Episode 037: Hemophilia 101, Pt 2

In this episode, we discuss the fundamentals and approaches to chronic management and treatment for patients with known inherited hemophilia.

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What is hemophilia?

• As name suggests, tendency to bleed

• Two types: genetic and acquired

Inherited hemophilia: 

• Genetic: sex-linked, meaning males will express it, females will, by and large be carriers 

  • Main ones to be worried about: Hemophilia A and Hemophilia B

    • Hemophilia A: deficiency in factor VIII (1:5000 men)

    • Hemophilia B: deficiency in factor IX (1:30,000 men)

  • Thousands of underlying mutations 

• We grade the severity of hemophilia using the factor activity levels: 

  • Severe: <1% activity

  • Moderate: 1-5% activity

  • Mild: 5-50% activity 

• Patients will often have objective severity and separate phenotype (someone with moderate severity may have phenotype of someone who is severe) - need to individualize 

• Treatment:

  • GOAL: Want to start patients on treatment after their first bleed – goal is to prevent bleeding + avoid joint damage

  • Prophylaxis (not in acute bleed; acute bleeds to be discussed in a future episode):

    • Factor Replacement: 

      • Typically started for patients with >1 bleed into the joints for patients with severe hemophilia (goal is to keep levels >1%)

      • In patients with moderate or mild can do intermittent dosing 

      • Hemophilia A/Factor VIII replacement (many options; here is what we use at Rouleaux):

        • Recombinant factor concentrates: Advate

        • Plasma-derived concentrates: Humate-P

      • Factor IX replacement: 

        • Recombinant factor concentrates: BenefIX

      • Bypassing agents:

        • For patients with inhibitors (to be discussed in a future episode) or can be used for Hemophilia A or B

        • Options:

          • Novoseven (activated recombinant factor VII): Activates the extrinsic pathway to bypass the need for factors VIII or IX

          • FEIBA (factor eight inhibitor bypassing agent): Activated prothrombin complex concentrate (FIIa, VIIa, Xa)

      • Emicizumab (Hemlibra): bispecific monoclonal antibody that binds factor activated IX and X → essentially doing the job of factor VIII and leads to activation of the downstream common pathway

        • Note that it binds activated factor IX not inactivated factor IX and this is why you won’t just constantly form clots by forcing down the common pathway like you would by giving a bypassing agent

        • ***cannot be used in Hemophilia B because it relies on the presence of factor IX***

      • Several new therapies have been introduced in recent years

• References:

  https://www.uptodate.com/contents/hemophilia-a-and-b-routine-management-including-prophylaxis?search=hemophilia%20treatment&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2: UpToDate article on current management of Hemophilia

  DOI: 10.1055/s-0042-1756188: “The More Recent History of Hemophilia Treatment.” Semin Thromb Hemost. 2022.

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The crew behind the magic: 

• Show outline: Ronak Mistry

• Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath

• Editing: Vivek Patel

• Shownotes, graphics, social media management: Ronak Mistry