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Immunohematology in Patients with Hemoglobinopathies Dr. Wendy Lau Director, Transfusion Medicine, The Hospital for Sick Children, Associate Medical Director, Canadian Blood Services Central Ontario Region, Toronto, Ontario, Canada Objectives • Three case studies • Present antibody investigation results in hemoglobinopathy patients • Discuss the challenges of finding compatible blood in hemoglobinopathy patients with antibodies • Review lessons learned in unusual cases Case # 1 • Male born in 1997 in Pakistan • Diagnosed thalassemia major aged 6 mo • Red cell transfusion- monthly with no iron chelation therapy • Emigrated to Canada in 2001 • • • • • Splenomegaly Anti- HCV Ab +ve Normal LFTs Rx. RBC transfusion to maintain Hb 90 g/L Deferoxamine SC 45 mg/kg/day X 7/7 Hep B vaccination Case # 1 • After 6 mo of deferoxamine • Liver iron content (biopsy) 21.1 11.4 mg Fe/g dry wt • HLA-typing: sibling match identified • Age 6 years • Plans for BMT • RBC transfusions 2-3 wkly ? Alloantibody • GI consult: HCV RNA +ve genotype 3A Normal LFT • Age 7 years • ALT 227 AST 110 • Liver biopsy: mild focal siderosis + portal fibrosis • Liver enzymes settled Case # 1 (Immunohematology) • Age 4 years – Another academic centre: anti-K, anti-Jka • Age 5 years – Came to Sick Kids – Transfused monthly, K neg Jka neg units compatible • Age 7 years – DAT +ve, eluate non-specific, K neg Jka neg units incompatible – Panel: pan-reactive, auto positive, unable to rule out additional antibodies – Sent to CBS for further testing Autoantibody investigations • Autoantibody may or may not case immune hemolysis • Children who have not been previously transfused and who have not been pregnant, extensive investigation not necessary • Acute WAIHA- transfuse small amount and slowly • Multiply transfuse patients- investigate for alloantibody Autoantibodies • Warm-Reactive Autoantibodies – – – – Simple Rh antibodies Antibodies to common RhD and Rh CE determinants Antibodies to non-Rh high-prevalence antigens Antibodies to non-Rh polymorphic gene products (e.g. N, K, Jka) • Cold-Reactive Antoantibodies – – – – Most are clinically benign Anti-I: Mycoplasma pneumonia Anti-i: infectious mononucleosis Anti-P (biphasic Donath-Landsteiner antibody): Paroxysmal Cold Hemoglobinuria (PCH) Adsorption studies • Autoadsorption – Cold autoadsorption – Warm autoadsorpion • Alloadsorption – R1R1, R2R2, rr cells – Jk(a+b-), Jk(a-b+) – Limitation: antibodies to high prevalence antigens also adsorbed Case # 1 (Immunohematology) – Multiply transfused: no phenotype, not autoadsorption, need alloadsorption Case # 1 (Immunohematology) • Phenotype unknown: What antibodies can he make? – Molecular typing Rh E/e DNA Genotyping: Result Rh E/e Rh c DNA Genotyping: Result Rh c The patient was tested for the RhE. Rhe, and Rhc alleles. The results indicate that the patient’s genotype is RhE positive, Rhe positive and Rhc positive. • Family studies – – – – Mom: C+E-c-e+ Dad: C+E+c+e+ Patient: C+ Transfusion continued with K neg, Jka neg units Case # 1 • Age 10 years • • • • Rx HCV infection: PEG-IFN & Ribavirin x 24 wks Complications: hemolytic anemia, neutropenia Blood bank: Autoantibody + alloantibody RBC transfusions: every 10-14 days • 3 months into anti-HCV therapy • Severe IFN/Ribavirin –induced hemolysis Hb 49 g/L • IFN/Ribavirin discontinued • PEG-IFN monotherapy restarted Case # 1 (Immunohematology) • Panel pan-reactive Case # 1 • 4 months anti-HCV therapy • • • • • HCV PCR- Neg IFN stopped RBC transfusion requirements 2.5- 3 weekly Liver iron content (MRI) 15 mg Fe/g (ferritin 2220) Deferoxamine switched to deferasirox (oral chelator) • Age 11 years • RBC transfusions 3 weekly • Liver iron content (MRI) 5.3 mg Fe/g Ferritin 1300 • Liver biopsy: mild fibrosis (0 - 1+) Case # 1 • Age 11 years – Sibling-donor BMT Bu/Cy/ATG conditioning – Complications: ALT 750, hemorrhagic cystitis – HCV PCR- neg – Engraftment 4 weeks – Blood bank: • DAT pos (anti-C3D and anti-IgG) • Ab screen- Jk(a) • DAT negative at discharge post- BMT Case # 1 (update) • • • • • Almost one year post-BMT No transfusions for 10 months Hb 105 Ferritin 1419 Plan: Therapeutic phlebotomy Case # 2 • Male born in 2003 in Nigeria • Diagnosed SCD aged 7 mo • Recurrent painful VOC • No RBC transfusion • Age 2 years • Emigrated to Canada • Transcranial Doppler (TCD) velocities: – MCA – dICA 244/201 110/210 • Brain MRI: T2 hyperintense area in Lt parietal, no restricted diffusion • Parents resisted prescribed chronic RBC transfusion therapy Case # 2 • Age 4 years • • • • TCD MCA 201/187 Sleep study: obstructive sleep apnea Underwent tonsillectomy & adenoidectomy Pre-operative RBC transfusion (first) – Blood Gp A POS Ab screen- NEG • Age 5 years • TCD MCA: 217/173 • RX options presented to parents dICA: 118/247 – Chronic RBC transfusions to keep Hb S < 30% (preferred) – Hydroxyurea therapy Case # 2 • Transfusion history – April 08 • transfusion # 2 Ab screen: Anti-S DAT neg – May 08 • DAT- pos anti- C3D pos anti-IgG neg • DAT- neg in June 08 – Aug 08 • Ab screen : anti-S, anti-Jk(b), unidentified Ab (?autoAb) – Dec 08 • Anti-S, anti-Jk(b) Case # 2 (Nov 2008) Case # 2 (Nov 2008) Case # 2 (Feb 2009) Case # 2 (Feb 2009) HTLA • High-titre, low avidity (low antigen) antibodies • Serologically difficult antibodies with Limited Clinical Significance (nuisance antibodies) • Knops antibodies, anti-Csa (Cost-Stirling), anti-Yka (York), anti-Chido/Rodgers, anti-Yta (Cartwright), anti-JMH (John Milton Hagen) • Ch and Rg antigens: polymorphisms in C4 (complement), in vitro neutralization, anaphylactic reactions from plasma products and platelets • anti-Yta: may be clinically significant Case # 2 (Feb 2009) Case # 2 (Mar 2009) Case # 2 (June 2009) Case # 2 (Aug 2009) Case # 2 (Sept 2009) Case # 2 (Nov 2009)