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• W1975798368 abstract "SummaryVenous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions. The added contribution of prothrombotic conditions to the occurrence of VTEs in children is not clear. This study reports the prevalence of prothrombotic conditions in 171 consecutive children with VTE followed in the Hospital for Sick Children Thrombosis Outpatient Clinic. The median age of the children at the time of VTE was 2.3 months (range 1 day to 16.5 years). An underlying medical condition and a central venous line (CVL) were present in 156 (91%) and 132 (77%) of 171 children, respectively. A positive family history was present in 8% of children. The prevalence of factor V Leiden was 4.7%, prothrombin G20210A polymorphism was 2.3%, protein S deficiency was 1.2%, protein C deficiency was 0.6% and increased plasma lipoprotein (a) concentration (>30 mg dL−1) was 7.5% (tested in 107 children). The overall frequency of inherited prothrombotic coagulation proteins was 13% (95% confidence interval 7 to 19%) and the frequency was not significantly different between neonates and older children with VTE. Inherited prothrombotic coagulation proteins were not associated with gender, CVL-related VTE, a positive family history of thrombosis or spontaneous VTE in neonates. Increased frequency of inherited prothrombotic coagulation proteins was, however, found in older children with spontaneous VTE (60%) compared with older children with VTEs secondary to an underlying medical condition (10%) (P = 0.02). In conclusion, this study indicates that inherited prothrombotic coagulation proteins do not contribute significantly to the pathogenesis of VTEs in neonates and children, in whom the most significant etiological factors are the presence of a CVL and/or other medical conditions. Venous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions. The added contribution of prothrombotic conditions to the occurrence of VTEs in children is not clear. This study reports the prevalence of prothrombotic conditions in 171 consecutive children with VTE followed in the Hospital for Sick Children Thrombosis Outpatient Clinic. The median age of the children at the time of VTE was 2.3 months (range 1 day to 16.5 years). An underlying medical condition and a central venous line (CVL) were present in 156 (91%) and 132 (77%) of 171 children, respectively. A positive family history was present in 8% of children. The prevalence of factor V Leiden was 4.7%, prothrombin G20210A polymorphism was 2.3%, protein S deficiency was 1.2%, protein C deficiency was 0.6% and increased plasma lipoprotein (a) concentration (>30 mg dL−1) was 7.5% (tested in 107 children). The overall frequency of inherited prothrombotic coagulation proteins was 13% (95% confidence interval 7 to 19%) and the frequency was not significantly different between neonates and older children with VTE. Inherited prothrombotic coagulation proteins were not associated with gender, CVL-related VTE, a positive family history of thrombosis or spontaneous VTE in neonates. Increased frequency of inherited prothrombotic coagulation proteins was, however, found in older children with spontaneous VTE (60%) compared with older children with VTEs secondary to an underlying medical condition (10%) (P = 0.02). In conclusion, this study indicates that inherited prothrombotic coagulation proteins do not contribute significantly to the pathogenesis of VTEs in neonates and children, in whom the most significant etiological factors are the presence of a CVL and/or other medical conditions. Deep vein thrombosis (DVT) and pulmonary embolism, collectively defined as venous thromboembolic events (VTEs), are uncommon in children but are becoming a recognized cause of morbidity and mortality [1Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. Bernstein M. Brisson L. Cairney B. DeSai D. Venous thromboembolic complications (VTE) in children. first analyses of the Canadian Registry of VTE.Blood. 1994; 83: 1251-7Crossref PubMed Google Scholar, 2Van Ommen C.H. Heijboer H. Büller H.R. Hirasing R.A. Heijmans H.S.A. Peters M. Venous thromboembolism in childhood: a prospective 2-year registry in the Netherlands.J Pediatr. 