Prothrombin G20210A Gene Mutation and Further Prothrombotic Risk Factors in Childhood Thrombophilia

Junker, Ralf; Koch, Hans-Georg; Auberger, K.; Münchow, N.; Ehrenforth, S.; Nowak‐Göttl, Ulrike

doi:10.1161/01.atv.19.10.2568

Cited by 124 publications

(110 citation statements)

References 29 publications

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“…18,19 The prevalence of the MTHFR667 mutation in our study was 41% in the heterozygous state, and 10% in the homozygous state, again comparable to previously published studies. 20 The prevalence of MTHFR1298 mutation in our study was comparable to the wide range of incidence reported in the United States population. 33 Previous studies have reported an increased prevalence of FVL and MTHFR mutations in neonates and children with thrombosis compared to the general population 16,34 and have also shown an increased risk of catheter-related thrombosis in patients with FVL; 12,13 however, we found no difference in the prevalence of MTHFR mutations and FVL mutation in infants with and without thrombosis.…”

Section: Discussionsupporting

confidence: 85%

“…This genetic mutation is present in 1 to 2% of the general population but the prevalence is 4 to 20% in selected high-risk groups such as patients with thrombosis. 20 Methylene-tetrahydrofolate reductase (MTHFR) 677C>T (MTHFR667) and MTHFR1298A>C (MTHFR1298) mutations cause altered MTHFR activity leading to increased plasma levels of homocysteine, 16,[20][21][22] especially in folate-deficient patients. Hyperhomocystenemia has been associated with an increased risk of thrombosis.…”

Section: Introductionmentioning

confidence: 99%

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Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

et al. 2007

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Objective: To evaluate the prevalence of hereditary prothrombotic mutations, and their effect on the incidence and severity of umbilical arterial or venous catheter (UAC or UVC)-associated thrombosis.Study Design: All neonates with a UAC or UVC were studied prospectively for the presence, severity and timing of thrombosis with duplex Doppler ultrasound scan. Genetic testing for factor V Leiden (FVL), prothrombin mutation (PTm) and methylene-tetrahydrofolate reductase (MTHFR) mutations was performed using PCR and restriction fragment length polymorphism assays.Result: Umbilical catheter (UC)-associated thrombosis developed in 16/53 (31%) neonates; 23% of UACs and 22% of UVCs were associated with thrombosis. The prevalence of a significant prothrombotic mutation was present in 10/51 (20%) of infants: FVL (8%), MTHFR667 homozygosity (10%), MTHFR1298 homozygosity (2%) and PTm (0%). There was no increase in the risk of UC-associated thrombus in patients carrying these prothrombotic mutations; our study had the power to detect a 2.5-fold increased risk of thrombosis for any of these significant mutations. In addition, MTHFR667 heterozygosity was found in 41% of infants and MTHFR1298 heterozygosity in 52% and also were not associated with increased risk of UC-associated thrombus. The risk of MTHFR double heterozygosity (db het) was 14%, the risk of a significant or db het was 17/51 (33%) and the risk of any mutation was 90%.Conclusion: Prothrombotic genetic mutations are common in our Neonatal Intensive Care Unit population but do not appear to increase the risk of UC-associated thrombosis.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

et al. 2007

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“…The diagnosis of protein S deficiency was based on reduced free protein S antigen levels combined with decreased or normal total protein S antigen concentrations respectively. Criteria for the hereditary nature of a haemostatic defect were its presence in at least one further first-or second-degree family member and/or the identification of a causative gene mutation (Ehrenforth et al, 1999a;Junker et al, 1999;Nowak-Go Èttl et al, 1999). Fasting homocysteine concentrations within the first year of life were classified as increased when repeated measurements were found .…”

Section: Methodsmentioning

confidence: 99%

Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors – a multicentre case–control study

