Approach to extracorpuscular hemolysis

approach

1. Approach to Extracorposcular Hemolytic Anemia Dr. Bikal Lamichhane Internal medicine resident

2. Extracorpuscular defects   those in which the RBCs are normal but are destroyed due to mechanical immunologic Infectious metabolic/oxidant damage. These abnormalities are almost always acquired. Exception is familial hemolytic-uremic syndrome (HUS; often referred to as atypical HUS).

3. Etiology:-

4. Non-immune Infection •Intracellular organisms, e.g. malaria •Toxins, e.g. C. perfringens Mechanical •Prosthetic valves •Microangiopathic, e.g. DIC, HUS, TTP •March haemoglobinuria Chemical/physical •Oxidative drugs,e.g . dapsone, maloprim •Copper (Wilson’s disease) •Burns •Drowning

5. Immune Hemolytic Anemias can arise through at least two distinct mechanisms . 1.when an antibody directed against a certain molecule (e.g., a drug) reacts with that molecule, red cells may get caught in the reaction (the so-called innocent bystander mechanism ) 2.a true auto-antibody is directed against a red cell antigen, i.e., a molecule present on the surface of red cells .

6. Based on the Coombs test findings as well as on the thermal characteristics and the antigenic specificities of the autoantibodies. AIHA has been classified into subtypes.

7. Warm Antibody AIHA more common type of AIHA. the auto-antibody reacts best at 37°C may be seen in isolation (and it is then called idiopathic ) or as part of a systemic auto-immune disorder such as systemic lupus erythematosus (SLE) May be seen in chronic lymphocytic leukemia (CLL), after BMT; and after solid organ transplantation entailing immuno-suppressive treatment. As a side effect of the use of immune checkpoint inhibitors, such as nivolumab, in patients with various types of cancer

8. Once a red cell is coated by an autoantibody In most cases, the Fc portion of the antibody will be recognized by the Fc receptor of macrophages, and this will trigger erythrophagocytosis. Thus, destruction of red cells will take place wherever macrophages are abundant, i.e., in the spleen, liver, and bone marrow . Spleen is the predominant site of red cell destruction.

9. COLD AGGLUTININ DISEASE AIHA that usually affects the elderly . 1. CAD is characteristically a chronic condition—in contrast to the abrupt onset of warm antibody AIHA. M ediated by antibodies, usually IgM, which bind to the red cells at low temperatures and cause them to agglutinate . M ay cause intravascular haemolysis if complement fixationoccurs . C an be chronic when the antibody is monoclonal,or acute or transient when the antibody is polyclonal.

10. The term cold refers to the fact that the autoantibody involved reacts with red cells poorly or not at all at 37°C, whereas it reacts strongly at lower temperatures. As a result, hemolysis is more prominent the more the body is exposed to the cold. The antibody is usually IgM; usually it has an anti-I specificity (the I antigen is present on the red cells of almost everybody), and it may have a very high titer (1:100,000 or more has been observed). The antibody is produced by an expanded B lymohocyte clone (a low-grade mature B cell lymphoma) and sometimes the antibody concentration in the serum is high enough to show up as a spike in plasma protein electrophoresis, i.e., as a monoclonal gammopathy . As this is a clonal disease and the antibody is IgM, CAD must be regarded

11. Alloimmune haemolytic anaemia Alloimmune haemolytic anaemia is caused by antibodies against non-self red cells. It has two main causes, occurring after : • unmatched blood transfusion . • maternal sensitisation to paternal antigens on fetal cells ( haemolytic disease of the newbor ).

12. Non-immune haemolytic anaemia • Mechanical heart valves . High flow through incompetent valves or periprosthetic leaks through the suture ring holding a valve in place result in shear stress damage. • March haemoglobinuria . Vigorous exercise, such as prolonged marching or marathon running, can cause red cell damage in the capillaries in the feet. • Thermal injury. Severe burns cause thermal damage to red cells, characterised by fragmentation and the presence of microspherocytes in the blood.

13. Microangiopathic haemolytic anaemia . Fibrin deposition in capillaries can cause severe red cell disruption . It may occur in a wide variety of conditions: Disseminated carcinomatosis, malignant or pregnancy-induced hypertension, haemolytic uraemic syndrome thrombotic thrombocytopenic purpura and disseminated intravascular coagulation

14. Infection Plasmodium falciparum malaria . may be associated with intravascular haemolysis ; Clostridium perfringens sepsis usually in the context of ascending cholangitis or necrotising fasciitis, may cause severe intravascular haemolysis with marked spherocytosis due to bacterial production of a lecithinase that destroys the red cell membrane

15. Chemicals or drugs Dapsone and sulfasalazine cause haemolysis by oxidative denaturation of haemoglobin . Denatured haemoglobin forms Heinz bodies in the red cells, visible on supravital staining with brilliant cresyl blue . Arsenic gas, copper, chlorates, nitrites and nitrobenzene derivatives may all cause haemolysis

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