2001; 139: 676-81Abstract Full Text Full Text PDF PubMed Scopus (550) Google Scholar]. The majority of children with VTEs have underlying conditions (e.g. cancer, congenital heart disease, trauma) known to predispose to VTEs. The presence of a central venous line (CVL) is the cause of VTE in more than 90% of neonates, and in approximately 60% of older children [1Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. Bernstein M. Brisson L. Cairney B. DeSai D. Venous thromboembolic complications (VTE) in children. first analyses of the Canadian Registry of VTE.Blood. 1994; 83: 1251-7Crossref PubMed Google Scholar]. Since the presence of a CVL and other associated conditions are already a strong stimulus for VTE in children, whether the presence of a prothrombotic coagulation protein further contributes to the risk for VTEs is not clear. In adults, for example, the factor (F)V Leiden mutation is not a significant risk factor for acute deep venous thrombosis in patients undergoing hip or knee replacement surgery (a high-risk clinical setting) [3Ryan D.H. Crowther M.A. Ginsberg J.S. Francis CW. Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.Ann Intern Med. 1998; 128: 270-6Crossref PubMed Scopus (73) Google Scholar]. The reported prevalence of prothrombotic coagulation proteins in children with VTE is extremely varied, from as high as 78% in the German Registry [including children with arterial and cerebral thromboembolic events (TEs)][4Ehrenforth S. Junker R. Koch H.G. Kreuz W. Munchow N. Scharrer I. Nowak-Göttl U. Multicenter evaluation of combined prothrombotic defects associated with thrombophilia in childhood.Eur J Pediatr. 1999; 158: S97-104Crossref PubMed Google Scholar], and as low as 10% in the Canadian Registry [1Andrew M. David M. Adams M. Ali K. Anderson R. Barnard D. Bernstein M. Brisson L. Cairney B. DeSai D. Venous thromboembolic complications (VTE) in children. first analyses of the Canadian Registry of VTE.Blood. 1994; 83: 1251-7Crossref PubMed Google Scholar]. Thus, studies are required to assess the contribution of prothrombotic coagulation proteins to the pathogenesis of VTE in children and to define the role of thrombophilia screening in children [5Chalmers EA. Heritable thrombophilia and childhood thrombosis.Blood Rev. 2001; 15: 181-9Crossref PubMed Scopus (14) Google Scholar]. An extensive range of inherited and acquired abnormalities of coagulation proteins or hemostatic regulatory mechanisms is associated with an increased risk of thrombosis. The established causes of thrombosis with known inheritance are deficiencies of antithrombin, protein C and protein S, activated protein C resistance/FV Leiden mutation and the prothrombin G20210A (IIG20210A) polymorphism [6Pineo G.F. Hull RD. Thrombophilia: disorders predisposing to venous thromboembolism.Baillières Clin Haematol. 1998; 11: 525-40Abstract Full Text PDF PubMed Scopus (13) Google Scholar]. Recently, increased levels of plasma lipoprotein (a) and homocysteine were found to be possible inherited prothrombotic conditions both in children and adults [7Von Depka M. Nowak-Göttl U. Eisert R. Dieterich C. Barthels M. Scharrer I. Ganser A. Ehrenforth S. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism.Blood. 2000; 96: 3364-8Crossref PubMed Google Scholar, 8Nowak-Göttl U. Junker R. Hartmeier M. Koch H.G. Munchow N. Assmann G. Von Eckardstein A. Increased lipoprotein (a) is an important risk factor for venous thromboembolism in childhood.Circulation. 1999; 100: 743-8Crossref PubMed Scopus (200) Google Scholar, 9Den Heijer M. Keijzer MB. Hyperhomocysteinemia as a risk factor for venous thrombosis.Clin Chem Lab Med. 2001; 39: 710-3PubMed Google Scholar]. Increased plasma concentrations of FVIII coagulant (FVIII:C), IX coagulant (FIX:C) and XI coagulant (FXI:C) have been linked with TEs in adults [10Kraaijenhagen R.A. Anker P.S. Koopman M.M.W. Reitsma P.H. Prins M.H. Van Den Ende A. Buller HR. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism.Thromb Haemost. 2000; 83: 5-9Crossref PubMed Scopus (451) Google Scholar, 11Meijers J.C.M. Tekelenburg W.L.H. Bouma B.N. Bertina R.M. Rosendaal FR. High levels of coagulation factor XI as a risk factor for venous thrombosis.N Engl J Med. 2000; 342: 696-701Crossref PubMed Scopus (580) Google Scholar, 12Van Hylckama Vlieg A. Van Der Linden I.K. Bertina R.M. Rosendaal FR. High levels of factor IX increase the risk of venous thrombosis.Blood. 