Acquired Haemolytic Anaemias

1. Acquired Haemolytic Anaemias

2. Haemolytic Anaemias - definitions Haemolytic conditions are those in which: • erythrocyte construction industry is healthy (usually) • red cells produced have shortened lifespan. They may be due to either • intrinsic defects in red cell structure or function • hostile external environment in which the cells live.

3. Haemolytic Anaemias - definitions haemolysis: Any condition characterized by a significantly decreased erythrocyte life span. Compensated haemolytic state: A state of haemolysis in which the resulting increased erythrocyte production is able to keep up with accelerated rbc destruction, thus averting anaemia. haemolytic anemia: A state of haemolysis in which increased erythrocyte production is insufficient to keep up with accelerated rbc destruction, thus producing anemia. This anaemia is characterized as normochromic/normocytic, except when sufficient outpouring of the larger reticulocytes produces a resulting elevation of the MCV

4. Diagnosis of haemolytic anaemia Four steps: • Establish anaemia exists • Demonstrate bone marrow response • Demonstrate red cell destruction • Establish the mechanism of haemolysis

5. Establish anaemia exists How is anaemia defined? • Age & sex ranges • Historical comparison

6. Demonstrate bone marrow response • reticulocyte count. • Reticulocytosis is not indicative of haemolysis, • merely shows increased bone marrow function

7. Demonstrate red cell destruction destroyed red cells and their component catabolites, such as • free haemoglobin • Methaemoglobin • Methemalbumin • Bilirubin • Urobilinogen specific binding proteins for these catabolites • haptoglobin • hemopexin

8. Establish the mechanism of haemolysis 1 determine whether the haemolysis is taking place: intravascular - in the bloodstream proper extravascular - in the sinusoids of the reticuloendothelial system Intravascular haemolytic conditions due to mechanical destruction of rbc's produce the helmet-shaped schistocytes, which can be seen in the blood film. intravascular haemolysis produces hemosiderin in the urine sediment, free haemoglobin in the serum (which may be grossly visible), and free denatured haemoglobin in the urine. Extravascular haemolytic anemias may produce spherocytes, which are the result of an rbc having a narrow escape from the clutches of the RES.

9. Establish the mechanism of haemolysis 2 thorough history and physical (including family and drug history) • peripheral blood film • direct antiglobulin (Coombs') test • Urine screen for haemosiderin • Haemoglobinopathy screening (not acquired!)

10. Specific Conditions

11. Mechanical haemolytic anemias • Red cells are destroyed due to hydrodynamic turbulence when they are: • forced over gross obstructions (such as an artificial heart valve) • "clotheslined" by innumerable fibrin strands • Disseminated intravascular coagulation • thrombotic thrombocytopenic purpura • The hallmark of a mechanical haemolytic anemia is the presence of schistocytes on the routine blood film.

12. Immunohaemolytic anemias • the body mounts an immune attack against its own rbc membrane antigens. • This condition occurs in autoimmune condtions, such as lupus erythematosus. • If the autoantibody is of the IgG class, haemolysis will usually occur at any temperature ( "warm autoimmune haemolytic anemia"). • Several drugs are known to produce warm autoimmune haemolytic anemia which goes away after withdrawal of the drug. • Typically the antibody in warm haemolysis is one directed against a component of the Rh system

13. Immunohaemolytic anemias • IgM Autoantibodies typically produce cold agglutinin syndrome • patient is at greater risk of symptoms in a low-temperature environment. • Cold agglutinin syndrome may occasionally occur transiently in cases of Mycoplasma pneumonia and rarely infectious mononucleosis. • Most cold autoagglutinins are directed against the I antigen, • Paroxysmal cold haemoglobinuria is a very rare syndrome in which intravascular haemolysis is produced upon exposure to cold temperature by an IgG autoantibody directed against the P antigen found on the red cells of nearly all individuals.

14. Paroxysmal nocturnal haemoglobinuria • Patient's rbcs develop an acquired mutation • affects the structure of the cell membrane • makes it more sensitive to complement activation in acidic conditions • (Body’s pH changes during sleep) • Causes intravascular haemolysis producing • anaemia • Haemoglobinuria (not always visible) • In cases of suspected chronic intravascular haemolysis stain the urine sediment with Prussian blue reagent to demonstrate hemosiderinuria

15. Hypersplenism • Any condition which causes enlargement of the spleen can induce the spleen to accelerate red cell destruction • The condition is termed (somewhat vaguely) hypersplenism. • Should be considered in patients with • Chronic liver disease • leukemia/lymphoma • congestive heart failure • Or any condition which may produce splenomegaly • Who present with a haemolytic anemia and a negative direct Coombs' test.

16. Infections of the RBC • intravascular haemolysis can be caused by. • Malaria – intracellular parasites • Babesiosis – simular to malaria • Carrión's disease – bacilli (Bartonella bacilliformis) adhere to red cells • Clostridium perfringens sepsis may produce acute haemolysis