Ask the Hematologist: September-October 2011
Published on: September 01, 2011
Professor of Medicine and Pathology, Duke University Medical Center
Dr. Ortel indicated no relevant conflicts of interest.
(Editor’s Note: The original question was submitted to Dr. Ortel through Consult a Colleague. He expanded his answer for print.)
A 48-year-old man with factor XI deficiency (2% activity) was first diagnosed at the age of 17 during evaluation for a prolonged aPTT. He underwent extraction of wisdom teeth without plasma or topical support uneventfully. Periodontal surgery led to oozing for which he was successfully treated with oral aminocaproic acid. He now needs arthroscopic surgery on his left shoulder for repair of a torn rotator cuff. Does he need factor replacement prior to surgery and afterward?
Inherited deficiency of factor XI was first described in 1953 as a mild to moderate bleeding disorder.1 Factor XI deficiency exhibits an autosomal inheritance pattern with a variable clinical penetrance, as described below. It has been described in a wide variety of population groups but is most common in Ashkenazi Jews. In this particular group, it is estimated that one in eight individuals are heterozygous and one in 190 are homozygous for mutations in the factor XI gene.2,3
Spontaneous bleeding, except for menorrhagia, is uncommon in patients with factor XI deficiency. Most bleeding episodes occur following surgical procedures or trauma. In contrast to patients with hemophilia A or B, the correlation between clinical bleeding and the baseline factor XI clotting activity is poor. For example, some patients with severe factor XI deficiency (factor XI level < 10-20 IU/dL) exhibit no increase in hemorrhage, whereas other individuals with levels that are only moderately below the lower limit of the normal range develop bleeding complications after surgery.3
Rates of hemorrhagic complication have also been shown to vary depending on the type of surgery being performed.4 In particular, procedures involving sites with increased local fibrinolytic activity, such as the oral mucosa, nose, and genitourinary tract, are more frequently associated with excessive bleeding compared to procedures involving tissues not expressing fibrinolytic activity, such as bones or muscles. This study included six patients who underwent trauma surgery and one total knee replacement, but none of the patients underwent an arthroscopic procedure. The implication from these observations is that conservative use of replacement therapy in patients with even severe factor XI deficiency undergoing certain types of surgery is possible.4
Management of bleeding episodes and prevention of bleeding in relation to surgery is not straightforward and needs to be tailored to the individual patient.5 In many patients with factor XI deficiency, antifibrinolytic therapy alone may be sufficient to prevent bleeding in most surgical settings. Factor XI levels can be raised with fresh frozen plasma, but relatively large volumes may be required. The hemostatic level of factor XI activity to target is debated, but a level of 30 to 45 IU/dL is probably sufficient in patients with severe deficiency.5 Factor XI concentrates have been associated with an increased thrombotic risk in certain patients and are not available in the United States.6
Good hemostasis helps to maintain arthroscopic visual clarity during surgery and is essential for the successful completion of the procedure. A variety of strategies have been used to control arthroscopic bleeding, including using electrocautery or a radiofrequency thermal probe, adding epinephrine to the inflow irrigation solution or increasing the irrigation fluid inflow pressure, and applying direct pressure via the shaver blade.7
Relatively limited information is available describing therapeutic arthroscopy of the shoulder in patients with clotting disorders. A single case series describing the management and outcomes of five patients undergoing a total of six shoulder arthroscopic procedures included one patient with a mild factor XI deficiency (baseline level of 60 U/dL) who underwent arthroscopic subacromial decompression.8 This patient was treated with a combination of intravenous and oral tranexamic acid without any bleeding complications.
Although shoulder arthroscopy is performed in a tissue not considered to have high fibrinolytic activity, the impact of even a minimal increase in bleeding during a surgical procedure in an enclosed space can be significant. The severely decreased factor XI activity level in this patient, and the fact that he had previously required antifibrinolytic therapy for periodontal surgery, are concerning for an increased bleeding risk. Consequently, it was recommended that the patient receive fresh frozen plasma to supplement the factor XI level prior to the procedure. Post operatively, depending on the factor XI activity levels and clinical outcome of the procedure, additional fresh frozen plasma could be administered or antifibrinolytic therapy could be substituted instead.
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- Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med. 1953;82:171-174.
- Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost. 2009;7: Suppl 1:84-87.
- Gomez K, Bolton-Maggs P. Factor XI deficiency. Haemophilia, 2008;14:1183-1189.
- Salomon O, Steinberg DM, Seligsohn U. Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy. Haemophilia. 2006;12:490-493.
- Bolton-Maggs P. Factor XI deficiency – resolving the enigma? Hematology 2009. 2009;97-105.
- Mannucci PM, Bauer KA, Santagostino E, et al. Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients. Blood. 1994;84:1314-1319.
- Levy O, Haddo O, Sforza G, et al. “Put your ‘extended’ finger on the bleeder”: the use of direct pressure from the shaver blade to achieve hemostasis. J Arthroscopic Related Surgery. 2011;27:867-869.
- Thomas JMC, Tuddenham EG, Ahrens PM. Therapeutic shoulder arthroscopy in patients with clotting disorders. Haemophilia. 2008;14:859-861.