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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)

• 300kD
• Heavy (A1 A2, B) + Light Chain (A3, C1, C2) bound by a metal ions *Calcium*
• A subunits are 30% homologous
• B subunit (variable region) is cleaved by thrombin to get Factor VIIIa
• C1 and C2 help bind to VWF
• Good to r/o VWF

10:55 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 mutations
• Amount of Factor VIII negatively correlates with severity (less VIII= more severe)

21:55 Presentation of Haemophilia A

• Spontaneous Joint and Muscle bleeds + Op bleeding
• Younger presentation = more severe
• Spontaneous ICH in baby/child inc. in birth trauma
• Think 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 yo

35:50 Investigations

• Bleeding and Family Hx
• FBC, PT/APTT (expect normal PT, abnormal APTT correcting with mixing studies)
  • severe  eg. APTT 100
  • moderate eg. APTT 60-100
• Factor 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 2M
• Genetic 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.

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