Factor XII deficiency associated with coronary stent thrombosis

Helft, Gérard; Feuvre, Claude Le; Metzger, J. P.; Vacheron, A; Monsuez, J.-J.; Lachurie, Marie Laure; Ahlenc‐Gelas, Martine

doi:10.1002/1096-8652(200008)64:4<322::aid-ajh18>3.3.co;2-2

Cited by 3 publications

(3 citation statements)

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“…Despite the important putative role of FXII-which is a serine protease precursor involved in the initiation of the intrinsic coagulation pathway, in fibrinolysis, in the generation of bradykinin, and in the complement system (Kaplan and Silverberg 1987;Kluft et al 1987)-its biologic role is not fully understood. Furthermore, there is controversy over the clinical significance of a decreased or increased FXII concentration on venous and arterial thrombosis (Halbmayer et al 1992;Helft et al 2000). Further investigation of FXII and other genes may enhance our understanding of the factors influencing thrombosis, especially the chromosome 10p13 region, which should be targeted for fine mapping, and gene-identification studies.…”

Section: Discussionmentioning

confidence: 99%

A Quantitative-Trait Locus in the Human Factor XII Gene Influences Both Plasma Factor XII Levels and Susceptibility to Thrombotic Disease

Soria¹,

Almasy²,

Souto³

et al. 2002

The American Journal of Human Genetics

101

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One approach to the identification of genetic loci that influence complex diseases is through the study of quantitative risk factors correlated with disease susceptibility. Factor XII (FXII) plasma levels, a related phenotype correlated with thrombosis, is such a risk factor. We conducted the first genomewide linkage screen to localize genes that influence variation in FXII levels. Two loci were detected: one on chromosome 5 and another on chromosome 10 (LOD scores 4.73 and 3.53, respectively). On chromosome 5, the peak LOD score occurred in the 5q33-5ter region, near the FXII gene. Addition of a 46C/T mutation in the FXII gene increased the multipoint LOD score to 10.21 (P=3.6 x 10(-12)). A bivariate linkage analysis of FXII activity and thrombosis further improved the linkage signal (LOD = 11.73) and provided strong evidence that this quantitative-trait locus (QTL) has a pleiotropic effect on the risk of thrombosis (P=.004). Linkage analysis conditional on 46C/T indicated that this mutation alone cannot explain the chromosome 5 signal, implying that other functional sites must exist. These results represent the first direct genetic evidence that a QTL in or near the FXII gene influences both FXII activity and susceptibility to thrombosis and suggest the presence of one or more still unknown functional variants in FXII.

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Section: Discussionmentioning

confidence: 99%

A Quantitative-Trait Locus in the Human Factor XII Gene Influences Both Plasma Factor XII Levels and Susceptibility to Thrombotic Disease

Soria¹,

Almasy²,

Souto³

et al. 2002

The American Journal of Human Genetics

101

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“…Interestingly, clinical and genetic reports point at a FXII role in thrombosis ( 19 – 21 ). Local and systemic thrombotic events has been described in MS potentially in relation to the overstimulation of innate immunity for both its inflammatory and coagulant components ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

Coagulation Factor XII Levels and Intrinsic Thrombin Generation in Multiple Sclerosis

et al. 2018

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BackgroundFactor XII (FXII) activation initiates the intrinsic (contact) coagulation pathway. It has been recently suggested that FXII could act as an autoimmunity mediator in multiple sclerosis (MS). FXII depositions nearby dentritic cells were detected in the central nervous system of MS patients and increased FXII activity has been reported in plasma of relapsing remitting and secondary progressive MS patients. FXII inhibition has been proposed to treat MS.ObjectiveTo investigate in MS patients multiple FXII-related variables, including the circulating amount of protein, its pro-coagulant function, and their variation over time. To explore kinetic activation features of FXII in thrombin generation (TG).MethodsIn plasma from 74 MS patients and 49 healthy subjects (HS), FXII procoagulant activity (FXII:c) and FXII protein (FXII:Ag) levels were assessed. Their ratio (FXII:ratio) values were derived. Intrinsic TG was evaluated by different triggers.ResultsHigher FXII:Ag levels (p = 0.003) and lower FXII:ratio (p < 0.001) were detected in MS patients compared with HS. FXII variables were highly correlated over four time points, which supports investigation of FXII contribution to disease phenotype and progression. A significant difference over time was detected for FXII:c (p = 0.031). In patients selected for the lowest FXII:ratio, TG triggered by ellagic acid showed a trend in lower endogenous thrombin potential (ETP) in MS patients compared with HS (p = 0.042). Intrinsic triggering of TG by nucleic acid addition produced longer time parameters in patients than in HS and substantially increased ETP in MS patients (p = 0.004) and TG peak height in HS (p = 0.008). Coherently, lower FXII:ratio and longer lag time (p = 0.02) and time to peak (p = 0.007) point out a reduced response of FXII to activation in part of MS patients.ConclusionIn MS patients, factor-specific and modified global assays suggest the presence of increased FXII protein level and reduced function within the intrinsic coagulation pathway. These novel findings support further investigation by multiple approaches of FXII contribution to disease phenotype and progression.

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“…Furthermore old papers which had reported thrombotic events in some of these patients but had received little attention were re-evaluated in their importance [16][17][18][19][20][21][22][23][24][25]. A few cases have been reported even in recent years [26][27][28][29][30][31][32]. However, often, authors fail to mention that the fatal event in Mr. Hageman occurred after a severe trauma which caused a fracture of the pelvis with consequent bed immobilization [6].…”

Section: Introductionmentioning

confidence: 99%

Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation

Girolami

Candeo

Marinis

et al. 2010

J Thromb Thrombolysis

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Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis.

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Factor XII deficiency associated with coronary stent thrombosis

Cited by 3 publications

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A Quantitative-Trait Locus in the Human Factor XII Gene Influences Both Plasma Factor XII Levels and Susceptibility to Thrombotic Disease

A Quantitative-Trait Locus in the Human Factor XII Gene Influences Both Plasma Factor XII Levels and Susceptibility to Thrombotic Disease

Coagulation Factor XII Levels and Intrinsic Thrombin Generation in Multiple Sclerosis

Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation

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