2000; 95: 3678-82Crossref PubMed Google Scholar]. Antiphospholipid antibodies are associated with the development of both arterial and venous TEs [13Greaves M. Cohen H. Machin S.J. Mackie I. Guidelines on the investigation and management of antiphospholipid syndrome.Br J Haematol. 2000; 109: 704-15Crossref PubMed Scopus (340) Google Scholar]. A screening program for prothrombotic conditions for all children with VTEs was established in 1998 at the Hospital for Sick Children, Toronto, Canada. The results from the screening program are presented in this paper in order to assess the prevalence of prothrombotic coagulation proteins in neonates and children with VTEs. A comprehensive in- and out-patient Thrombosis Program in the Hospital for Sick Children (HSC), Toronto, Canada follows all children diagnosed with VTEs. Clinical data collected for each patient includes the underlying medical condition(s), presence of a CVL, personal history of thrombosis, age at the time of VTE and location of the VTE. Family history of thrombosis, defined as a first and/or second degree relative with a TE, is recorded. The diagnosis of VTE is based on clinical findings followed by confirmatory ultrasound, ventilation/perfusion scan, echocardiography and/or conventional venography. According to the HSC protocol, children with VTE receive 3–6 months of full dose anticoagulation therapy. Prophylaxis after completion of therapy is administrated to children with a cardiac shunt or decreased cardiac output, children that need a long-term CVL for chemotherapy, total parenteral nutrition or dialysis and children with extensive idiopathic VTE. Recurrence of VTE is based on clinical findings followed by confirmatory diagnostic imaging. Since 1998, children diagnosed with VTEs were evaluated for acquired or inherited prothrombotic conditions either at diagnosis before therapy is initiated, at the end of therapy or at the clinic follow-up visit, if the relevant investigation had not been performed earlier. Abnormal results of protein assays that may be affected by the presence of a thrombus (within 1 week of the thrombotic event) or by anticoagulant treatment were labeled indeterminate and were repeated. All assay results were compared with previously published age appropriate normal ranges [14Andrew M, Monagle PT, Brooker L. Thromboembolic complications during infancy and childhood. Canada: BC Decker, 2000.Google Scholar]. The protocol for sample collection, data interpretation and measurement of antithrombin, protein C, free protein S, activated protein C resistance, FV Leiden, prothrombin G20210A mutation and methylenetetrahydrofolate reductase (MTHFR) mutation, lupus anticoagulant and anticardiolipin antibodies has been described previously [15DeVeber G. Monagle P. Chan A. MacGregor D. Curtis R. Lee S. Vegh P. Adams M. Marzinotto V. Leaker M. Massicotte M.P. Lillicrap D. Andrew M. Prothrombotic disorders in infants and children with cerebral thromboembolism.Arch Neurol. 1998; 55: 1539-43Crossref PubMed Scopus (256) Google Scholar]. Plasma lipoprotein (a) concentration was measured with an ELISA technique [Lp (a) ELISA, Trinity Biotech, New York, USA]. A plasma lipoprotein (a) level of >30 mg mL−1 was considered to be elevated [8Nowak-Göttl U. Junker R. Hartmeier M. Koch H.G. Munchow N. Assmann G. Von Eckardstein A. Increased lipoprotein (a) is an important risk factor for venous thromboembolism in childhood.Circulation. 1999; 100: 743-8Crossref PubMed Scopus (200) Google Scholar]. FVIII:C, FIX:C and FXI:C were measured by a standard one-stage clotting assay. High plasma levels of these factors were defined as above the 97.5 percentile for previously published age-match normal [14Andrew M, Monagle PT, Brooker L. Thromboembolic complications during infancy and childhood. Canada: BC Decker, 2000.Google Scholar]. FVIII:C, FIX:C and FXI:C were measured if testing was done at least 6 months after the acute VTE. For the purposes of this analysis, only children with non-cerebral VTEs were included and data collection was complete up to and including December 2001. Data are presented as mean, median and range, where