Prothrombotic Risk Factors in Children with Acute Lymphoblastic Leukemia Treated with Delayed E. coli Asparaginase (COALL-92 and 97 Protocols)

2000 ◽  
Vol 83 (06) ◽  
pp. 840-843 ◽  
Author(s):  
Christine Mauz-Körholz ◽  
Ralf Junker ◽  
Ulrich Göbel ◽  
Ulrike Nowak-Göttl
Keyword(s):  
Risk Factors ◽  
Methylenetetrahydrofolate Reductase ◽  
Lymphoblastic Leukemia ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
E Coli ◽  
Prothrombotic Risk Factors ◽  
Reported Data

SummaryHereditary prothrombotic risk factors have been shown to increase the risk of venous thrombosis in children treated with the combination of E. coli asparaginase and steroids. In the present study the role of prothrombotic risk factors in children with ALL treated according to the COALL study protocol was investigated in 108 consecutively recruited childhood patients. The prevalence rates of prothrombotic risk factors [factor V G1691A mutation, the prothrombin G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype, deficiencies of protein C, protein S, antithrombin, elevated lipoprotein (a)] in this cohort were within the range reported for healthy Caucasians, and comparable to previously reported data for other leukemic patients. Venous thromboembolism occurred in 3 of the 108 children (induction n = 1; reinduction n = 2: 2.8%), and none of these children carried a prothrombotic risk factor. The results of the present study, suggest that the role of hereditary and acquired disturbances of coagulation in the development of thromboses might depend on the treatment regimen.

Symptomatic Onset of Severe Hemophilia A in Childhood is Dependent on the Presence of Prothrombotic Risk Factors

2001 ◽  
Vol 85 (02) ◽  
pp. 218-200 ◽  
Author(s):  
S. Halimeh ◽  
K. Kurnik ◽  
R. Schobess ◽  
C. Wermes ◽  
R. Junker ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Hemophilia A ◽  
Protein S ◽  
Type I ◽  
Factor V ◽  
Severe Hemophilia ◽  
Multicenter Cohort Study ◽  
Prothrombotic Risk Factors ◽  
Reported Data

SummaryIt has been recently suggested that the clinical phenotype of severe hemophilia A (HA) is influenced by co-inheritance with the factor V G1691A mutation. We therefore investigated 124 pediatric PUP patients with hemophilia (A: n = 111) consecutively admitted to German pediatric hemophilia treatment centers. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, antithrombin, protein C, protein S and anti-thrombin were investigated. 92 out of 111 HA patients (F VIII activity < 1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe HA was no different from previously reported data: FV G1691A 6.5%, PT G20201A 3.2%, and protein C type I deficiency 1.1%. No deficiency states of antithrombin or protein S were found in this cohort of hemophilic patients. The first symptomatic bleeding leading to diagnosis of severe hemophilia (< 1%) occurred with a median (range) age of 1.6 years (0.5-7.1) in children carrying defects within the protein C pathway or the PT gene mutation compared with non-carriers of prothrombotic risk factors (0.9 years (0.1-4.0; p = 0.01). The cumulative event-free bleeding survival was significantly prolonged in children carrying additionally prothrombotic defects (log-rank/Mantel-Cox: p = 0.0098). In conclusion, data of this multicenter cohort study clearly demonstrate that the first symptomatic bleeding onset in children with severe HA carrying prothrombotic risk factors is significantly later in life than in non-carriers.

Prospective Evaluation of the Thrombotic Risk in Children With Acute Lymphoblastic Leukemia Carrying the MTHFR TT 677 Genotype, the Prothrombin G20210A Variant, and Further Prothrombotic Risk Factors

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1595-1599 ◽  
Author(s):  
Ulrike Nowak-Göttl ◽  
Cornelia Wermes ◽  
Ralf Junker ◽  
Hans-Georg Koch ◽  
Rosmarie Schobess ◽  
...  
Keyword(s):  
Protein C ◽  
Lymphoblastic Leukemia ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
Free Survival ◽  
Mthfr Genotype ◽  
Prothrombotic Risk Factors ◽  
Factor V G1691a

Abstract The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (&gt;30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P &lt; .0001). In addition, a clear-cut positive correlation (P &lt; .0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations.

