SHEIKHA HEMOLYTIC ANEMIAS

SHEIKHA Abnormalities of the Environment of the Red Cells Abnormalities of the Red Cells Premature destruction of the red cells

HEMOLYTIC ANEMIAS SHEIKHA Abnormalities of the Red Cells

HEMOLYTIC ANEMIAS SHEIKHA Membrane Hb Enzymes 120 days

HEMOLYTIC ANEMIAS SHEIKHA Membrane Hb Enzymes HS HE H. Stomatocytosis

HEMOLYTIC ANEMIAS SHEIKHA Membrane Hb Enzymes HS HE H.St. Hemoglobinopathies Thalassemia Sickle

HEMOLYTIC ANEMIAS SHEIKHA Membrane Hb Enzymes HS HE H.St. Hemoglobinopathies Thalassemia Sickle G6PDH ↓ PK ↓ ALL CONGENITAL

HEMOLYTIC ANEMIAS SHEIKHA PNH Paroxysmal Nocturnal Hemoglobinuria ACQUIRED

HEMOLYTIC ANEMIAS SHEIKHA Abnormalities of the Environment of the Red Cells

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA Abnormal Physical Environment Fragmentation Hypersplenism Burn SHEIKHA WARMCHAD Infections Malaria Cl. Welchii

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA SHEIKHA WARMCHAD

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: HDN Drugs AIHA SHEIKHA WARMCHAD IMMUNE HEMOLYTIC ANEMIAS

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA SHEIKHA WARMCHAD AIHA WARM IDIOPATHIC Associated with: SLE CLL LYMPHOMA OTHER AUOIMMUNE DISORDERS MISCELANEOUS

HEMOLYTIC ANEMIAS SHEIKHA Coomb’s Test

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA SHEIKHA WARMCHAD AIHA CHAD ACUTE CHRONIC ATYPICAL MYCO- PLASMA PNEMONIA IM IDIO- PATHIC LYMPH- OMA

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA SHEIKHA WARMCHAD AIHA WARMCHAD PCH ACUTE Measles Mumps Flu Idiopathic CHRONIC Idiopathic

Management of AIHA STEROID SPLENECTOMY RITUXIMAB CYCLOSPORIN FOLATE

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Physical Environment Fragmentation Hypersplenism Burn SHEIKHA March Hb-uria Abnormal Blood Vessels MAHA Microangiopathic Hemolytic Anemia TTP/ HUS Thrombotic Thrombocytopenic Purpura / Hemolytic Uremic Syndrome Mechanical HA From damaged Valves Malignancy “Mucin Secreting Adeno- Carcinoma” Septicemia Malignant HTN

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT SHEIKHA Infections Malaria Cl. Welchii

HEMOLYTIC ANEMIAS due to ABNORMAL RBC ENVIRONMENT Abnormal Plasma Constituents IMMUNE: DRUGS HDN TOXINS Drugs AIHA Abnormal Physical Environment Fragmentation Hypersplenism Burn SHEIKHA WARMCHAD Infections Malaria Cl. Welchii

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS LABORATORY FINDINGS: Hyperbilirubinemia “mild & unconjugated” Anemia Increased Urinary Urobilinogen Reduced Haptoglobin Reticulocytosis & Polychromasia Increased Marrow Activity RBC shape changes: Spherocytosis Fragmentation SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA CLINICAL FEATURES Jaundice “usually mild” Pallor Acholuric jaundice Splenomegaly Gall stones Leg ulcers Crises: Aplastic Hemolytic Sequestration

HEMOLYTIC ANEMIAS SHEIKHA LABORATORY FINDINGS: Hyperbilirubinemia Anemia Increased Urinary Urobilinogen Reduced Haptoglobin Reticulocytosis & Polychromasia Increased Marrow Activity RBC shape changes CLINICAL FEATURES Jaundice “usually mild” Pallor Acholuric jaundice Splenomegaly Gall stones Leg ulcers

