Perioperative management of a patient with severe factor XII deficiency

Abstract

EDITOR: Factor XII deficiency is a hereditary state that is usually discovered because of an unexpected prolongation of activated partial thrombin time (aPTT) during preoperative evaluation. We report the perioperative management of an orthopaedic patient with severe factor XII deficiency. An 18-yr-old male (height: 175 cm, weight: 72 kg) with a lateral malleolar fracture was transferred to our institution from a county hospital for operative stabilization. A pre-anaesthetic laboratory screen during his first admission revealed an extremely prolonged aPTT that did not return to normal after the transfusion of 3 units of fresh frozen plasma (see Table 1). He had no relevant past medical history and he did not report any symptoms of abnormal haemostasis after traumatic injuries. The physical examination showed no pathologic findings, except for painful ankle oedema. A detailed investigation of haemostasis was performed, including the assessment of protein C, protein S, antithrombin, lupus anticoagulant, prekallikrein and activated protein C resistance. The only pathologic finding was a significant reduction in factor XII activity (4.6%, normal range >80%). This explained the marked prolongation in aPTT. The patient's haemostasis was regarded as sufficiently effective [1]. Nevertheless, he was considered at increased risk for thromboembolic complications and prophylaxis was started with reviparin sodium, 3500 anti-Xa units subcutaneously once daily [2]. The following morning (12 h after reviparin administration), an epidural catheter was placed atraumatically in L4-L5 interspace and the patient underwent an uneventful operative stabilization under epidural anaesthesia with levobupivacaine 0.5% 15 mL plus morphine 3 mg. No abnormal bleeding was observed during the 40 min of the surgical procedure. Postoperative analgesia consisted of patient controlled epidural analgesia with morphine (2.5 mg morphine bolus, 30 min lockout) and parecoxib sodium 40 mg once daily intravenously or intramuscularly. Pain relief was successful, allowing early mobilization. The epidural catheter was removed on the third postoperative day. The postoperative period was uneventful with no signs of deep venous thrombosis or spinal cord compression. Prophylaxis with low-molecular-weight heparin was continued until the 5th postoperative day and the patient was discharged.Table 1: PT and aPTT.The factor XII protein is synthesized in the liver. It has a half-life of about 60 h and its concentration in normal plasma is 30 μg mL−1. Factor XII deficiency is inherited in an autosomal recessive pattern. Factor XII, prekallikrein and high-molecular-weight kininogen are the major factors involved in the so-called 'contact' phase of coagulation. Factor XII is activated by plasma kallikrein during endothelial injury. Activated factor XII is the first component of the intrinsic pathway of the coagulation cascade, while simultaneously, factor XII fragments activate plasminogen during the initiation of normal fibrinolysis. The overall prevalence of factor XII deficiency in the normal population is estimated as 1.5-3.0%, with the severe factor XII deficiency (activity <1%) in a minority. In these rare individuals, aPTT is seriously prolonged with values exceeding 120 s [3]. We believed that our patient had severe factor XII deficiency because of the extreme prolongation of the initial aPTT (238 s) and the significantly decreased factor XII activity (4.6%) 24 h after the transfusion of three units of fresh frozen plasma. The question arises as to why our patient did not report a bleeding tendency in spite of the very low factor XII levels. Although factor XII is necessary for in vitro coagulation during aPTT testing, its presence seems unimportant for in vivo haemostasis. The role of factor XII and other contact factors in coagulation is not so clear and the extrinsic pathway is sufficient for the initiation of coagulation in human beings [1]. Patients with even severe factor XII deficiency are free of haemostatic problems. Therefore, transfusion with fresh frozen plasma or cryoprecipitate for the correction of low factor XII plasma concentration in patients with isolated severe factor XII deficiency is not justified. Patients with severe factor XII deficiency do not have a bleeding tendency. On the contrary, they have a high rate (8-10%) of premature venous thromboembolic events [1]. Factor XII deficiency may lead to hypercoagulability through a defective activation of fibrinolysis. Surgical trauma and immobilization increase the risk of thromboembolic complications. Severe factor XII deficiency places the patient at a moderately increased thromboembolic risk level even during minor surgery and necessitates the application of effective preventing measures such as low-molecular-weight heparin administration, early mobilization and regional anaesthesia [2,4]. Epidural anaesthesia and analgesia have favourable effects on fibrinolysis and offer conditions for sufficient postoperative analgesia and early mobilization [5]. If the placement and removal of an epidural catheter are carefully timed with the low-molecular-weight heparin administration, epidural anaesthesia can be used safely in the perioperative anaesthetic management of these patients. C. Dragoumanis G. Vretzakis T. Vogiatzaki Department of Anesthesiology; Cardiac Anesthesia Unit; University Hospital of Alexandroupolis; Alexandroupolis, Greece