Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Hemolytic Anemias
Document related concepts
Signal transduction wikipedia , lookup
Cell encapsulation wikipedia , lookup
Extracellular matrix wikipedia , lookup
Cellular differentiation wikipedia , lookup
Cell membrane wikipedia , lookup
Cell culture wikipedia , lookup
Cell growth wikipedia , lookup
Endomembrane system wikipedia , lookup
Organ-on-a-chip wikipedia , lookup
Transcript
Introduction to Hemolytic Anemias HEMOLYTIC ANEMIAS Introduction • • • • • Definition Pathogenesis Classification General clinical features Laboratory evaluation of hemolysis Hemolytic Anemias Definition • A group of disorders leading to anemia caused by a reduction in red cell life span. • RBC’s normally survive 60 - 120 days . • Bone marrow has the capacity to increase erythropoiesis 6 - 8 times than normal. • Anemia is the result of premature destruction of red cells exceeding the erythropoietic capacity of the bone marrow. Hemolytic Anemias Classification • Hemolytic anemias may be classified as I- Hereditary or acquired or II- Intracorpuscular or Extracorpuscular Hemolysis may occur in two compartments I- Intravascular or II- Extravascular ( eg: spleen ) Red cell destruction Extravascular Hb Intravascular Hpt and Hpx RES Free plasma Hb Globin Haem Haem+globin Hb- Hpt complex Plasma protein pool Plasma iron pool methem Haemopexin-methem Excess Hb Protoporphyrin Expired CO Liver Unconjugated bilirubin Liver Conjugated bilirubin GI tract Faeces methaemalbumin Kidney Hb Urine Urobilinogen metHb Haemosiderin • In some types of hemolytic anemias hemolysis occurs particularly as an intravascular hemolysis. eg: Paroxsysmal nocturnal hemoglobinuria Traumatic or microangiopathic hem. anemia (eg:cardiac hemolytic anemia,march hemoglobinuria,TTP) Acute hemolytic transfusion reaction etc A Simple Classification of Hemolytic Anemias 1- Abnormalities of RBC interior a. Enzyme defects Hereditary b. Hemoglobinopathies & Thalassemia Maj 2-RBC membrane abnormalities a. Hereditary spherocytosis, elliptocytosis etc b. Paroxysmal nocturnal hemoglobinuria c. Spur cell anemia 3- Extrinsic factors a. Hypersplenism b. Antibody : immune hemolysis c. Traumatic & Microangiopathic hemolysis d. Infections , toxins , etc Acquired Clinical Manifestations in Summary • Onset may be acute or insidious • Symptoms and signs of anemia • Jaundice – Acholuric – Without pruritus • Symptoms and signs spesific to the type of hemolytic anemia • Symptoms related to the underlying disease • Splenomegaly – Most congenital hem. anemias except sickle cell – Some of the acquired hem. anemias • • • • Cholelithiasis (gall stones) symptoms Leg ulcers (sickle cell, spherocytosis) Skeletal abnormalities (thalassemia) Crises (chronic hemolytic disease) – Aplastic crises (HPV-B19) – Hemolytic – Megaloblastic • Changes in urine color Laboratory findings I- Increased RBC destruction • Decreased RBC life span • Increased haem(heme) catabolism – Increased serum unconjugated bilirubin* – Increased endogenous CO production – Increased urobilinogen excretion • Increased serum LDH* • Absence or decrease of serum haptoglobin* • > 1 g /dl /week fall in blood Hb level* • Reduced glycosylated Hb • Signs of intravascular hemolysis – Hemoglobinemia* – Hemoglobinuria* – Hemosiderinuria* – Methemalbuminemia – Reduced serum hemopexin level *common practice Laboratory findings II-Increased bone marrow activity and RBC production • Blood – – – – – Reticulocytosis Macrocytosis Polychromatophilia Erythroblastosis Leukocytosis and thrombocytosis • Bone marrow – Erythroid hyperplasia • Ferrokinetic – Increased plasma iron turnover – Increased RBC iron turnover • Biochemical – Increased RBC creatine – Increased activity of RBC enzymes eg: hexokinase, etc Laboratory Evaluation of Hemolysis Extravascular Intravascular Hematologic • Blood film Polychromatophilia Polychromatophilia • Reticulocyte Increased Increased • Bone marrow Erythroid hyperplasia Erythroid hyperplasia Plasma or serum • Bilirubin unconjugated unconjugated • Haptoglobin , absent absent • Plasma free Hb N• LDH Urine • Bilirubin 0 0 • Hemosiderin 0 + • Hemoglobin 0 + ( severe cases) • Urobilinogen Laboratory tests useful in differential diagnosis • Examination of peripheral blood • Special Lab. examinations Morphologic abnormalities in hemolytic anemias • Polychromasia : Reticulocytes • Spherocyte : Her. Spherocytosis, immune hem. anemia, burns, chemical injury to RBC • Elliptocytes: Hereditary ovalocytosis, • Stomatocytes: Hereditary stomatocytosis, alcoholism • Acanthocytes: Spur cell anemia with liver disease, abetalipoproteinemia • Echinocytes: Pyruvate kinase deficiency, uremia Morphologic abnormalities in hemolytic anemias • Sickle cell: Sickle cell anemia • Target cels: Thalassemia, HbC disease, liver disease, splenectomy • Schistocytes: Microangiopathic hem anemia, uremia, DIC, malignant hypertesion, eclampsia, disseminated vasculitis or malignancy, • Agglutination: Cold agglutinin disease • Heinz bodies: Unstable Hb, G6PD deficiency and oxidant stress • Bite cells -Blister cells – G6PD deficiency – Unstable Hemoglobin • RBC fragmentation – Helmet Cell, schistocytes • • • • • • • • • Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic uremic syndrome (HUS) Disseminated Intravascular Coagulation Vaskulitis Renal graft rejection Malignant hypertention Burns Artificial cardiac valves March hemoglobinuria • Target cells – Liver disease – Thalassemia – Hb C – Splenectomy – Sickle cell anemia – Iron deficiency • Howell-Jolly bodies (Nuclear remnants) – Splenectomy – Hyposplenism – Megaloblastic anemia – Hemolytic anemia • Basophylic stippling Ribosomes/RNA/mitochondrial bodies – – – – – – Lead poisoning Thalassemia, Unstable hemoglobines MDS Megaloblastic anemia Other hemolytic anemia • Eg. 5-Nucleotidase deficiency • Heinz Bodies (Denaturated Hemoglobin) – – – – RBC Enzyme defects Unstable hemoglobin Thalassemia Sickle cell anemia Special Lab. Examinations • • • • • • Coombs antiglobulin test - immune hemolysis Osmotic fragility test - spherocytosis Autohemolysis- G6PD,PK, spherocytosis Membrane protein analysis- membrane defects Red cell sickling- sickle cell anemia Hemoglobin electrophoresis and HbA2, Hb F , HHb,etc - Hemoglobinopathies and thalassemias • Red cell enzyme assays- RBC enzyme defects • HAM and sucrose lysis tests and GPI-linked protein analysis by flow cytometry- PNH • Oxygen dissociation curve- High oxygen affinity Hb Diagnostic approach • Is there anemia? • Detailed history including disease related symptoms, bleeding, drugs,ethnics, occupation , toxic exposure etc. family history • Physical exam.: Signs of hemolytic anemia (common and specific ) in addition to anemia and any signs of underlying disease Diagnostic approach • What are the changes in red cell morphology? – Smear examination – Red cell indexes • Are there any changes in other cell lines ? • Is there evidence of increased red cell production? Reticulocytes • Is there evidence of hemolysis? • What is the type/diagn. of hemolysis? – Special tests • Is there evidence of intravascular hemolysis?
