Association of the protein C promoter CG haplotype and the factor II G20210A mutation is a risk factor for cerebral venous thrombosis

2005 ◽  
Vol 16 (7) ◽  
pp. 495-500 ◽  
Author(s):  
Véronique Le Cam-Duchez ◽  
Aude Bagan-Triquenot ◽  
Jean-François Ménard ◽  
Bruno Mihout ◽  
Jeanne-Yvonne Borg
Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 276-276
Author(s):  
Gili Kenet ◽  
Fenella Kirkham ◽  
Thomas Niederstadt ◽  
Karin Kurnik ◽  
Rosemarie Schobess ◽  
...  

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.


Stroke ◽  
2000 ◽  
Vol 31 (2) ◽  
pp. 543-548 ◽  
Author(s):  
Pieter Jan Simons ◽  
Geert Vanhooren

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1311-1318 ◽  
Author(s):  
Beatrice Saposnik ◽  
Jean-Luc Reny ◽  
Pascale Gaussem ◽  
Joseph Emmerich ◽  
Martine Aiach ◽  
...  

Abstract The endothelial cell protein C (PC) receptor (EPCR) facilitates PC activation by the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR) found in plasma inhibits both activated PC (aPC) activity and PC activation by competing for PC with membrane-associated EPCR. Elevated sEPCR levels are found in approximately 20% of healthy subjects, but the mechanisms underlying this interindividual variability are unknown. We measured sEPCR levels in 100 healthy male volunteers, and observed 2 phenotypic groups of subjects. The temporal stability of sEPCR levels suggested genetic control. Extensive analysis of the EPCR gene in these subjects revealed 13 polymorphisms in complete linkage disequilibrium; these defined 3 haplotypes, 1 of which (A3) was strongly associated with high sEPCR levels. The high constitutive sEPCR levels observed in A3 haplotype carriers might reduce the efficiency of the PC system and predispose these subjects to venous thrombosis. By studying 338 patients with venous thrombosis and 338 age- and sex-matched healthy subjects, we found that the A3 haplotype was overrepresented in the patients. In multivariate analysis, subjects carrying the A3 haplotype had an increased risk of thrombosis (odds ratio [OR] = 1.8; P = .004). Thus, the A3 haplotype, which is associated with elevated plasma sEPCR levels, is a candidate risk factor for venous thrombosis.


2011 ◽  
Vol 154 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Astrid Bergrem ◽  
Anders Erik Astrup Dahm ◽  
Anne Flem Jacobsen ◽  
Marie-Christine Mowinckel ◽  
Leiv Sandvik ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2145-2145
Author(s):  
Andrea Gerhardt ◽  
Nadja Howe ◽  
Jan S. Krussel ◽  
Hans G. Bender ◽  
Rudiger E. Scharf ◽  
...  

Abstract Background: As previously shown, the risk of cardiovascular disease is higher after a maternal placental syndrome, especially in the presence of fetal compromise. The HPA1-b allele of the ß3 subunit of the essential platelet integrin Alphallbbeta3 is a risk factor for increased platelet thrombogenicity, leading to arterial vascular occlusion also triggered by inflammatory endothelial alterations. We performed a case-control study to assess hereditary risk factor for arterial thrombosis in addition to the known risk determinants for venous thrombosis as risk determinants for fetal IGR. Materials and Methods: 121 women with severe fetal IGR (defined by birth weight below the 5th- percentile for gestational age and sex) and 300 normal women were evaluated. Women with other reasons of IGR (history of venous thrombosis, fetal loss, and preeclampsia, neonatale immunthrombocytopenia) were excluded. The fetuses were born alive after the 24th week of gestation. Results: A significant risk association could be shown for the HPA-1b/1b genotype OR 3.1 (95%CI 1.2–8.8), increased levels of lipoprotein (a) (&gt;0.2g/l) OR 1.7 (95%CI 1.0–2.9), increased levels of fibrinogen (&gt;median 284mg/dl) OR 2.8 (95%CI 1.8–4.4) increased levels of FVIII:C (&gt;median 147%) OR 1.7 (95%CI 1.1–2.7), and increased levels of von-Willebrand-factor antigen (vWF-Ag) (&gt;median 129%) OR 2.7 (95%CI 1.1–2.7). The combination of risk determinants led to a further increase in risk (e.g. HPA-1b allele, increased lipoprotein (a) and vWF-Ag OR 14.0) There was no significant risk association for factor V Leiden G1691A OR 1.3 (95% CI 0.7–2.81), and prothrombin G20210A mutation. OR 2.0 (95% CI 0.6–6.5) Conclusions: Increased platelet thrombogenicity via interaction with an inflammatory vascular process and/or via plasma levels of components of hemostasis/receptor ligands appear to be more important in women with IGR than the established risk determinants for venous thrombosis. Pharmacological control of the observed platelet thrombogenicity in patients at risk may be of clinical relevance. In consequence, it will be of importance to examine whether the critical subgroup of patients can benefit from prevention with specific antiplatelet agents.


Blood ◽  
2014 ◽  
Vol 124 (9) ◽  
pp. 1531-1538 ◽  
Author(s):  
Farida Omarova ◽  
Shirley Uitte de Willige ◽  
Paolo Simioni ◽  
Robert A. S. Ariëns ◽  
Rogier M. Bertina ◽  
...  

Key Points Fibrinogen, and particularly fibrinogen γ′, counteracts plasma APC resistance, the most common risk factor for venous thrombosis. The C-terminal peptide of the fibrinogen γ′ chain inhibits protein C activation, but still improves the response of plasma to APC.


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