Hemolytic Anemias Testing Click here for topics associated with this algorithm

ORDER Abbreviations Presence of the following may provide clues to the etiology of the anemia: aHUS Atypical hemolytic uremic syndrome • CBC with platelet count and • Increased reticulocyte count, LDH, bilirubin DIC Disseminated intravascular coagulation INDICATIONS FOR automated differential LDH Lactate dehydrogenase • Decreased haptoglobin TESTING • Reticulocytes, Percent and Number HHA Hereditary hemolytic anemia • Abnormal peripheral smear (eg, polychromasia, spherocytes, HELLP Hemolysis, elevated liver enzymes, Anemia and evidence of • Lactate Dehydrogenase, Serum or schistocytes, sickle cells, stomatocytes, Heinz bodies, basophilic low platelet count hemolysis Plasma HPLC High-performance liquid stippling, unusual RBC inclusions, and agglutination) chromatography • Haptoglobin Note: Lack of any of the above does not rule out hemolytic anemia HUS Hemolytic uremic syndrome • Bilirubin, Total, Serum or Plasma PCH Paroxysmal cold hemoglobinuria PNH Paroxysmal nocturnal hemoglobinuria RBC Red blood cell TMA Thrombotic microangiopathy TTP Thrombotic thrombocytopenic purpura WBC White blood cell Consider Hereditary Hemolytic CONSIDER Anemia Cascade if HHA is DIC, TTP, HELLP, suscpected (eg, thalassemias, Normal HUS, aHUS, Consider sickle cell disease hereditary spherocytosis, G6PD AND ORDER mechanical cardiac Sickle cells (diverse genotypes): SS, SC, HPLC deficiency) Clinical presentation D-Dimer valve, vasculitis, SE, Sβ thalassemia, S Lepore consistent with TMA malignant hypertension Congenital 5' Consider 5' No nucleotidase Increased Nucleotidase testing deficiency Basophilic Acquired stippling ORDER Pregnant Microangiopathic ADAMTS13 Reflex Panel or DIC RBC destruction Consider Consider Lead, ADAMTS13 Activity Yes lead Blood (Venous) OR Consider poisoning E. coli Shiga-like Toxin by EIA HELLP Schistocytes, Polychromasia (depending on presentation) thrombocytopenia only with or Consider ORDER without platelet PNH PNH, High Sensitivity, RBC and WBC decrease ADAMTS13 Positive Shiga toxin Normal activity <10% and history of Consider one or more of diarrheal illness If infection suspected, consider Consider the following tests Unusual RBC Polychromasia without malaria, bartonella (oroya • Pyruvate kinase deficiency • Pyruvate kinase inclusions other reproducible fever), babesia • Hexokinase deficiency • Hexokinase TTP aHUS morphologic abnormality Classical HUS • Other enzyme defects • Glucose phosphate isomerase

Consider Consider molecular Positive RBC membrane Warm testing disorder Consider ORDER No autoimmune Consider Spherocytes, (hereditary cold Direct hemolytic anemia RBC Band pyropoikilocytes, Positive for spherocytosis, Agglutination agglutinins Coombs 3 Protein elliptocytes or complement hereditary disease (Anti-Human Reduction acanthocytes Direct Coombs elliptocytosis, Globulin) (Anti-Human Negative autoimmune Cold Cold Globulin) hemolysis) Yes agglutinins agglutinins testing disease

Consider Consider one or more of the IgG+ +C3 • Glucose-6-phosphate following tests dehydrogenase For hemoglobin • Isopropanol heat stability deficiency disorders, consider No Yes Heinz testing Cold agglutinins • Unstable hemoglobin Hemoglobin bodies • Glucose-6-Phosphate disease, PCH defects Evaluation Dehydrogenase (G6PD) 2 • Glutathione metabolism Reflexive Cascade Recluse spider Autoimmune hemolytic anemia (consider defects Mutations venom, clostridium drug induced, hemolytic disease of the • Hemoglobin H disease • Enzymes of glutathione cycle sepsis newborn, autoimmune disease) Confirm PCH with Donath Landsteiner testing © 2006 ARUP Laboratories. All Rights Reserved. www.arupconsult.com Content reviewed: December 2020 Last updated: September 2021