applicable. To assess for differences between groups, the Fisher exact test was used for categorical data. The following variables were used for analysis: gender, underlying medical condition, presence of a CVL, family history of thrombosis, presence of an inherited prothrombotic coagulation proteins or high plasma concentrations of FVIII:C, FIX:C and FXI:C. A separate analysis was performed for neonates that had the initial VTE at the first month of life (corrected for gestational age) and for older children that had the initial VTE after the first month of life. Analysis was performed by means of SAS for Windows (SAS Institute Inc., Cary, NC, USA; version 8.2). A P-value < 0.05 was considered significant. From January 1998 to December 2001, 171 consecutive children with VTEs (79 girls, 92 boys) were followed in the outpatient clinic. The mean age of children at the time of the VTE was 3.5 years (median 2.3 months, range 1 day to 16.2 years). Seventy-seven children (45%) were neonates at the time of VTE, of whom 56 were born at term and 21 were born prematurely (<37 weeks gestational age). Underlying medical conditions were present in 91% (156/171) of children and consisted of congenital heart disease (n = 58, 34%), prematurity (n = 21, 12%), infection (n = 17, 10%), cancer (n = 15, 9%) and other (n = 45, 26%). A CVL was present in 77% (132/171) of all patients; in 83% (64/77) of neonates and in 72% (68/94) of older children. The location of the VTE was as follows, extremities (n = 112, 66%), abdomen (n = 31, 18%), right atrium (n = 5, 3%), isolated pulmonary embolism (n = 2, 1%) and multiple locations (n = 21, 12%). A family history, information available in 68% (117/171) of children, was positive for thromboembolic disease in nine children (8%). The prevalence of the different inherited prothrombotic coagulation proteins is presented in Table 1. One child had three coexisting prothrombotic coagulation proteins; FV Leiden, the MTHFR mutation and increased lipoprotein (a). Eight children had two coexisting prothrombotic coagulation proteins; FV Leiden with the MTHFR mutation (n = 4), prothrombin gene polymorphism with the MTHFR mutation (n = 3) and FV Leiden with protein S deficiency (n = 1). Completed testing for inherited thrombophilia was done in 107 children at a mean of 2 years (median 1.4 years, range 1 day to 9.7 years) from the time of the initial VTE. Ninety-eight percent of children were tested at least 3 months from the acute VTE. The mean age at the time of testing was 5.6 years (median 3.1 years, range 3 months to 17.5 years); only 11 children were younger than 1 year at the time of testing. The children with complete testing were not significantly different from the children without complete testing with respect to age at the time of the VTE, underlying medical condition, presence of CVL, location of VTE or family history of thrombosis. The prevalence of having at least one inherited prothrombotic coagulation protein in children who had complete testing was 13% [95% confidence interval (CI): 7% to 19%]. The prevalence was similar in neonates and older children with VTE. The presence of an inherited prothrombotic coagulation protein was not associated with gender, CVL, a family history of thrombosis or spontaneous VTE in neonates (Table 2). Of the five older children with spontaneous VTE, 3 (60%) were found to have inherited prothrombotic coagulation proteins compared with six (10%) of 58 older children with a VTE secondary to an underlying medical condition (P = 0.02, odds ratio 13, 95% CI: 1.8–94). The diagnosed prothrombotic coagulation proteins in the former group were FV Leiden with MTHFR mutation and increased lipoprotein (a), FV Leiden with protein S deficiency, and protein S deficiency. All three were adolescents (12.4, 14.8 and 15.9 years old) at the time of the VTE. One had a VTE associated with the use of oral contraceptive.Table 1Prevalence of inherited prothrombotic coagulation proteins in children with venous thromboembolic eventsTestAffected / testedPrevalencePresent studyNormal populationFactor V Leiden mutation8/1714.7% (95% CI 0.16% to 7.8%)4% (25)*Prothrombin G20210A polymorphism4/1712.3% (95% CI 0.1% to 4.5%)2% (25)*Protein S deficiency2/1711.2% (95% CI 0.0% to 