In pediatric chronic renal failure cases with venous thromboembolismanticoagulant treatments and retrospective evaluation of results

Introduction Chronic renal failure (CRF) is associated with increased risk of bleeding and thromboembolism in pediatric patients. Hemostatic imbalance and impaired renal metabolism of low molecular weight heparins (enoxoparin) in pediatric CRF patients with venous thromboembolism, hinder appropriate dose determination and follow up of due to the increased risk of bleeding. Despite differences in management protocols among institutions, guidelines regarding optimal thrombosis management are still unavailable. Aim In this study, we retrospectively evaluated treatment modalities and outcomes in pediatric patients with chronic kidney failure and venous thromboembolism. Method Patients aged 0-18 years with chronic renal failure ( estimated glomerular filtration rate <50 ml/min/1.73m2), who underwent hemodialysis or peritoneal dialysis, and had venous thromboembolism while being followed up at our hospital between 2000 and 2020 were included. Thrombosis localization, thrombosis risk factors, antifactor Xa levels, treatment outcomes and side-effects were retrospectively evaluated. The data were analyzed using Microsoft Excel 2013 program. Results Of the 12 subjects (6 males, 6 females), the mean age at diagnosis was 11.8 years. All the patients had creatinine clearance <30 ml/min/1.73m2 and underwent hemodialysis. Thrombosis localizations were variable with external iliac vein (26%) and jugular vein (21%) being the most common sites. Thrombophilia risk factors was present in 9 patients (75%). The most common thrombophilia risk factor was increased factor VIII levels. All of the patients received enoxoparin treatment. Enoxoparin 50 U/kg/day was initiated in 8 of 12 patients (66.6 %). Other 4 patients received enoxoparin at 100 U/kg/day, 66 U/kg/day, 62.5U /kg/day, and 30U/kg/day doses. Anti-factor Xa level were checked 4.6 days after the initiation of the treatment. Antifactor Xa follow-up results were unavailable in 3 patients. Mean antifactor Xa level was 0.58 U/ml. The mean duration of treatment with enoxaparin vii was 2.6 (1-6) months. Thrombosis resolution was recorded in all patients. Mild mucosal bleeding was detected in one case as a side effect of treatment. 4 patients (33%) died due to underlying primary disease while there was no mortality associated with thrombosis in our patients. Conclusion The most important drawback of enoxaparin treatment for thrombosis in pediatric patients with chronic renal failure is increased risk of bleeding. There are no studies regarding neither optimal enoxaparin dose nor enoxaparin-associated bleeding frequency in pediatric hemodialysis patients with thromboembolism. While adult studies suggest 50% dose reduction in cases with low creatine clearance, the only pharmacokinetic study in children recommends 30% dose reduction. In our study, 66,6% of the cases received 50 U/kg/day enoxaparin and the dose was reduced by 75%. Administration of 50 U/kg/day enoxoparin subcutaneously on non-dialysis days and 50 U/kg/day during dialysis session seems to be safe and effective for treating thromboembolism in pediatric patients with creatinine clearance <30 m/min/1.73 m2 while on hemodialysis. Future randomized controlled trials in this issue are warranted. Keywords: Thromboembolism, Bleeding, Chronic renal failure, Anticoagulation, Anti- factor Xa, Low molecular weight heparin (LMWH)