Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort

Abstract

Introduction: Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS.

Methods: From 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage.

Results: Eight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3-26 weeks, dose 3.2-5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6-11 weeks, dose 0.22-0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5).

Conclusions: Achieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.

Keywords: Anticoagulation; Infantile nephrotic; Low molecular weight heparin; Venous thromboembolism; Warfarin.

Fig. 1

Enoxaparin data. Graphs demonstrating individual patient enoxaparin dosing, therapeutic monitoring using anti-factor Xa, eGFR, and serum albumin. The left y-axis displays eGFR and serum albumin data; the right y-axis displays enoxaparin dose and anti-factor Xa level. The grey shaded area represents the target therapeutic range for thromboprophylaxis. The vertical grey dotted line represents an adverse event

Fig. 2

Warfarin data. Graphs demonstrating individual patient warfarin dosing, therapeutic monitoring using INR, eGFR, and serum albumin. The left y-axis displays eGFR and serum albumin data; the right y-axis displays warfarin dose and INR. The grey shaded area represents the target therapeutic range for thromboprophylaxis. The vertical grey dotted line represents an adverse event