2.8%)0.3% (25)Protein C deficiency1/1710.6% (95% CI 0.0% to 1.74%)0.3% (25)Antithrombin deficiency0/1710.0% (95% CI 0.0% to 1.75%)0.02% (31), 0.04% (25)Lipoprotein (a), >30 mg dL−18/1077.5% (95% CI 2.5% to 12.5%)7% (7),10.3% (8)*Based on studies in Caucasian populations. Open table in a new tab Table 2Characteristics of the neonates and older children with or without prothrombotic coagulation proteins (n = 107)With prothrombotic coagulation proteinsWithout prothrombotic coagulation proteinsNeonates*Initial VTE occurred at the first month of life (corrected for gestational age). Gender, male (%)4/5 (80%)21/39 (54%)NS Presence of CVL5/5 (100%)28/39 (72%)NS Family history of thrombosis†Initial VTE occurred after the first month of life.0/4 (0%)4/29 (14%)NS Spontaneous VTE0/5 (0%)6/39 (14%)NSOlder children‡Information was available for 99/107 children. Gender, male (%)2/9 (22%)28/54 (52%)NS Presence of CVL6/9 (67%)41/54 (76%)NS Family history of thrombosis†Initial VTE occurred after the first month of life.1/6 (17%)3/30 (10%)NS Spontaneous VTE3/9 (33%)2/54 (4%)0.02CVL, central venous line; VTE, venous thromboembolic event; NS, not statistically significant.* Initial VTE occurred at the first month of life (corrected for gestational age).† Initial VTE occurred after the first month of life.‡ Information was available for 99/107 children. Open table in a new tab *Based on studies in Caucasian populations. CVL, central venous line; VTE, venous thromboembolic event; NS, not statistically significant. High FVIII:C, FIX:C and FXI:C plasma concentrations were found in 33 (38%), 19 (22%) and seven (8%) of 86 available children, respectively. High FVIII:C was found in 24% (9/37) of neonates with VTE compared with 49% (24/49) of older children (P = 0.03, odds ratio 3, 95% CI: 1.2–7.6); such difference was not found in the frequency of high FIX:C or FIX:C plasma concentrations. High plasma factor concentrations were not associated with gender, CVL, or spontaneous VTE, in either neonates or older children with VTEs (Table 3). Lupus anticoagulant was positive in 12 (8.7%) of 127 children tested. Only six children were tested again and five became negative. Anticardiolipin antibody was positive in 45 (38%) of 117 children tested; 40 had mildly positive (>20 GPL units) and five had strongly positive (>60 GPL units) anticardiolipin antibody. One patient with multiple site thrombosis was diagnosed to have an antiphospholipid syndrome.Table 3Characteristics of the neonates and older children with or without high plasma factor concentration (n = 86)Factor VIII:CFactor IX:CFactor XI:CHighLowPHighLowPHighLowPNeonates* Gender, male (%)5/9 (56%)15/28 (54%)NS3/9 (33%)17/28 (61%)NSNA‡Only one neonate had high factor XI:C plasma concentration.NA‡Only one neonate had high factor XI:C plasma concentration. Presence of CVL6/9 (67%)21/28 (75%)NS6/9 (67%)21/28 (75%)NSNA‡Only one neonate had high factor XI:C plasma concentration.NA‡Only one neonate had high factor XI:C plasma concentration. Spontaneous VTE2/9 (22%)4/28 (14%)NS2/9 (22%)4/28 (14%)NSNA‡Only one neonate had high factor XI:C plasma concentration.NA‡Only one neonate had high factor XI:C plasma concentration.Older children†Initial VTE occurred after the first month of life. Gender, male (%)10/24 (42%)11/25 (44%)NS5/10 (50%)16/39 (41%)NS2/6 (33%)12/43 (44%)NS Presence of CVL16/24 (67%)22/25 (88%)NS8/10 (80%)30/39 (77%)NS4/6 (67%)34/43 (79%)NS Spontaneous VTE4/24 (17%)1/25 (4%)NS2/10 (20%)3/39 (8%)NS1/6 (17%)4/43 (9%)NSFactor VIII:C, factor VIII coagulant; factor IX:C, factor IX coagulant; factor XI:C, factor XI coagulant; NS, not statistically significant; NA, not applicable. *Initial VTE occurred at the first month of life (corrected for gestational age).† Initial VTE occurred after the first month of life.