Hemophilia A

Not an actual patient.

The characteristic phenotype of Hemophilia A is a tendency to bleed.1,2

Hemophilia A results from missing or defective clotting protein factor VIII (FVIII), and the frequency and severity of bleeding manifestations generally correlates with the degree of FVIII deficiency.1,2

Hemophilia A

Epidemiology

Hemophilia A is typically an X-linked recessive genetic disorder that most often affects males, with an incidence of approximately 1 in 5,000 male births.1,2 Between 2012 and 2018, there were an estimated 20,000 to 33,000 males with Hemophilia A living in the U.S.

Children can inherit Hemophilia A from a father with Hemophilia A, or from a mother who is a carrier.1,2,3 Around one-third of people with Hemophilia A have no prior family history (spontaneous). Females with hemophilia are rare, but may result in females with both X chromosomes affected or when one X chromosome is inactive — females account for 3% of people with Hemophilia A.

Acquired Hemophilia A (AHA), a rare autoimmune form of Hemophilia A in which an individual develops autoantibodies to FVIII, has an estimated incidence of 1.5 to 2 cases per million per year.4,5,6,7 It is more common in the elderly, with a median age of 73.9 at diagnosis, and can affect men and women equally.

Diagnosis

In some cases, infant boys with genetic risk factors are tested shortly after birth.2 In other cases, testing is done after clinical suspicion of hemophilia due to symptoms.

Due to a variety of chromosomal abnormalities, the symptoms of hemophilia can vary greatly from one patient to another and they correlate to plasma FVIII levels.1 Severe Hemophilia A is typically diagnosed at a very young age due to joint bleeds or intramuscular bleeding, bleeding associated with a minor medical procedure (venipuncture, circumcision, central line placement, or heel prick), mucocutaneous bleeding, or extracranial bleeding.1,2

Individuals with mild Hemophilia A may rarely experience spontaneous bleeding, but can experience major bleeding with trauma or surgery.1 Individuals with moderate Hemophilia A may experience occasional spontaneous bleeding, and are at risk for prolonged bleeding with minor trauma or surgery. When including mild and moderate cases, 36% of Hemophilia A cases were expected to be undiagnosed in the U.S. based on data from 2016.8

Pathophysiology

FVIII is a glycoprotein synthesized mainly in hepatocytes.9,10,11,12 Von Willebrand Factor (VWF) stabilizes FVIII, protects it from premature proteolysis, and transfers it to the site of endothelial injuries.

In primary hemostasis, which involves the formation of a platelet plug after endothelial injury, VWF:FVIII complex is critical for the recruitment and activation of platelets, and binding to collagen.10,11,13 In this process, FVIII is freed from VWF, which activates FVIII. Activated FVIII plays a role in secondary hemostasis, which is the process of forming a stable fibrin clot.14

FVIII deficiencies, which can result from a variety of mutations to the FVIII gene, lead to varying degrees of inability to form a stable fibrin clot and thus stop bleeding.1,14

Navigating Hemophilia A

Even a single bleed in an individual with Hemophilia A may be life-threatening or lead to debilitating joint disease.1,15,16 Therefore, prevention of all bleeds is the goal of optimal hemophilia patient care.17,18

One of the most serious complications of factor treatment is neutralizing antibodies to FVIII (FVIII inhibitors).1,2 Testing for inhibitors is required in any individual with hemophilia in the following circumstances:1

 

  • When clinical or laboratory response to concentrate is suboptimal;
  • Before and after a switch of treatment;
  • Before elective invasive procedures; and 
  • Within 4 weeks after intensive treatment (≥5 consecutive days of clotting factor administration) or before surgery

  1. Srivastava A, Santagostino E, Dougall A, et al. Haemophilia. 2020;26(S6):1-158.
  2. Centers for Disease Control and Prevention. What is Hemophilia? Available at: https://www.cdc.gov/ncbddd/hemophilia/facts.html. Updated June 3, 2019. Accessed October 24, 2022.
  3. World Federation of Hemophilia. Report on the Annual Global Survey, 2018. Available at: http://www1.wfh.org/publications/files/pdf-1731.pdf. Accessed October 24, 2022.
  4. Collins P, Baudo F, Huth-Kuhne A, et al. BMC Res Notes. 2010;3:161.
  5. Kessler CM and Knöbl P. Eur J Haematol. 2015;95(Suppl 81):36-44.
  6. Sakurai Y and Takeda T. J Immunol Res. 2014;2014:1-10.
  7. Knoebl P, Marco P, Baudo F, et al. J Thromb Haemost. 2012;10(4):622-631.
  8. Brouwer ES, et al. Presented at ISTH 2019, Melbourne; Poster PB1420.
  9. Mazurkiewicz-Pisarek A, Plucienniczak G, Ciach T, et al. Acta Biochim Pol. 2016;63(1):11-16.
  10. Terraube V, O’Donnell JS, Jenkins PV. Haemophilia. 2010;16(1):3-13.
  11. Rauch A, Wohner N, Christophe OD, et al. Mediterr J Hematol Infect Dis. 2013;5(1):e2013046.
  12. Pipe S, Montgomery RR, Pratt KP, et al. Blood. 2016; 128(16):2007-2016.
  13. Cito S, Mazzeo MD, Badimon L. Thromb Res. 2013;131(2):116-124.
  14. Adams RLC and Bird RJ. Nephrology. 2009;14(5):462-470.
  15. Melchiorre D, Manetti M, Matucci-Cerinic M. J Clin Med. 2017;6(7):63.
  16. Rodriguez-Merchan EC. HSS J. 2010 Feb;6(1):37-42.
  17. Poon M-C and Lee A. Thrombosis J. 2016;14(Suppl 1):32
  18. Ar MC, Vaide I, Berntorp E, et al. Eur J Haematol. 2014;93(Suppl 76):16-20.

