EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Hemophilia C is a rare bleeding disorder, and such patients with chronic kidney disease are at risk for bleeding during kidney transplant surgery. Kidney transplant patients with hemophilia C can be managed meticulously through a protocol to maintain a coagulation profile in the reference range. Here, we present a case study that focused on a treatment protocol for a patient with chronic kidney disease and hemophilia C who underwent kidney transplant surgery. Patients with hemophilia C who develop chronic kidney disease stage 5 can safely undergo a kidney transplant or any other major surgery using the defined protocol.

Key words : Chronic kidney disease, Factor XI deficiency, Hematuria, Spontaneous bleeding

Introduction
Hemophilia C is a rare bleeding disorder, which is often underdiagnosed because spontaneous bleeding complications are unusual. Patients with hemophilia appear to have a higher prevalence of chronic kidney disease (CKD) than the general population.¹ The increased prevalence can be attributable to increased life expectancy, which leads to age-related diseases such as diabetes and hypertension in patients with hemophilia. The further management of renal diseases in patients with hemophilia, especially when such patients are candidates for renal transplant surgery, obliges coagulation factor administration during surgery.

Here, we report the case of a young male patient with CKD who was referred for kidney transplant surgery and was diagnosed with hemophilia C during the course of the pretransplant workup. The renal transplant was successfully performed after preparation of a meticulous preoperative and postoperative management regimen in collaboration with the hematology team. To our knowledge, this is the first reported case of a patient with hemophilia C who underwent a successful kidney transplant.

Case Report
A 27-year-old Indian male patient was diagnosed with CKD stage 5 and had been receiving hemodialysis since January 2021. He was referred for kidney transplant surgery with his brother as donor. General examination of the patient showed unremarkable findings. Routine investigations indicated all parameters to be within the reference range, with one exception: during the pretransplant workup, the patient was found to have isolated a prolonged activated partial thromboplastin time (aPTT) ranging from 95 to 110 seconds (reference range, 20.5 to 30.5 seconds) on multiple occasions.

An evaluation of past records revealed that the patient had presented 13 years ago with pedal edema, proteinuria, and high serum creatinine. A renal biopsy confirmed the etiology of immunoglobulin A nephropathy. A review of records indicated a prebiopsy aPTT of 48 seconds. However, no further workup was performed by the treating unit for the abnormal aPTT report. The patient had no history of postbiopsy hematuria or any spontaneous bleeding over the last 13 years. In addition, the patient had no history of prolonged bleeding after dental procedures and no history in childhood or adolescence of easy bruising, nose bleeds, or hematuria prior to kidney biopsy.

In view of the repeated prolonged aPTT report, despite strict heparin-free dialysis, the patient was referred to a hematologist. Mixing studies were performed and were suggestive of a factor deficiency. A detailed investigation of each factor revealed that factor XI levels were 2.5%, (which is below the reference threshold of 20%) and suggestive of factor XI deficiency, thereby confirming the diagnosis of hemophilia C. Serum levels of factor VIII, factor IX, and factor XII were within reference ranges. A joint review of hematology concluded that the appropriate treatment protocol for the correction of his bleeding disorder should be fresh-frozen plasma (FFP) transfusion.

On the day before the operation, his pretransfusion aPTT was 92.1 seconds, and 4 units of FFP were transfused; the posttransfusion aPTT was 32.5 seconds. The patient was taken to surgery after he received an antithymocyte globulin immunosuppression induction agent (Grafalon). The patient was also given tacrolimus, steroids, and mycophenolate mofetil as immunosuppression therapy. The donor with single left renal artery and vein underwent left donor nephrectomy. The transplant surgery to the recipient was uneventful, with blood loss of approximately 200 mL and no other immediate complications. After the renal transplant surgery, the patient had a clear urine output. In the postoperative period, the patient was given 4 units of FFP every day for the next 3 consecutive days. He was monitored twice daily for complete blood count, kidney function tests, and specifically his aPTT levels, before and after transfusion, which were maintained in the reference range. Although the patient had a reduction in hematocrit values, he did not require any postoperative blood transfusion. He was also thoroughly examined daily for any bleeding manifestations and other clinical complications, which included daily abdominal ultrasonography. The patient remained stable and was discharged on postoperative day 7 with a patent, functional graft.

