18. Kasuistik: homozygote MTHFR-Variante und heterozygote Prothrombin-Mutation bei einer Schwangeren

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

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Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

Clinical Science ◽

10.1042/cs20030073 ◽

2003 ◽

Vol 105 (3) ◽

pp. 279-285 ◽

Cited By ~ 31

Author(s):

Dietmar SCHLEMBACH ◽

Ernst BEINDER ◽

Juergen ZINGSEM ◽

Ute WUNSIEDLER ◽

Matthias W. BECKMANN ◽

...

Keyword(s):

Blood Flow ◽

Intrauterine Growth Restriction ◽

Hellp Syndrome ◽

Factor V Leiden ◽

Growth Restriction ◽

Control Group ◽

Factor V ◽

Intrauterine Growth ◽

Prothrombin Mutation ◽

Thrombophilic Mutations

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.

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Prevalence of factor V Leiden and G20210A prothrombin mutation in the Dutch Famine Birth Cohort: A possible survival advantage?

Thrombosis and Haemostasis ◽

10.1160/th12-03-0145 ◽

2012 ◽

Vol 108 (08) ◽

pp. 399-401 ◽

Cited By ~ 3

Author(s):

Susanne R. de Rooij ◽

Marjolein Veenendaal ◽

Cristina Razzari ◽

Gessica Fontana ◽

Elena M. Faioni ◽

...

Keyword(s):

Birth Cohort ◽

Factor V Leiden ◽

Survival Advantage ◽

Factor V ◽

Prothrombin Mutation

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Clinical and Laboratory Management of the Prothrombin G20210A Mutation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-1319-calmot ◽

2002 ◽

Vol 126 (11) ◽

pp. 1319-1325 ◽

Cited By ~ 1

Author(s):

Ronald C. McGlennen ◽

Nigel S. Key

Keyword(s):

Significant Risk ◽

Factor V Leiden ◽

Initial Assessment ◽

Prothrombin G20210a ◽

Factor V Leiden Mutation ◽

Published Evidence ◽

G20210a Mutation ◽

Key Points ◽

Prothrombin Mutation ◽

History Of

Abstract Objective.—To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. Data Sources.—Review of the medical literature, primarily since 1996. Data Extraction and Synthesis.—After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. Conclusions.—Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.

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