Medication Resources

Advate®

[Antihemophilic Factor (Recombinant)]

Adynovate®

[Antihemophilic Factor (Recombinant), PEGylated]

Feiba®

[Anti-Inhibitor Coagulant Complex]

Hemofil M®

[Antihemophilic Factor (Human), Method M, Monoclonal Purified]

Obizur®

[Antihemophilic Factor (Recombinant), Porcine Sequence]

Recombinate®

[Antihemophilic Factor (Recombinant)]

Upcoming & Past Conferences in Hematology

  • Upcoming

  • Past

American Society of Hematology (ASH), 2024

December 7 - 10, 2024 | Link to Event

The premier global congress from the world's largest professional society serving both clinicians and scientists working in malignant and classical hematology.

Hemostasis and Thrombosis Research Society (HTRS), 2025

March 13 - 15, 2025 | Link to Event

Scientific meeting open to all medical, research, and allied health professionals interested in disorders of hemostasis and thrombosis.

Academy of Managed Care Pharmacy (AMPC), 2025

March 30 - April 3, 2025 | Link to Event

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

International Society on Thrombosis and Haemostasis (ISTH), 2025

June 21 - 25, 2025 | Link to Event

Global congress featuring the world’s leading experts on thrombosis, hemostasis and vascular biology presenting the most recent advances, the latest science, and the newest clinical applications designed to improve patient care.

American Thrombosis and Hemostasis Network Data Summit (ATHN Data Summit), 2024

October 22 - 23, 2024

Annual meeting discussing important research areas of hemophilia, health equity, thrombosis, Von Willebrand disease, rare blood disorders, and data management.

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2024

October 14 - 17, 2024

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

Bleeding Disorders Conference (BDC), 2024

September 12 - 14, 2024

The National Bleeding Disorders Foundation (formally NHF)’s Annual Bleeding Disorders Conference brings the bleeding disorders community together for educational sessions, networking opportunities, and exhibits.

International Society on Thrombosis and Haemostasis (ISTH), 2024

June 22 - 26, 2024

Global congress featuring the world’s leading experts on thrombosis, hemostasis and vascular biology presenting the most recent advances, the latest science, and the newest clinical applications designed to improve patient care.

  • Global Prevalence of Anticoagulant Reversal for Major Bleeding and Urgent Surgery in Patients with Atrial Fibrillation and Venous Thromboembolism: A Systematic Review of Data from 38 Countries

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)] & "other FVIII replacement therapies"

  • Physical Activity Engagement and Health-Related Quality Of Life in Patients with Hemophilia A Receiving Either Octocog Alfa Or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies
  • Clinical Outcomes in Patients with Hemophilia A Receiving Octocog Alfa or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies: Insights From The Ahead, CHESS II, and CHESS PAEDS Studies
  • The Impact of Recombinant Factor VIII Products on Inhibitor Development in Previously Untreated and Previously Treated Children with Hemophilia A: A Systematic Review

Ceprotin® [Protein C Concentrate (Human)]

  • High-Concentration Protein C Concentrate: In Vitro and In Vivo Feasibility Studies
  • Pharmacokinetics of Protein C in Neonates with Severe Congenital Protein C Deficiency
  • Pharmacokinetics of Protein C Concentrate After Intravenous and Subcutaneous Administration in Göttingen Minipigs

Obizur® [Antihemophilic Factor (Recombinant), Porcine Sequence]

  • Evaluation of Factor VIII Population Pharmacokinetics and Exposure-Response to Support Dosing of Recombinant Porcine Factor VIII in Patients with Acquired Hemophilia A

TAK-330 (4-factor prothrombin complex concentrate [4F-PCC])

  • A Phase 3 Trial of TAK-330 (4-Factor Prothrombin Complex Concentrate [4F-PCC]) vs Standard-Of-Care 4F-PCCs for FXa Inhibitor-Induced Anticoagulation Reversal Before Urgent Surgery/Invasive Procedure

Prothromplex® (Human Prothrombin Complex)

  • Safety Assessment of Prothromplex®, a 4-Factor Prothrombin Complex Concentrate, Focused on Heparin-Related Adverse Events

Professional Society for Health Economics and Outcomes Research (ISPOR), 2024

May 5 - 8, 2024

Leading global conference discussing how to establish, incentivize, and share value sustainable for health systems, patients, and technology developers.

Thrombosis and Hemostasis Societies of North America (THSNA), 2024

April 4 - 6, 2024

A summit of 10 of the leading non-profit organizations in hemostasis and thrombosis, providing expertise and insight on improving patient care.

American Society of Hematology (ASH), 2023

December 9 - 12, 2023

The premier global congress from the world's largest professional society serving both clinicians and scientists working in malignant and classical hematology.

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)]

  • Clinical Outcomes of Noninhibitor Patients with Hemophilia A Switching from Prophylaxis with Factor VIII to Emicizumab: a Meta-analysis of Real-world Evidence Studies
  • Identifying Ideal Individuals for PK-guided Dosing: Recreational Risks and Elevated Breakthrough Bleeding

Vonvendi® [von Willebrand factor (recombinant)]

  • Real-world Use of Recombinant Von Willebrand Factor in People with Clinically Severe Congenital Von Willebrand Disease: Interim Analysis of ATHN 9, A Natural History Study for People with Severe VWD

Videos

 

Watch videos focused on Hemophilia.

GOAL-Hēm

Learn about GOAL-Hēm, a hemophilia-specific patient-centered outcome measure and clinical engagement tool to aid in individualized goal setting.