MLAB 1315- Hematology Fall 2007 Keri Brophy-Martinez Unit 16: Extracorpuscular Defects

Immune Hemolytic Anemia Mechanisms of Immune Hemolysis Intravascular Intravascular immune hemolysis occurs within the vascular system and results from activation of the classic complement pathway via immunoglobulin G (IgG) or IgM antibodies. Antibodies bind to antigens on red cells and activate complement resulting in lysis of the cell. Extravascular Antibody coated red cells are fully or partially phagocytized by cells in the reticuloendothelial system (RES), particularly in the spleen and liver. Partially phagocytized cells are seen as spherocytes on the peripheral smear.

Laboratory findings Peripheral smear - spherocytes Serum bilirubin Urine and stool urobilinogen Positive direct antiglobulin test (DAT

Classification Alloimmune Hemolytic Anemia A foreign antigen stimulates the host’s immune system to produce a corresponding antibody called an alloantibody.

Types of Alloimmune Hemolytic Anemia Acute transfusion reaction The wrong ABO type of blood is transfused. If a patient develops symptoms such as fever, shaking, chills, pain or burning at the site of the iv, the transfusion should be stopped immediately. Delayed transfusion reaction Sensitization to non-ABO blood groups occurs during a primary transfusion. When re-exposed during a second transfusion, antibodies build up and a delayed reaction occurs. Symptoms are usually mild and non-specific.

Types of Alloimmune Hemolytic Anemia Hemolytic Disease of the Newborn (HDN) This is caused when the mother’s and baby’s blood groups are incompatible and there is an exchange of fetal-maternal blood during delivery. The mother builds antibodies against the fetal red cells which then become coated with antibody and are destroyed in the baby’s RES. This could be associated with ABO or Rh incompatibility. It can be severe and treatment would consist of an exchange transfusion of the newborn.

Classification Autoimmune Hemolytic Anemia (AIHA) Caused by an altered immune response resulting in production of antibody against the patient’s own red cells, with subsequent hemolysis.

Types of Autoimmune Hemolytic Anemia Warm AIHA IgG coats red cells with or without complement fixation Cold agglutinins - non-pathologic Almost all adults have cold antibodies in low quantity which cause no problems because they react in the temperature range of 4̊ to 22̊ C. The antibody is usually anti-I. Cold Agglutination Syndrome – pathologic Caused by a cold autoantibody that reacts at or above 30̊ C. Seasonal hemolytic anemia during the winter months. Usually not severe. RBC’s agglutinate at room temperature and will be seen as clumps on a peripheral smear. This can also be secondary to an infection, especially Mycoplasma pneumoniae. Paroxysmal Cold Hemoglobinurea Caused by a cold-reacting IgG autoantibody. Can be severe. Treatment is to avoid the cold.

Drug-Induced Immune Hemolytic Anemia Represents about 12% of immune hemolytic anemias. Usually an IgM antibody and may be cause by many drugs, some of which are methyldopa (Aldomet), penicillin, cephalosporins and streptomycins.

Nonimmune Hemolytic Anemia These anemias represent a group of conditions that lead to the shortened survival of red cells by various mechanisms.

Mechanisms of nonimmune hemolytic anemia Intracellular infections Malaria - this parasite carried by a mosquito lives in the red cell at one of the stages in its life cycle and causes the red cell to burst, releasing the parasite into the bloodstream.. This is the most common infectious disease in the world that causes a hemolytic anemia. Species of malaria include: Plasmodium vivax P. faciparum - most fatal P. malariae - uncommon P. ovale - uncommon Peripheral smear examination will reveal intracellular parasites. Babesiosis - Tick-borne parasite

Mechanisms of nonimmune hemolytic anemia Extracellular infections Bartonellosis Clostridium perfringens (welchii) - causes gangrene

Mechanical etiologies Cardiac prothesis Peripheral smear shows RBC fragments, helmet cells and occasional spherocytes. March hemoglobinurea Caused by traumatic destruction of the red cells in strenuous and sustained physical activity such as marching. Microangiopathic hemolytic anemia Caused by fragmentation of the red cells by fibrin strands as they pass through abnormal arterioles. The fibrin strands are the results of intravascular coagulation as seen in hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenia purpura (TTP). (To be discussed in coagulation)

Mechanical etiologies con’t Venoms Some spiders contain enzymes that lyse the red cell membrane. Snake venoms rarely cause lysis in vivo. Osmotic effects Burns over more than 15% of the body can cause hemolysis. It is thought that the direct effect of the heat causes the red cells to fragment and burst.