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Acquired Factor VIII Inhibitors: Pathophysiology and Treatment

Release Date: July 30, 2008

Expiration Date: July 30, 2009

Estimated time to complete this Activity: 0.75 hours

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Overview

In both congenital and acquired hemophilia, the development of inhibitors is often associated with severe bleeding. Inhibitor development in congenital hemophilia differs, however, from that of acquired hemophilia in terms of antibody characteristics/kinetics and clinical features. In congenital hemophilia, the inhibitors are alloantibodies directed against infused Factor VIII, whereas in acquired hemophilia, the inhibitors are spontaneously arising autoantibodies directed against the patient’s own FVIII. These autoantibodies are time and temperature dependent and display nonlinear kinetics. The clinical features of acquired hemophilia are distinct from those of congenital hemophilia with inhibitors. Affected patients tend to be adults and often have comorbid conditions which can include autoimmune disorders (eg, systemic lupus erythematosus, rheumatoid arthritis, or Sjögrens disease), malignant conditions (eg, solid tumors and lymphoproliferative disorders), and infections. The condition can also be associated with the use of certain therapeutic agents or the postpartum state. Acquired hemophilia is associated with high mortality (8% to 22%) due to comorbid conditions and delays in diagnosis. Individuals with acquired hemophilia will exhibit prolonged activated partial thromboplastin time (aPTT) values while prothrombin time (PT), thrombin clotting time (TCT), and bleeding time values are all normal. A mixing study is required to differentiate between a FVIII deficiency and a FVIII inhibitor followed by the modified Bethesda assay to determine the inhibitor titer. The Bethesda titer (reported as Bethesda Units) determines the strategy used for hemorrhage control. Patients with high-responding or high-titer inhibitors require treatment with a bypassing agent such as activated prothrombin complex concentrate (aPCCs) or recombinant activated FVII (rFVIIa) to achieve hemostasis and control acute bleeding in acquired hemophilia. Eradication of the inhibitor with plasmapheresis may be an effective adjunct to bypassing therapy for acute treatment of hemorrhage; however, immunosuppression is necessary for long-term inhibitor elimination. Because acquired inhibitors may be transient, the decision to begin immunosuppressive therapy is not straightforward. Most published guidelines and algorithms recommend early inhibitor eradication, unless the inhibitor is associated with childbirth or drug treatment.

Target Audience

This activity is intended for physicians, nurses, and pharmacists interested in the management of patients with bleeding associated with acquired hemophilia.

Learning Objectives

After completing this continuing education (CE) activity, participants should be able to:

• Describe the role of factor VIII (FVIII) in hemostasis
• Review the epidemiology of acquired hemophilia (AH)
• Identify the clinical presentation of a patient with an acquired inhibitor
• Explain how laboratory assays may be used to differentiate between an acquired FVIII inhibitor and a lupus inhibitor
• Review the principles of treating a patient with AH

Accreditation Statement

	This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of The FCG Institute for Continuing Education ("The FCG Institute") and IME, LLC. The FCG Institute is accredited by the ACCME to provide continuing education for physicians.
	The FCG Institute is an approved provider of continuing nursing education (CNE) by the Colorado Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.
	The FCG Institute is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Program Number assigned to the program by the accredited provider is: 086-999-08-001-H01-P.

Designation Statement

For CME, The FCG Institute designates this educational activity for a maximum of 0.75 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

For CNE, The FCG Institute designates this educational activity for 0.75 contact hour.

For CPE, The FCG Institute designates this activity for 0.75 contact hour of CE credit (0.075 CEUs) for "Acquired Hemophilia: Pathophysiology and Treatment." The type of activity: knowledge. There is no fee for this online CE activity.

How to Get Credit

To obtain CME credit, you should read the continuing education information then view and participate in the webcast. Your answers from the posttest will be tallied and a passing score of 70% or higher must be attained to receive credit. You must also complete the online evaluation and credit request form. Then print your certificate of participation online.

To obtain CNE credit, you should read the continuing education information then view and participate in the webcast. Your answers from the posttest will be tallied and a passing score of 70% or higher must be attained to receive credit. You must also complete the online evaluation and credit request form. Then print your certificate of contact hours earned online.

To obtain CPE credit, you should read the continuing education information then view and participate in the webcast. Your answers from the posttest will be tallied and a passing score of 70% or higher must be attained to receive credit. You must also complete the online evaluation and credit request form. Then print your statement of CE credit online.

Faculty Disclosure

It is the policy of the FCG Institute that faculty participating in continuing education activities are expected to disclose to the program audience (1) any real or apparent conflict(s) of interest related to the content of their presentation and (2) discussion of unlabeled or unapproved uses of drugs or medical devices. Faculty disclosure statements can be found together with their biographical sketches.

The following staff members from The FCG Institute and IME, LLC, who were involved in the development of the content for this CE activity, have no financial relationships or affiliations to disclose.

• Jeffrey Palmer, PhD
• Anu Hosangadi, MS
• Laurie Ermentrout
• Jennifer Wall
• Lynn Sample
• Claire Coneghen

Conflict of Interest Resolution

When individuals in a position to control or influence the development of the content have reported Financial Relationships with one or more commercial interests, The FCG Institute utilizes a process to identify and resolve potential conflicts to ensure that the content presented is free of commercial bias. The content of this presentation was vetted through The FCG Institute’s process of peer review and content validation and modified as required to meet this standard.

Notice About Investigational or Off-Label Use

This educational activity may include discussion of drugs or devices or uses of drugs and devices that have not been approved by the FDA or have been approved by the FDA for specific uses only. It is the responsibility of the healthcare professional to determine the FDA clearance status of each drug or device he or she wishes to use in clinical practice. The FCG Institute is committed to the free exchange of medical education. Inclusion of any product or device discussion, including discussion of investigational or off-label uses, does not imply endorsement by The Institute of the uses, products, or techniques presented.

Disclaimer

This CME/CE activity is designed for use by healthcare professionals for educational purposes only. The information and opinions expressed by the faculty are their own and do not necessarily reflect those of The FCG Institute. The FCG Institute does not define a standard of care, nor does it intend to dictate an exclusive course of management but presents through the educational activities it sponsors recognized methods and techniques of clinical practice for consideration by physicians and other healthcare providers for incorporation into their practices. Participants should use their own clinical judgment before applying information, whether provided here or by others, for any professional use.

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