HEMOLYTIC ANEMIAS SHEIKHA Intravascular Hemolysis HemoglobinemiaHemoglobinuria Hemosiderinuria

HEMOLYTIC ANEMIAS SHEIKHA Hemoglobinuria

HEMOLYTIC ANEMIAS SHEIKHA Hemosiderinuria

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA Hereditary Spherocytosis

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA Hereditary Elliptocytosis

MANAGEMENT OF HS SPLENECTOMY OPSI PNEUMOVAX Hib Folate

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA Glucose 6 Phosphate Dehydrogenase Deficiency

HEMOLYTIC ANEMIAS SHEIKHA Glucose 6 Phosphate Dehydrogenase Deficiency Sex-linked 200 million Middle East Mediterranean Africa Saudis13% Kurds40% Suly Study 6% Malaria protection

SHEIKHA G-6-P F-6-P F 1,6 DP DHAP Ga3P 1,3 DPG 3 PG 2 PG PEP LactatePyruvate Glucose Glycolysis Embden-Meyerhof Pathway

SHEIKHA G-6-P F-6-P F 1,6 DP DHAP Ga3P 1,3 DPG 3 PG 2 PG PEP LactatePyruvate Glucose Glycolysis ATP ADP ATP ADP OXIDATIVE DAMAGE

SHEIKHA G-6-P F-6-P F 1,6 DP DHAP Ga3P 1,3 DPG 3 PG 2 PG PEP LactatePyruvate 6PGRu5P NADP NADP H * Glucose NADPNADPH * OXIDATIVE DAMAGE G6PDH PPP

SHEIKHA G-6-P F-6-P F 1,6 DP DHAP Ga3P 1,3 DPG 3 PG 2 PG PEP LactatePyruvate 6PGRu5P NADP NADP H * Glucose NADPNADPH * G6PDH A- Mediterranean 10% of Blacks 10% Activity

HEMOLYTIC ANEMIAS SHEIKHA Glucose 6 Phosphate Dehydrogenase Deficiency Favism Highly Palatable Easily Cultivated Staple Food in G6PDH areas High Protein High Nutritional Value

HEMOLYTIC ANEMIAS SHEIKHA Glucose 6 Phosphate Dehydrogenase Deficiency Favism Specific to Fava beans Peas & others are safe Erratic Only in 25% of G6PDH Deficient Patients Same Patient “Only Occasionally” Dosage “Children” Bean Maturity Food Processing

HEMOLYTIC ANEMIAS SHEIKHA Acute drug-induced hemolysis Favism Chronic hereditary non- Spherocytic Anemia Neonatal jaundice Glucose 6 Phosphate Dehydrogenase Deficiency

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

G-6-P F-6-P F 1,6 DP DHAP Ga3P 1,3 DPG 3 PG 2 PG PEP LactatePyruvate Glucose 2,3 DPG PK PK Deficiency

SHEIKHA Drugs and Chemicals Associated with Hemolysis in G6PDH-Deficient Subjects DrugsDefinite AssociationPossible AssociationDoubtful Association AntimalarialsPrimaquineChloroquineQuinacrine Pamaquine--Quinine SulfonamidesSulfanilamideSulfadimidineSulfoxone SulfacetamideSulfasalazineSulfadiazine SulfapyridineGlyburideSulfisoxalone Sulfamethoxazole-- SulfonesDapsone-- NitrofuransNitrofurantoin-- Antipyretic/analgesicAcetanilidAspirinAcetaminophen -- Phenacetin

SHEIKHA DrugsDefinite Association Possible Association Doubtful Association Other drugsNalidixic acidCiprofloxacinPAS NiridazoleChloramphenicolDoxorubicin Methylene blueVitamin K analogsProbenecid PhenazopyridineAscorbic acidDimercaprol SeptrinPAS-- Other chemicalsNaphthaleneAcalypha indica-- Trinitrotoluene-- Drugs and Chemicals Associated with Hemolysis in G6PDH-Deficient Subjects

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA

HEMOLYTIC ANEMIAS SHEIKHA