Hypersensitivity Type II PDF

Hypersensitivity Type II E.g. Haemolytic Disease of the Foetus and New-born (HDFN) and Haemolytic Transfusion Reactions (HTRs) Learning Aims and Outcomes In these videos I aim to cover: How the immune response to blood group...

Hypersensitivity Type II E.g. Haemolytic Disease of the Foetus and New-born (HDFN) and Haemolytic Transfusion Reactions (HTRs) Learning Aims and Outcomes In these videos I aim to cover: How the immune response to blood group antigens form in HDFN and HTRs How this links into pregnancy and pathogenesis of HDFN. How HDFN can be prevented or disease monitored and treated. By the end of these videos you should be able to explain: The immune response to blood group antigens in HDFN and HTRs How pregnancy increases the risk of this How these antibodies can be prevented from forming, tested for and the mother monitored for disease progression. Contents Type II hypersensitivity: alloantibodies (atypical antibodies) and HDFN Normal Immunity during pregnancy Patient symptoms of atypical antibodies / Maternal and foetal symptoms of HDFN Diagnosis of HDFN, detection and monitoring Laboratory Tests for HDFN Prevention or Cure TYPE II HYPERSENSITIVITY: ALLOANTIBODIES (ATYPICAL ANTIBODIES) AND HDFN Learning objectives 1) Learn about the sensitisation leading to type II hypersensitivity reactions. 2) Understand how sensitisation to blood group antigens leads to haemolytic anaemia. 3) Be aware of and understand the nature and process of extravascular haemolysis. Alloantibodies (Atypical antibodies vs Natural antibodies) Natural antibodies: IgM anti-A or anti-B No immune challenge directly from foreign blood required Atypical alloantibodies Requires exposure to someone else's red cells Made to antigens patient does not express Clinically significant usually IgG in nature Routes of Exposure Blood transfusion Mandatory and standard discretionary grouping, Mandatory ABO, RhD, discretionary, Rh phenotype, K antigen Blood matched on mandatory and available discretionary grouping. Foetal maternal haemorrhage Mixing of maternal and foetal blood streams Labour / birth 3rd trimester miscarriage What is Type II Hypersensitivity? Type II, hypersensitivity is an inappropriate IgG response to an immunological challenge. Type II hypersensitivity follows a similar paradigm to type I but with IgG not IgE. Sensitisation: Large immunological challenge stimulates response 2nd immune response: repeated smaller stimulations produces larger IgG response Each subsequent immune challenge increases antibodies concentration Differences between sensitisation and subsequent immunisation Primary immunological challenge Large volume 4mL anti-D Ig - Standard Dose standard dose standard dose for postnatal treatment in UK is 500i.u. this protects against FMHs of 4mL foetal cells only 0.7% of FMHs at delivery are greater than this volume these require administration of further anti-D Ig the size of the FMH is estimated in the laboratory and the amount of extra anti-D Ig required is calculated Current Guidelines for Administration of Rh Prophylaxis Postnatally administered to RhD Neg females at delivery if neonate is RhD Pos or unknown administer at least 500i.u. within 72 hours of delivery estimate of size of FMH administer further 125i.u. of anti-D Ig for each 1mL of FMH greater than 4mL Rh Prophylaxis - a Success Story ‘major triumph of modern medicine’ introduced post-natally in 1969 in UK standard dose must be administered within 72 hours of delivery incidence of perinatal death reduced 100- fold immunisation rate reduced from 21% to 1.5% Rh Prophylaxis - a Success Story? “myth that Rhesus disease has been eradicated” (Consensus Conference, Edinburgh 1997) immunisations were still occurring due to non-adherence to guidelines (40%) antenatal immunisation (40%) despite anti-D administration (10%) no records (10%) NICE (2002) recommends routine antenatal anti-D prophylaxis (RAADP) for all non-sensitised pregnant women who are RhD neg protects against maternal immunisation following a silent FMH in the antenatal period from week 28 Summary The theory and history of RAADP and its route into clinical practice. The potential modes of action of RAADP. The impact of RAADP on cases of HDFN.