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Feedback '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!

Feedback '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!

Feedback Clinical Presentation Classifications of VWD '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!

Feedback Haider steps out of the shadows.... Make sure you send us the questions you're too afraid to ask your haem reg (or consultant) - email address below! '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!

Feedback We are delighted to have Dr. Noémi Roy Consultant Haematologist at Oxford University Hospitals NHS Foundation Trust join us for this very special episode! '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!

Feedback Welcome to the Red Cell Series! Timestamps and notes to follow... '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!

Feedback Timestamps to follow! '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!

Feedback This is a discussion about possible factors and strategies to consider and should not be used as a guideline for clinical practice. Always discuss complicated cases with the attending H&T consultant. 00:52 Intro 01:30 Case 1: 41M Severe Haemophilia A, acute MI needing PCI Try the 4 steps! Bleeding RiskAnticoagulant characteristicsIntensity of anticoagulant (prophylactic vs therapeutic)Duration of anticoagulant therapy11:20 Cardiac Disease in Haemophilia: thoughts and considerations  20:40 Case 1: a potential algorithm in action 24:15 Case 2: 60M Moderate Haemophilia A, positive cardiac Hx, AF on ECG 33:30 Case 3: Moderate Haemophilia A, lobectomy, DVT on USS doppler of leg 40:00 Golden nuggets with a side of ffries '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!

Feedback 00:52 Intro and chuckles 01:40 Case study: 75M, left calf swelling, put on DOAC, 24 hrs later haematoma and deep bleed on CT 06:00 General information Elderly (>65), Mortality 8-40%Common presentations: GI and UG bleeding, Retroperitoneal and muscle bleeds (compartment syndrome)Ptegnancy, TTP, Malignancy (15%), Autoimmune disease (17%)08:56 Pathogenesis and diagnosis: AutoAb against F8 *Bethesda units do not correlate with bleeding phenotype in Acquired HA- second orfer kinetics*HistoryAPTT, PT (isolated raised APTT)Mixing studies: 50/50 or 80/20 mixFactor Assays (**Intrinsic**)Decreased Factor VIII + Non-paralellism -> Bethesday Assay20:20 Non-clotting investigations 22:05 Treatment MDT + Comprehensive Care Center escalationRICE., TXA, Bypassing agentsLimit iatrogenic bleedingReview medicationsPregnancy: birth plan!!!  inhibitor can cross palcentaSteroid +/- Cyclophosphamide27:10 Bypassing Agents in Acquired Haemophilia A FENOC + EACH2 study: FEIBA vs NovoSeven = No difference in bleeding/thrombosis rates- more info at 33:25 for EACH2Obizor can be titrated according to response whereas FEIBA and NovoSeven cannotEmicizimab +/- Immunosuppression  = Not currently licesnsed in the UK 32:25 Inhibitor eradication Mean time to remission: 5 weeksGood prognostic markers: FVIII 1 or more, Inhibitor titre Steroids + Cyclophosphamide -> Steroids + Cyclo + RituximabBiggest cause of death: infection36:45 Follow up  Weekly FVIII levels and inhibitor monitoring till remission then monthly for 6 months then 2-3 monthly for a yearPlanned procedure; FVIII level38:45 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!

Feedback 00:52 Intro - very important topic 02:00 Case Study: Haem/Obstetrics clinic, Family Hx Severe Haemophilia A, 12wks pregnant 04:15 Clotting changes in pregnancy Increased: FVII, FVIII, FX, VWF, FibrinogenDecreased: FXIII   Protein S, Antithrombin Stable: FIX07:57 New born to 6 months clotting: FVIII (8) similar to adultFIX (9) lower and rises after 6 months09:30 GUEST STARRING Dr. William Jones MRCP FRCA St6 Anaesthetics SpR with a special interest in Obstetrics 10:25 Will speaks about Delivery, Instrumentations,  Anaesthetics/Analgesia aspects of Obstetrics. 13:28 David asks about big needles, bleeding risks and Will explains Spinal vs Epidural 15:40 Three Stages of Labour (briefly, very briefly) *** ‘Haematologists advise active management of the third stage’ means: Management of process of delivering the placenta ie. Uterotonic - Syntometrine IM- helps reduce bleeding and get placenta outPlacental traction?Cord clampingThanks Will. 17:40 All the nuggets you'll need **avoiding a traumatic ICH to a baby boy** 1/ Pre-conception: baseline factor levels, family Hx (genetic mutations), discussion of treatments and risks   2/ Antenatal:  Male identification (IVF, fetal free DNA testing in maternal blood from 9 wks)Offer CVS (11-14 wks, miscarriage risk) or Amniocentesis (15-20 wks, pre-term delivery risk)Faetal anomaly scan @ 20wksCheck FVIII/FIX at booking, pre-procedure, 28wks and 34 wksMDT (haematologist, anaesthetist, obstetrician, nenonatolgist, lab) haemophilia centre, 24hr access to haenostasis labClear delivery plan by 37 weeks3/ Labour/deliver Avoid instrumentationRisk of bleeding: Forceps > Ventouse > Vaginal > C Section (high mortality for mother)FVIII >50 IU/dL : TXAFVIII 80 IU/dLAvoid faetal blood sampling, fetal scalp electrodes, ventouse, forceps, external cephalic version4/ Post partum Uncomplicated: maintain FVIII >50 for three daysComplicated/C-Section: maintain FVIII >50 for five daysContinue TXA till minimal Lochia If FVIII >50 needs VTEpNewborn: PT/APTT, FVIII and FIX (cord blood),Newborn: Routine screen for bleed with USS, Give factor if ANY suspicion of ICH- don't wait for a scan. CT/MRI head.Newborn: if ICH, maintain FVIII approx 80-100 for first 3 days, then above 50 for 2 weeks and will need prophylaxis going forwards. ?Vitamin K. SC vaccinations not IM. Give parent info. 40:15 David attempts the case study 44:20 How to write the delivery plan: A Practical Guide to the Management of the Fetus and Newborn With Hemophilia - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Suggested-Contents-of-the-Written-Delivery-Plana_tbl2_328606634 [accessed 10 Jan 2026] 47:20 Summary  '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!

