Hypercoagulability Evaluation in Pediatric Kidney Transplant Recipients to Optimize Outcomes

Introduction:

Kidney transplant has been shown to be the best treatment for children with end-stage kidney disease. Graft thrombosis is a well-recognized complication following kidney transplant and is one of the leading causes of early graft loss. Hypercoagulability has been implicated as a risk factor leading to graft thrombosis. Pre-transplant hypercoagulability evaluation can guide prophylactic strategies to mitigate thrombotic events and early graft loss, yet utility of universal screening for hypercoagulability in the pre-transplant population remains controversial. We report a single center experience of standardized pre-transplant thrombophilia screening and corresponding antithrombotic prophylaxis regimens that were implemented to predict and prevent thrombosis in pediatric kidney transplant (PKT) recipients.

Methods:

This is an IRB-exempt, single institution, quality improvement study of PKT recipients who underwent pre-transplant hypercoagulable evaluations to assess thrombotic risk at 6 months post-kidney transplant between 2017-2024. Data collected included personal and family history of thrombosis and laboratory tests for thrombophilia, including lipoprotein(a), serum homocysteine, factor VIII activity, protein C functional activity, protein S functional activity and free antigen, antithrombin III, antiphospholipid antibody panel, factor V Leiden and prothrombin gene mutation. Risk level for hypercoagulability concern was assessed based on history and laboratory results. Hematology recommendations were as follows: no antithrombotic therapy following transplant (Category 1: no history of thrombosis or laboratory abnormalities), prophylaxis with low-dose aspirin (LDA) post-transplant (Category 2: no history of thrombosis and 1-2 minor risk factors), or prophylaxis with heparin/Lovenox post-transplant (Category 3: personal history of thrombosis, major laboratory risk factor or >2 minor laboratory risk factors). Postoperative outcomes were focused on bleeding and clotting complications.

Results:

Among the 44 patients, the median age was 7 years (range: 1-18), with approximately 80% being male. Congenital anomalies of the kidney and urinary tract were present in 29 patients (65%). Eighteen patients fell into Category 1, with 10 of them initiated on LDA and one on clopidogrel despite hematology recommendations of no antithrombotic therapy. Category 2 included 20 patients, with 17 who received prophylaxis with LDA, one with clopidogrel, and two with no thromboprophylaxis. Category 3 comprised 6 patients (4 with a prior history of thrombosis), with 5 on Lovenox and one on LDA.

Two patients experienced both bleeding and thrombosis and one patient with thrombosis only. All 3 patients received LDA due to their risk factor categorization. Patient #1 initially received heparin due to an intra-operative renal artery clot and was later transitioned to Lovenox before being switched to LDA prior to discharge. Around one month post-op, the patient developed bleeding around his central line, at which time LDA was discontinued. Patient #2 had focal segmental glomerulosclerosis (FSGS) with nephrotic range proteinuria at the time of transplantation and underwent kidney biopsy, which confirmed recurrence of FSGS. Her post-op course was further complicated by hematoma around the biopsy site, requiring surgical evacuation and eventually embolization. A superficial vein thrombus was simultaneously found during evacuation of the hematoma. Additionally, she required numerous blood product transfusions during this time. Patient #3 developed a portal vein thrombus less than one month post-transplant and was transitioned to Lovenox. Of note, two of the above patients with thrombotic events had elevated lipoprotein(a). Fortunately, there were 15 other patients in our study with elevated Lp(a), in whom thrombosis was successfully prevented with the use of antithrombotic therapy.

Conclusion:

Our findings highlight the critical role of pre-transplant hypercoagulability evaluation in predicting and managing thrombosis risk in pediatric kidney transplant recipients. There were few bleeding and thrombotic complications, and these did not compromise transplant outcomes. Effective pre-transplant assessment and tailored prophylactic strategies are essential in reducing thrombotic risks and optimizing kidney transplant outcomes.

Crary:Novartis: Consultancy; ASC Therapeutics: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Medexus: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.