Abstract

Abstract 3415

Background:

The incidence of venous thrombotic events (VTE) in children has risen substantially over the past decade, resulting in increasing use of anticoagulants and making it imperative that pharmacokinetic (PK) and pharmacodynamic studies be performed in children. Fondaparinux has several advantages over low molecular weight heparins including once-daily dosing, no risk for heparin-induced thrombocytopenia, and possibly reduced effects on bone mineral metabolism. A PK, dose-finding, and safety study of fondaparinux was published; however it only studied relatively short-term outcomes and adverse effects. The purpose of this study was to investigate the long-term safety, dosing, and efficacy of fondaparinux in children.

Methods:

The study included all children 1–18 years (yrs) old treated consecutively with fondaparinux in a single institution between September 1, 2007 and June 20, 2011. The following data were abstracted from the medical records: demographics, location of initial VTE, fondaparinux dosing and levels, bleeding events, other adverse events, status of VTE at each subsequent imaging study (complete resolution, partial resolution, no change, or progression), and VTE recurrence. Descriptive statistics are used to describe the patients and the outcomes.

Results:

Data from 22 patients were collected and all were available for the safety analysis while 19 were analyzed for dosing (1 excluded due to only receiving 2 doses secondary to an allergic reaction and 2 excluded for ineligible diagnoses) and 16 for efficacy (1 excluded due to allergic reaction, 1 because fondaparinux was given as prophylaxis, and 4 due to ineligible diagnoses/insufficient data). There were 11 females (F) and 11 males (M) (10 F and 9 M analyzed for dosing; 9 F and 7 M for efficacy). The mean age of the patients was 9 yrs (median: 10 yrs; range: 1–17 yrs). The mean duration of treatment with fondaparinux was 377 days (d) (median: 171 d; range: 6–1566 d). The mean dose of fondaparinux was 0.1 mg/kg/dose (median: 0.1 mg/kg/dose; range: 0.07–1.4 mg/kg/dose). Nine of 16 evaluable patients (56.3%) had complete resolution of their thrombus while 6/16 (37.5%) had partial resolution, and 1/16 (6.3%) had no change in their thrombus. Thus, 15/16 (93.8%) patients had either a complete or partial response and 0/16 had progression. The mean time to best outcome from initiation of fondaparinux was 110.5 d (median: 63 d; range: 4–487 d). Seven patients needed a total of 12 dose adjustments (one subject with 3 adjustments and one with 4) to achieve therapeutic levels. Three patients (18.8%) (2 had prior complete resolution of the initial VTE) had a recurrent VTE. Two patients were on fondaparinux at the time of recurrence and 1 was on warfarin. There were 2 major (intracranial hemorrhage- occurred prior to initiation of fondaparinux and subretinal hemorrhage) and 3 minor (all with blood in stool) bleeding events. One patient had an allergic reaction after starting fondaparinux.

Conclusions:

In this long-term follow-up study on children treated with fondaparinux for VTE, 95% of patients had either complete or partial resolution while the recurrence rate was in line with previous studies. There were 5 bleeding events (2 major and 3 minor), though only 1 event required the discontinuation of fondaparinux. Given the advantages of fondaparinux over other anticoagulants, this study suggests that fondaparinux could be considered a safe and effective alternative for the management of VTE in children.

Table 1.

Demographics, Treatment Information, and Outcomes of Patients Eligible for Efficacy Analysis

Subject Age (yrs) Gender Ethnicity/Race Duration of Tx (d) Final Dose (mg/kg) # of Dose Adj. Response to Tx Duration of Tx for Response (d) Recurrent Event Bleeding Events 
F-1 H/O 1566 0.12 487 
F-2 17 H/O 20 0.12 49 
F-3 16 H/O 1537 0.1 102 
F-4 H/O 18 0.1 13 Minor: BRBPR 
F-6 H/O 72 0.1 
F-7 NH/W 294 0.11 62 
F-8 12 NH/O 216 0.13 215 
F-10 17 NH/W 72 0.09 63 
F-11 14 H/W 314 0.11 61 
F-12 12 H/W 0.1 11 Major: ICH 
F-13 15 NH/AfAm 89 0.1 22 
F-14 H/W 171 0.1 139 
F-15 H/W 13 0.1 104 
F-16 H/W 357 0.14 153 
F-20 16 NH/W 719 0.07 37 Minor: BRBPR 
F-21 15 H/O 96 0.09 28 Major: sub-retinal 
Subject Age (yrs) Gender Ethnicity/Race Duration of Tx (d) Final Dose (mg/kg) # of Dose Adj. Response to Tx Duration of Tx for Response (d) Recurrent Event Bleeding Events 
F-1 H/O 1566 0.12 487 
F-2 17 H/O 20 0.12 49 
F-3 16 H/O 1537 0.1 102 
F-4 H/O 18 0.1 13 Minor: BRBPR 
F-6 H/O 72 0.1 
F-7 NH/W 294 0.11 62 
F-8 12 NH/O 216 0.13 215 
F-10 17 NH/W 72 0.09 63 
F-11 14 H/W 314 0.11 61 
F-12 12 H/W 0.1 11 Major: ICH 
F-13 15 NH/AfAm 89 0.1 22 
F-14 H/W 171 0.1 139 
F-15 H/W 13 0.1 104 
F-16 H/W 357 0.14 153 
F-20 16 NH/W 719 0.07 37 Minor: BRBPR 
F-21 15 H/O 96 0.09 28 Major: sub-retinal 

Tx-treatment, H-Hispanic, NH-non-Hispanic, W-white, O-other, AfAM-African-American, C-Complete Resolution, P-Partial Resolution, U-Unchanged, BRBPR-bright red blood per rectum, ICH-intracranial hemorrhage.

Disclosures:

Off Label Use: fondaparinux: anti-coagulation for the treatment of venous thromboembolic events in children. Young:Biogen Idec: Research Funding; Baxter: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.