Organ transplant in patients with congenital bleeding disorders is a challenge requiring an integrated approach of various specialists. Inherited factor VII deficiency is the most common of the rare bleeding disorders, with a wide set of hemorrhagic features. Although a kidney allograft is the most frequent type of solid-organ transplant, it is rarely performed in individuals with congenital hemorrhagic disorders. Here, we highlight the course of a patient with coagulation factor VII deficiency who underwent successful kidney transplant without significant coagulopathy. Our patient was a 19-year-old man with end-stage kidney disease and congenital coagulation factor VII deficiency. Perioperative bleeding was successfully prevented by administration of recom-binant factor VII, confirming its safety in solid-organ transplants. Success requires evaluation of doses and therapeutic schedules, as well as a multidisciplinary approach.
Key words : Bleeding disorder, Congenital coagulation, End-stage kidney disease
Coagulation factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder resulting from mutations of the gene encoding for FVII, the protein that starts the extrinsic coagulation pathway.1-3 Coagulation factor VII deficiency produces an isolated prolongation of the prothrombin time combined with a normal activated partial throm-boplastin time.4 Once suspected, the FVII assay (FVII:C) can be easily performed. Clinical mani-festations include bleeding symptoms ranging from mild gum and muscle bleeding to severe life-threa-tening intracranial and gastrointestinal bleeding. Unlike hemophilia, there is a poor correlation between the level of residual circulating FVII and the severity of bleeding, which makes bleeding in FVII-deficient patients unpredictable.4
Surgical operations are challenging, and bleeding is common, often requiring replacement therapy with concentrates of the missing factor. However, clear data regarding therapeutic schedules and experiences in major surgeries are lacking. Bleeding has been reported among a fraction of patients treated with replacement therapy.5 Among solid-organ transplant recipients with this bleeding disorder, the data are extremely limited. Therefore, we aimed to highlight the course of the transplant in a patient with FVII deficiency who underwent successful kidney transplant and postoperative graft biopsy using recombinant activated FVII (rFVIIa), without significant coagulopathy.
A 19-year-old male patient presented with a history of type 1 diabetes mellitus, with its microvascular complications, in addition to congenital deficiency of coagulation FVII. He was hypertensive and started hemodialysis via a chronic silicone oval catheter in the right internal jugular vein (Permcath; Medtronic, Minneapolis, MN, USA). The catheter was smoothly inserted, without any bleeding events, a few months before a planned related living-donor renal trans-plant from his father.
We were faced with the dilemma of balancing the perioperative risk of bleeding due to his FVII deficiency and the induced risk of thrombosis when using rFVIIa. A multidisciplinary committee recom-mended transplant with rFVIIa replacement with close perioperative monitoring of international normalized ratio (INR), which ranged between 4.7 and 5.2 before transplant.
In view of his low immunologic risk (multiple myeloma risk = 2, negative panel reactive antibodies, negative complement-dependent cytotoxicity, and flow cytometry crossmatch), the patient received basiliximab as induction, and he was maintained on prednisolone, cyclosporine, and mycophenolate mofetil. Recombinant activated FVII was administered 30 minutes before incision, with a measurement of INR at 6 hours after the dose (which was normal) and then monitoring of INR on a timely basis. Repeat dosing of rFVIIa (total of 6 doses) was given for the next 3 days postoperatively when the INR exceeded 2.5, to prevent possible thrombosis. For this, we depended only on the practicality of INR monitoring, not on FVII activity itself. On day 7, his serum creatinine plateaued to around 180 μmol/L for 4 days. Pretransplant and posttransplant renal causes were excluded, and graft biopsy was performed after reversal of FVII deficiency with only 1 dose of rFVIIa of 45 μg/kg. The biopsy showed severe acute tubular necrosis and negative C4d. Currently, graft function remains stable in this patient.
Congenital FVII deficiency is a challenging disorder to manage.6 The risk of bleeding should not be underestimated during hemostatic challenges, such as major surgery, even in asymptomatic individuals, as the minimal safe levels of FVII:C to ensure hemostasis in different clinical situations has not been well defined.7,8 Furthermore, there are no standard guidelines for the management of con-genital FVII deficiency. However, data from the International Registry of FVII Deficiency have been helpful in providing clinical guidance.9,10
In a retrospective analysis of 157 patients with FVII deficiency, the authors described an algorithm for surgical intervention based on age, FVII:C levels, type of procedure, and personal bleeding history. These authors also suggested that not all patients should receive replacement therapy, as the treatment is expensive and not required for all surgical procedures.7 For our patient, we depended on the INR level to monitor the risk of bleeding and not on the level of FVII. We administered rFVIIa 30 minutes before the incision, and then we followed INR levels on a timely basis. There were no significant inci-dences of intraoperative or postoperative bleeding, even after a kidney graft biopsy.
Lapecorella and associates reported that they depended on both the level of FVII and INR to adjust doses of rFVII over the first 6 days posttransplant.11 Sander and colleagues described a kidney transplant patient who recovered from massive intraoperative bleeding after thrombectomy and receiving rFVII.12 Guy and associates reported a case of a deceased liver donor with FVII deficiency that conveyed to the recipient; however, the operation had no incidences of bleeding, and the recipient did not require replacement with rFVII.13 Ranucci and associates concluded from their meta-analysis that treatment with rFVIIa is effective in reducing the rate of patients undergoing transfusion with allogeneic packed red blood cells.14 Ranucci and associates also reported that treatment with rFVIIa is not associated with increased rates of thromboembolic events or mortality.14 Another meta-analysis published in 2008 concluded that 73% of the patients who received rFVII achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa.15 Use of rFVIIa was not associated with an increased risk of throm-boembolism compared with placebo.15 This finding is in agreement with our case, as our patient did not develop any thrombotic events during the main surgery or during graft biopsy.
Renal transplant surgery is feasible among patients with coagulation FVII deficiency with close monitoring of INR after its replacement.
Volume : 17
Issue : 1
Pages : 142 - 144
DOI : 10.6002/ect.MESOT2018.P9
From the 1Nephrology Department, Hamed Al-Essa Organ Transplant Center, Sabah
Area, Kuwait; the 2Department of Dialysis and Transplantation, Urology
Nephrology Center, Mansoura University, Egypt; and the 3Department of
Hematology, Ibn Sina Hospital, Kuwait
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Osama Ashry Gheith, Hamed Al-Essa Organ Transplant Center, Ministry of Health – Ibn Sina Hospital, Kuwait
Phone: +96 566641967