Fraxiparine

Retrospective single-center PK study was conducted at Children’s Hospital of Fudan University from July 2021 to December 2023. This study enrolled preterm or term neonates and infants under 8 months with suspected or diagnosed arterial or venous thrombosis who were receiving nadroparin (Fraxiparine^®; GlaxoSmithKline, Brentford, UK). All eligible patients were treated in accordance with the local protocol, receiving subcutaneous nadroparin at a dose of 150–200 IU/kg q12 h. Participants with anti-Xa levels below the limit of quantitation were excluded from pharmacokinetics evaluation. The protocol was approved by the Ethics Committee of our hospital.
The following data were collected from electronic medical records: gender, gestational age (GA), postnatal age (PNA), postmenstrual age (PMA), birth body weight (BBW), body weight (BW), height (HT), body surface area (BSA, $BSA{\left(m\right)}^2=\sqrt{\frac{HT\left(cm\right)*BW\left(kg\right)}{3600}}$ ), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), urea nitrogen (BUN), serum creatinine (SCR), creatinine clearance rate (CLCR, $CLcr\left(mL/\mathit{min}/1.73m^2\right)=k*HT\left(cm\right)/Scr\left(mg/dL\right)$ , where k = 0.33 for preterm infants and k = 0.45 for term infants throughout the first year of life) (Schwartz et al., 1984 (link)), cystatin C (CysC), and serum albumin (ALB).

Patients are discharged on the day after surgery after being instructed by a physiotherapist about using crutches and rehabilitation for the first 2 weeks. We do not use any immobilisation neither orthosis. Thromboprophylaxis is provided with Fraxiparine (nadroparin calcium, GlaxoSmithKline) 0.6 ml administered subcutaneously once a day. Partial weight bearing is allowed immediately after the surgery and full weight bearing after 2 weeks if tolerated. There are no limitations in the active range of motion of the operated foot. A follow-up postoperative x-ray is obtained at 2 weeks post-surgery.

Confluent WISH cell monolayers were detached by trypsin-EDTA treatment (Sigma-Aldrich, St. Louis, MO, USA) and were seeded in a 96-well plate (Corning^®, Corning, NY, USA) at a density of 1 × 10⁶ cells/mL. Cells were treated with:

100 ng/mL IFNγ purified as described in [13 (link)],

IFNγ (100 ng/mL) supplemented with Fraxiparine (GlaxoSmithKline Pharmaceuticals S.A.) in concentrations varying from 1.5 to 150 anti-Xa IU/mL pre-incubated for 1 h at room temperature, and

Fraxiparine in the same concentrations as in ii. Further, the antiproliferative activity of IFNγ was measured by a modified kynurenine bioassay as described earlier [12 (link)].