Feedback 00:52 Intro 02:10 Definition Common: Alloantibody neutralizes FVIIIRare: causes increased clearance of FVIII1/3 of Severe Haemophilia A patientsMedian time 10-15 emergency dosesRF: Mutation types (INSIGHT study), 60, African/Hispanic, HIVneg, large rFVIII doses, FVIII + inflammatory stimulus07:05 Inhibitor classifications Titres: Low (5 BU)Responder: Low vs HighTime: Dependent (FVIII inh.) vs Independent (FIX inh.)09:50 Presentation in practice Treatment 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 Treatments Bypass 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 Prophylaxis EmicizumabImmune tolerance induction pts: Emicizumab, NovoSeven > FIBABreakthrough bleeding: increase frequency38:22 Immune Tolerance Induction: start ASAP if inhibitor present UKHCDO: 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 500 BU titres46:20 International Immune Tolerance Study (Hay, DiMichele)- Blood 2012 47:50 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!

Feedback 00:52 Intro 02:35 Structure of Haemophilia A care 05:10 Key aspects of management (On-demand vs prophylaxis) 07:00 Prophylaxis: reduce death rates from ICH and reducing joint bleeds - Primary prophylaxis: before the 2nd joint bleed Severe haemophiliaAny child spontaneous ICHModerate haemophilia A (1-3 IU/dL)- Secondary prophylaxis: After the 2nd joint bleedLimit joint damage and maximize long term functionESPRIT trial- Tertiary prophylaxis: If joint disease already establishedSlow progression, reduce pain and improve QOLSPINART study13:10 Phases of treatment in Primary Prophylaxis - Modify dose during according to needs at that stage of life - By adulthood, 30% of severe patients can safely stop primary prophylaxis! 15:50 Prophylactic medications - IV Recombinant FVIII, 1 IU/kg increases by 2 IU/dL (2%) - Half life: 8-12 hrs  - Primary Prophylaxis: (needs CVC) Aim trough level 1-3 IU/dL25-40 IU/kg approx 3-4x per weekTitrate clinically which is individual to the patient- Extended half life...ratio of regular:half-life should be at least 1:1.3 - Cannot START them on this as can cause inhibitor 25:40 Efanesoctocog (EFA) only needs once weekly IV dosing - Very extended half life - XTEND 1 and XTEND-KIDS trials 27:52 Emicisimab: Bi-specific Ab, SC, half life 30 days - Binds FIXa to FX thereby replacing FVIII - Phenotypically makes patients have mild haemophilia A - Used for ANY haemophilia with inhibitor OR severe haemophilia without an inhibitor - HAVEN 3 study - Breakthrough bleeds ?management challenges at home - FIBA can cause MAHA (don't use together)  - Thrombosis risk - Reduces APTT and interferes with measuring FVIII and inhibitor 45:50 On-demand therapy (inhibitor dependent) 47:50 Joint bleeds - Moderate bleed: Aim peak of 50- 60 IU/dL - Severe bleed: Aim peak of 60-80 IU/dL - Daily dosing - Assess within 15 mins , treat within 30 mins - TXA + analgesia, PT + PRICE  52:20 Other bleeds - Peak 80-100 IU/dL: Iliopsoas, ICH, GI bleeds, Neck/throat - Deep cut: aim peak 50 IU/dL - Keep at peak for 1-3 days then 50% decrease in peak level for the next week 54:10 Case-study: 24M, swollen knee, FVIII 0.3 IU/L - Patients usually have an emergency plan - Assume severe if no info. 01:00:15 Case study: 38M, Appendicectomy, FVIII 30 IU/dL - Hari tricks David, David is tricked - Give DDAVP because rFVIII can cause an inhibitor 01:03:05 DDAVP (Vasopressin)- IV/SC- 3-5 fold increase of FVIII - 0.3micrograms/kg - Releases a pool of FVIII from endothelium *lung*- tachyphylaxis - Check protocol, side effects and contraindications 1:08:36 Management planning in elective surgery (MDT) - TXA! - Calculate dose of Recomb. FVIII - Check levels at 15mins(pre-op), 4hrs (post-op), next morning - May need VTEp 01:12:05 Comprehensive Care Centre Annual Review checklist- exam pearl NB: Target joint- 3 or more bleeds into one joint in a 6 month period 1:16:24 Rapid fire cases for David 1:22:06 Summary '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!

