HEMOLYTIC ANEMIA HOSEA NJOKU 1405

CLASSIFICATION OF HEMOLYTIC ANEMIA 1. Intrinsic (intracorpuscular) abnormalities    (A) HEREDITARY      (i) Membrane abnormalities:  Membrane skeleton: Spherocytosis, Elliptocytosis, Membrane lipids: Abetalipoproteinemia      (ii) Enzyme deficiencies: Glycolytic enzymes: pyruvate kinase, hexokinase; Enzymes of HMP shunt: G-6PD      (iii) Disorders of Hemoglobin:  Deficient globin synthesis: Thalassemia syndromes; Structurally abnormal globin: Sickle cell anemia, unstable Hb    (B) ACQUIRED     Membrane defect: Paroxysmal Nocturnal Hemoglobinuria 2. Extrinsic (extracorpuscular) abnormalities    (A) ANTIBODY MEDIATED:  Isohemagglutinins: Transfusion reactions, Erythroblastosis fetalis; Autoantibodies: idiopathic drug- associated, SLE    (B) MECHANICAL TRAUMA: Microangiopathic hemolytic anemias: TTP, DIC, Defective cardiac valves (C) INFECTIONS: Malaria

BASIC FEATURES Abnormal and accelerated destruction of red cells and, in some anemias, their precursors Increased breakdown of hemoglobin, which may result in: increased bilirubin level (mainly indirect-reacting) with jaundice increased fecal and urinary urobilinogen Hemoglobinemia, methemalbuminemia, hemoglobinuria and hemosiderinuria (where there is significant intravascular hemolysis). Bone marrow compensatory reaction: Erythroid hyperplasia with accelerated production of red cells, reflected by reticulocytosis, and slight macrocytosis in peripheral blood Expansion of bone marrow in infants and children with severe chronic hemolysis - changes in bone configuration visible on X-ray

CLINICAL FEATURES OF HEMOLYTIC ANEMIA PALLOR JAUNDICE SPLENOMEGALY

GLOBIN > Amino Acids Heme > Iron and Protoporphyrin Protoporphyrin > Unconjugated bilirubin.

Extravascular Hemolysis RBC is broken down by the Reticuloendothelial cell > Liver , Spleen, Kidney. CLINICAL FEATURES OF EH anemia with splenomegaly Jaundice with unconjugated bilirubin Marrow hyperplasia with corrected reticulocyte count of >3%

INTRAVASCULAR HEMOLYSIS Rbc Broken Down In Blood Vessels Hemoglobin Released Hb Binds To Haptoglobin CLINICAL FEATURES Hemoglobinemia hemoglobinuria hemosiderinuria decreased haptoglobin level in blood.

LABORATORY FEATURES -Anemia -reticulocytosis -increased serum iron -antiglobulin coombs test is positive.

-Anisopoikilocytosis, sperocytosis BLOOD SMEAR -Anisopoikilocytosis, sperocytosis -erythroblasts -schistocytes BONE MARROW SMEAR -erythroid hyperplasia

PROGNOSIS The prognosis for patients with hemolytic anemia depends on the underlying cause. Overall, mortality rates are low in hemolytic anemias. However, the risk is greater in older patients and patients with cardiovascular impairment. Morbidity depends on the etiology of the hemolysis and the underlying disorder, such as sickle cell anemia or malaria.

Heriditary Spherocytosis Life span of RBC ↓10 to 20 days (normal: 120 days) Mutations: mostly affect spectrin, ankyrin, band 3,or band 4.2

HERIDITARY ELIPTOCYTOSIS Mutation in spectrin/band 4.1 Intrinsic defect with extravascular hemolysis

G6PD DEFICIENCY GSH PRODUCTION is impaired- GSH is supposed to stop oxidants generated by phagocytes during an infection. This resuults in hemolysis. Could also be caused by Fava beans. Oxidative stress causes the Hb to form heinz bodies.

PYRUVATE KINASE DEFICIENCY

HEMOGLOBINOPATHIES SICKLE CELL ANEMIA Mutation in β-globin gene creates sickle hemoglobin (HbS) by the substitution of valine for glutamic acid at the 6th amino acid residue of β-globin

SIICKLE CELL ANEMIA… Severe hemolytic anemia - life span of RBC only 20 days Microvascular obstructions (Vaso-occlusive crises) ↑ transit time for red cells through the microvasculature (sluggish blood flow in spleen and bone marrow) 90% HbS, 8% HbF, 2% HbA2, (No HbA)

INCREASES RISKS FOR SICKLING Hypoxemia Acidosis Dehydration DECREASES RISKS FOR SICKLING HbF

B- THALASSEMIA Mutations leading to aberrant RNA splicing most common no mature mRNA, complete failure of β-globin production (β0) New splice junctions in abnormal positions normal & abnormal splicing, some normal β-globin mRNA (β+) In β-globin promoter ↓transcription, some normal β-globin is synthesized (β+) “Stop” codons - No synthesis of β-globin (β0) Leading to poorly hemoglobinized RBC

A-THALASSEMIA More common in South East Asians and Africans Deletions involving one or more of the α-globin genes Severity of disease is proportional to missing α-globin genes

Paroxysmal Nocturnal Hemoglobinuria Intrinsic defect with intravascular hemolysis In paroxysmal nocturnal hemoglobinuria, hemolysis is due to intravascular complement-mediated destruction of erythrocytes. > lack of CD55.

Immunohemolytic Anemias WARM TYPE ANTIBODIES COLD TYPE ANTIBODIES

WARM TYPE ANTIBODIES CONFIRMATION- Direct coombs test. Primary (idiopathic) Secondary: B cell neoplasms (e.g., chronic lymphocytic leukemia), Autoimmune disorders (e.g., systemic lupus erythematosus), Drugs(e.g., α-methyldopa, penicillin, quinidine) CONFIRMATION- Direct coombs test.

COLD TYPE ANTIBODY. IgM against bodies own RBC Infection- Mycoplasma Pneumonia, Infectious mononucleosis.

Hemolytic Disease of the Newborn Maternal antibodies cross the placenta and react with fetal red cells causing hemolysis of fetal RBCs Rh Incompatibility: maternal allo-immunization to fetal red cell antigens (D antigen of Rh blood group) No problems during first pregnancy, but anti-Rh antibodies may cause problems in subsequent pregnancies

INFECTION Malaria- intravascular hemolysis, severly called blackwater fever.

TREATMENT Definitive therapy depends on the cause: Symptomatic treatment can be given by blood transfusion, if there is marked anemia. In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary. Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen

References http://www.nhlbi.nih.gov/health/health-topics/topics/ha/types http://www.nlm.nih.gov/medlineplus/ency/article/000528.htm http://emedicine.medscape.com/article/201066-overview#aw2aab6b2b3aa http://en.wikipedia.org/wiki/Hemolytic_anemia Current Medical Diagnosis and Treatment 2009 By Stephen J. McPhee, Maxine A. Papadakis page 436 http://books.google.com/books?