At the 3-month posttransplant follow-up, the patient continued to demonstrate a stable graft function with no further episodes of spontaneous bleeding or other complications. His complete blood count and kidney function test values have remained in the reference range, but the aPTT remained deranged.

Discussion
Hemophilia is a group of rare genetic blood disorders caused by coagulation factor deficiency. Of these disorders, hemophilia A is the most common and also has the most severe bleeding episodes. Hemophilia C is a rarer form of hemophilia caused by a deficiency in clotting factor XI and has a global prevalence of only 1 case per million population.² Unlike other types of hemophilia (hemophilia A and hemophilia B), patients with hemophilia C demonstrate less serious symptoms with fewer reported cases of spontaneous or excessive bleeds; thus, hemophilia C remains an underdiagnosed disease.

Hemophilia C was first recognized in 1953 in patients who experienced severe bleeding after dental extractions. Furthermore, despite a definitive diagnosis, there is no correlation between factor XI levels and coagulation studies, so the nature of bleeding in such patients remains rather unpredictable.³ These patients are usually asymptomatic, and the common clinical presentation is a tendency for injury-related bleeding that commonly occurs after surgery or trauma involving tissues rich in fibrinolytic activators.^4,5 Hence, even today, most cases of hemophilia C are diagnosed incidentally after excessive bleeding is discovered as a complication during a surgical procedure. There is paucity of data for renal replacement therapy in hemophilia. We are not aware of any previous report of kidney transplant in hemophilia C. An optimal perioperative protocol for hemophilia C patients is yet to be determined.⁵

In our index case, there was no significant history of any unusual bleeds reported in the patient after kidney biopsy or during arteriovenous fistula creation. He also did not have any prolonged ooze during any of his hemodialysis sessions despite routine use of anticoagulation. Kidney transplant remains a high-risk surgery for these patients, as surgeries involving the mucosal surfaces and urinary tract (which have a higher fibrinolytic activity) are more prone to excessive bleeding.⁶ Close monitoring, replenishment with factor XI concentrate, or use of FFP is recommended. Because of lack of availability of factor XI concentrate, FFP is used as the primary modality for management and has shown equivalent outcomes. One must not forget that FFP transfusions carry a risk of anaphylaxis as well as overload if not used judiciously.⁷ Monitoring aPTT levels can help to diagnose a bleeding tendency but also can help monitor the course of anticoagulant therapy. The goal is to maintain the aPTT levels close to the established reference range using preemptive FFP transfusions and regular monitoring.

Renal transplant surgery in such cases can be also complicated by intravesicular thrombosis, which may lead to graft dysfunction.⁸ Fortunately, our patient had an uneventful course and did not experience any postsurgical complications. This positive outcome was the result of a rigorous collaborative approach with the hematology team and meticulous planning in the pretransplant period to devise a therapeutic protocol for FFP infusions and for monitoring in the postoperative period. Therefore, we emphasize the importance of a thorough pretransplant workup including coagulation profile as a screening measure in all patients with CKD. Patients with deranged coagulation profile should be investigated further in collaboration with a hematology team.

Thus a meticulous pretransplant workup including a coagulation profile should be applied in all patients with CKD stage 5 who are scheduled for kidney transplant so that a previously undiagnosed coagulation disorder can be discovered in the preoperative period. Patients with hemophilia C who develop CKD stage 5 can be safely planned for a kidney transplant or any other major surgery using the protocol we have devised and presented in this report.

Volume: 22 Issue: 11 November 2024

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