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Lymphoid malignancies Lymphoproliferative disorders Etiology: Overstimulation Defect of regulation (X-linked lymphoproliferative syndrome) Defects of apoptosis B cell development B cells malignancies T cell malignancies Lymphomas - clinical features lymphadenopathy Infections Storage diseases: Niemann-Pick disease, Gaucher disease Drug reactions Infectious mononucleosis Roseola infantum (caused by human herpes virus 6), cytomegalovirus (CMV), varicella, and adenovirus Human immunodeficiency virus (HIV) Salmonella typhi, syphilis, , and tuberculosis. Malignant etiologies Mephenytoin pyrimethamine, phenylbutazone, allopurinol, isoniazid. Autoimmune etiologies juvenile rheumatoid arthritis sarcoidosis Lymphomas - clinical features lymphadenopathy Lymphomas - clinical features splenomegaly Infection Bacterial Viral Rickettsial Fungal Protozoal Inflammatory Collagen-vascular disorders Hypersensitivity reactions Serum sickness Drug reactions Hematologic neoplasms Acute leukemia Lymphoproliferative disorders Lymphoma Chronic lymphocytic leukemia Hairy-cell leukemia Myeloproliferative diseases Myelodysplastic syndromes Nonhematologic neoplasm Primary Secondary Nonmalignant hematologic disorders Autoimmune hemolytic anemia Congenital hemolytic anemias Hemoglobinopathies Hereditary spherocytosis Megaloblastic anemias Iron-deficiency anemia Angioimmunoblastic lymphadenopathy Congestive splenomegaly Portal hypertension Splenic or portal vein compression or thrombosis Congestive heart failure Budd-Chiari syndrome Infiltrative disorders Gaucher's and other lipid storage diseases Histiocytic disorders Amyloidosis Lymphomas - clinical features skin lesions Lymphomas - clinical features B – symptomes night sweats weight loss fever Lymphomas - examination Personal history, current complains Palpation Biochemistry (LDH) CT PET Lymphomas - examination Lymphomas - staging Lymphomas -treatment Watch and wait Surgery Radiation Immunochemotherapy Bone marrow transplantation Lymphoma (DLBCL) - prognosis Lymphoma (FL) - prognosis Immunohematology Jan Novak Immunohematology Demonstration of red cell antigen-red cell antibody reactions is the key to immunohematology Combination of antibody and antigen can result in observable reactions, most commonly: Agglutination Hemolysis Precipitation Pretransfusion Testing ABO/Rh typing other blood group antigen typing detection of red cell alloimmunization (unexpected antibodies) compatibility testing (crossmatching) Immune mediated red cell destruction (DAT,eluate) Blood Group Antigens Carbohydrates, proteins or lipids Over 250 antigens in 23 Blood Group Systems ABO, Rh, Kell, Duffy, Kidd, MNSs Detected by: serologic techniques molecular techniques Multiple alleles within each system/dominant/codomina Red cell phenotypes are highly individualized Red Cell Antibodies Immunoglobulin Class: Antigen they are directed against: IgG vs. IgM carbohydrate vs. protein Optimum temperature of reaction Cold vs. Warm Complement fixation In vitro vs. in vivo effect Intravascular Hemolysis vs. Extravascular Hemolysis vs. Nonhemolytic Agglutinating IgG vs IgM IgG Binds at warm temperature (37ºC) Fc portion carries macrophage receptor Only 2 Fab sites High concentration required to activate complement Extravascular hemolysis IgM E.g. anti-A and anti-B Binds at room or cold temperatures 10 Fab sites per molecule Efficient at activating complement Intravascular hemolysis Blood Group Antibodies Naturally Occurring Antibodies E.g. ABO Blood Group System Combination of A and B antigens make up the ABO Blood Groups (A,B,AB,O) “naturally” occurring antibody will be made against antigens that the individual does not have Usually IgM Irregular Antibodies There are many other red cell antigens Exposure by pregnancy, transfusion or transplant can result in an alloantibody if the person does not possess that antigen Usually IgG E.g. anti-D formation in a D negative woman who gives birth to a D-positive infant….. How are red cell antibodies formed? No expression of the antigen on patient own cells Exposure to the antigen from: Pregnancy (fetal red cell antigens from a fetomaternal bleed or at delivery) Transplant Transfusion Anti-human Globulin (Coomb’s Reagent) Anti-IgG reagent prepared by immunizing rabbits Anti-IgG reagent prepared as a monoclonal antibody Anti-IgG will “bridge” IgG attached to red cells Common clinical uses: preparation of blood for transfucion in cross-matching screening for atypical antibodies in the blood plasma of pregnant women as part of antenatal care and detection of antibodies for the diagnosis of immunemediated haemolytic anemias Coomb’s tests Major Causes of Positive DAT Alloantibodies E.g. delayed hemolytic transfusion reaction Autoimmune Antibodies Hemolytic Disease of the Newborn Anti-D Anti-A or anti-B