Inherited Thrombophilia: Part 1

Lane, David A.; Mannucci, Pier Mannuccio; Bauer, Kenneth A.; Bertina, Rogier M.; Бочков, Н. П.; Boulyjenkov, Victor; Chandy, Mammen; Dahlbäck, Björn; Гинтер, Е. К.; Miletich, Joseph P.; Rosendaal, Frits R.; Seligsohn, Uri

doi:10.1055/s-0038-1650638

Cited by 574 publications

(369 citation statements)

References 135 publications

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“…This is in concordance with what has been reported previously in Caucasian populations [2,[13][14][15]. Intriguingly, the APC resistance phenotype could be explained by the factor V Leiden mutation, only in 40% of the cases.…”

Section: Discussionsupporting

confidence: 92%

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

et al. 2006

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The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paú l, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR 5 6.08, 95% CI 5 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR 5 12.56, 95% CI 5 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia. Am. J. Hematol. 81:933-937, 2006. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 92%

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

et al. 2006

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“…One might question whether this relatively small change in activation rate is biologically important. The answer would appear to be yes because it is now well established that even a 2-fold reduction in protein C concentration can result in an increased risk of venous thrombosis (36). This propensity toward thrombosis is almost certainly the result of a reduction in protein C activation rates associated with the decrease in circulating protein C concentration rather than consumption because very little protein C is activated tonically (37).…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of the Human Endothelial Cell Protein C Receptor with Thrombomodulin in Phosphatidylcholine Vesicles Enhances Protein C Activation

Esmon

1999

Journal of Biological Chemistry

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Blocking protein C binding to the endothelial cell protein C receptor (EPCR) on the endothelium is known to reduce protein C activation rates. Now we isolate human EPCR and thrombomodulin (TM) and reconstitute them into phosphatidylcholine vesicles. The EPCR increases protein C activation rates in a concentration-dependent fashion that does not saturate at 14 EPCR molecules/TM. Without EPCR, the protein C concentration dependence fits a single class of sites (K m ‫؍‬ 2.17 ؎ 0.13 M). With EPCR, two classes of sites are apparent (K m ‫؍‬ 20 ؎ 15 nM and K m ‫؍‬ 3.2 ؎ 1.7 M). Increasing the EPCR concentration at a constant TM concentration increases the percentage of high affinity sites. Holding the TM: EPCR ratio constant while decreasing the density of these proteins results in a decrease in the EPCR enhancement of protein C activation, suggesting that there is little affinity of the EPCR for TM. Negatively charged phospholipids also enhance protein C activation. EPCR acceleration of protein C activation is blocked by anti-EPCR antibodies, but not by annexin V, whereas the reverse is true with negatively charged phospholipids. Human umbilical cord endothelium expresses approximately 7 times more EPCR than TM. Anti-EPCR antibody reduces protein C activation rates 7-fold over these cells, whereas annexin V is ineffective, indicating that EPCR rather than negatively charged phospholipid provide the surface for protein C activation. EPCR expression varies dramatically among vascular beds. The present results indicate that the EPCR concentration will determine the effectiveness of the protein C activation complex.

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“…According to this view, several scientific societies involved in this field have elaborated guidelines suggesting a list of recommended tests for the screening of congenital or acquired thrombophilic diseases (De Stefano et al 1996;Lane et al 1996) in categories of risk patients. In addition, in different studies mutations of genes not involved in clot formation and regulation have been found to play a crucial role in the susceptibility for arterial thrombotic disorders (Lio et al 2004;Listì et al 2008;Billeci et al 2009), but generally they're not retained useful in public health programs for the risk's evaluation profile, due to their modest contribution to the benefits/costs balance.…”

Section: Introductionmentioning

confidence: 99%

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction

et al. 2011

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Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered an important risk factor for acute myocardial infarction in aged patients (55-80 years old). On the other hand, in spite of a not different genotypic and allelic distribution for the Leiden FV G1691A mutation, the presence of one or both the two polymorphisms is significantly higher among cases than in controls. In conclusion, our data suggest that FII G20210A and/or Leiden FV might be involved as risk factor for arterial disorders in about 5% of old subjects, justifying the opportunity of a genetic screening and an eventual preventive treatment, in particular in old subjects in which other and major risk factors, as hypertension and atherosclerosis, are detected.

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Inherited Thrombophilia: Part 1

Cited by 574 publications

References 135 publications

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population

Reconstitution of the Human Endothelial Cell Protein C Receptor with Thrombomodulin in Phosphatidylcholine Vesicles Enhances Protein C Activation

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction

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