Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation

Mitrio, V. De; Marino, Renato; Scaraggi, F. A.; Bari, L. Di; Giannoccaro, F.; Petronelli, Morgan; Ranieri, P; Tannoia, N; Schiraldi, O

doi:10.1097/00001721-199910000-00002

Cited by 19 publications

(9 citation statements)

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“…When adjusted for ABO blood group, an odds ratio of 4·8 [95% confidence interval (CI) 2·3-10·0] was determined for individuals with FVIII:C levels >150 iu/dl compared to those with FVIII:C levels <100 iu/dl. This high prevalence of elevated FVIII:C levels in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) has subsequently been confirmed in a number of other cohort and case-control studies (O'Donnell et al, 1997;Bloemenkamp et al, 1999;Kamphuisen et al, 1999;De Mitrio et al, 1999;Kraaijenhagen et al, 2000;Patel et al, 2003;Oger et al, 2003;Ota et al, 2011;Ryland et al, 2012). In addition, the increased risk of VTE associated with high plasma FVIII levels has consistently been shown to be a dose-dependent phenomenon (Koster et al, 1995;Kamphuisen et al, 1999;Kraaijenhagen et al, 2000;Patel et al, 2003;Ota et al, 2011).…”

Section: Elevated Fviii Levels and Venous Thrombosismentioning

confidence: 79%

“…This high prevalence of elevated FVIII:C levels in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) has subsequently been confirmed in a number of other cohort and case–control studies (O'Donnell et al , ; Bloemenkamp et al , ; Kamphuisen et al , ; De Mitrio et al , ; Kraaijenhagen et al , ; Patel et al , ; Oger et al , ; Ota et al , ; Ryland et al , ). In addition, the increased risk of VTE associated with high plasma FVIII levels has consistently been shown to be a dose‐dependent phenomenon (Koster et al , ; Kamphuisen et al , ; Kraaijenhagen et al , ; Patel et al , ; Ota et al , ).…”

Section: Elevated Fviii Levels and Venous Thrombosismentioning

confidence: 84%

“…Nevertheless, elevated FVIII may exert other prothrombotic mechanisms by diminishing the influence of the anticoagulant pathway. In particular, a direct inverse relationship between plasma FVIII:C levels and activated protein C resistance has also been reported (Laffan & Manning, ; De Mitrio et al , ), and may further contribute to thrombotic phenotype observed in patients with high FVIII:C levels.…”

Section: Elevated Fviii and Thrombogenicitymentioning

confidence: 89%

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Elevated factor VIII levels and risk of venous thrombosis

et al. 2012

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SummaryModern thrombophilia testing fails to identify any underlying prothrombotic tendency in a significant number of patients presenting with objectively confirmed venous thromboemboembolism (VTE). This observation has led to a search for other novel inherited or acquired human thrombophilias. Although a number of putative mechanisms have been described, the evidence behind many of these candidates remains weak. In contrast, an increasing body of work supports the hypothesis that increased plasma factor VIII (FVIII) levels may be important in this context. An association between elevated plasma FVIII levels and VTE was first described in the Leiden Thrombophilia Study (LETS). Subsequently, these conclusions have been supported by an increasing number of independent case-control studies. Cumulatively, these studies have clearly demonstrated that high FVIII levels constitute a prevalent, dose-dependent risk factor for VTE. Furthermore, more recent studies have shown that the risk of recurrent venous thrombosis is also significantly increased in patients with high FVIII levels. In this review, we present the evidence supporting the hypothesis that elevated FVIII levels constitute a clinically important thrombophilia. In addition, we examine the biological mechanisms that may underlie persistently elevated FVIII levels, and the pathways through which high FVIII may serve to increase thrombotic risk.

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Section: Elevated Fviii Levels and Venous Thrombosismentioning

confidence: 79%

Section: Elevated Fviii Levels and Venous Thrombosismentioning

confidence: 84%

Section: Elevated Fviii and Thrombogenicitymentioning

confidence: 89%

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Elevated factor VIII levels and risk of venous thrombosis

et al. 2012

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“…In addition, elevated FVIII may exert its prothrombotic effect by negatively influencing anticoagulant pathway mechanisms. An inverse relationship between plasma FVIII levels and activated protein C resistance has been reported [26]. Recent data suggest that in patients of VTE, the elevated FVIII levels may be a result of amplification of FVIII gene copy numbers [27].…”

Section: Discussionmentioning

confidence: 94%

Coagulation factor VIII, IX and XI levels in north Indian patients with venous thromboembolism

Chougule¹,

Rajpal²,

Ahluwalia³

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

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Studies have shown elevated levels of certain coagulation factors as risk factors for venous thromboembolism (VTE). In this study, we investigated the levels of coagulation factor VIII (FVIII), FIX and FXI in north Indian patients with VTE. A total of 123 patients with VTE were screened prospectively for FVIII, FIX and FXI levels and the conventional risk factors - deficiencies of protein C, S and antithrombin, positivity for antiphospholipid antibodies and the factor V Leiden mutation. Age-matched and sex-matched controls were included. VTE was secondary to known circumstantial and thrombophilic risk factors in 66 (53.7%) patients. In 46.3% (idiopathic VTE) patients, no cause was identified. The mean FVIII levels in idiopathic (187 IU/dl) and secondary VTE patients (185.4 IU/dl) were significantly higher compared with controls (129.6 IU/dl; P < 0.001). However, there was no statistically significant difference in the levels of FIX and FXI between patients and controls (P = 0.214 and 0.198, respectively). Patients with elevated FVIII levels had increased risk of VTE compared with controls (odds ratio: 9.4, 95% confidence interval: 4.7-18.79). On logistic regression analysis after adjusting for surgery and presence of antiphospholipid antibodies, this risk remained unchanged (odds ratio: 9.54, 95% confidence interval: 4.68-19.44). A dose-response relationship was observed with progressive increase in FVIII levels. Elevated FVIII levels constitute an independent risk factor for VTE in the north Indian population. Elevated levels of FIX and FXI were not associated with increased risk of VTE.

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“…Measurement of FVIII levels by one stage clotting assay, chromogenic assay and antigen assay all gave very similar results [28]. More recently it was reported that in families with thrombophilia and FV Leiden, FVIII levels >150 IU/dl contribute to the risk of venous thrombosis of FV Leiden carriers [29,30].…”

Section: Factor VIIImentioning

confidence: 83%

Elevated Clotting Factor Levels and Venous Thrombosis

Bertina¹

2003

Pathophysiol Haemos Thromb

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Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation

Cited by 19 publications

References 0 publications

Elevated factor VIII levels and risk of venous thrombosis

Elevated factor VIII levels and risk of venous thrombosis

Coagulation factor VIII, IX and XI levels in north Indian patients with venous thromboembolism

Elevated Clotting Factor Levels and Venous Thrombosis

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