Announcer: This medical industry feature, titled “Congenital vs. Acquired Hemophilia: Different Disorders, Different Approaches” is sponsored by Takeda. This program is intended for healthcare professionals.
Dr. Tarantino: Hi, I’m Dr. Michael Tarantino, Medical Director and President of the Bleeding and Clotting Disorders Institute in Peoria, Illinois and I’m going to take a few minutes to talk to you about some bleeding disorders that you may not be familiar with - Congenital Hemophilia A and B with inhibitors and Acquired Hemophilia A. After this, you’ll have a better understanding of how to recognize and diagnose these conditions as well as the risks these patients face.
Inhibitors are antibodies that neutralize clotting factors, leading to bleeding that can be difficult to treat and potentially dangerous. a
Mortality is a significant concern. For a patient with Congenital Hemophilia A, the risk of death during a bleeding episode may be up to 70% higher when a patient has an inhibitor to factor VIII (FVIII). b And the mortality of patients with Acquired Hemophilia A is estimated to be between 9 and 22%.c
While many advances have been made in the management of Congenital Hemophilia A and B, patients with inhibitors face different challenges and require a different management approach. d There are several differences between Congenital Hemophilia A and B with inhibitors and Acquired Hemophilia A, beginning with the primary cause for the clotting factor- targeting antibodies. e
Congenital Hemophilia A and B with inhibitors is the result of an alloantibody response against replacement FVIII and FIX therapy. These antibodies are referred to as “inhibitors”. e Since clotting factor genes are located on the X chromosome, this condition mostly affects males. f Up to 33% of severe Congenital Hemophilia A patients and up to 6% of severe Congenital Hemophilia B patients will develop an inhibitor. g For these conditions, bleeding occurs mostly in the joints and muscles. f
Acquired Hemophilia A, on the other hand, is caused by an autoantibody response against endogenous FVIII.e It can affect men and women, and is mostly seen in elderly patients, with a median age at diagnosis of approximately 74 years.h These patients usually have no history of bleeding disorders.c It’s a rare condition, with approximately 1.5 cases per 1 million people.c Bleeding occurs mostly in the skin, soft tissues, and mucous membranes. i
Now, Congenital Hemophilia A and B with inhibitors and Acquired Hemophilia A result in abnormal bleeding due to impaired coagulation.c,f However, since these are different conditions, it’s important to properly identify and distinguish between them in order to develop an appropriate management plan.i Different patient- and management-related factors place Congenital Hemophilia patients at risk of developing an inhibitor.j,k Health care professionals who suspect an inhibitor should look to consult with a hematology colleague or bleeding condition specialist immediately.
The recent National Hemophilia Foundation Medical and Scientific Advisory Council Guidelines recommend testing Hemophilia A or B patients for inhibitors at least 1-2 times annually or as a result of elective invasive procedures, switching factor products, or intensive treatment or surgery. For severe Hemophilia A or B patients, testing should occur every 3 exposure days or every 3 months until they reach 20 exposure days. After that, they should be screened every 3 to 6 months until they reach 150 exposure days.l Bypassing agents are a treatment option for severe Hemophilia with high-titer inhibitors to FVIII or FIX.m
In comparison with the development of inhibitors in patients with Congenital Hemophilia A or B, Acquired Hemophilia A has distinct signs and presentation.
Diagnosis of Acquired Hemophilia A can be confirmed through the assessment of the clinical presentation and a mixing test with normal plasma.c
In the absence of an aPTT correction, it’s important to exclude a lupus anticoagulant. The next step is then to check FVIII levels and inhibitor titers. Reduced FVIII levels in the presence of a FVIII inhibitor titer may indicate Acquired Hemophilia A.c Management goals for this condition focus on immediate control of acute bleeding and long-term management of the underlying causes.c
Remember, Congenital Hemophilia A and B with Inhibitors and Acquired Hemophilia A are distinct conditions,c-h each with their own cause, presentation, and considerations for patient management. Early recognition of these conditions is critical,c and hematologists and other health care professionals should work together to establish accurate diagnosis and appropriate management plans.
The case study videos in this series highlight important aspects of managing patients with Congenital Hemophilia A and B with Inhibitors or Acquired Hemophilia A.
Announcer: This program was sponsored by Takeda. If you missed any part of this discussion or to find others in this series, visit ReachMD.com/InhibitorInsights. This is ReachMD. Be part of the knowledge.
References for Transcript
a) Hemophilia. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/Hemophilia/facts.html. Updated August 26, 2014. Accessed January 12, 2017.
b) Walsh CE, Soucie JM, Miller CH, et al. Impact of inhibitors on Hemophilia a mortality in the United States. Am J Hematol. 2015;90(5):400-405.
c) Collins P, Baudo F, Huth-Kühne A, et al. Consensus recommendations for the diagnosis and treatment of Acquired Hemophilia A. BMC Res Notes. 2010; 3:161.
d) National Hemophilia Foundation. MASAC Recommendation Regarding the Use of Bypassing Agents in Patients with Hemophilia A or B and Inhibitors. Document #167. https://www.Hemophilia.org/sites/default/files/ document/files/167.pdf. Published June 3, 2006. Accessed January 10, 2017.
e) Ma AD, Carrizosa D. Acquired Factor VIII Inhibitors: Pathophysiology and Treatment. Hematology Am Soc Hematol Educ Program. 2006:432-437.
f) Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of Hemophilia. Haemophilia. 2013;19(1):e1-47.
g) DiMichele DM. Inhibitors in haemophilia: A primer. In Schulman S, ed. Treatment of Hemophilia. 4th ed. Quebec, Canada. WFH. 2008:7;1-9.
h) Knoebl P, Marco P, Baudo F, et al. Demographic and clinical data in Acquired Hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622-631.
i) Franchini M, Mannucci PM. Acquired haemophilia A: A 2013 update. Thromb Haemost. 2013;110(6):1114-1120.
j) Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia. 2006;12(Suppl 6):15-22.
k) Collins PW, et al. Diagnosis and treatment of factor VIII and IX inhibitors in Congenital haemophilia: (4th edition). Br J Haematol. 2013;160(2):153-170.
l) National Hemophilia Foundation. MASAC recommendations on standardized testing and surveillance for inhibitors in patients with Hemophilia A and B. Document #236. https://www.Hemophilia.org/sites/default/files/ document/files/236.pdf. Published October 6, 2015. Accessed January 10, 2017.
m) National Hemophilia Foundation. MASAC recommendation regarding prophylaxis with bypassing agents in patients with Hemophilia and high titer inhibitors. Document #220. https://www.Hemophilia.org/sites/default/ files/document/files/246Text.pdf. Published October 6, 2013. Accessed January 10, 2017.