Polymorphisms and Mutations in <i>vWF</i> and <i>ADAMTS13</i> Genes and Their Correlation With Plasma Levels of FVIII and vWF in Patients With Deep Venous Thrombosis

Bittar, Luis Fernando; Paula, Erich Vinícius De; Mello, Tayana Bezerra Teixeira; Siqueira, Lúcia H.; Orsi, Fernanda Andrade; Annichino‐Bizzacchi, Joyce Maria

doi:10.1177/1076029610375815

Cited by 21 publications

(21 citation statements)

References 25 publications

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“…No association was found for this SNP, while variant c.2699C>T showed increased risk. The variant c.1852C>G was also studied in relation to deep venous thrombosis (DVT), with no association observed [34]. The rarer variants c.3178C>T and c.4143_4144dupA have not previously been investigated in association studies.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

Krogh

Hovinga

Romundstad

et al. 2015

Thrombosis Research

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Section: Discussionmentioning

confidence: 99%

ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

Krogh

Hovinga

Romundstad

et al. 2015

Thrombosis Research

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“…Cancer patients have been shown to have higher VWF levels and lower ADAMTS‐13 levels than the general population, often also in a stage‐dependent intensity …”

Section: Introductionmentioning

confidence: 99%

“…In a recent study VWF and ADAMTS‐13 were shown to be associated with occurrence of VTE in cancer patients, with ADAMTS‐13 exhibiting predictive potential in risk scores . Patients with VTE or history of VTE have been repeatedly shown to have higher mean levels of VWF, however, patients with underlying malignancy have always been excluded. Data on ADAMTS‐13 and its association with VTE, on the other hand, is ambiguous.…”

Section: Introductionmentioning

confidence: 99%

The role of ADAMTS‐13 and von Willebrand factor in cancer patients: Results from the Vienna Cancer and Thrombosis Study

Obermeier

Riedl

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Cancer is associated with increased risk of developing venous thrombosis. Cancer patients were studied for ADAMTS‐13 and VWF levels and occurrence of venous thrombosis. Increased VWF in cancer patients is associated with a higher risk of venous thrombosis. Low levels of ADAMTS‐13 and/or increased VWF in cancer patients are associated with worse survival. Background Cancer‐associated venous thromboembolism (VTE) is an important complication in the course of a malignant disease. Low ADAMTS‐13 (a disintegrin‐like and metalloproteinase with thrombospondin type 1 motif 13) and increased von Willebrand Factor (VWF) levels in cancer patients have been described numerously. Objectives Investigation of the influence of ADAMTS‐13 and VWF on the probability of VTE and survival in malignancy. Patients/Methods In the framework of the ongoing prospective Cancer and Thrombosis Study (CATS) ADAMTS‐13 activity and VWF antigen levels were investigated in cancer patients. Results In total, 795 patients with various tumor types (364 female/431 male, median age 62 years) were included; of those, 56 developed VTE and 359 patients died during a median follow‐up time of 730 days. The hazard ratio (HR) of VTE per doubling of VWF level was 1.56 (95% confidence interval [CI] 1.13‐2.16) in multivariable competing risk analysis. ADAMTS‐13 levels showed no correlation with the incidence of VTE in univariate competing risk analysis. The HR of mortality per doubling of VWF level was 1.46 (95% CI 1.28‐1.66) and per SD increment of ADAMTS‐13was 0.90 (95% CI 0.81‐1.00) in multivariable Cox regression analysis. Patients with VWF >75th percentile and concomitant low (<25th percentile) or medium (25‐75th percentile) ADAMTS‐13 values had the highest probability of mortality (HR 4.31 and 4.75, respectively). Conclusions High VWF levels were significantly associated with the risk of developing VTE in cancer patients, whereas ADAMTS‐13 was not. Low ADAMTS‐13 and increased VWF levels were independently associated with worse overall survival.

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“…In humans both immobilization that decreases blood flow and tissue damage from a traumatic event increase the risk of DVT by 10- to 20-fold (Heit et al 1999, 2000; Esmon 2009). An increase in the level of procoagulant proteins (e.g., clotting factors, fibrinogen, von Willebrand factor-vWF) or a reduced level of anticoagulant proteins (e.g., antithrombin, protein C) increases the risk for thrombosis and embolism (Bertina 2003; Kuipers et al 2009; Bittar et al 2010; Flinterman et al 2010; Ribeiro et al 2012). Platelets, monocytes, and neutrophils also contribute to DVT through the formation of DNA neutrophil extracellular traps (NETS) in baboon and mouse models (Chauhan et al 2007; Fuchs et al 2010; Brill et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Von Willebrand factor is reversibly decreased during torpor in 13-lined ground squirrels

et al. 2015

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During torpor in a hibernating mammal, decreased blood flow increases the risk of blood clots such as deep vein thrombi (DVT). In other animal models platelets, neutrophils, monocytes and von Willebrand factor (VWF) have been found in DVT. Previous research has shown that hibernating mammals decrease their levels of platelets and clotting factors VIII (FVIII) and IX (FIX), increasing both bleeding time and activated partial throm-boplastin time. In this study, FVIII, FIX and VWF activities and mRNA levels were measured in torpid and non-hibernating ground squirrels (Ictidomys tridecemlineatus). Here, we show that VWF high molecular weight multimers, collagen-binding activity, lung mRNA and promoter activity decrease during torpor. The VWF multimers reappear in plasma within 2 h of arousal in the spring. Similarly, FIX activity and liver mRNA both dropped threefold during torpor. In contrast, FVIII liver mRNA levels increased twofold while its activity dropped threefold, consistent with a post-transcriptional decrease in FVIII stability in the plasma due to decreased VWF levels. Finally, both neutrophils and monocytes are decreased eightfold during torpor which could slow the formation of DVT. In addition to providing insight in how blood clotting can be regulated to allow mammals to survive in extreme environments, hibernating ground squirrels provide an interesting model for studying.

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Polymorphisms and Mutations in vWF and ADAMTS13 Genes and Their Correlation With Plasma Levels of FVIII and vWF in Patients With Deep Venous Thrombosis

Abstract: Despite the tempting assumption that genetic factors that change ADAMTS13 activity might modulate the risk of DVT by altering vWF and FVIII levels, the polymorphisms analyzed in this study did not correlate with DVT risk among patients investigated.

Cited by 21 publications

References 25 publications

ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

ADAMTS13 gene variants and function in women with preeclampsia: A population- based nested case- control study from the HUNT Study

The role of ADAMTS‐13 and von Willebrand factor in cancer patients: Results from the Vienna Cancer and Thrombosis Study

Von Willebrand factor is reversibly decreased during torpor in 13-lined ground squirrels

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