Pathophysiology of Hemolytic Anemia - Defects in RBC internal contents (thalassemia, hemoglobinopathies,

Hemolytic Anemias - Differential Diagnosis Algorithm Signs of anemia and hemolysis: • ↓ Haptoglobin • ↑ LDH • ↑ Indirect / unconjugated bilirubin • ↑ Reticulocytes • Abnormal peripheral smear Immune-mediated Hemolysis: • Autoimmune Hemolytic Anemias (AIHAs) • Alloimmune Hemolytic Anemias (AHAs) Nonimmune-mediated Hemolysis: • Extrinsic RBC Defects: Hypersplenism, Infection, Toxic, Mechanical, Macroangiopathic, Microangiopathic • Intrinsic RBC Defects: Membrane defects, Enzyme deficiencies, Hemoglobinopathies Matthew Ho, MD PhD @MatthewHoMD #Hemolytic #Anemias #Differential #Diagnosis #Algorithm #hematology

Causes of Hemolytic Anemia - Differential Diagnosis Inherited • Membrane • Internal - Hemoglobin - Enzyme Acquired • Environment - Microangiopathic - Macroangiopathic • Membrane - Antibody/DAT+ - Complement/DAT- • Internal - Infectious - Toxic - Sophia Hayes MD @Sophia_Hayes_MD #Hemolytic #Anemia #Differential #Diagnosis #Causes #hematology

Hemolytic anemia in Wilson's disease #Wilsons #Disease #hemolytic #anemia #Hematology #pathophysiology

Pathophysiology, Signs and Symptoms of Hemolytic Anemia #Pathophysiology #Hemolytic #Anemia #hematology #diagnosis #signs #symptoms

Hemolytic Anemia - Differential Diagnosis Algorithm • Sickle cells - Consider sickle cell disease (diverse genotypes): SS, SC, SE, Sβ thalassemia, S Lepore • Basophilic stippling - Congenital 5' nucleotidase deficiency, lead poisoning • Polychromasia only with or without platelet decrease - PNH • Polychromasia without other reproducible morphologic abnormality - Pyruvate kinase deficiency, Hexokinase deficiency, Other enzyme defects • Agglutination - Cold agglutinins disease • Heinz bodies - Glucose-6-phosphate dehydrogenase deficiency, Unstable hemoglobin defects, Glutathione metabolism defects, Hemoglobin H disease • Schistocytes, thrombocytopenia - DIC, TTP, HELLP, HUS, aHUS, mechanical cardiac valve, vasculitis, malignant hypertension • Unusual RBC inclusions - If infection suspected, consider malaria, bartonella (oroya fever), babesia • Spherocytes, pyropoikilocytes, elliptocytes or acanthocytes - Consider RBC membrane disorder (hereditary spherocytosis, hereditary elliptocytosis, autoimmune hemolysis) ARUPConsult @ARUPLabs #Hemolytic #Anemia #Differential #Diagnosis #Algorithm #workup #hematology #testing

Diagnostic Framework for Hemolysis - Intravascular vs Extravascular Causes Intravascular Hemolysis: • Mechanical Trauma (Microangiopathic hemolytic anemia): - Disseminated intravascular coagulation (DIC) - HELLP syndrome - Thrombotic microangiopathy: Thrombotic thrombocytopenic purpura (TTP), Hemolytic uremic syndrome (HUS) • Other: Transfusion reaction, Paroxysmal nocturnal hemoglobinuria (PNH) Extravascular Hemolysis: • Immune-mediated: - Autoimmune (AIHA) "Warm" (usually IgG) (e.g. lupus, CLL, lymphoma, idiopathic) - Autoimmune (AIHA)"Cold" (usually IgM) (e.g. primary cold agglutin disease, lymphoproliferative disorders, Mycoplasma pneumoniae infection) - Drugs (Beta lactam antibiotics are the most frequently implicated) - Transfusion reaction • Intrinsic RBC Defects: Enzyme deficiencies (e.g. G6PD deficiency), Hemoglobinopathies (e.g. sickle cell disease, thalassemias), Membrane defects (e.g. hereditary spherocytosis) • Infections: Malaria, Babesiosis • Other: Hypersplenism, Wilson's disease, Copper and lead poisoning - Dr. Eric Strong @DrEricStrong - Strong Medicine https://www.youtube.com/c/EricsMedicalLectures/ #Hemolysis #Hemolytic #Intravascular #Extravascular #Causes #differential #diagnosis #hematology #anemia

