The course of fibrinolytic proteins in children with malignant bone tumours

Abstract

To evaluate the role of fibrinolytic and proteolytic proteins in children and adolescents suffering from Ewing sarcoma or osteosarcoma with respect to postoperative complications and late outcome, a prospective two-arm two-centre study was conducted. Plasminogen, plasminogen activator inhibitor (PAI)-1, tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) were investigated in the pre-surgical period and in the postoperative follow-up period in children suffering from Ewing sarcoma (ES; n = 36) or osteosarcoma (OS; n = 39). In addition, the factor V mutation (FV) Q⁵⁰⁶, protein C, protein S, antithrombin and lipoprotein (a) were determined. All children received LMWH (Enoxaparin^R) 1 mg/kg sc. once daily over a period of 6 weeks to 3 months. Besides a short-lasting increase of PAI-1 in patients with OS on day 1 and in children with Es on day 14, a small and significant but clinically irrelevant difference was found on days 7–10 for plasminogen, t-PA and u-PA. No thromboembolic complications occurred in patients treated with LMWH and having a prothrombotic genetic risk factor. Within one year of surgery 7 out of 36 patients with ES and 5 out of 39 children with OS showed a relapse of their disease. Prior to the first local tumour therapy, 5 out of 7 children with ES and relapse had elevated u-PA concentrations compared with 2 out of 5 children in the OS group. No such differences were found for PAI-1- or t-PA antigen.

Conclusion The role of u-PA as a possible follow-up marker for a poorer outcome in children with ES should be evaluated in a prospective multicentre study.