IMMUNE HEMOLYSIS Definition : red cell life span is shortened because abnormalities in the components of the immune system are specifically directed against the patients own erythrocytes. 1.Auto-immune hemolytic anaemia. 2.Transfusion related hemolysis. 3.Drug-related immune hemolysis.

AUTO- IMMUNE HEMOLYTIC ANAEMIA The auto antibodies can be activated by either heat or cold. Warm reactive auto immune hemolysis (37oC) Causes : 1- idiopathic 2- secondary : I. Drugs (Methyldopa) II. Connective tissue disease (SLE) III. Lymphoproliferative (CLL, HD, NHL)

CLINICAL MANIFESTATION Onset rapid lead to anaemia, tiredness, fatigue. Elderly pts. with atherosclerosis lead to chest pain. Splenomegaly and Jaundice, may be absent in acute phase. Abdominal pain and fever may also occur.

Diagnosis spherocytosis, reticulocytosis, increase LDH, decrease serum haptoglolbin, increase indirect bilirubin positive direct coomb’s test; Patient’s CELLS are tested for surface Ab’s Around 10% of all warm autoimmune haemolytic anaemias are Coombs test-negative.

Treatment 1.Removal of the underlying cause 2.Corticosteroid : 1mg/kg prednisone (3-4 weeks / check-Hb. & retics.)70-80% response,then slow tapering over about 10 weeks. 3.Splenectomy : In case of steroid failure, or decrease Hb following cessation / reduction of steroid. 4. Immunosuppressive therapy with azathioprine or cyclophosphamide. 5.The anti-CD20 (B cell) monoclonal antibody, rituximab. 6. Blood transfusion?.

*Cold-reactive auto immune hemolysis Auto Antibodies usually are IgM. Occasionally IgG. Low temp make the antigen(Ag) more prominent on the membrane lead to antibodies reaction. Warm temp hiding the Ag below the membrane below the lipid component lead to prevention of Ag-Antibodies(Ag-Ab.) reaction . This can be chronic when the antibody is monoclonal, or acute or transient when the antibody is polyclonal

CAUSES Chronic cold agglutinin disease; It causes 1.Idiopathic 2.Secondary: *Infection(mycoplasma pneumonia, infectious mononucleosis) *Lymphoma Chronic cold agglutinin disease; It causes a low-grade intravascular haemolysis with cold, painful and often blue fingers, toes, ears or nose (so-called acrocyanosis).

Other causes of cold agglutination Paroxysmal cold haemoglobinuria is a very rare cause seen in children, in association with viral or bacterial infection. An IgG antibody binds to red cells in the peripheral circulation but lysis occurs in the centralcirculation when complement fixation takes place

Paroxysmal Nocturnal Hemoglobinuria (PNH) GlycosylphosPhatidylInositol ACQUIRED, NOT INHERITED like all the previous hemolytic anemias were ACQUIRED mutations in phosphatidylinositol glycan A (PIGA) It is “P” and “N” only 25% of the time. Triad of intravascular hemolysis,pancytopenia and thrombosis. PNH is also associated with hypoplastic bone marrow failure, aplastic anaemia and myelodysplastic syndrome.

Management Diagnosis: Treatment: Flow-cytometry shows reduced cluster of differentiation (CD) CD55 & CD59. Treatment: * supportive with transfusion and treatment of thrombosis. * Anti-complement C5 monoclonal antibody eculizumab was shown to be effective in reducing haemolysis.