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Islet Transplantation in a Recipient Presenting the Factor V Leiden Mutation

2005; Wolters Kluwer; Volume: 79; Issue: 12 Linguagem: Inglês

10.1097/01.tp.0000159031.85420.16

1534-6080

Axel Andrés, Domenico Bosco, Philippe Morel, Christian Toso, Reto M. Baertschiger, Pietro Majno, Léo H. Bühler, Thierry Berney,

Blood groups and transfusion

The case of a diabetic patient who developed portal vein thrombosis after islet transplantation, leading to the diagnosis of Factor V Leiden (FVL) mutation, was recently reported by Brennan et al. (1). Because of the high prevalence of this mutation in the general population, the authors propose systematic screening of prospective islet transplant recipients for thrombophilia, and optimized islet preparation (high purity and low volume) in case of positive findings. Herein we present the case of a 30-year-old white female patient with a 27-year history of type 1 diabetes, and a heterozygous FVL mutation diagnosed after a transient ischemic attack in December 1998. The patient underwent simultaneous kidney-pancreas transplantation in April 1999. On postoperative day 7, the pancreas was removed due to complete thrombosis of the artery and vein. Acenocoumarol anticoagulation was introduced. She received two intraportal islet infusions by a percutaneous approach in 2003 (Table 1). Anticoagulation was reversed with 2,400 units of a preparation of coagulation factors (Prothromplex; Baxter, Volketswil, Switzerland) just prior to islet infusion. Full-dose intravenous heparin therapy was started immediately upon completion of the procedure.TABLE 1: Characteristics of islet infusionsNo adverse event occurred after the first infusion. On the day after the second infusion, a mild intraperitoneal hematoma was seen on routine ultrasound. Her hemoglobin level decreased only slightly from 8.2 mg/dl preoperatively to 7.8 mg/dl. She was transfused with 3 units of packed red blood cells. Heparin infusion was switched to a prophylactic dose and bleeding stopped spontaneously. Liver ultrasound follow-up revealed no portal vein thrombosis. Acenocoumarol was resumed on postoperative day 7. Patient became insulin-independent shortly after the second infusion. As of October 2004, she was still free of insulin with normalized HbA1c (6%) and oral glucose tolerance test. Heterozygosity for FVL is a common occurrence in the general population (2). In case of islet transplantation, the further issue of hypercoagulability associated with type 1 diabetes must also be considered (3). In the case of portal vein thrombosis reported by Brennan et al., two additional risk factors were present. First, the patient was on oral contraception. This type of birth control should be discontinued in FVL patients because of the increased risk of thrombosis (4). Second, the islet preparation contained a large tissue volume (9 ml) with a purity at the limit of release criteria (30%). A large tissue volume is the consequence of the addition to the final preparation of the islet fractions of lower purity. This big expansion in total volume is accompanied by only a marginal increase in transplanted islet mass, and is thought to increase the risk of portal thrombosis. In our patient, the second preparation contained 6 ml of tissue with low-purity fractions corresponding to half the volume of the final preparation and 15% of the infused islets. In our experience, although tissue volume was strongly correlated with the rise in portal pressure during islet transplantation, we could not find a relationship between tissue volume infused and occurrence of portal vein thrombosis in a series of 93 intraportal islet infusions (5). There are no clear guidelines as to the need for long-term anticoagulation in the presence of thrombophilic disorders. The discovery of a thrombophilic disorder during a screening workup, in the absence of spontaneous thrombotic events, does not require indefinite anticoagulation as a rule. However, there is a consensus in recommending vigorous anticoagulation in high-risk settings, such as intraportal islet infusion (6). Immediate anticoagulation carries a higher risk of bleeding, which could be prevented by performing the intraportal infusion through an open surgical approach at the cost of losing the benefits of a minimally invasive procedure (5). This case report shows that FVL per se is not an absolute contraindication for islet transplantation. It requires tight coagulation control in order to balance the risks of developing portal vein thrombosis or intraperitoneal bleeding, which are the two most common complications of percutaneous intraportal islet infusion. In accordance with Brennan et al. (1), we recommend that all candidates for islet transplantation be screened for thrombophilia and all thrombogenic stimuli (oral contraceptives, smoking) be discontinued whenever possible. Effective anticoagulation by intravenous heparin should be started immediately upon completion of the procedure, at the risk of developing intraperitoneal bleeding. Infusing the islet preparation with an open approach should be considered. Axel Andres Domenico Bosco Philippe Morel Christian Toso Reto Baertschiger Pietro E. Majno Leo Buhler Thierry Berney Cell Isolation and Transplantation Center Department of Surgery Geneva University Hospitals Geneva, Switzerland