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Total Knee Arthroplasty Using Recombinant Factor VII in Hemophilia-A Patients with InhibitorsA Report of Three Cases
Samir Mehta, MD1; Charles L. Nelson, MD1; Barbara A. Konkle, MD2; Brian Vannozzi, MD1
1 Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, 3400 Spruce Street, 2 Silverstein, Philadelphia, PA 19104. E-mail address for C. Nelson: charles.nelson@uphs.upenn.edu
2 Department of Medicine, Penn Comprehensive Hemophilia and Thrombosis Program, University of Pennsylvania School of Medicine, 38th and Market Streets, Philadelphia, PA 19104
View Disclosures and Other Information
The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2004 Nov 01;86(11):2519-2521
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case


Elective orthopaedic surgery, including total joint arthroplasty, has become a safe and effective therapeutic option for most patients with hemophilic arthropathy and has been reported to reduce the rate of hemarthrosis and the clinical consequence of severe joint damage1. However, the 10% to 30% of patients with severe hemophilia who have development of neutralizing antibodies (inhibitors) to factor VIII (FVIII) or factor IX (FIX) do not fare as well2. The development of an inhibitor is one of the most serious complications associated with hemophilia because inhibitors may neutralize clotting factor concentrates. Patients with inhibitors often have substantially worse joint function secondary to inadequate treatment and traditionally have not been candidates for elective joint replacement surgery3. The orthopaedic literature regarding total knee arthroplasty in patients with hemophilia is limited, with little emphasis on patients with inhibitors4-9. Previous studies of total knee arthroplasty in patients with inhibitors, involving a variety of treatment regimens (including immune therapy, Factor VIIa, and Factor VIII), have been reported in the literature, but the duration of clinical follow-up has been limited and no consensus has been reached with regard to the appropriate dosing regimen2,10-13. Recombinant Factor VIIa has a short half-life but a high bioavailability when administered intravenously, and therefore the clinical impact has been difficult to predict in patients undergoing elective surgery14,15. In the present report, we describe three successful total knee arthroplasties that were performed with use of recombinant human factor VIIa (rFVIIa) in two patients who had different inhibitor characteristics and who were followed for more than two years.
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    E. Carlos Rodriguez-Merchan, M.D., Ph.D.
    Posted on January 12, 2005
    Total Knee Arthroplasty in Hemophilic Patients with Inhibitors Using rFVIIa.
    Traumatology & Orthopaedic Surgery, Haemophilia Unit, La Paz University Hospital, Madrid, Spain

    To the Editor:

    In a very interesting paper published in the November issue of 2004 of the JBJS-American, Mehta, et al. have presented the results of three TKAs performed in two hemophilic patients with inhibitors using rFVIIa as a hemostatic drug (1). In their article they state that “the orthopedic literature regarding TKA in patients with hemophilia is limited, with little emphasis on patients with inhibitors”. They also state that “no consensus has been reached with regard to the appropriate dosing regimen” to be used in hemophilic patients with inhibitors.

    I would like to supplement the information presented by Mehta et al by citing two publications in which I have participated. One of them is a multicenter study in which 6 TKAs were carried out with good results and similar conclusions to those reached by Mehta et al (2). The other publication makes reference to a consensus reached regarding the dosing regimen in these type of patients (3).

    To sum up, I would like to congratulate Metha et al for their 3 cases, but I bring to the attention of the reader the other articles mentioned to note that the topic is not as unusual as they state. Moreover, it should be of help to readers of the Journal to know that a consensus does exist regarding the dosing regimen for surgery in hemophilic patients with inhibitors, not only with rFVIIa but also with another product called FEIBA.


    1.Mehta S, Nelson CL, Konkle BA, Vannozzi B. Total knee arthroplasty using recombinant factor VII in hemophilia A patients with inhibitors. A report of three cases. J Bone Joint Surg Am 2004; 86-A:2519-21.

    2. Rodriguez-Merchan EC, Wiedel JD, Wallny T, et al. Elective orthopaedic surgery for inhibitors patients. Haemophilia 2003; 9:625-31.

    3. Rodriguez-Merchan EC, Rocino A, Ewenstein B, et al. Consensus perspectives on surgery in haemophilia patients with inhibitors: summary statement. Haemophilia 2004; 10 (Suppl. 2): 50-2.

    Charles L Nelson
    Posted on November 30, 2004
    Dr. Nelson responds to Drs. Panotopoulos and Trieb
    University of Pennsylvania

    To the Editor:

    We agree with the comments of Drs. Panotopoulos and Trieb regarding our use of recombinant factor VIIa in three patients with hemophilia-A and inhibitors who underwent total knee arthroplasty.

    Total knee arthroplasty can be performed safely using recombinant factor VIIa as described in our cases. Alternatively, immune tolerance can be successfully established in some patients with inhibitors allowing surgery using Factor VIII. We have previously published an article in which different strategies were discussed to safely perform total knee replacement in such patients (1). We recommend review of this article for interested individuals.


    1.Konkle BA, Nelson C, Forsyth A, Hume E. Approaches to successful total knee arthroplasty in haemophilia A patients with inhibitors. Haemophilia.2002; 8:706 -10.

    Joannis Panotopoulos
    Posted on November 22, 2004
    Orthopaedic surgery in a patient with inhibitors
    Medical Unniversity of Vienna, Dept. of Orthopedics, Vienna, Austria

    To the Editor:

    We read with interest the case report “Total knee arthroplasty using recombinant factor VII in hemophilia-A patients with inhibitors” by Metha et al.(2004; 86-A: 2519-21).

    As the authors report, TKA in patients with inhibitors poses a challenging problem. Nevertheless the authors were able to show that TKA in patients with inhibitors is possible when adequate replacement therapy is carried out.

    We treated about 70 patients with bleeding disorders. Only one patient had the development of high-titer inhibitors (high responder) with a Bethesda Unit of 30 at an age of 5 years. High dose therapy with F VIII was unable to eliminate the inhibitors. Severe bleeding episodes were treated with Feiba TM (F II, VII, IX, X). Tolerance was induced with the Malmö protocol in 1994. In 1994 the patient received a TKA on the right knee because end stage hemophilic arthropathy of this joint. The factor replacement consisted of a bolus given preoperatively. Postoperatively the substitution consisted of a continuous infusion with a recombinant F VIII concentrate (500 IE / h). The patient received during the stay in hospital 3 red blood concentrates.

    5 years later we performed a total hip arthroplasty and last year a synovectomy of the elbow. For both operations the replacement therapy remained unchanged. No complications were observed during the postoperative course.

    We agree with the authors that total joint arthroplasty is an effective therapeutic option for patients with hemophilic arthropathy and that even in patients with inhibitors, as the authors proved, total joint arthroplasty is possible under adequate management.

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