Feedback 00:52 Intro 02:00 What is Haemophilia A? 03:00 Factor VIII, Pathogenesis of Haemophilia A 07:10 Structure of Factor VIII (exam pearl) 300kDHeavy (A1 A2, B) + Light Chain (A3, C1, C2) bound by a metal ions *Calcium*A subunits are 30% homologousB subunit (variable region) is cleaved by thrombin to get Factor VIIIaC1 and C2 help bind to VWFGood to r/o VWF10:55 Epidemiology and history taking- X-linked recessive Factor VIII is (mostly) feminist.....Turners syndrome, Androgen Insensitivity syndrome, Consanguinity etc. can present with HA  Hari talks about cats 50% of severe haemophilia A have an Intron 22 mutation (non-coding)1/3 de-novo mutationsAmount of Factor VIII negatively correlates with severity (less VIII= more severe)21:55 Presentation of Haemophilia A Spontaneous Joint and Muscle bleeds + Op bleedingYounger presentation = more severeSpontaneous ICH in baby/child inc. in birth traumaThink about On/Off recurrent oromucosal bleeding (can become anaemic)30:00 Non-accidental injury in pre-mobile child- check BSH guidance** 33:35 Diagnosis Factor VIII 40 IU/dL in general (units useful to think as percentages- 40%)Mild 6-40%Moderate 1-5%Severe 1%, presents 2 yo and diagnosed 4 yo35:50 Investigations Bleeding and Family HxFBC, PT/APTT (expect normal PT, abnormal APTT correcting with mixing studies)severe  eg. APTT 100moderate eg. APTT 60-100Factor VIII, IX, XI , XII assay (intirnsic)1 stage and 2 stage chromogenic assay VWF assay (antigen and activity)VW Factor VIII binding assay to r/o VWF 2MGenetic testing (HCDO)- mutational analysis. Can inform likelihood of inhibitor formation and **female carrier identification**Factor V and VIII can be co-inherited in an autosomal inherited pattern*** Biggest cause of death is intracranial death *** *** Biggest cause of disability is target joint deformation *** 47:52 Summary  '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!

Feedback 01:45 Case: Neonate with repeated umblical bleeding. IC haemorrhage.  Normal Factors (so far), Normal VW screen, Normal FBC and normal film. 05:35 Factor XIII (13): function and presentations in deficiency  09:45 Testing, testing!  ELISA/Ammonia Release Assay then a Mutational Analysis Honarable mention: Clot Solubility Assay16:00 Fibrinolysis definition and pathway 21:00 Activators of Fibrinolysis: tPA vs. uPA  23:23 Inhibitors of Fibrinolysis: PAI-1, PAI-2, TAFI, α2-antiplasmin, and Factor XIII (13) 26:28 Thrombolysis: defintion, examples and uses 32:20 Case: Thromboembolic stroke, thrombolysis 24 hours prior, haemorrhagic transformation 36:19: Tranexamic Acid (Hari’s favourite drug) Honarable mention: Dr Utako Okamoto and the WOMAN trialCRASH 2 and CRASH 3 trialsHALT-IT trial41:22 D-Dimer  44:00 Summary '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!

Feedback 00:52 Intro: definition and prompts 04:25 Intro to Case 1: Haemophilia B, 3rd dose of BeneFix Anaphylaxis  06:03 Intro to Case 2: Severe Haemophilia A, joint bleed, non-responsive to emergency Factor VIII 07:30 Initial screening tests  NB: Inhibitors: Time Dependent vs. Immediate Acting14:54 Flash examples of Mixing Study importance 16:35 Bethesda Assay  **Bethesda Studios made the Elder Scrolls and Fallout games: they Inhibit Haider from doing any work** 28:45 Bethesda Assay Summary 30:00 Nijmegen Modification of Bethesda Assay 34:30 Heat Treatment of Bethesda Assay  36:25 ELISA Assay  40:30 Auto vs Allo Antibodies 42:00 Kinetics of a Time Dependent Inhibtor  44:45 Case 1 results 45:50 Case 2 results 51:00 Case 3 (real-life scenario): young girl, subdural bleed after fall, deranged clotting found incidentally  59:30 Summary  '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!