From the *Department of Cardiology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel; and the §Department of Hematology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. The authors report no conflicts of interest regarding the content herein. Manuscript submitted March 3, 2009, and accepted April 10, 2009. Address for correspondence: Avi Shimony, MD, Department of Cardiology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. E-mail: email@example.com ; firstname.lastname@example.org
_______________________________________________ ABSTRACT: Factor XI deficiency is a rare coagulopathy occurring primarily in Ashkenazi Jews, and is associated with bleeding diathesis. This disorder complicates management during invasive procedures and poses a challenge during the performance of percutaneous coronary intervention (PCI). This situation is unique because there is a contradictory need to achieve procedural anticoagulation while minimizing the risk of bleeding. There is only one case report on the management of anticoagulation during PCI in patients with Factor XI deficiency advocating the avoidance of anticoagulation during the procedure. There is some evidence to suggest that severe Factor XI deficiency may be protective against ischemic stroke, but not against myocardial infarction. It appears, therefore, that the prolonged aPTT observed in these patients might not reflect a complete anticoagulant state and cannot be relied upon to provide procedural anticoagulation during PCI. We report our experience which suggests that PCI in these patients may be performed safely in the usual manner following the administration of plasma.
J INVASIVE CARDIOL 2009;21:E178–E179 Key words: Factor XI deficiency; myocardial infarction; percutaneous coronary intervention; hemophilia C; coronary artery disease Case Presentation. An 82 year-old patient was admitted to our hospital for a non-ST-elevation acute myocardial infarction (NSTEMI). Eleven years previously he sustained an acute inferior STEMI. He was treated with intravenous (IV) streptokinase, but required rescue percutaneous coronary intervention (PCI) following which he experienced profound bleeding around the femoral access site and required surgical correction of a pseudoaneurysm. At that time, the patient was found to have Factor XI deficiency. There was no other history of surgery, trauma or major bleeding. Two months prior to the index admission, the patient suffered a NSTEMI. Pre-angiographic evaluation revealed severe Factor XI deficiency (levels of 2.8 U/dL; norm 65–153). The patient was prepared for the procedure by the administration of 2 units of fresh frozen plasma 1 hour before angiography. Diagnostic coronary angiography was performed via the transradial approach and the patient received 2,000 unit of intravenous heparin. Triple-vessel disease was found, but the patient declined any form of intervention. The patient’s index admission was prompted by another episode of NSTEMI. His admission aPTT level was 77 seconds. The patient was given clopidogrel and aspirin, but no heparin. After obtaining the patient’s consent for PCI, he received 2 units of fresh frozen plasma (FFP) and diagnostic coronary angiography was performed an hour later via the transradial approach using 2,000 units of IV heparin. After critical lesions were found in the proximal left circumflex and ramus medianus arteries, the patient was given an additional 7,000 units of heparin. The activating clotting time was 270 seconds. The patient then underwent successful drug-eluting stent implantation in both arteries. A minor side branch of the left circumflex artery was compromised by the stent implanted in that artery, causing some residual chest pain for a few hours. The procedure was otherwise uneventful, and no bleeding complications were observed. The patient was discharged 2 days later on maintenance therapy of aspirin and clopidogrel. Discussion. Factor XI glycoprotein participates in the early phase of blood coagulation through the intrinsic pathway and is essential for normal homeostasis.3 Factor XI deficiency, also known as hemophilia C, was first described in the early 1950s.1 This inherited coagulopathy is caused by a number of mutations in the genes which encode for Factor XI on chromosome 4.2,3 This rare disorder is primarily seen in Ashkenazi Jews and is associated with a bleeding diathesis.4 The bleeding manifestations vary widely and there is no good correlation between Factor XI levels and the severity of clinical bleeding. Bleeding is usually not spontaneous, but is associated with trauma or surgery. Procedures involving mucosal surfaces such as dental or genitourinary tract procedures are more likely to be associated with profound bleeding.3,5 Cardiac surgery, which requires heparin for extracorporeal circulation, poses a management challenge in patients with Factor XI deficiency due to the higher risk of major bleeding. There are limited data, mostly based on case studies concerning the appropriate approach in these patients.6–8 PCI also requires procedural anticoagulation, but carries a risk of access-site bleeding. There is only one published case report describing the management of a patient with Factor XI deficiency during PCI.2 In this report, Mungee et al suggested PCI should be performed without any anticoagulation in lieu of “native” prolonged aPTT at baseline. Their patient was treated via the femoral approach. These authors suggested that stenting should be avoided if possible and that if clopidogrel is felt to be necessary, only a short course of 2 weeks should be given. Since stent implantation with subsequent dual antiplatelet therapy is the mainstay of current PCI, it would be advisable to perform PCI in this standard manner, as recommended by current practice guidelines, and as was done in our patient.9 Conventionally, FFP is used for coagulation factor replacement.3 Factor XI concentrates are available and offer the advantages of reduced volume and the avoidance of infusion of other coagulation factors. Factor VII has also been used successfully in patients with Factor XI deficiency. However, life-threatening thrombotic complications, including arterial thrombi, have been observed to occur in about 10% of treated patients, particulary in older patients with preexisting coronary artery disease.10 The standard practice of PCI requires full procedural anticoagulation to avoid thrombotic complications.11 There is some evidence to suggest that severe Factor XI deficiency may be protective against ischemic stroke, but not against MI.12,13 It appears, therefore, that the prolonged aPTT observed in these patients might not reflect a complete anticoagulant state and cannot be relied upon to provide procedural anticoagulation during PCI. This may be explained by the fact that patients with Factor XI deficiency have normal levels of Factors VIII, IX, V and X to form the X-ase and prothrombinase complex, and by the activity of platelet Factor XI, which may substitute for plasma Factor XI.14 In view of these considerations and in an effort to ensure a predictable anticoagulant state, we decided to restore the patient’s coagulation status to near-normal by the use of FFP, and then administer heparin in the usual manner. We chose to administer FFP and heparin only for the interventional procedure. The patient was not given full anticoagulation upon admission, as is standard practice for patients with non-ST-elevation acute coronary syndromes. The risk/benefit ratio of anticoagulation in this setting is unknown, but it appears prudent to perform coronary intervention as early as possible in these patients in order to minimize the period of time during which the patient does not receive full anticoagulation. Another possible approach might have been the use of bivalirudin. Bivalirudin was successfully used in multivessel PCI and in patients with Factor VIII deficiency15–17 and may be a safe substitute for heparin infusion in patients with Factor XI deficiency. After PCI and stent implantation, we followed standard practice and advised long-term aspirin and clopidogrel therapy. The safety of this combination in a patient with Factor XI deficiency is uncertain, but we viewed this as the best option for our patient.
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