Foetal Growth Restriction in Children with Prothrombotic Risk Factors

2001 ◽  
Vol 86 (10) ◽  
pp. 1012-2001 ◽  
Author(s):  
Rüdiger von Kries ◽  
Ralf Junker ◽  
Doris Oberle ◽  
Andrea Kosch ◽  
Ulrike Nowak-Göttl
Keyword(s):  
Risk Factors ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Foetal Growth Restriction ◽  
Prothrombotic Risk Factors ◽  
Factor V G1691a

SummaryPlacental infarction is frequently observed in low birth weight children. To evaluate whether low birth weight in healthy term neonates is associated with foetal inherited prothrombotic risk factors this retrospective study was conducted. Outcome measures were “birth weight in the lowest quartile” and “birth weight in the lowest decile” in singletons with a gestational age of ≥37 weeks.The analyses were based on 375 Caucasian children screened at the Münster childhood thrombophilia centre with complete data for all prothrombotic risk factors (factor V G1691A, prothrombin G20210A, elevated lipoprotein (a), protein C-, protein S-, antithrombin-deficiency). The proportion of children in the lowest birth weight quartile increased from 23.7% to 30.5% to 48.0% for children with no, only single heterozygous and multiple or homozygous defects respectively. The respective adjusted odds ratios (95% confidence intervals) of thrombophilia for birth weight in the lowest quartile (lowest decile) were 1.53 (0.76-3.08) in carriers of one prothrombotic risk factor and 4.01 (1.48-10.84) in subjects carrying multiple or homozygous defects. We identified foetal thrombophilia as an additional cause of low birth weight.

Prospective Evaluation of the Thrombotic Risk in Children With Acute Lymphoblastic Leukemia Carrying the MTHFR TT 677 Genotype, the Prothrombin G20210A Variant, and Further Prothrombotic Risk Factors

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1595-1599 ◽  
Author(s):  
Ulrike Nowak-Göttl ◽  
Cornelia Wermes ◽  
Ralf Junker ◽  
Hans-Georg Koch ◽  
Rosmarie Schobess ◽  
...  
Keyword(s):  
Protein C ◽  
Lymphoblastic Leukemia ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
Free Survival ◽  
Mthfr Genotype ◽  
Prothrombotic Risk Factors ◽  
Factor V G1691a

The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (>30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P < .0001). In addition, a clear-cut positive correlation (P < .0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations.

Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage

2005 ◽  
Vol 93 (05) ◽  
pp. 867-871 ◽  
Author(s):  
Manuela Krause ◽  
Barbara Sonntag ◽  
Robert Klamroth ◽  
Achim Heinecke ◽  
Carola Scholz ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Recurrent Miscarriage ◽  
Univariate Analysis ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Factor V ◽  
Prothrombotic Risk Factors ◽  
Caucasian Women ◽  
Unexplained Recurrent Miscarriage

SummaryFrom 1998 to 2003, 133 Caucasian women aged 17–40 years (median 29 years) suffering from unexplained recurrent miscarriage (uRM) were consecutively enrolled. In patients and 133 age-matched healthy controls prothrombotic risk factors (factor V (FV) G1691A, factor II (FII) G20210A, MTHFR T677T, 4G/5G plasminogen activator inhibitor (PAI)-1, lipoprotein (Lp) (a), protein C (PC), protein S (PS), antithrombin (AT), antiphospholipid/anticardiolipin (APA/ACA) antibodies) as well as associated environmental conditions (smoking and obesity) were investigated. 70 (52.6%) of the patients had at least one prothrombotic risk factor compared with 26 control women (19.5%; p<0.0001). Body mass index (BMI; p=0.78) and smoking habits (p=0.44) did not differ significantly between the groups investigated. Upon univariate analysis the heterozygous FV mutation, Lp(a) > 30 mg/dL, increased APA/ACA and BMI > 25 kg/m2 in combination with a prothrombotic risk factor were found to be significantly associated with uRM. In multivariate analysis, increased Lp(a) (odds ratio (OR): 4.7/95% confidence interval (CI): 2.0–10.7), the FV mutation (OR:3.8/CI:1.4–10.7), and increased APA/ACA (OR: 4.5/CI: 1.1–17.7) had independent associations with uRM.

