Haemolytic Anaemia

Haemolytic AnaemiaDr Maryam Jameelah AizuddinDr Siti NurzafiraPresentation OutlineDefinitionTypes of haemolytic disorders HaemoglobinopathyEnzymopathyMembranopathyExtrinsic FactorsImmune Haemolytic AnemiaPresentation (signs and symptoms)Pathophysiology InvestigationsManagement

Haemolytic Anaemia:DefinitionsHaemolysis: Premature destruction of RBCs.Anaemia results => destructions exceed capacity of BM to produce RBCsNormal RBCs survival time => 110-120 daysNormal Blood FilmNormal peripheral blood smear showing RBCs. The RBCs are uniform in size, and the central areas of pallor are slightly less than half the total diameter of an RBC. The four dark objects (arrows) outside the RBCs are platelets.(From Hoffbrand AV: Color Atlas: Clinical Hematology, 3rd ed. St. Louis, Mosby, 2000, p 22, Fig. 1-62.)

1. Squeezing through the capillaries of active tissues damages red blood cells. 2. Macrophages in the spleen and liver phagocytize damaged RBCs3. Hemoglobin from the RBCs is decomposed into heme and globin4. Heme is decomposed into iron and biliverdin5. Iron is made available for reuse in the synthesis of new hemoglobin or is stored in the liver as ferritin6. Some biliverdin is converted into bilirubin7. Biliverdin and bilirubin are excreted in bile as bile pigments8. The globin is broken down into a.a. metabolized by macrophages or released into the blood5

Haemolytic Anaemia:Clinical FeaturesJaundice: generally mild and often not noticed by the patient.

Anaemia: Recent onset = acquired Long-standing = possibly congenital.

Haemoglobinuria:intravascular haemolysis.Urobilinogenuria:increased Hb catabolism.

Splenic pain: spenomegaly or splenic infarction.

Leg ulcers: intrinsic red cell disorders, e.g. sickle cell disease.Skeletal hypertrophy: severe congenital haemolytic anaemias and thalassaemias.What happened during haemolyis?RBCs survival shorthened => RBCs EPO (stimulation in BM to RBCs) => Reticulocytosis (2-3) (Ddx: acute blood loss, vit B 12 or folate deficiency)Haemolytic Anaemia:LABORATORY FINDINGS Features of increased erythrocyte breakdown:

Unconjugated bilirubinaemia.Urobilinogenuria.Haptoglobins decreased.

Features of increased erythrocyte production:

ReticulocytosisPolychromasia and nucleated red cells in peripheral blood film.Erythroid hyperplasia in bone marrow aspirate.Radiological changes, e.g. "hair on end" appearance of cranial X-ray.

Features specific to intravascular haemolysis:

Haemoglobinaemia(haptoglobin and haemopexin exhausted).Methaemoglobinaemia.Haemoglobinuria.Haemosiderinuria.

Classification of Haemolytic anaemiaCellular defect:Hereditary SperocytosisThe most common inherited abnormality of RBCs membranePrevalence ~1 in 5000 people of Nothern European decsent but has been described in most ethnics groupOthers:Hereditary elliptocytosisUsually no anemiaAutosomal dominant, affecting 1/2500 EuropeansHereditary pyropoikilocytosis

Cellular defect:Hereditary SperocytosisAutosomal Dominant traitPatients develop hemolysis and abdominal pain with even trivial infectious illnessesDefect is in proteins of the membrane skeleton, usually spectrin or ankyrinLipid microvesicles are pinched off in the spleen and other RE organs, causing decreased MCV and spherocytic change.

PathophysiologyThe defective red cells in HS have an increased flux of Na+ ions into the cell, because of weakened membrane structure, leading to greatly increased activity of the cation pump and necessitating an increased rate of glycolysis. Normally, the osmotic balance of the red cell is maintained with sufficient glucose and ATP to expel sodium at a rate equal to its influx. However, spherocyte consume glucose at a higher rate. When the amount of glucose is low, as in splenic cords, there is an increased rate of destruction of red cells. The water content of red cells is increases, and as a result, swelling and haemolysis of the red blood cells occur.

15Cellular defect:Hereditary Sperocytosis

NormalAbnormal-HS cells lyse more readily at low ionic strength Diagnosed by Osmotic Fragility16Cellular defect:Hereditary SperocytosisBlood FilmPeripheral blood with spherocytes in hereditary spherocytosis. Numerous, round, dense red blood cells without central areas of pallor represent spherocytes (arrows). The mean corpuscular hemoglobin concentration is increased.(From Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, p 75, Fig. 5-7.)

Hereditary spherocytosisHow do we treat?None : if Hb > 10g/dL and reticulocytes counts 10%Transfusion : if severe anaemia, poor growth, aplastic crises and age