‡ Only one neonate had high factor XI:C plasma concentration. Open table in a new tab Factor VIII:C, factor VIII coagulant; factor IX:C, factor IX coagulant; factor XI:C, factor XI coagulant; NS, not statistically significant; NA, not applicable. *Initial VTE occurred at the first month of life (corrected for gestational age). Recurrence of a VTE occurred in 18 (10.5%) of 171 children. In 12 children, recurrence occurred while the patients were on anticoagulation therapy at a mean of 35 (median 15, range 6–169) days after initial VTE. In six children, recurrence was off anticoagulation therapy at a mean of 238 (median 221, range 157–372) days after initial VTE. Only two children were found to have prothrombotic coagulation proteins; FV Leiden with MTHFR mutation and strongly positive anticardiolipin antibodies 3 months from the time of recurrence in 1, and strongly positive anticardiolipin antibodies 41 months from the time of recurrence in the other. In all children, the same acquired risk factor was present in the first and the recurrent VTE. For example, two teenage girls had VTEs when they were diagnosed with acute leukemia and had recurrent VTEs when the leukemia relapsed. For analysis of variables associated with recurrence, 18 children that received long-term anticoagulation (>6 months) were excluded. The reasons for prophylaxis were cardiac shunt (n = 3), long-term presence of CVL (n = 10), extensive life-threatening VTE (n = 4), and nephritic syndrome with proteinuria (n = 1). Six of the 18 children were diagnosed with inherited prothrombotic coagulation proteins. Of 153 available children, recurrence of VTE off therapy (n = 6) was not associated with gender, presence of an inherited prothrombotic coagulation proteins and presence of high plasma concentrations of FVIII:C, FIX:C or FXI:C. In this study, the prevalence of inherited prothrombotic coagulation proteins in unselected neonates and children with VTEs is low and not considerably different from that reported in the general population. This suggests that inherited prothrombotic coagulation proteins do not contribute significantly to the occurrence of VTEs in children, expect in older children with spontaneous VTE. A similar low prevalence of inherited prothrombotic coagulation proteins in children with VTE was found in recent studies from Netherlands and Argentina [2Van Ommen C.H. Heijboer H. Büller H.R. Hirasing R.A. Heijmans H.S.A. Peters M. Venous thromboembolism in childhood: a prospective 2-year registry in the Netherlands.J Pediatr. 2001; 139: 676-81Abstract Full Text Full Text PDF PubMed Scopus (550) Google Scholar, 16Bonduel M. Hepner M. Sciuccati G. Pieroni G. Torres A.F. Maradarz C. Frontroth JP. Factor V Leiden and prothrombotic gene G20210A mutation in children with venous thromboembolism.Thromb Haemost. 2002; 87: 972-7Crossref PubMed Scopus (23) Google Scholar]. Other studies in children with TEs reported a wider range for the prevalence of inherited prothrombotic coagulation proteins (Table 4; 4Ehrenforth S. Junker R. Koch H.G. Kreuz W. Munchow N. Scharrer I. Nowak-Göttl U. Multicenter evaluation of combined prothrombotic defects associated with thrombophilia in childhood.Eur J Pediatr. 1999; 158: S97-104Crossref PubMed Google Scholar, 17Hagstrom J.N. Walter J. Bluebond-Langner R. Amatniek J.C. Manno C.S. High KA. Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease.J Pediatr. 1998; 133: 777-81Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 18Lawson S.E. Butler D. Enayat M.S. Williams MD. Congenital thrombophilia and thrombosis: a study in a single center.Arch Dis Child. 1999; 81: 176-8Crossref PubMed Scopus (50) Google Scholar, 19Heller C. Becker S. Scharrer I. Kreuz W. Prothrombotic risk factors in childhood stroke and venous thrombosis.Eur J Pediatr. 1999; 158: S117-21Crossref PubMed Google Scholar, 20Kosch A. Von Kries R. Nowak-Göttl U. Thrombosen im kindesalter.Monatsschr Kinderheilkd. 2000; 148: 387-97Crossref Scopus (11) Google Scholar]. The variation in the reported prevalence (range 13–78.6%) most probably reflects the differences in the clinical characteristics of the children studied (Table 5). Inclusion of children with arterial and cerebral TEs in the study [4Ehrenforth S. Junker R. Koch H.G. Kreuz W. Munchow N. Scharrer I. Nowak-Göttl U. Multicenter evaluation of combined prothrombotic defects associated with thrombophilia in childhood.Eur J Pediatr. 1999; 158: S97-104Crossref PubMed Google Scholar, 17Hagstrom J.N. Walter J. Bluebond-Langner R. Amatniek J.C. Manno C.S. High KA. Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease.J Pediatr. 1998; 133: 777-81Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 18Lawson S.E. Butler D. Enayat M.S. Williams MD. Congenital thrombophilia and thrombosis: a study in a single center.Arch Dis Child. 