Blood transfusion as a management strategy for Haemoglobinopathy. Corrina McMahon Our Lady s Children s Hospital, Dublin, Ireland
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1 Blood transfusion as a management strategy for Haemoglobinopathy Corrina McMahon Our Lady s Children s Hospital, Dublin, Ireland
2 Rationale for BT Sickle cell Disease Reduce the production of Hb Significant Thalassaemia Improve Hb Erythropoietin Ineffective erythropoiesis Hypermetabolism
3 Transfusion for SCD Acute Hb Life threatening event Chronic CNS events Abnormal TCDs Stroke? Silent Infarct Recurrent Chest crisis Frequent pain events
4 What are the alternatives? Hydroxycarbamide Hyperhaemolysis Recurrent pain Chest events?tcds (Twitch trial)?stroke (SWiTCH) Haematopoietic stem cells Cerebrovascular events Chest events Recurrent pain Problems Donors Side effects
5 Problems associated with Blood Transfusion Acute Pulmonary oedema Stroke Allergic reaction Haemolytic reaction Chronic Infection Antibody formation Iron overload
6 Transfusion associated Infection
7 BT associated Infection Bacterial contamination (22 cases/28m units) Yersinia Serratia Pseudomonas Viral Hepatitis B (1:1,205,000) Hepatitis C (1:1,935,000) HIV (1:2,135,000) West Nile Virus Prion vcjd
8 Spread BT Organ transplant Mothers/babies Symptoms Fever, rash, lymphadenopathy GI upset Myalgia, sore throat Diagnosis Serology Treatment Complications Encephalitis/death West Nile Virus
9 Iron Overload
10 Iron overload 1ml RCC = 1mg iron 1mg = normal adult male daily requirement Measurement of iron overload problematic Ferritin is not a good measurement T2*/R2 scanning Liver biopsy
11 Erythrocytapheresis Advantages Controlled Volume HCT HbS level Reduces Iron overload Disadvantages IV access Trained staff Increased red cell requirement (20%) No increase in antibody formation
12 Transfusion Reactions and RC Antibody Formation
13 Reactions and Antibody formation Allergic reactions Leucocytes/Plasma/Platelets Urticaria Fever Wheeze Anaphylaxis Haemolytic reactions Red cell antibodies Immediate (ABO) Delayed (Duffy Fy a, Kidd Jk a )
14 Red Cell Antigens
15 Blood group considerations
16 Transfusion Reaction
17 Examination of Urine
18 Delayed Transfusion reactions Pathophysiology 4-11% transfusions Days weeks post transfusion Antibody reaction activated macrophages Damaged RC membrane - apoptosis erythropoiesis Diagnosis Pain/fever haemolysis Haemoglobinuria Hb + reticulocytes ± DCT pos/new antibody HPLC - HbS level Management IvIg + steroids Rituximab
19 Why is this so common?
20 ABO phenotype and prevalence Phenotype Caucasians African-Americans A 40% 27% B 11% 20% AB 4% 4% O 45% 49%
21 Other Red Cell Antigen Systems Antigen System Tx Reaction Caucasians (%) D Rhesus Mild-severe C Rh Mild-severe E Rh Mild-mod c Rh Mild-severe e Rh Mild-mod K Kell Mild-severe 9 2 k Kell Mild-mod 99.8 >99 Kp a Kell Mild-mod 2 <1 Fy a Duffy Mild-severe Fy b Duffy Mild-severe Jk a Kidd None-severe Jk b Kidd None-severe U MNS Mild-severe 100 >99 African-Americ
22 How Significant is this mismatch? Alloimmunisation rates 19-37% age and number of transfusions If 1 antibody more likely to develop more + autoabs Anti-E, C, Kell 50% abs Extended antigen matching for C,E and Kell - ab formation by 40-90%
23 Other ethnic antigen issues D antigen partial expression Can make an anti-d C/e antigens Can be misdiagnosed as autoantibody Can make anti-c and anti-e antibodies K subtypes
24 Can anything be done to prevent antibody formation?
25 Minority group donations Donation rates in African Americans (AA) 25-50% that of caucasians Deferral rates Fear and distrust marketing strategies Whites right thing to do (62% vs 45%) AA to save a life (63% vs 47%) Shaz and Hillyer et al 2009;2010
26 Comments & Recommendations BT remains a cornerstone of treatment Patients should be phenotyped prior to first transfusion Patients should be genotyped and if partial D or C antigen give D and C neg RCC All should receive minimum of ABO, Rh, K matched RCC Increase ethnic minority donor representation
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