Role of Inherited Thrombophilia Risk Factors in Patients with CKD-5 Receiving Haemodialysis

2020 ◽  
pp. 1-12
Author(s):  
Dimitra Liapi ◽  
Aikaterini Sfiridaki ◽  
Aikaterini Livadiotaki ◽  
Athanasios Alegakis ◽  
Kostas Stylianou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Control Group ◽  
Factor V ◽  
Unknown Aetiology ◽  
Vascular Events ◽  
Thrombophilic Mutations

<b><i>Background:</i></b> The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. <b><i>Objectives:</i></b> The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. <b><i>Methods:</i></b> A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. <b><i>Results:</i></b> The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (<i>p</i> &#x3e; 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; <i>p</i> = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. <b><i>Conclusion:</i></b> The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.

scholarly journals Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population

2016 ◽  
Vol 23 (2) ◽  
pp. 105-115 ◽  
Author(s):  
S. Moussaoui ◽  
P. Saussoy ◽  
J. Ambroise ◽  
J. P. Defour ◽  
R. Zouitene ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Protein C ◽  
Protein S ◽  
Jak2 V617f ◽  
Genetic Risk Factors ◽  
Prothrombin G20210a ◽  
Factor V ◽  
S Deficiency ◽  
Calr Mutations

Many genetic risk factors have been identified for causing venous thromboembolism (VTE). Most of them affect the function of natural anticoagulant pathways, particularly the protein C system, although recent studies suggest a role of components of the hematopoietic pathway in the etiology of venous thrombosis. In this case–control study, we aimed to determine the frequency of prothrombin G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S, and antithrombin III deficiencies in the East Algerian population and to investigate whether these genetic factors are associated with VTE. On the other hand, our study tends to evaluate the status of JAK2V617F and calreticulin (CALR) mutations among these cases. The participants consisted of 121 cases with VTE and 146 healthy controls. Polymorphisms of FVL G1691A and prothrombin G20210A were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. JAK2-V617F and calreticulin mutations were analyzed by quantitative PCR and PCR followed by capillary electrophoresis sequencing, respectively. Protein C, protein S, and antithrombin levels were determined and then hereditary deficiencies were identified. Of all cases and controls, none was a carrier of the antithrombin III deficiency, prothrombin gene G20210A, and CALR mutations. Only 1 case reported having a positive JAK2 mutation (mutant allele burden was 15%). The FVL mutation (GA/AA) was found in 14 (11.6%) cases and 2 (1.4%) controls and it was significantly different between both the groups ( P = .001). Deficiencies of protein S and protein C were detected in 17 (18.8%) cases. The univariate analysis resulted in a significant impact of FVL (odds ratio [OR] = 9.4, 95% confidence interval [CI] = 2.1-42.3; P = .003) and of protein S deficiency (OR = 16.9, 95% CI =2.1-132.8, P = .007) on the VTE status. Both factors stayed significant after adjustment for sex and age. The OR of the protein C deficiency was slightly elevated (OR = 6.4, 95% CI = 0.7-55.5), but it did not reach the level of statistical significance ( P = .091), and it was therefore not considered as a risk factor. In conclusion, coagulant factor V gene G1691A mutation and protein S deficiency constitute important genetic risk factors in patients with VTE in Eastern Algeria. The somatic mutation of JAK2 V617F and CALR mutations are less frequent causes of VTE, thus routine testing for these mutations is not recommended.

Evaluation of Inherited Prothrombotic Risk Factors in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3953-3953
Author(s):  
Valerie Li Thiao Te ◽  
Remi Favier ◽  
Jeanne-Yvonne Borg ◽  
Estelle Cadet ◽  
Jacqueline Reynaud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Protein C Deficiency ◽  
Antithrombin Deficiency ◽  
Mthfr Genotype ◽  
G20210a Mutation ◽  
Family Medical History ◽  
Prothrombotic Risk Factors