Differential Diagnosis for Hemolytic Anemia Intrinsic Causes: • Enzyme deficiencies ex. G6PD, pyruvate kinase • Hemoglobinopathies ex. SCD, thalassemias • Membrane defects ex. Hereditary spherocytosis / elliptocytosis Extrinsic Causes: • Liver disease • Hypersplenism • AIHA: warm, cold, drug induced • Infections ex. Bartonella, Babesia, Malaria • Oxygen agents ex. dapsone, nitrates • Other agents ex. lead, copper, spider/snake bites • IVIG infusion Intravascular Causes: • MAHA: TTP, HUS, DIC, HELLP, AS, prosthetic valve • Transfusion reactions ex. ABO incompatibility • Paroxysmal Nocturnal Hemoglobinuria • S/p IV infusion of Rhogam • S/p IV infusion of hypotonic solutions Dr. Uday Gulati @udaygulati #Hemolytic #Anemia #Differential #Diagnosis #causes #classification #hematology

Autoimmune Hemolytic Anemia (AIHA) Pathophysiology - Warm vs Cold AIHA Warm AIHA: - 70%; IgG mediated - DAT: IgG positive, C3 positive or negative - Smear: spherocytes Cold AIHA: - 20%; IgM mediated - DAT: IgG negative, C3 positive - Smear: agglutination, rouleaux BWH Medicine Residency @BrighamMedRes #AIHA #Autoimmune #Hemolytic #Anemia #Pathophysiology #diagnosis #hematology

Red Blood Cell (RBC) Morphology Atlas • Microcytic - Iron-deficiency anemia, Thalassemia, Sideroblastic anemia, Lead poisoning • Macrocytic - Megaloblastic anemia, Liver diseases, Myelodysplastic syndrome, Increased reticulocyte count • Spherocytes - Hereditary spherocytosis, Hemolytic anemia, Post transfusion • Target cells - Thalassemia, Liver diseases, Sideroblastic anemia, Hemoglobinopathies • Teardrop cells - Severe anemia, Pernicious anemia, Myeloproliferative anemia • Elliptocytes - Hereditary elliptocytosis, Thalassemia, Iron-deficiency anemia • Sickle cells - Sickle cell anemia, Sickle-thalassemia • Stomatocytes - Malignant tumors, Acute alcoholism • Burr cells - Renal diseases, Liver diseases, Bleeding gastric ulcer, Severe burns • Acanthocytes - Alcohol intoxication, Post-splenectomy, Vitamin E deficiency, Congenital abetalipoproteinemia • Hemet cells - G-6-PD deficiency, Pulmonary emboli • Schistocytes - Hemolytic uremic syndrome, Thrombotic idiopathic thrombocytopenia (ITP), Disseminated intravascular coagulopathy (DIC) #RBC #Morphology #Atlas #key #diagnosis #differential #hematology

Common RBC Inclusions and Associations • Howell Jolly Bodies: Hyposplenism, Asplenism, Severe hemolytic anemia • Heinz Bodies: G6PD deficiency, Oxidant drugs, Unstable hemoglobin • Pappenheimer Bodies: Thalassemia, Sideroblastic anemia, Hemolytic anemia, Post-splenectomy • Hemoglobin H Inclusion: Hemoglobin H disease • Basophilic Stippling: Lead poisoning, Thalassemia, Sickle cell, MDS #RBC #Inclusions #Bodies #diagnosis #hematology