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.

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%

scholarly journals Factor V Leiden, Prothrombin G20210A, and Protein C Mutation Frequency in Turkish Venous Thrombosis Patients

2007 ◽  
Vol 14 (4) ◽  
pp. 415-420 ◽  
Author(s):  
Julide Altinisik ◽  
Omer Ates ◽  
Turgut Ulutin ◽  
Mujgan Cengiz ◽  
Nur Buyru
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Cerebral Vein ◽  
Factor V ◽  
Pulmonary Emboli ◽  
Protein C Deficiency ◽  
Vein Thrombosis ◽  
G20210a Mutation

Several inherited polymorphisms are associated with risk of venous thrombosis, including mutation at codon 506 of the factor V gene, mutation at position 20210 of the prothrombin gene, and mutations in the protein C gene. In this study, genotyping for factor V, prothrombin, and protein C mutations was performed in 50 patients and 25 control subjects by polymerase chain reaction—based analysis. The prevalence of factor V and prothrombin mutations was not significantly different from that in the general population. Nine of the patients had heterozygous protein C mutation. There was a high prevalence of the mutated protein C allele in the pulmonary emboli group (42.8%). Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups. These results indicate that patients with protein C deficiency have a greater risk of thrombosis than patients with factor V or prothrombin G20210A mutation.

Resistance to Activated Protein C and Factor V Leiden as Risk Factors for Venous Thrombosis

1995 ◽  
Vol 74 (01) ◽  
pp. 449-453 ◽  
Author(s):  
Rogier M Bertina ◽  
Pieter H Reitsma ◽  
Frits R Rosendaal ◽  
Jan P Vandenbroucke
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V

The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1686-1692 ◽  
Author(s):  
Rory R. Koenen ◽  
Guido Tans ◽  
René van Oerle ◽  
Karly Hamulyák ◽  
Jan Rosing ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Factor V Leiden ◽  
Protein S ◽  
Prothrombin G20210a ◽  
Healthy Population ◽  
Factor V ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractProtein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa–based one-stage clotting assay was developed that enables quantification of the APC-independent activity of protein S in plasma from the ratio of clotting times (protein S ratio [pSR]) determined in the absence and presence of neutralizing antibodies against protein S. The pSR was 1.62 ± 0.16 (mean ± SD) in a healthy population (n = 60), independent of plasma levels of factors V, VIII, IX, and X; protein C; and antithrombin, and not affected by the presence of factor V Leiden. The pSR strongly correlates with the plasma level of protein S and is modulated by the plasma prothrombin concentration. In a group of 16 heterozygous protein S–deficient patients, the observed mean pSR (1.31 ± 0.09) was significantly lower than the mean pSR of the healthy population, as was the pSR of plasma from carriers of the prothrombin G20210A mutation (1.47 ± 0.21; n = 46). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation.

THROMBOPHILIC RISK FACTORS IN PATIENTS WITH CRANIAL AND SPINAL DURAL ARTERIOVENOUS FISTULAE

Neurosurgery ◽  
2008 ◽  
Vol 63 (4) ◽  
pp. 693-699 ◽  
Author(s):  
Rüediger Gerlach ◽  
Martina Boehm-Weigert ◽  
Joachim Berkefeld ◽  
Judith Duis ◽  
Andreas Raabe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Arteriovenous Fistulae ◽  
Factor V Leiden Mutation ◽  
Exact Test ◽  
G20210a Mutation ◽  
Cardiolipin Antibodies ◽  
Prothrombin Gene

ABSTRACT OBJECTIVE Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P < 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

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.