Heller

Schobeß²,

Kurnik³

et al. 2000

Br J Haematol

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The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, together with fasting homocysteine (HCY) concentration, lipoprotein (Lp)(a), anti‐thrombin (AT), protein C (PC), protein S (PS) and anti‐cardiolipin antibodies were investigated in 65 consecutively recruited infants (neonate to < 12 months) with renal venous thrombosis (RVT; n = 31), portal vein thrombosis (PVT; n = 24) or hepatic vein thrombosis (HVT n = 10), and 100 age‐ and sex‐matched healthy controls. FV G1691A was found in 14 babies (heterozygous: RVT n = 9, PVT n = 4; homozygous HVT n = 1) and five controls, the MTHFR TT677 genotype together with increased HCY in four infants with thrombosis (RVT n = 2; PVT n = 1; HVT n = 1) compared with one control, and the PT G20210A variant was present in one control only. PC type I deficiency was diagnosed in three patients (RVT n = 2; PVT n = 1) and AT deficiency in two patients (RVT n = 1; PVT n = 1). Three neonates with spontaneous thrombosis showed FV G1691A combined with Lp(a) and the FV G1691A was combined with the PT G20210A genotype in two infants. Additional triggering factors were reported in 27 patients (41·5%). The overall odds ratios (ORs) and 95% confidence intervals (CIs) with respect to the different thrombosis locations were: RVT (OR/CI: 10·9/3·85–31·1; P < 0·0001), PVT (5·47/1·7–17·6; P < 0·0007) and HVT (3·3/0·58–18·7; P = 0·18). The data presented here suggest that genetic prothrombotic risk factors also play an important role in abdominal venous thrombosis during infancy.

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“…Platelet-poor plasma was prepared by centrifugation at 3000 ϫ g for 20 min at 4°C, aliquoted in polystyrene tubes, stored at Ϫ70°C, and thawed immediately before the assay procedure (16). Amidolytic protein C and antithrombin activities were measured on an ACL 300 analyzer (Instrumentation Laboratory, Munich, Germany) using chromogenic substrates (Chromogenix, Møln-dal, Sweden).…”

Section: Plasma-based Assaysmentioning

confidence: 99%

Outcome of Kidney Transplantation in Patients with Inherited Thrombophilia

Heidenreich

Junker²,

Lang³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Inherited prothrombotic risk factors predispose patients to thromboembolic events. In kidney transplant recipients, thrombophilia may manifest itself with venous thrombosis, microvascular occlusion, or acute rejection with major consequences for allograft survival. This is a prospective study on 165 renal allograft recipients to evaluate the contribution of genetic thrombophilic risk factors to transplant outcome. Besides antithrombin, protein C, and protein S deficiencies, none of which was found in our patient group, factor V G1691A (FV G1691A), prothrombin G20210A (PT G20210A) mutations, and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms were studied. The primary endpoint of the study was occurrence of an acute rejection within the first 90 d and transplant loss within 1 yr. Heterozygous FV G1691A and PT G20210A mutations and the MTHFR T677T variant were significantly associated with acute rejections with rejection rates of 68%, 67%, and 71%, respectively, as compared with 35% in patients not carrying these genotypes. Many rejections that were histologically proven were acute vascular ones. Transplant loss was significantly associated exclusively with the PT G20210A group (50% 1-yr graft survival; odds ratio, 10.0; 95% confidence interval, 1.8 to 56.1). PT G20210A patients exerted the highest prothrombotic activity pretransplant, as determined by prothrombin 1.2 fragments (PT F1.2), which may be the background for minor outcome. In conclusion, common prothrombotic mutations are significantly associated with acute rejections, especially vascular rejections, and for PT G20210A also with early transplant failure. Screening for hypercoagulable states pretransplant is recommended to intensify anticoagulatory treatment posttransplant. heidenr@uni-muenster.de

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Prothrombin G20210A Gene Mutation and Further Prothrombotic Risk Factors in Childhood Thrombophilia

Cited by 124 publications

References 29 publications

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis

Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors – a multicentre case–control study

Outcome of Kidney Transplantation in Patients with Inherited Thrombophilia

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