Case #5 Maria De Leon and Melissa Koç Microbiology and Serology; Spring 2010 California State University, Los Angeles

History of the Patient  34-year-old healthy female  No history of illness; Only minor colds and the usual childhood infections Patient’s Symptoms  Development of a feverish cough  Extreme paleness, particularly at palms of hands  Scattered rhonchi / patchy infiltrates at bases of both lungs  High temperature: 38.5°C  High respiratory rate: 30/min.  Low hematocrit (26%) and hemoglobin (9.5 g/dl) levels  Elevated neutrophil count  Physician suspects Mycoplasma pneumonia infection

 RBC became clumped and looked clotted at 4°C; RBC were dispersed at 37°C  Direct and indirect Coombs Test proved negative results for presence of anti-red cell IgG Ab in warmed sample  Coombs Test: blood test for identifying Ab attached to RBC (direct) or unbound in bloodstream (indirect)  RBC were strongly agglutinated by an antibody to the complement component C3  Suspected Mycoplasma pneumonia infection. Symptoms abated after intravenous erythromycin administration  Symptoms cleared after continued oral erythromycin administration and avoidance of cold weather

 Cold Autoimmune Hemolytic Anemia (‘Warm' or ‘cold' types, depending on whether the antibody attaches better to RBCs at body temp. (37°C) or lower temp.)

 To prove that the patient’s anemia is, in fact, an autoimmune hemolytic anemia, perform a DAT. The DAT will be positive in cold AIHA because the DAT looks for both IgG and complement bound to the patient’s red cells  Reticulocyte count  blood test that measures how fast RBC are made by the bone marrow and released into the blood. The reticulocyte count rises when there is a lot of blood loss or in certain diseases in which red blood cells are destroyed prematurely.

 Cure underlying cause: In this case, treatment of Mycoplasma pneumonia by erythromycin  Avoid cold exposure  Corticosteroid such as prednisone if RBC destruction is increasing  Surgery to remove spleen if corticosteroids are ineffective  Immunosuppressive drugs such as Azathioprine and Cyclophosphamide may be effective

 The prognosis varies depending on the underlying cause and whether symptoms are managed in an appropriate and timely manner.  If symptoms are mild then no treatment is needed.  Some cases lead to acute severe disease where blood transfusion is needed.

 “Your body cannot differentiate friend from foe! Your immune system thinks your RBCs are foreign substances, so it is 1) producing antibodies to attack and destroy them and 2) fixing complement, which is a system of proteins that kill foreign cells in your body, to your RBCs. The antibodies are IgM in nature, which bind best at colder temperatures, and the complement proteins are consistently poking holes in your RBCs. This is called Cold Autoimmune Hemolytic Anemia. The most likely cause is M. pneumonia infection.”

 Antibodies against his/her red blood cells. The red cells are destroyed at a rapid rate which leads to anemia.  There is complement fixed to the patient’s red cells. (This is where hemolysis starts)  The abnormal destruction of red blood cells is more active when the patient is exposed to cold temperatures.  May occur as a secondary disorder such as Mycoplasma pneumonia infection

 Mycoplasma pneumonia produces peroxidase, which alters the I-antigen locus of erythrocytes  This altered Ag initiates Ab production  Antibodies neutralize, opsonize, activate complement, activate NK cells, and agglutinate to prevent spread  The cold agglutinins are usually IgM which is a pentamer that can span several red cells  The destruction of erythrocytes is complement mediated and by pore formation, which is fixed in cold temperatures

 Cerdas-Quesada, 2010, Transf. Apheres. Sci.  Research objectives: To test the therapeutic success of plasma exchange in a case of AIHA  52 yr-old man with severe AIHA caused by pan- agglutinant IgG-class antibodies was treated with therapeutic plasma exchange, transfusions and steroids. TPE was used to maintain acceptable hemoglobin levels and reduce the titer of auto-Ab. During each TPE, 3500 mL of plasma was processed and fresh frozen plasma was provided as part of the return fluid to avoid excessive depletion of coagulation factors in the patient bloodstream  Results: Every procedure removed up to 65% of the serum IgG. AIHA was resolved with therapeutic plasma exchange

Hb level pattern during the plasma exchange. Plasma exchange started at day 5

 Cold autoimmune hemolytic anemia is due to antibodies, which attach to RBCs at lower temperatures and produce complement mediated intravascular hemolysis  Typical symptoms are fever, cough, and paleness  Diagnostics include blood tests to test for increased amount of antibodies attached to RBCs  Therapies include curing underlying cause such as bacterial infection, Corticosteroid such as prednisone if RBC destruction is increasing, and/or keeping the body warm  The prognosis varies depending on the underlying cause and whether symptoms are managed in an appropriate and timely manner

REFERENCE      Lecture material from Immunology and Serology (Micro 304)  Cerdas-Quesada. (2010) A life-threatening case of autoimmune hemolytic anemia successfully treated by plasma exchange. Transfus Apher Sci.