European Collaborative Paediatric Database on Cerebral Venous Thrombosis: Risk Factors for Recurrent Venous Thromboembolism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 276-276
Author(s):  
Gili Kenet ◽  
Fenella Kirkham ◽  
Thomas Niederstadt ◽  
Karin Kurnik ◽  
Rosemarie Schobess ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Cox Regression ◽  
Treatment Guidelines ◽  
Cox Regression Analysis ◽  
G20210a Mutation ◽  
Thrombosis Risk ◽  
Factor Ii ◽  
Prothrombotic Risk Factors

Abstract Background: Risk factors for cerebral venous thrombosis (CVT) in children include local and systemic underlying conditions, drug toxicity, and hereditary prothrombotic risk factors. Their relevance to the risk of a second venous thrombosis (VT), compared with other clinical, neuroimaging and treatment variables, is unknown. Methods: 330 of 407 consecutively enrolled CVT-patients aged newborn to <18 years (median 5.3 years; male 55%) were prospectively followed for a median (range) of 33 (12–84) months. In accordance to international treatment guidelines, 259 children (78.5%) received acute antithrombotic therapy (AT) with UFH or LMWH, followed by long-term AT with LMWH or warfarin in 218 cases (66.0%). Findings: Recurrent VT was diagnosed in 19 of 330 children (5.8%) at a median (range) age of 6 (0.5–84) months following CVT, with no difference observed between the study centres (p=0.84). Multivariate Cox regression analysis revealed that the risk of recurrence was significantly higher in those with older age at first CVT onset (p=0.02), those in whom AT was not administered prior to recurrence (p=0.0003), those who did not have complete patency rates on repeat venography at 3–6 months (p=0.01), and those subjects carrying the factor II G20210A mutation (p=0.03). Interpretation: Age at CVT onset, administration of AT, poor patency rates, and the factor II G20210A variant were of relevance to recurrent VT in children with CVT. Until evidence-based data derived from randomized treatment trials are available the message of this follow-up study is to administer any AT prophylaxis on an individual patient basis in paediatric CVT cases in newly identified VT risk situations.

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2055-2061 ◽  
Author(s):  
Elizabeth F. W. van Vlijmen ◽  
Nic J. G. M. Veeger ◽  
Saskia Middeldorp ◽  
Karly Hamulyák ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Contraceptive ◽  
Factor V Leiden ◽  
Informed Choice ◽  
Rational Approach ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractCurrent guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.

Effects of Hereditary and Acquired Risk Factors of Venous Thrombosis on a Thrombin Generation-Based APC Resistance Test

2002 ◽  
Vol 88 (07) ◽  
pp. 5-11 ◽  
Author(s):  
Joyce Curvers ◽  
M. Christella Thomassen ◽  
Janet Rimmer ◽  
Karly Hamulyak ◽  
Jan van der Meer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Thrombin Generation ◽  
Contraceptive Use ◽  
Hormone Replacement ◽  
Protein S ◽  
Resistance Test ◽  
Prothrombin G20210a ◽  
Apc Resistance

SummarySeveral hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.We determined the effects of hereditary and acquired risk factors of venous thrombosis on an APC resistance test that quantifies the influence of APC on the time integral of thrombin formation (the endogenous thrombin potential, ETP) initiated in plasma via the extrinsic coagulation pathway. APC sensitivity ratios (APCsr) were determined in plasma from carriers of factor VLeiden (n = 56) or prothrombin G20210A (n = 18), of individuals deficient in antithrombin (n = 9), protein C (n = 7) or protein S (n = 14) and of women exposed to acquired risk factors such as hormone replacement therapy (n = 49), oral contraceptive use (n = 126) or pregnancy (n = 35). We also analysed combinations of risk factors (n = 60).The thrombin generation-based APC resistance test was sensitive for the factor VLeiden and prothrombin G20210A mutation, to protein S deficiency, hormone replacement therapy, oral contraceptive use and pregnancy. The assay was not influenced by antithrombin-or protein C deficiency. The presence of more than one risk factor of venous thrombosis resulted in more pronounced APC resistance. The APCsr of individuals with a single or combined risk factors of VTE correlated well with reported risk increases.The thrombin generation-based APC resistance test identifies individuals at risk for venous thrombosis due to acquired risk factors and/or hereditary thrombophilic disorders that affect the protein C pathway.

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