Autoimmune Hemolytic Anemia

Autoimmune Hemolytic Anemia

Antibodies produced against own RBCs, leading to premature death of RBCs and, subsequently, anemia 50% of cases are idiopathic, the remainder are caused by other autoimmune disorders, infections, medications or hematologic disorders such as Evan's syndrome Clinical presentation and symptoms depend upon extent of RBC destruction (which depends on the amount of antibody) and how quickly RBC destruction occurs in relation to how quickly the bone marrow produces new reticulocytes. 

Autoimmune Hemolytic Anemia-

Lysis occurs one of two ways: Intravascular- antibodies bind to antigens of RBCs, triggering the complement cascade and damaging the cell well, leading to excessive osmosis, increased osmotic pressure, and eventually rupture Extravascular- complement fixation (between antibody and antigen) is not strong enough to trigger the cascade, but is detected by macrophages within the lungs, liver and spleen, leading to phagocytosis of the RBCs 

Autoimmune Hemolytic Anemia

Signs and symptoms depend on rate of hemolysis but may include: Skin- Jaundice (free bilirubin in the subcutaneous fat secondary to rapid destruction of red blood cells releasing hemoglobin which is  converted to unconjugated bilirubin in the spleen) and pallor General- fatigue, irritability, behavior changes, malaise Cardiopulmonary- palpitations, dizziness, dsypnea, murmurs, adventitious breath sounds Genitourinary- hemoglobinuria (secondary to severe intravascular hemoloysis leading to filtering of hemoglobin by the kidney when the spleen or liver are overloaded) Neuro- headaches, dizziness, LOC

Autoimmune Hemolytic Anemia

Lab tests are as follows: Direct Coombs Test- RBCs are separated from serum and washed, then incubated with antihuman globulin. In the presence of immunoglobulins or complement attached to the RBC's, the blood will agglutinate, thus indicating a POSITIVE test. A positive direct coombs test indicates a possible diagnosis of AIHA Decreased hemoglobin- depending on bone marrow compensation, this can be mild or severe Increased reticulocyte count- reticulocytes are immature RBCs that still contain nuclear RNA and therefore stain differently. They are an indicator that the bone marrow is attempting to compensate for anemia. Normally at 1% or less, they can increase to >4% if compensating for severe anemia.  Blood smear- showing spherocytes (spherical RBCs), schistocytes (RBC fragments), or erythrocyte agglutination Unconjugated bilirubin, LDH, haptoglobin- elevated due to lysis of RBCs, which spills hemoglobin and LDH into the bloodstream. Hemoglobin is either converted to unconjugated bilirubin in the spleen or binds to haptoglobin, thus leading to increased bilirubin and LDH, with decreased haptoglobin

Autoimmune Hemolytic Anemia

First line therapy Corticosteroids- Prednisone 2-4 mg/kg/day for severe or worsening hemolysisSecond line: Rituximab- 375mg/kg weekly for 3-4 doses for refractory, non-responsive to corticosteroids or steroid dependencySevere AIHA that is unresponsive to medical therapies:Splenectomy

Further treatment for refractory disease: Immunosuppressive therapy High dose IVIG (5gm/kg)- usually transient (1-3wks) Plasmapheresis to reduce IgM in intravascular space, usually transient Cytotoxic agents such as antimetabolites, antimitotic agents and alkylating agents Hormonal therapy Supportive therapy Transfusions- for severe anemia only. Bone marrow will usually stimulate production of reticulocytes 3-5 days after drop in hemoglobin. Folic acid supplementation-

Autoimmune Hemolytic Anemia

Warm antibody AIHA: 98.6F/37C or greater Most common type (75%) IgG responsible for binding to RBCs RBCs destroyed in spleen leading to splenomegaly Can be caused when some drugs, like penicillin or cephalosporins bind directly to RBC membrane creating an RBC-drug complex that antibodies bind to 50% of cases are idiopathic and primary Secondary causes include infection, medication and chronic disease (particularly autoimmune) Most cases are transient, lasting less than 3mos Can be severe and life threatening Presentation of acute pallor, jaundice, splenomegaly, dark urine (spilling hemoglobin)

Cold antibody AIHA: well below normal body temperature Cold reacting IgM/IgG cross react with ABO antigens on RBC surface Occurs in colder peripheral circulation Intracellular/extracellular lysis Hemolysis occurs primarily in the liver Primary disease >50yo Secondary: children/teens, usually due to Mycoplasma pneumoniae or other infections such as measles, mumps, flu, EBV, adenovirus, varicella, CMV, H.influenzae and syphilis-  Secondary is usually transient (1-3 weeks), self limiting and mild Avoid cold exposure, PRBCs should always be warmed and washed prior  Rituximab with or without Fludarabine can be effective treatment but high risk of toxicitiy