Factor V deficiency is a congenital bleeding diathesis that, in selected cases, may be managed with liver transplant. In this case, we describe the treatment of an adult patient with kidney failure secondary to juvenile onset polycystic kidney disease who received a combined liver-kidney transplant as a method to manage the risks associated with the need for a kidney transplant in the setting of factor V deficiency and high sensitization.
Key words : Congenital bleeding diathesis, Juvenile onset polycystic kidney disease, Kidney failure, Rare inherited coagulation disorder
Isolated factor V deficiency is a rare inherited coagulation disorder (RICD) with an estimated prevalence of around 1 in 1 000 000 population. The chief clinical consequence is a higher propensity for bleeding.1-3 Factor V is a clotting factor produced by the liver and is involved in the common coagulation pathway. Patients with factor V deficiency typically have derangements in both prothrombin time (PT) and activated partial thromboplastin time (aPTT).4 The likelihood and severity of bleeding manifestations can vary depending on genetic characteristics and serum levels,5 and this can pose a challenge in the treatment of any surgery patient, let alone a candidate for a solid-organ transplant. Factor V deficiency, among other RICDs, is often managed perioperatively with coagulation factor replacements, typically in the form of fresh frozen plasma (FFP).4,6 However, ongoing use of blood products exposes high-risk immunosup-pressed solid-organ recipients to the significant consequences of volume overload, transfusion reactions, and transmission of potential pathogenic organisms.7 There is a scarcity of available data to guide the management of isolated factor V deficiency in surgery, especially with regard to solid-organ transplant.
This case represents, to our knowledge, the first report in the literature to describe combined liver-kidney transplant as concurrent management of factor V deficiency and end-stage kidney disease. It demonstrates the feasibility of a combined liver-kidney transplant as a method to negate the need for coagulation factor replacement after solid-organ transplant surgery with good short-term outcomes.
A 23-year-old male patient with a history of isolated factor V deficiency (factor V levels <3%) presented for consideration of isolated kidney transplant for end-stage kidney disease secondary to autosomal recessive juvenile polycystic kidney disease. He had commenced peritoneal dialysis at the age of 14 years; although a transplant had been considered, progress was hampered because of combined concerns of bleeding risk and high sensitization with panel reactive antibody results of 100% (Figure 1). His factor V deficiency caused frequent episodes of epistaxis but no major bleeding and no regular requirement for factor V replacement. His liver function was otherwise normal.
After multidisciplinary assessment by hepatolo-gists, nephrologists, hematologists, and transplant surgeons, the decision was made to proceed with a combined liver-kidney deceased donor transplant, given the concern for the short-term and long-term bleeding risks after transplant. Previous exposure to blood products had caused this patient to become broadly and highly sensitized, with class 1 and class 2 human leukocyte antigen antibodies. This meant that the chance of being allocated a kidney alone was low and that the risk of rejection was relatively high. The former meant that the mortality risk by staying on dialysis was higher than transplant, and the latter meant the likelihood of multiple kidney biopsies and thus risk of bleeding in a patient with Factor V deficiency following an isolated kidney transplant would be significant. Therefore, we decided to proceed with combined transplant. Preoperatively, the patient had mild anemia (hemoglobin = 108 g/L, mean corpuscular volume = 90 fL) and deranged coagulation test results (PT = 30.2 seconds, aPTT = 70 seconds, international normalized ratio = 2.6) with a factor V level of 3%. His liver function and electrolyte test results were within reference ranges.
Immediately prior to his surgery, the patient received 4 U of FFP. It was known that the patient had a 6/6 human leukocyte antigen mismatch and donor-specific antibodies (class 1), so he received induction with 500 mg of intravenous methylprednisone and 1 mg/kg thymoglobulin for 4 days, with maintenance therapy of tacrolimus, mycophenolate, and prednisone. A combined liver-kidney transplant was performed via 2 separate incisions (right side, hockey stick; left side, Rutherford-Morrison). His operation was uncomplicated, with an estimated blood loss of 1000 mL that required 4 U of packed red blood cells, 10 U of intraoperative cryoprecipitate, and 237 mL of blood returned from cell salvage. No intraoperative FFP was required. The patient had a good postoperative recovery, with a creatinine level that fell to 160 μmol/L by postoperative day 20. He did not have any hemorrhagic complications and did not require postoperative transfusion of blood or blood products. His coagulation normalized (PT = 11.1 seconds, aPTT = 25 seconds, international normalized ratio = 1.0) with a factor V level of 156% on postoperative day 20 (Figure 2).
Factor V deficiency is a rare disease, and there are very limited available data to guide management of the bleeding risk generally and even less data with regard to the context of the requirement for procedures such as transplant with a high risk of bleeding, both at the time of surgery and with the potential requirement for repeat kidney allograft biopsies. It is difficult to predict or quantify the degree of bleeding risk in such patients, and thus, the prediction of the extent of intervention is also uncertain. The limited reports of surgery in the context of factor V deficiency have described a range of frequency and duration of FFP transfusion requirements, dependent on the degree of severity of factor V deficiency, as well as the occurrence of perioperative and postoperative bleeding.6,8-11 However, such reports have shown few details on the types of surgery and the associated bleeding risk profiles.
There is a paucity of data on liver transplantation for the treatment of factor V deficiency. We have identified 2 case reports that documented this strategy in the setting of severe symptomatic isolated factor V deficiency. Both of these cases occurred in infants, aged 2 years and 11 months, respectively, who underwent liver transplant to address recurrent intracranial hemorrhage secondary to factor V deficiency.12,13 Factor V levels were corrected by the liver transplant, and the recipients did not require further plasma infusions.
With regard to the bleeding risk associated with RICDs in patients who require solid-organ transplant, there is also a scarcity of data to provide guidance. In 2 cases, excellent outcomes and absence of bleeding complications have been reported with use of recombinant factor VII perioperatively in patients with factor VII deficiency who required kidney transplant.14,15 However, both of these cases describe the use of large volumes of recombinant factor VII before and after surgery.14,15
In our highly sensitized kidney transplant recipient, the combined liver-kidney transplant eliminated the long-term risk of hemorrhage in a young person with many potential future years at risk by correcting the factor V deficiency. In addition, the liver aspect of the combined transplant provided an increased opportunity to find a suitable immunological match due to the immune protection afforded by the liver transplant. To our knowledge, there are no previously published reports to date of a combined liver-kidney transplant for this indication.
Our case demonstrates, for the first time to our knowledge, that a combined liver-kidney transplant is feasible in cases where kidney transplant is considered high risk because of a condition of RICD such as factor V deficiency.
Volume : 20
Issue : 11
Pages : 1043 - 1045
DOI : 10.6002/ect.2022.0229
From the 1Department of Transplant Surgery, the 2Department of Renal Medicine, the 3A. W. Morrow Gastroenterology and Liver Centre, and the 4Department of Haematology, Royal Prince Alfred Hospital, Camperdown; and the 5Institute of Academic Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Jerome Martin Laurence, Department of Transplant Surgery, Royal Prince Alfred Hospital, Missenden Road, Camperdown, 2050, NSW, Australia
Phone: +61 2 6515 6111
Figure 1. Transplant Immunology
Figure 2. Postoperative Factor V Levels