Haemophilia A: Inhibitors

Feedback00:52 Intro02:10 DefinitionCommon: Alloantibody neutralizes FVIIIRare: causes increased clearance of FVIII1/3 of Severe Haemophilia A patientsMedian time 10-15 emergency dosesRF: Mutation types (INSIGHT study), <5 or >60, African/Hispanic, HIVneg, large rFVIII doses, FVIII + inflammatory stimulus07:05 Inhibitor classificationsTitres: Low (<5 BU) vs. High (>5 BU)Responder: Low vs HighTime: Dependent (FVIII inh.) vs Independent (FIX inh.)09:50 Presentation in practiceTreatment failure, change in bleeding pattern, anaphylaxisScreening: prior to invasive procedures, before/after treatment changesRoutine surveillance:Mild- moderate: Yearly + 2-3 wks after emergency treatmentSevere: Every 3rd emergency dose or 3 monthly13:55 Tests (needs repeat)Mixing studyFVIII assay (48 hours post dose)Bethesda assay (if 80-100% residual FVIII = no inhibitor)Specialist: ELISA, In-vivo recoveryMost sensitive: FVIII half-life studiesInhibitor Assays (Bovine chromogenic assay)19:45 Preventative measures?Mild to moderate: DDAVP when possibleSevere: prophylaxis 23:40 TreatmentsBypass agent: skips intrinsic pathway, straight to extrinsic F.I.B.A: activated PCC (II, VIII, IX, X)Onset 15-30 minsDose: 50-100IU/kgHalf life 8-12 hrsNB: Plasma derived: FVIII contamination, infectionContraindicated: EmicizimabNovoSeven: activated rFVIIaPeak 15 minsDose: 270ug/kg, fixed dose, can’t titrateNB: Half life 2 hours, can’t titrateObizor: Porcine rVIIIPeak 30 minsDose: 200IU/kg and titrateablePorcine Bethesda before use34:35 ProphylaxisEmicizumabImmune tolerance induction pts: Emicizumab, NovoSeven > FIBABreakthrough bleeding: increase frequency38:22 Immune Tolerance Induction: start ASAP if inhibitor presentUKHCDO: Long term FVIII tolerance induction and maintenance is key for severe Haemophilia A - don't rely on Emicizumab Success rate: 70%, consistent treatment, fewer emergency doses prior to starting, Historic peak titre <200 BU, <10 BU titres at the start, < 5yrs from inhibitor presentationSuper responder antibody, >500 BU titres46:20 International Immune Tolerance Study (Hay, DiMichele)- Blood 201247:50 Monitoring and Response Assessment Success: FVIII half-life  >7 hours BU negativeMeasurable trough levels at 48 hoursFailure: escalated to max rFVIII but still uptrending titres or fall of <20% in 6 months (alternative systemic agents)NB: rule out intercurrent infection50:33  VerITI-8 trial 51:28 Golden Nuggets 'Basics to Brilliance: Haematology Podcast' has been accredited for CPD credit by the Royal College of Pathologists UK. Medical professionals and clinical scientists holding career-grade positions, who are registered with any of the Royal Colleges for CPD, will be eligible to earn 1 credit for every hour of learning. Email: [email protected] Insta: BasicstoBrilliance X: @basics_2_brill Send us your feedback!

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