Hemolytic Anemias Defined as those anemias result from an increased in the rate of red cell destruction. The red cell destruction is usually removed extravascular by macrophages of reticuloendothelial system (RE) [BM, liver & spleen]. Acute destruction or chronic destruction Extravascular or Intravascular hemolysis Hereditary or Acquired hemolytic anemia SJAOUNI, KAU

Classification of hemolytic anemias Hereditary Acquired Membrane Hereditary spherocytosis, hereditary elliptocytosis Immune Autoimmune Warm antibody type Metabolism Cold antibody type G6PD deficiency, pyruvate kinase deficiency Alloimmune Hemolytic transfusion reactions Hemoglobin Thalassemia disorders Hemolytic disease of the newborn Allografts, especially marrow transplantation Abnormal (Hb S, Hb C, unstable); Drug associated Red cell fragmentation syndromes Arterial grafts, cardiac valves SJAOUNI, KAU

Thrombotic thrombocytopenic purpura Hemolytic uraemic syndrome cont. of Classification of hemolytic anemias Hereditary Acquired Microangiopathic Thrombotic thrombocytopenic purpura Hemolytic uraemic syndrome Meningococcal sepsis Pre-eclampsia Disseminated intravascular coagulation March hemoglobinuria Infections Malaria, clostridia Chemical and physical agents Especially drugs, industrial/domestic substances, burns Secondary Liver and renal disease Paroxysmal nocturnal hemoglobinuria G6PD, glucose-6-phosphate dehydrogenase; Hb, hemoglobin. SJAOUNI, KAU

Diagnosis History Clinical features Laboratory findings CBC (Hb & MCV), Plt, (WBC & diff) Retic Blood film Specific tests SJAOUNI, KAU

CBC WBC 8.3 10^3/L NE % 64.5 % LY % 27.6 % MO % 5.1 % EO % 2.6 % BA % 0.2 % NRBC %0.0 % NE # 5.3 10^3/L LY # 2.3 10^3/L MO # 0.4 10^3/L EO # 0.2 10^3/L BA # 0.0 10^3/L NRBC #0.0 10^3/L RBC 4.94 10^6/L HGB 14.3 g / dL HCT 40.8 % MCV 82.6 fL MCH 28.9 pg MCHC 35.0 g / dL RDW 12.8 % PLT 268 10^3/L MPV 7.5 fL RET % RET # IRF MRV CBC SJAOUNI, KAU

Laboratory findings in Hemolytic Anemia Features of increased red cell destruction: S. bilirubin,  urine urobilinogen breakdown, fecal stercobilinogen, s. haptoglobins absent. Feature of  red cell productions Reticulocytosis BM erythroid hyperplasia Damaged red cell Morphology Osmotic fragility & autohemolysis Red cell survival SJAOUNI, KAU

Autoimmune Hemolytic Anemia (AIHAs) Caused by antibody production by the body against its own red cells. Characterized by a positive direct antiglobulin test (DAT) called Coombs test Divided into warm and cold according Abs react at 37oC or 4oC. SJAOUNI, KAU

Autoimmune Hemolytic Anemia Warm Type Cold Type Idiopathic Secondary: Systemic lupus erythematosus, other connective tissue disorders chronic lymphocytic leukaemia malignant lymphoma ulcerative colitis ovarian teratoma drugs, e.g. methyldopa Secondary: Mycoplasma pneumonia infectious mononucleosis paroxysmal cold hemoglobinuria: rare; may be primary or associated with infection SJAOUNI, KAU

Cold Autoimmune Hemolytic Anemia In these syndromes the antibodies whether: Monoclonal: Idiopathic cold agglutination lymphomas. Polyclonal as infection: Infectious mononucleosis, Mycoplasma pneumonia Patient may have a chronic hemolytic anemia aggravated by cold. Sometimes associated with intravascular hemolysis. Laboratory: Similar like warm AIHA Less spherocyte, more red cell agglutination DAT reveals complement (C3d) SJAOUNI, KAU

Causes of intravascular hemolysis Mismatched blood transfusion (usually ABO) G6PD deficiency with oxidant stress Red cell fragmentation syndromes Some autoimmune hemolytic anemias Some drug- and infection-induced hemolytic anemias Paroxysmal nocturnal hemoglobinuria March hemoglobinuria Unstable hemoglobin G6PD, glucose-6-phosphate dehydrogenase. SJAOUNI, KAU

Hereditary Hemolytic Anemia Causes of hereditary hemolytic anemia. Hereditary Hemolytic Anemia Hemoglobin defects Metabolic defects Membrane defects defective synthesis, deficiency of: hereditary e.g. thalassemia spherocytosis ( or ) pyruvate kinase abnormal variants, triose phosphate elliptocytosis e.g. Hb S, Hb C, isomerase unstable pyrimidine-5- stomatocytosis nucleotidase glucose-6-phosphate etc. dehydrogenase glutathione synthetase SJAOUNI, KAU

INHERITANCE ■ AUTOSOMAL ■ SEX-LINKED SJAOUNI, KAU

Sex-linked Inheritance SJAOUNI, KAU

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Sex-linked hereditary hemolytic anemia Acute intravascular hemolysis due to oxidant stress. Episodes of acute hemolytic anemia Most patients are asymptomatic 4 Clinical syndromes: oxidative stress-induced hemolysis by certain drugs, infection and other illness. Favism (fresh and uncooked beans are more dangerous than dried cooked ones. Neonatal jaundice Chronic hemolytic anemia SJAOUNI, KAU