1999; 81: 176-8Crossref PubMed Scopus (50) Google Scholar, 20Kosch A. Von Kries R. Nowak-Göttl U. Thrombosen im kindesalter.Monatsschr Kinderheilkd. 2000; 148: 387-97Crossref Scopus (11) Google Scholar] could increase the prevalence of prothrombotic coagulation proteins in the cohort [15DeVeber G. Monagle P. Chan A. MacGregor D. Curtis R. Lee S. Vegh P. Adams M. Marzinotto V. Leaker M. Massicotte M.P. Lillicrap D. Andrew M. Prothrombotic disorders in infants and children with cerebral thromboembolism.Arch Neurol. 1998; 55: 1539-43Crossref PubMed Scopus (256) Google Scholar, 20Kosch A. Von Kries R. Nowak-Göttl U. Thrombosen im kindesalter.Monatsschr Kinderheilkd. 2000; 148: 387-97Crossref Scopus (11) Google Scholar, 21Kenet G. Sadetzki S. Murad H. Martinowitz U. Rosenberg N. Gitel S. Rechavi G. Inbal A. Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children.Stroke. 2000; 31: 1283-8Crossref PubMed Scopus (290) Google Scholar]. A higher proportion of children with spontaneous VTE could also increase the prevalence of prothrombotic coagulation proteins [4Ehrenforth S. Junker R. Koch H.G. Kreuz W. Munchow N. Scharrer I. Nowak-Göttl U. Multicenter evaluation of combined prothrombotic defects associated with thrombophilia in childhood.Eur J Pediatr. 1999; 158: S97-104Crossref PubMed Google Scholar, 19Heller C. Becker S. Scharrer I. Kreuz W. Prothrombotic risk factors in childhood stroke and venous thrombosis.Eur J Pediatr. 1999; 158: S117-21Crossref PubMed Google Scholar]. We have found a 60% prevalence of inherited prothrombotic coagulation proteins in children with spontaneous VTE. Therefore, the low prevalence of prothrombotic coagulation proteins reported can be explained by the large number of patients with underlying medical problems and the restriction to children with non-cerebral VTE in this study population.Table 4Inherited prothrombotic coagulation proteins in children with thromboembolic eventsReferenceTotalPCPSATFV LeidenPro-IILp (a) >30 mg dL−1Other frequent prothrombotic abnormalitiesHagstrom et al. 1998 [17Hagstrom J.N. Walter J. Bluebond-Langner R. Amatniek J.C. Manno C.S. High KA. Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease.J Pediatr. 1998; 133: 777-81Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar]19%0/853/851/8512/85NDNDAnti-phospholipid AbLawson et al. 1999 [18Lawson S.E. Butler D. Enayat M.S. Williams MD. Congenital thrombophilia and thrombosis: a study in a single center.Arch Dis Child. 1999; 81: 176-8Crossref PubMed Scopus (50) Google Scholar]42%3/282/281/284/303/26NDHomocystinuriaHeller et al. 1999 [19Heller C. Becker S. Scharrer I. Kreuz W. Prothrombotic risk factors in childhood stroke and venous thrombosis.Eur J Pediatr. 1999; 158: S117-21Crossref PubMed Google Scholar]71%*Other potential prothrombotic disorders were tested.6/170/171/174/17NDNDLupus anticoagulantEhrenforth et al. 1999 [4Ehrenforth S. Junker R. Koch H.G. Kreuz W. Munchow N. Scharrer I. Nowak-Göttl U. Multicenter evaluation of combined prothrombotic defects associated with thrombophilia in childhood.Eur J Pediatr. 1999; 158: S97-104Crossref PubMed Google Scholar]78.6%*Other potential prothrombotic disorders were tested.41/28524/28517/285120/285‡ND46/90HomocystinuriaKosch et al. 2000 [20Kosch A. Von Kries R. Nowak-Göttl U. Thrombosen im kindesalter.Monatsschr Kinderheilkd. 2000; 148: 387-97Crossref Scopus (11) Google Scholar]57.1%†Children with isolated elevated lipoprotein (a) are not included.24/26115/2619/26183/261‡Children homozygous for factor V Leiden mutation are included.11/26178/186Van Ommen et al. 2001 [2Van Ommen C.H. Heijboer H. Büller H.R. Hirasing R.A. Heijmans H.S.A. Peters M. Venous thromboembolism in childhood: a prospective 2-year registry in" @default.
• W1975798368 created "2016-06-24" @default.
• W1975798368 creator A5024863498 @default.
• W1975798368 creator A5053680340 @default.
• W1975798368 creator A5056094943 @default.
• W1975798368 creator A5070607078 @default.
• W1975798368 date "2003-05-01" @default.
• W1975798368 modified "2023-10-15" @default.
• W1975798368 title "Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease" @default.
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