Text of Introduction to Hemolytic Anemias. HEMOLYTIC ANEMIAS Introduction Definition Pathogenesis...
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. RBCs 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 Intravascular RES Haem Globin Plasma iron pool Plasma protein pool Protoporphyrin Expired CO Unconjugated bilirubin Liver Conjugated bilirubin GI tract Urobilinogen Faeces Urine Free plasma Hb Hb- Hpt complex Liver Hpt and Hpx Haemopexin-methem Excess Hb methaemalbumin Kidney Hb Haemosiderin Haem+globin Hb methem metHb
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
1- Abnormalities of RBC interior a. Enzyme defects 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 Intracorpuscular Extracorpuscular Hereditary Acquired A Simple Classification of Hemolytic Anemias
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 Hematologic Blood film Polychromatophilia ReticulocyteIncreased Bone marrowErythroid hyperplasia Plasma or serum Bilirubin unconjugated Haptoglobin, absent Plasma free Hb N - LDH Urine Bilirubin0 Hemosiderin0 Hemoglobin 0 Urobilinogen Intravascular Polychromatophilia Increased Erythroid hyperplasia unconjugated absent 0 + + ( severe cases)
Laboratory tests useful in differential diagnosis Examination of peripheral blood Special Lab. examinations
Morphologic abnormalities in hemolytic anemias Polychromasia Spherocyte : Elliptocytes: Stomatocytes: Acanthocytes: Echinocytes: : Reticulocytes Her. Spherocytosis, immune hem. anemia, burns, chemical injury to RBC Hereditary ovalocytosis, Hereditary stomatocytosis, alcoholism Spur cell anemia with liver disease, abetalipoproteinemia Pyruvate kinase deficiency, uremia
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?