Abstract This retrospective study was designed to determine the prevalence of inherited prothrombotic risk factors (Factor V Leiden (FV) G1691A and prothrombin G20210A mutations, TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR), protein C, protein S, antithrombin deficiencies) in a population of children with ALL treated according to the FRALLE 2000 study Protocol (High Risk and Standard Risk groups). The study was performed in 5 French Centers including Amiens, Angers, Paris Trousseau, Rouen and Saint-Etienne. From December 2000 to March 2006, 354 children aged 1 to 18 years old were consecutively admitted for ALL and were enrolled in the FRALLE 2000 Protocol. Among them, 281 patients were investigated for hereditary prothrombotic defects at the time of ALL diagnosis. Informed parental consent was required for gene analysis. Abnormal test results for protein S (functional activity and free protein S antigen concentration), protein C and antithrombin were controlled on a second blood sample after induction. In the population studied, the prevalence of one established prothrombotic risk factor was 19,2%: the FV G1691A mutation was diagnosed in 10 patients (3.6%), all heterozygous, 10 patients (3.6%) showed the heterozygous prothrombin G20210A mutation, the TT677 MTHFR genotype was found in 34 children (12.7%), 1 patient showed protein C deficiency (0.4%). No antithrombin deficiency was detected. The prevalence of inherited protein S deficiency could not be evaluated because of missing data in the family medical history. Combined prothrombotic defects were found in 2 patients (0.71%): heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A mutation in 1 patient and combined with TT677 MTHFR genotype in the second patient. Except for TT677 MTHFR genotype, the prevalence of hereditary prothrombotic risk factors in children with ALL in France were found within the prevalence reported for children treated for ALL (table 1) and comparable to the prevalence in healthy Europeans (Junker et al. 1999, Margaglione et al 2001, Mueller et al. 2005). Comparison of the prevalence of inherited prothrombotic risk factors in children with ALL Country Population FV G1691A +/− ++ PT G20210A +/− +/+ MTHFR TT677 AT PC AT: antithrombin deficiency ; PC: protein C deficiency ; NE : non evaluated NowakGöttl et al 1999 (n=301) Germany ALL children 5.3% 0.3% 2% 0% 7.7% 0.7% 2.3% Mauz-Körholz et al. 2000 (n=108) Germany ALL children 5.6% 0% 2.8% 0% 5.6% 0% 2.7% Mitchell et al. 2002 (n=60) Canada ALL children 3.3% 0% 2% 0% NE NE NE Present study (n=281) France ALL children 3.6% 0% (n=277) 3.6% 0%(n=279) 2.7% (n=268) 0% 0.4%

Haemophilia and thrombophilia

2003 ◽  
Vol 23 (01) ◽  
pp. 36-40 ◽  
Author(s):  
C. Escuriola ◽  
K. Kurnik ◽  
R. Schobess ◽  
S. Horneff ◽  
A. Kosch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Viii ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Haemorrhagic Stroke ◽  
Type I ◽  
Haemophilia A ◽  
Factor V ◽  
Severe Haemophilia ◽  
Prothrombotic Risk Factors

SummaryFor the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis. Conclusion: The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.

Evaluation of the Prothrombotic Risk Factors in Children with Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5355-5355
Author(s):  
Aysegul Unuvar ◽  
Arzu Akcay ◽  
Ebru T Saribeyoglu ◽  
Deniz Tugcu ◽  
Zeynep Karakas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Screening Program ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Vascular Events ◽  
Jugular Vein Thrombosis ◽  
G20210a Mutation ◽  
Prothrombotic Risk Factors

Abstract Pediatric patients with malignancy are at high risk of thromboembolic complications due to complex interactions of a variety of factors such as the malignancy, chemotherapy, central venous catheters (CVCs), infections, dehydration, and hereditary thrombophilia. In this study, deficiencies of protein C (PC), protein S (PS), and antithrombin (AT), activated protein C resistance (APCR), the factor V G1691A mutation, the prothrombin G20210A mutation, and increased factor VIII, IX, fasting homocysteine levels were assessed at the diagnosis of leukemia, retrospectively. The aim was to evaluate the role of the thrombophilic risk factors on vascular events during treatment period. Thirty children (11 F, 19 M) with leukemia (24 patients with ALL, 4 AML, one biphenotypic leukemia, one infant leukemia) were enrolled in this study. The median age of the patients was 56 months (range 7–215 months). All patients had CVCs, and thromboprophylaxis was not given to the any patients. We detected main prothrombotic risk factors at the diagnosis of leukemia as following: low PC (8/30), PS (11/30), AT activity (3/25), APCR (5/22), increased FVIII (5/22), FIX (2/22), and homocysteine levels (2/8), and FV Leiden mutation (1/24; heterozygous). The prothrombin G20210A mutation was not detected in any patient. The parents of these patients with abnormal test results were also evaluated to discriminate congenital or acquired deficiencies. In addition; PC, PS, AT levels were followed-up, and MTHFR genotype for the patients with high homocysteine levels was studied, also. In spite of, 24 of these 30 patients had at least one abnormal laboratory test result at the diagnosis of leukemia, venous thrombosis (7 with CVC-related venous thrombosis, one CVC-related jugular vein thrombosis and VOD, one vena saphena parva thrombosis) developed in 9 of 24 patients. In conclusion, leukemic children with at least one prothrombotic risk factor have high venous thrombosis risk. Further trials are needed to clarify the necessarity of screening program for thrombophilia and thromboprophylaxis in children with leukemia and CVCs, and, especially for the patients carrying hereditary prothrombotic risk factors.

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