Hemolytic anemias

Objectives Define Haemolytic anaemias and their classification. Define the terms "intravascular hemolysis" and "extravascular hemolysis" and identify which mechanism predominates in normal red cell destruction. Describe the fate of free hemoglobin following red blood cell destruction. Listing the lab. Findings in extra & intravascular hemolysis.

Definition This is a Normocytic, normochromic anemia Hemolytic Anemias are defined as those anaemias which result from an increase in the rate of red cell destruction. Any condition which leads to a reduction in the mean lifespan of the red cell is a hemolytic disorder

In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so about 1% of human red blood cells break down each day. The bone marrow is the main organ that removes old and damaged RBCs from the circulation. In healthy individuals, the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.

In conditions where the rate of RBC breakdown is increased, the body initially compensates by producing more RBCs; however, breakdown of RBCs can exceed the rate that the body can make RBCs, and so anemia can develop.

The normal adult marrow, after full expansion, is able to produce red cells at 6-8 times the normal rate and this leads to reticulocytosis. Therefore Hemolytic Anemias may not be seen until the red cell lifespan is less than 30 days.

Normal Red cell Break down Occurs extravascularly by macrophages of RE system, especially Bone marrow, but also in liver & spleen. Red blood cells have no nucleus, so they cannot replace metabolism enzymes which deteriorate.

Mechanisms of hemolysis: - intravascular - extravascular Intravascular hemolysis has a very little or NO role in Normal red cell break down. It occurs inside blood vessels. Hb is liberated and binds Haptoglobin. The complex is removed from plasma by RES.

Classification of Hemolytic anemias A. Hereditary (intracorpuscular : inside RBCs) 1. Membrane defects (Hereditary spherocytosis, Hereditary elliptocytosis) 2. Metabolic defects (Glucoze-6-Phosphate- Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable Hb, thalassemias, Hb S, Hb C ) Classification of Hemolytic anemias

B. Acquired (Extracorpuscular : outside RBCs) A B. Acquired (Extracorpuscular : outside RBCs) A. Immune hemolytic anemias 1. Autoimmune hemolytic anemia - caused by warm-reactive antibodies - caused by cold-reactive antibodies 2. Alloimmune hemolytic anemia -caused by hemolytic transfusion reaction - caused by hemolytic disease of newborn 3. Drug associated B. Nonimmune hemolytic anemias 1. Chemical & physical agents (drugs, industrial, burns) 2. Infections (parasitic or bacterial : malaria, clostridia) 3. Red cell fragmentation syndromes - hemolytic - uremic syndrome (HUS) - thrombotic thrombocytopenic purpura (TTP) - prosthetic heart valves 4. Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH : Paroxysmal Nocturnal Hemoglobinuria is an exception of this classification , as it is an acquired disease but the red cells has an intrinsic defect.

Clinical features: - pallor to mucus membranes - jaundice - splenomegaly - pigment gallstones - leg ulcers - a plastic crisis usually due to infections

Jaundiced Urine Normal Urine

Jaundice = Raised Serum bilirubin

leg ulcers in sickle cell anemia

Laboratory findings The lab. Findings are divided into 3 groups: 1- Features of increased red cell breakdown. 2- Features of increased red cell production. 3- Damaged red cells.

1-Features of increased red cell breakdown: Raised Serum bilirubin Increased urine urobilinogen. Increased faecal stercobilinogen. Absent Serum haptoglobins (saturated with Hb and removed by the RE cells).

2-Features of increased red cell production: Reticulocytosis Bone marrow erythroid hyperplasia. (normally, myeloid : erythroid ratio is 2 : 1 to 12 – 1 This is reduced to 1 : 1 or even reversed. Polychromatic cells

Polychromatic cells

3-Damaged red cells: Morphology– microspherocytes, elliptocytes, fragmented cells ,bite cells ….. etc Special tests: Osmotic fragility, ham test autohaemolysis, Coomb’s Test Red cell survival is shortened; this is best shown by 51Cr labelling with study of the sites of destruction.

Fragmented cells = Schistocytes

Spherocytes are red blood cells that are almost spherical in shape Spherocytes are red blood cells that are almost spherical in shape. They have no area of central pallor . Microspherocytes Macrospherocytes

Causes of Intravascular hemolysis : 1 Causes of Intravascular hemolysis : 1. Mismatched blood transfusion (usually ABO) 2. G6PD deficiency with oxidant stress 3. Red cell fragmentation syndromes 4. Some autoimmune hemolytic anemias 5. Some drug and infection - induced hemolytic anemias 6. Paroxysmal Nocturnal Hemoglobinuria (PNH) 7. Unstable Hb 8. March Hemoglobinuria

Lab. Findings in Intravascular hemolysis : 1. Erythroid hyperplasia 2 Lab. Findings in Intravascular hemolysis : 1. Erythroid hyperplasia 2. Hemoglobinemia 3. Methemoalbuminemia 4. Hemoglobinuria 5. Absence or reduced of free serum haptoglobin 6. Hemosiderynuria