More Information on Patients with Factor XI Deficiency

To the Editor:-

It has been called to our attention that our recent Clinical Concepts and Commentary article, Current Concepts of Hemostasis: Implications for Therapy, contains a statement that implies that postoperative bleeding in patients with factor XI deficiency is usually mild.¹ We wish to clarify this implication. Patients with factor XI deficiency over a lifetime are mild bleeders who do not usually experience the chronic, crippling hemarthrosis or other severe bleeding episodes so typical of severe classic hemophilia or hemophilia B. Nonsurgical bleeding episodes in factor XI-deficient patients are usually mild over a lifetime. We wish to make it clear, however, that it is quite possible for patients with factor XI deficiency undergoing surgery to bleed severely unless they are pretreated. The replacement therapy for factor XI deficiency in the United States usually consists of plasma replacement therapy before an operation. More recently, recombinant factor VIIa has been used for factor XI deficiency, and it has been found to be effective, although it is not yet approved by the US Food and Drug Administration for this indication.² One of the readers of the journal pointed out to one of us via e-mail that patients with factor XI deficiency undergoing cardiopulmonary bypass may bleed excessively. We agree with this statement, and at our institution, such patients would be treated, preoperatively and postoperatively, with recombinant factor VIIa or with plasma replacement therapy, which may require plasma exchange transfusions to increase factor XI to 50% or greater. Factor XI concentrates are available in Europe but not in the United States, and these concentrates have occasionally been associated with thrombotic side effects. In summary, we wish to emphasize that even though patients with factor XI deficiency usually have mild bleeding episodes over a lifetime, this does not mean that they may not experience extensive hemorrhage after severe trauma or surgery. Although some patients with factor XI deficiency do not bleed after operative procedures, a family history of bleeding after surgery is suggestive that relatives of such patients will also bleed during surgery.

It has been recommended that replacement therapy for factor XI deficiency also include the use of antifibrinolytic agents such as tranexamic acid because it seems that one function of factor XI is to boost thrombin generation to the extent that the thrombin activatable fibrinolytic inhibitor (TAFI) can be activated.³ Adding tranexamic acid enhances the antifibrinolytic effect.

We are grateful to the reader who called this potential interpretation of factor XI deficiency to our attention.

Harold R. Roberts M.D.,*

Miguel Escobar M.D.,

Dougald M. Monroe Ph.D.

* The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. [e-mail]