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

被引：288

作者：

Kenet, Gili ^{[2
]}

Luetkhoff, Lisa K. ^{[1
]}

Albisetti, Manuela ^{[3
]}

Bernard, Timothy ^{[4
,5
,6
]}

Bonduel, Mariana ^{[7
]}

Brandao, Leonardo ^{[8
]}

Chabrier, Stephane ^{[9
]}

Chan, Anthony ^{[10
]}

deVeber, Gabrielle ^{[8
]}

Fiedler, Barbara ^{[11
]}

Fullerton, Heather J. ^{[12
]}

Goldenberg, Neil A. ^{[4
,5
,6
]}

Grabowski, Eric ^{[13
]}

Guenther, Gudrun ^{[14
]}

Heller, Christine ^{[15
]}

Holzhauer, Susanne ^{[16
]}

Iorio, Alfonso ^{[17
]}

Journeycake, Janna ^{[18
]}

Junker, Ralf ^{[19
]}

Kirkham, Fenella J. ^{[20
,21
]}

Kurnik, Karin ^{[22
]}

Lynch, John K. ^{[23
]}

Male, Christoph ^{[24
]}

Manco-Johnson, Marilyn ^{[4
,5
,6
]}

Mesters, Rolf ^{[25
]}

Monagle, Paul ^{[26
]}

van Ommen, C. Heleen ^{[27
]}

Raffini, Leslie ^{[28
]}

Rostasy, Kevin ^{[29
]}

Simioni, Paolo ^{[30
]}

Straeter, Ronald D. ^{[1
]}

Young, Guy ^{[31
]}

Nowak-Goettl, Ulrike ^{[1
]}

机构：

[1] Univ Hosp Munster, Dept Pediat Hematol Oncol, D-48149 Munster, Germany

[2] Chaim Sheba Med Ctr, Israel Natl Haemophilia Ctr, IL-52621 Tel Hashomer, Israel

[3] Univ Childrens Hosp, Div Hematol, Zurich, Switzerland

[4] Univ Colorado, Dept Pediat Hematol Oncol BMT, Denver, CO 80202 USA

[5] Univ Colorado, Mt States Reg Hemophilia & Thrombosis Ctr, Denver, CO 80202 USA

[6] Childrens Hosp, Denver, CO 80218 USA

[7] Hosp Pediat Prof Dr JP Garrahan, Serv Hematolgia & Oncol, Buenos Aires, DF, Argentina

[8] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[9] CHU, Unit Neonatol & Reanimat Pediat, St Etienne, France

[10] McMaster Univ, Hamilton, ON, Canada

[11] Univ Hosp Munster, Dept Pediat Neurol, D-48149 Munster, Germany

[12] Univ Calif San Francisco, Dept Neurol & Pediat, San Francisco, CA 94143 USA

[13] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA

[14] Univ Hosp Magdeburg, Dept Pediat, Magdeburg, Germany

[15] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany

[16] Charite, Dept Pediat Hematol Oncol, Berlin, Germany

[17] Univ Perugia, Internal & Vasc Med & Hemophilia Ctr, I-06100 Perugia, Italy

[18] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Med Ctr Dallas, Dallas, TX 75390 USA

[19] Univ Hosp Kiel, Dept Clin Chem, Kiel, Germany

[20] UCL, Neurosci Unit, Inst Child Hlth, London, England

[21] Southampton Gen Hosp, Dept Child Hlth, Southampton SO9 4XY, Hants, England

[22] Univ Hosp Munich, Dept Pediat, Munich, Germany

[23] Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut, Bethesda, MD USA

[24] Med Univ Vienna, Dept Pediat, Vienna, Austria

[25] Univ Hosp Munster, Dept Internal Med, D-48149 Munster, Germany

[26] Royal Childrens Hosp, Parkville, Vic, Australia

[27] Emma Childrens Hosp AMC, Dept Pediat Hematol, Amsterdam, Netherlands

[28] Univ Penn, Sch Med, Div Hematol, Dept Pediat,Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[29] Med Univ Innsbruck, Dept Pediat 4, Div Pediat Neurol & Inherited Metab Disorders, Innsbruck, Austria

[30] Univ Padua, Dept Cardiol Thorac & Vasc Sci, Chair Internal Med 2, Padua, Italy

[31] Childrens Hosp, Div Hematol Oncol, Los Angeles, CA 90027 USA

来源：

CIRCULATION | 2010年 / 121卷 / 16期

关键词：

cerebrovascular disorders; meta-analysis; pediatrics; thrombophilia; FACTOR-V-LEIDEN; VENOUS SINUS THROMBOSIS; GENE G20210A MUTATION; PROTHROMBIN; 20210; G; PROTEIN-C; METHYLENETETRAHYDROFOLATE REDUCTASE; CHILDHOOD STROKE; ANTIPHOSPHOLIPID ANTIBODIES; HOMOCYSTEINE METABOLISM; PEDIATRIC STROKE;

D O I：

10.1161/CIRCULATIONAHA.109.913673

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-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. Methods and Results-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). Conclusions-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 investigated. (Circulation. 2010; 121: 1838-1847)

引用

页码：1838 / U92

页数：25

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