title: Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters.
abstract: We prospectively evaluated the clinical relevance of genetic risk factors of thrombosis in 137 paediatric patients with solid tumours or leukaemia/lymphoma. The factor V G1691A (FV-L), the prothrombin G20210A (FII-L) and the homozygous MTHFR variant were examined. In addition, protein C, protein S and antithrombin (AT) deficiency were evaluated in patients with ALL or thrombosis. The inter-group incidence of risk factors and thrombotic events was compared. 73 of the 137 patients had ALL and 64 another form of leukaemia, lymphoma or a solid tumour. They were treated according to the established paediatric tumour protocols ALL-BFM, NHL-BFM, COSS, CWS and others. All patients had central venous lines. No patient received heparin or any other anticoagulant. Endpoints of the study were thrombosis, regular completion of chemotherapy or death. Incidence of mutations in the whole group: FV-L (7.3% heterozygous, 0.7% homozygous); FII-L (2.9% heterozygous, no homozygotes); MTHFR (51.8% heterozygous, 10.9% homozygous). Ten patients (7.3%), 6 with ALL and 4 with solid tumours, developed thrombosis. 4 of the 6 patients with ALL and thrombosis (67%) but only 21% of ALL patients without thrombosis had a genetic risk factor (P < 0.013, chi2). No genetic defect was found in the 4 patients with other malignancies and thrombosis. However, besides a tumour, these patients had additional exogenous risk factors including diabetes insipidus and hemiparesis.
  
  
  CONCLUSIONS
  Genetic mutations appear to be additional risk factors for the development of thrombosis in patients with ALL. In contrast, these mutations do not appear to be relevant risk factors for thrombosis in the small number of children with other malignant diseases reported here. This difference may be due to asparaginase and corticosteroids being used in ALL but not in solid tumour protocols.
authors.affiliation: Department of Paediatric Haematology and Oncology, Hanover Medical School, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wermes
authors.forename: M
authors.initials: M
authors.lastname: von Depka Prondzinski
authors.forename: R
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: M
authors.initials: M
authors.lastname: Barthels
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: K W
authors.initials: KW
authors.lastname: Sykora
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D001215:Asparaginase / Q000009:adverse effects; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D011446:Prospective Studies; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase