Individualization of bypassing agent treatment for haemophilic patients with inhibitors utilizing thromboelastography G. YOUNG, R. BLAIN, P. NAKAGAWA and D. J. NUGENT Department of Hematology, Children’s Hospital of Orange County, Orange, CA, USA Summary. The treatment of bleeding for haemo- philic patients with inhibitors relies on the use of the bypassing agents, recombinant factor VIIa and factor eight inhibitor bypass activity (FEIBA). While both therapies are effective in the majority of bleeding episodes, there is a significant amount of interindividual variability when it comes to the response to therapy. As of yet, there is no reliable laboratory parameter that can predict the response to therapy in the same manner that factor VIII and factor IX levels predict response in non-inhibitor patients. Developing such a laboratory parameter is vital in order to maximize the clinical efficacy of these agents. Thromboelastography (TEG) is a device, which assesses clot formation over time in whole blood and has several characteristics which suggest it may be an effective way to monitor bypass agent therapy. We studied the ability of TEG to individualize the treatment regimens of three patients with high titre inhibitors assessing the response to recombinant factor VIIa, FEIBA, and when both were used sequentially. The TEG allowed for individualization of treatment for each of the three patients and resulted in more effective, convenient and less expensive treatment regimens. We thus believe that TEG is a promising device for monitoring of bypass agent therapy and should be studied further. Keywords: haemophilia, inhibitors, thromboelastog- raphy, treatment Introduction Haemophilia results from the deficiency of either factor VIII (FVIII) or factor IX (FIX) leading to a lifelong bleeding disorder with frequent bleeding into deep tissues such as the joints and muscles. With the advent of replacement therapy in the form of purified (and now recombinant) FVIII and FIX, patients can lead nearly normal lives with few bleeding episodes especially if they are receiving factor prophylactical- ly. Unfortunately, approximately 15% of patients develop neutralizing antibodies (inhibitors) against these therapies rendering them ineffective [1]. While the inhibitor may be eradicated via immune tolerance therapy, so-called inhibitor patients often develop serious bleeding episodes prior to and during immune tolerance and approximately 30% of patients with inhibitors fail to respond to immune tolerance and have inhibitors for life. Treating bleeding episodes for inhibitor patients requires what has come to be known as bypass therapy. Currently, there are two bypass agents available, recombinant activated factor VII (rFVIIa, Novoseven; Novo Nordisk, Bagsvaerd, Denmark) and factor eight inhibitor bypass activity [FEIBA; Baxter, Glendale, CA, USA] [2]. Porcine FVIII, another bypass agent is no longer available though a recombinant form is in development [3]. These agents are not as effective as native FVIII or FIX in controlling bleeding and importantly, there is no accepted method to monitor the clinical effective- ness. While for non-inhibitor patients, measurement of the level of the specific factor is correlated with the expected clinical response, there is no laboratory assay that predicts the clinical response of bypass agents. This becomes even more important as there appears to be significant interindividual differences in how patients respond to bypass therapy which becomes critically important during surgical proce- dures [2]. Correspondence: Guy Young, MD, Children’s Hospital of Orange County, 455 S. Main Street, Orange, CA 92868, USA. Tel.: +1 714 532 8459; fax: +1 714 532 8771; e-mail: gyoung@choc.org Accepted after revision 20 June 2006 Haemophilia (2006), 12, 598–604 DOI: 10.1111/j.1365-2516.2006.01319.x Ó 2006 The Authors 598 Journal compilation Ó 2006 Blackwell Publishing Ltd