AIHA and Hypersensitivity type III PDF

AIHA and Hypersensitivity type III Learning Objectives In these videos I aim to cover: The normal development of red cells and their life in circulation. Pathophysiology of immune mediated haemolytic reactions. How the pathophysiology of auto and allo immune haemolytic reactio...

AIHA and Hypersensitivity type III Learning Objectives In these videos I aim to cover: The normal development of red cells and their life in circulation. Pathophysiology of immune mediated haemolytic reactions. How the pathophysiology of auto and allo immune haemolytic reactions are detected in laboratory tests. By the end of these videos you should be able to: Explain how normal red cell development, plays into intra and extra vascular destruction. Explain different types of immune haemolysis. Contrast the different types of results from different immune mediated haemolytic reactions. Contents Normal function of red cells, iron absorption and re-absorption. Pathology, pathophysiology and signs and symptoms Laboratory interpretation of tests Normal function of red cells, iron absorption and re-absorption. Immune haemolytic anaemias Learning objectives Understand how red cells can be isolated in vivo for destruction extravascularly. Understand how haemoglobin and bilirubin are transported around the body to prevent toxicity with either. Erythropoiesis and erythrocyte life Cell repair stops at erythroblast stage. 3-4 months circulating Moving through peripheral circulation In plasma Pressure of the heart etc. Erythrocyte membrane: Cholesterol Red cell senescence Taken from: Loss of pliability https://www.learnhaem.com/courses/anaemia/lesso ns/normal-haematopoiesis/topic/normal-erythropoi esis/ Lysis: Intravascular or extravascular 19/11/2022  Function of the spleen and red cell Red cell functions Deliver oxygen Be flexible to travel down capillaries Splenic functions Check for signs of infection / immune reaction Check flexibility of red cells Eliminate inflexible, infected / marked cells Taken from: https://www.thoughtco.com/spleen-anatomy-37324 8 date 19/11/2022  Process of iron re-use, absorption and re-absorption Utilisation of iron Fe2+ or Fe3+ Iron toxicity Movement of iron within the Blood Conjugated form vs unconjugated Bile, conjugated bilirubin, myoglobin, urobilinogen Anaemia, drop in concentration of iron in haemoglobin in red cells 19/11/2022Taken from: https://www.researchgate.net/figure/Iron-cycle-in-humans- The-rate-of-iron-absorption-and-iron-loss-is-well-balanced- 1-2_fig1_324423584 19/11/2022 Summary How the structure and function of red cells can help in their destruction. The anatomical, physiological and biochemical properties of extravascular haemolysis. Pathology, pathophysiology and signs and symptoms Immune haemolytic anaemias Learning Objectives The different types of immune mediated haemolysis. How different antibodies mediate different reactions. How certain drugs can cause immune mediated haemolysis. Immune haemolytic anaemia Antibodies capable of binding red cell antigens, can be: Developed in response to other person’s cells (allo-antibodies) (type II) Due to pregnancy, transfusion (transfusion reaction, immediate or delayed) Developed to patient’s own red cell (auto-antibodies) (type II) Primary (idiopathic) Secondary (malignancy / viral infection) Developed due to exposure to certain drugs (type III) Creation of novel antigens Warm or cold AIHA AIHA IgG destruction: (extravascular haemolysis) 37C, binding at body temperature Exclusion through liver and spleen (Reticuloendothelial system) liberates bilirubin AIHA IgM: (Intravascular haemolysis) IgM active at cooler temperatures releases haemoglobin in the vascular system. Pathogenesis and physiology Transfusion with incompatible blood / B-cell / plasma cell derangement (myeloma/EBV infection, etc.) Familial link with auto immune disease Destruction of red cells, complement mediated (IgG:C3b, IgM:MAC) Intravascular Extravascular Haemolysed blood Jaundice Risk of DIC Hepato/splenomegly Haemoglobinaemia Ictuerus Haemoglobinuria Patient presentation Immune mediated haemolytic reactions produce some identical and some different symptoms Identical: Anaemia Pallor Shortness of breath Different: Jaundice Haemoglobinuria Drug adsorption mechanism hapten mechanism drug or metabolite is adsorbed onto red cell surface e.g. penicillin, cephalosporins drug specific IgG alloantibodies produced attach to the drug coating the surface results in extravascular haemolysis Lab findings DAT positive no antibodies detected Lab investigation sensitise reagent red cell with drug antibody (anti-drug) can now be found Immune complex mechanism anti-drug alloantibodies (IgM) produced that bind to drug in circulation. resulting immune complexes loosely attach to red cell surface complement activation follows and results in intravascular or extravascular haemolysis can be severe/fatal causes ‘innocent bystander’ destruction e.g. quinine, cephalosporins Immune complex mechanism a hapten immune mechanism probably involved lab findings DAT positive no antibodies detected lab investigation incubate drug, serum and reagent cells together result should now be positive Membrane modification mechanism drug modifies red cell membrane results in non-specific attachment of proteins including Immunoglobulin not generally associated with a haemolytic process e.g. Cephalothin lab findings find unexpected positive DAT lab investigation no antibodies found Summary Definition of different types of immune mediated haemolysis. How different antibodies modulate and mediate different forms of haemolysis. How specific drugs can react with rede cells and or form immune complex that then cause haemolysis. Laboratory interpretation of tests Immune haemolytic anaemias Learning objectives To understand the presentation of samples and how that can affect the interpretation of test results. How to interpret antigrams and understand how generalised reaction patterns can be indicative of certain diseases. The differences between IATs and DATs and how they are used to differentiate immune haemolysis.  B C D A Lipemic Icteric Normal Haemolysed How the tests work IAT (Indirect globulin test) Expose known phenotype cells to unknown patient plasma Detects free antibody in patient plasma (plasma being tested) AHG used to detect antibodies that become membrane bound. DAT (Direct anti-globulin test) Expose cells suspected of having antibody bound to known detection reagents Detects presence / absence of bound antibody on cell populations Identifies substance opsonising red cells Reaction scoring 4+: Positive 3+: Positive but lower titre or avidity than 4 2+: Moderate positive 1+: Weak positive 0: Negative MF: Some cells (1 or more populations are positive), other cells (1 or more populations are negative)  + + + 0 0 0 0 0 0 0 Auto MF MF 0 0 MF MF +  IAT 3 3 3 3 3 3 3 4 3 4 Auto 4 4+ 0 0 2+ 3+ 4+  IAT 0 0 0 0 0 0 0 0 0 0 Auto 0 0 0 0 2+ 3+ 4+  Tests performed at 37 IAT 3 3 3 3 3 3 3 4 3 4 Auto 4 0 0 0 2+ 3+ 4+  IAT 0 0 0 0 0 0 0 0 0 0 Auto 4 4+ 0 0 2+ 3+ 4+ Summary How sample presentation can affect tests and their results. Antigram results can be: specific against an antigen. indicative of a condition yet be non-specific in pattern. highlight production of allo-antibodies. Comprehend the difference between IAT and DAT and how the results are indicative of disease.