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.Red cell membrane defects
AUTO- IMMUNE HEMOLYTIC ANAEMIAWarm autoimmune hemolysis
1-Primary idiopathic 50%2-Secondary•Autoimmune, e.g. SLE, RA•Drugs, e.g. L-dopa, methyldopa, mefenamic acid, penicillin, quinidine, fludarabine•Lymphoid malignancy, e.g. CLL, myeloma,lymphoma•Other malignancy, e.g. lung, colon, kidney,ovary, thymoma•Others, e.g. ulcerative colitis, HIVCLINICAL 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 haptoglobin, increase indirect bilirubin Positive direct coomb’s test; Patient’s CELLS are tested for surface Ab’sAround 10% of all warm autoimmunehemolytic anaemias are Coombs test-negative.Treatment
1.Removal of the underlying cause2.Corticosteroid :1mg/kg prednisone (3-4 weeks /arise in haemoglobin will be matched by a fall in bilirubin, LDH and reticulocyte levels)then slow tapering over about 10 weeks.70-80%= response. 3.Splenectomy : In case of steroid failure, or decrease Hb following cessation / reduction of steroid. 50–60%= response 4. Immunosuppressive therapy with azathioprine, ciclosporin,mycophenolate or cyclophosphamide.5.The anti-CD20 (B cell) monoclonal antibody, Rituximab(Mabthera). 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 polyclonalCAUSES
1.Idiopathic 2.Secondary: *Infection(mycoplasma pneumonia, syphillis infectious mononucleosis) *Lymphoproliferative disorders,e.g. Lymphoma Chronic cold agglutinin disease; This typically affects elderly patients and may be associated with an underlying low-grade B-cell lymphoma . It causes a low-grade intravascular haemolysis with cold, painful and often blue fingers, toes, ears or nose (so-called acrocyanosis).1.positive direct coomb's test2.IgM Ab’s present in high titer.Treatment : Directed at the cause 1.infection : transient, self limited 2.supportive treatment (transfusion , avoid cold temp). 3.Lymphoma : specific therapy. 4.Idiopathic :common(No response to steroid, splenectomy) I-alkalating agent, II-Rituximab(mabthera) III-plasmapheresis. Diagnosis
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 is termed the Donath–Landsteiner antibody binds to red cells in the peripheral circulation but lysis occurs in the central circulation when complement fixation takes placeParoxysmal Nocturnal Hemoglobinuria (PNH)
GlycosylphosPhatidylInositol anchor proteinACQUIRED, NOT INHERITED ;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.PNH
GPI anchors several key molecules to cells and its absence results in clinical outcomes that reflect this, causing intravascular haemolysis and anaemia because of increased sensitivity of red cells to lysis by complement. This happens because key defence mechanisms that protect cells from complement-mediated lysis (CD55 and CD59) are GPI-anchored to red cells under normal circumstances.