Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies

BACKGROUND: The aim of the present study was to estimate the impact of inherited thrombophilia (IT) on the risk of venous thromboembolism (VTE) onset and recurrence in children by a meta-analysis of published observational studies. METHODS AND RESULTS: A systematic search of electronic databases (Medline, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2007 was conducted using key words in combination as both MeSH terms and text words. Citations were independently screened by 2 authors, and those meeting the inclusion criteria defined a priori were retained. Data on year of publication, study design, country of origin, number of patients/controls, ethnicity, VTE type, and frequency of recurrence were abstracted. Heterogeneity across studies was evaluated, and summary odds ratios and 95% CIs were calculated with both fixed-effects and random-effects models. Thirty-five of 50 studies met inclusion criteria. No significant heterogeneity was discerned across studies. Although >70% of patients had at least 1 clinical risk factor for VTE, a statistically significant association with VTE onset was demonstrated for each IT trait evaluated (and for combined IT traits), with summary odds ratios ranging from 2.63 (95% CI, 1.61 to 4.29) for the factor II variant to 9.44 (95% CI, 3.34 to 26.66) for antithrombin deficiency. Furthermore, a significant association with recurrent VTE was found for all IT traits except the factor V variant and elevated lipoprotein(a). CONCLUSIONS: The present meta-analysis indicates that detection of IT is clinically meaningful in children with, or at risk for, VTE and underscores the importance of pediatric thrombophilia screening programs

Port-a-cath-related thrombosis and postthrombotic syndrome in pediatric oncology patients

OBJECTIVE: To investigate Port-A-Cath (PAC)-related thrombosis and postthrombotic syndrome (PTS) in children with cancer. STUDY DESIGN: The study population was a consecutive cohort of children diagnosed with cancer and a PAC implanted at diagnosis. Children were evaluated for the presence of PAC-related thrombosis by magnetic resonance venography and the presence of congenital prothrombotic risk factors and PTS. RESULTS: A total of 114 children (median age, 6.04 years) were included. Of these children, 48 (42%) were treated for solid tumors and 66 (58%) were treated for hematopoietic tumors, including 38 for acute lymphoblastic leukemia. At the time of magnetic resonance venography, 42 children (37%) had the PAC still in place, and 72 (63%) had the PAC removed. Overall, PACs were in place for a total of 324.92 PAC-years. PAC-related thrombosis was detected in 45 children (39.5%) with a current or previous PAC. Of these, 21 (47%) had a solid tumor, 14 (31%) had acute lymphoblastic leukemia, and 10 (22%) had another hematopoietic tumor. Younger age at diagnosis, female sex, duration of PAC use, and left-side PAC placement were independently associated with an increased risk of thrombosis, whereas asparaginase therapy and the presence of inherited prothrombotic risk factors were not. Mild PTS (ie, presence of prominent collateral vessels in the skin) was present in 5.6% of the children. CONCLUSION: PAC-related thrombosis is common in pediatric oncology patients. In some children, thrombotic complications can lead to the development of PTS

Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies

The aim of this study was to estimate the impact of thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). The present meta-analysis indicates that thrombophilias serve as risk factors for incident stroke. However, the impact of thrombophilias on outcome and recurrence risk needs to be further investigate