia Can be classified morphologically using RBC indices (MCV, MCH, and MCHC). Can also be classified based on etiology/cause. Suspected when the hemoglobin is 25% ovalocytes on the peripheral blood smear b. Membrane defect is caused by polarization of cholesterol at the ends of the cell rather than around pallor area. 52 53 Hereditary stomatocytosis a. Autosomal dominant; variable degree of anemia; up to 50% stomatocytes on the blood smear b. Membrane defect due to abnormal permeability to both sodium and potassium; causes erythrocyte swelling 54 55 Hereditary acanthocytosis (abetalipoproteinemia) a. Autosomal recessive; mild anemia associated with steatorrhea, neurological and retinal abnormalities; 50-100% of erythrocytes are acanthocytes b. Increased cholesterol:lecithin ratio in the membrane due to abnormal plasma lipid concentrations; absence of serum p-lipoprotein needed for lipid transport 56 57 G6PD (glucose-6-phosphate dehydrogenase) deficiency a. Sex-linked enzyme defect; most common enzyme deficiency in the hexose monophosphate shunt b. Reduced glutathione levels are not maintained because of decreased NADPH generation. 58 G6PD (glucose-6-phosphate dehydrogenase) deficiency c. Results in oxidation of hemoglobin to methemoglobin (Fe3+); denatures to form Heinz bodies d. Usually, not anemic until oxidatively challenged (primaquine, sulfa drugs); then severe hemolytic anemia with reticulocytosis 59 60 61 Pyruvate kinase (PK) deficiency a. Autosomal recessive; most common enzyme deficiency in Embden- Meyerhof pathway b. Lack of ATP causes impairment of the cation pump that controls intracellular sodium and potassium levels. c. Decreased erythrocyte deformability reduces their life span. d. Severe hemolytic anemia with reticulocytosis and echinocytes 62 Paroxysmal nocturnal hemoglobinuria (PNH) a. An acquired membrane defect in which the red cell membrane has an increased sensitivity for complement binding as compared to normal erythrocytes b. Etiology unknown c. All cells are abnormally sensitive to lysis by complement. 63 Paroxysmal nocturnal hemoglobinuria (PNH) d. Characterized by: Pancytopenia; chronic intravascular hemolysis causes hemoglobinuria and hemosiderinuria at an acid pH at night; PNH noted for low leukocyte alkaline phosphatase (LAP) score; Ham's and sugar water tests used in diagnosis; increased incidence of acute leukemia 64 Paroxysmal nocturnal hemoglobinuria (PNH) e. Although Ham's and sugar water tests have been traditionally used in diagnosis of PNH, the standard now used is flow cytometry to detect deficiencies for surface expression of glycosyl phosphatidylinositol (GPI)-linked proteins such as CD55 and CD59. 65 66 Hemolytic Anemias Due to Extrinsic Defects/ Immune Defects  “ All cause a normocytic/normochromic anemia due to defects extrinsic to the RBC. All are acquired disorders that cause accelerated destruction with reticulocytosis. 68 Warm autoimmune hemolytic anemia (WAIHA) RBCs are coated with IgG and/or complement. Macrophages may phagocytize these RBCs, or they may remove the antibody or complement from the RBC's surface, causing membrane loss and spherocytes. 60% of cases are idiopathic; other cases are secondary to diseases that alter the immune response (e.g., chronic lymphocytic leukemia, lymphoma); can also be drug induced. 69 Warm autoimmune hemolytic anemia (WAIHA) Laboratory: Spherocytes, MCHC may be >37 g/dL, increased osmotic fragility, bilirubin, reticulocyte count; occasional nRBCs present; positive direct antiglobulin test (DAT) helpful in differentiating from hereditary spherocytosis. 70 71 72 Cold autoimmune hemolytic anemia (CAIHA) RBCs are coated with IgM and complement at temperatures below 37°C. RBCs are lysed by complement or phagocytized by macrophages. Antibody is usually anti-I but can be anti-i. Can be idiopathic, or secondary to Mycoplasma pneumoniae, lymphoma, or infectious mononucleosis 73 Cold autoimmune hemolytic anemia (CAIHA) Laboratory: Seasonal symptoms; RBC clumping can be seen both macroscopically and microscopically; MCHC >37 g/dL; increased bilirubin, reticulocyte count; positive DAT detects complement-coated RBCs If antibody titer is high enough, sample must be warmed to 37°C to obtain accurate RBC and indices results. 74 75 Paroxysmal cold hemoglobinuria (PCH) An IgG biphasic Donath-Landsteiner antibody with P specificity fixes complement to RBCs in the cold (less than 20°C); the complement- coated RBCs lyse when warmed to 37°C. Can be idiopathic, or secondary to viral infections (e.g., measles, mumps) and non- Hodgkin lymphoma 76 Paroxysmal cold hemoglobinuria (PCH) Laboratory: Variable anemia following hemolytic process; increased bilirubin and plasma hemoglobin, decreased haptoglobin; DAT may be positive; Donath-Landsteiner test positive 77 Hemolytic transfusion reaction Recipient has antibodies to antigens on donor RBCs; donor cells are destroyed. ABO incompatibility causes an immediate reaction with massive intravascular hemolysis that is complement induced. 1) Usually IgM antibodies 2) Can trigger DIG due to release of tissue factor from the lysed RBCs Laboratory: Positive DAT, increased plasma hemoglobin 78 79 Hemolytic disease of the newborn (HDN) May be due to Rh incompatibility (erythroblastosis fetalis) 1) Rh negative woman is exposed to Rh antigen from fetus and forms IgG antibody; this antibody will cross the placenta and destroy RBCs of the next fetus that is Rh positive. 2) Laboratory: Severe anemia, nRBCs, positive DAT; very high bilirubin levels cause kernicterus leading to brain damage 80 Hemolytic disease of the newborn (HDN) 3) Exchange transfusions in utero or shortly after birth 4) No longer a common problem with use of Rh immunoglobulin (RhoGam) 81 82 Hemolytic disease of the newborn (HDN) May be due to ABO incompatibility 1) Group O woman develops IgG antibody that crosses the placenta and coats fetal RBCs when fetus is group A or B. The coated RBCs are phagocytized. 2) Laboratory: Mild or no anemia, few spherocytes, weakly positive DAT, slightly increased bilirubin 83 84 Hemolytic Anemias Due to Extrinsic Defects/ Non- Immune Defects  “ All cause a normocytic/normochromic anemia caused by trauma to the RBC. All are acquired disorders that cause intravascular hemolysis with schistocytes and thrombocytopenia. 86 Microangiopathic hemolytic anemias (MAHAs) a. Disseminated intravascular coagulation (DIC) 1) Systemic clotting is initiated by activation of the coagulation cascade due to toxins or conditions that trigger release of procoagulants (tissue factor). Multiple organ failure can occur due to clotting. 2) Fibrin is deposited in small vessels, causing RBC fragmentation. 87 Microangiopathic hemolytic anemias (MAHAs) b. Hemolytic uremic syndrome (HUS) 1) Occurs most often in children following a gastrointestinal infection (e.g., E. coli) 2) Clots form, causing renal damage. 88 Microangiopathic hemolytic anemias (MAHAs) c. Thrombotic thrombocytopenic purpura (TTP) 1. Occurs most often in adults. 2. Due to a deficiency of the enzyme ADAMTS 13 that is responsible for breaking down large von Willebrand factor multimers. When multimers are not broken down, clots form, causing RBC fragmentation and central nervous system impairment. 89 March hemoglobinuria Transient hemolytic anemia that occurs after forceful contact of the body with hard surfaces (e.g., marathon runners, tennis players) 90 91 Other Causes a. Infectious agents (e.g., P. falcipamm, Clostridium perfringens) damage the RBC membrane. Schistocytes and spherocytes are seen on the blood smear. b. Mechanical trauma, caused by prosthetic heart valves (Waring blender syndrome), chemicals, drugs, and snake venom, damage the RBCs through various mechanisms. 92 Other Causes c. Thermal burns (third degree) cause direct damage to the RBC membrane, producing acute hemolysis, which is characterized by severe anemia with many schistocytes and micro-spherocytes. 93 94