Von Willebrand Factor and ADAMTS13

Stépanian, Alain; Cohen-Moatti, Marie; Sanglier, Thibaut; Legendre, Paulette; Ameziane, Nejma; Tsatsaris, Vassilis; Mandelbrot, Laurent; Prost, Dominique de; Veyradier, Agnès

doi:10.1161/atvbaha.111.223610

Cited by 73 publications

(37 citation statements)

References 50 publications

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“…This supports lack of association between functional ADAMTS13 variants and preeclampsia, but diverges from the findings of Stepanian et al in their study on VWF/ADAMTS13 interplay in preeclampsia [9]. They found increased VWF antigen levels and decreased ADAMTS13 activity and antigen with strong association to preeclampsia, indicating a misbalance favouring microvascular thrombosis.…”

Section: Discussioncontrasting

confidence: 61%

“…Whether also partial deficiencies of ADAMTS13 play a role in the development of preeclampsia is not established. A casecontrol study found an association between low ADAMTS13 levels and preeclampsia [9], however, from this study it remains unclear whether low ADAMTS13 activity is a risk factor or a marker of disease. Similar observations of mild ADAMTS13 deficiencies have been made for cardiovascular disease and ischaemic stroke, conditions that share a pathophysiology of endothelial cell dysfunction, inflammatory response and vascular reactivity with preeclampsia [10][11][12][13][14].…”

Section: Introductioncontrasting

confidence: 55%

“…This underscores that ADAMTS13 results in the present study were independent of the outcome. Stepanian et al investigated inflammatory cytokines and CRP as well as ADAMTS13 activity in their study [9]. They suggest that the decrease in ADAMTS13 activity found in preeclampsia was at least partly dependent on increased mediators of inflammation (IL-6, CRP), as adjustment for IL-6 and CRP suppressed the observed association between ADAMTS13 activity and preeclampsia.…”

Section: Discussionmentioning

confidence: 98%

“…We considered a difference in prevalence of 6% in women with preeclampsia versus 2% in controls to be of clinical interest, resulting in 89% power to detect such a difference with a sample size of 500 in each group and α=0.05. 2) A study performed by Stepanian et al [9] on the association between VWF/ADAMTS13 and preeclampsia found an ADAMTS13 activity of 66% (SD 17) in preeclampsia cases versus 78% (SD 16) in controls. A two-sided test with power 90% and α=0.05 would require a sample size of 86 based on these numbers.…”

Section: Power Estimatesmentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 61%

Section: Introductioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 98%

Section: Power Estimatesmentioning

confidence: 99%

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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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“…First, it may be a consequence of the feminine predominance of TTP (being itself at least partially linked to the feminine predominance classically observed in any disease with an autoimmune background); furthermore, most women with TTP (between 60 and 70%) are child-bearing age women [1,2]. Second, pregnancy is associated with physiological coagulation changes predisposing to hypercoagulability and particularly to a dysbalance of the VWF/ADAMTS13 system: indeed, during the course of pregnancy, VWF levels in plasma increase progressively to reach levels 2.5-3 fold higher levels at term (with peak values occurring immediately following delivery) while ADAMTS13 decreases progressively (ADAMTS13 activity decreases of about 30% at term when compared to baseline levels before pregnancy) (Supplementary Table 1) [16][17][18][19][20][21][22][23]. The physiological decrease of ADAMTS13 during pregnancy may be due either to a consumption mechanism by its VWF substrate [16], or to a direct effect of hormonal substances on ADAMTS13 metabolism [24].…”

Section: Epidemiology and Pathophysiologymentioning

confidence: 99%

ADAMTS, Thrombotic Thrombocytopenic Purpura and Pregnancy

Veyradier¹,

Stépanian²,

Coppo³

2013

Hereditary Genetics

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Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) which pathophysiology mainly relies on a severe deficiency (either acquired or inherited) of ADAMTS13, the specific von Willebrand factor (VWF) protease. TTP is characterized by a feminine predominance and pregnancy is a precipitating factor for TTP boots. Obstetrical TTP represents at least 20% of all TTP occurring in child-bearing age women.In this review, an analyze of the English-language literature from 1955 to 2011 found about 350 cases of obstetrical TTP including about 40 case-reports/-series with well documented ADAMTS13 investigation (32 inherited and 17 acquired TTP with severe ADAMTS13 deficiency). In the 32 patients with inherited TTP, the first pregnancy was systematically associated with a TTP boot, mostly occurring during the third trimester; curative plasma therapy (PT) allowed a good maternal outcome although the fetal outcome was almost systematically bad. In the 17 patients with acquired TTP, TTP also occurred mostly de novo during the first pregnancy and after 20 weeks gestation; curative PT usually allowed a good maternal outcome and the birth of an alive baby in about 2 cases/3.The diagnosis of obstetrical TTP is challenging because it mostly occurs in women with no antecedent of TTP and it has no specific clinical/biological symptoms except a severely deficient ADAMTS13. However, because of the severity of the prognosis in the absence of urgent treatment, any thrombocytopenia +/-hemolytic anemia in a pregnant woman with no alternative diagnosis to TMA should be considered as TTP.The management of an obstetrical TTP boot consists in a blood collection for ADAMTS13 investigation followed by an emergency first-line treatment with PT yielding a maternal response rate of about 80% although the global stillbirth rate is likely to be close to 50%.The follow-up of women who recovered from an obstetrical TTP boot should include a complete ADAMTS13 investigation to distinguish between the inherited and the acquired form of TTP, in order to both estimate the risk for relapse and optimize prophylaxis indication during subsequent pregnancies. The relapse rate appears to be 100% in inherited TTP and about 20% in acquired TTP. Early prophylactic PT is thus indicated systematically in inherited TTP as it is clearly beneficial for both the mother and the fetus outcomes. In contrast, the optimal management is still debated in subsequent pregnancies of women with acquired TTP whose clinical and biological monitoring should be very careful.TTP is a very rare complication of pregnancy (about 1/100,000 pregnancies) but it is a life-threatening disease for both the mother and the fetus. Many advances have been performed in the last 10 years in terms of diagnosis and treatment. However, clear guidelines are still needed to optimize the management of subsequent pregnancies, which may be significantly different as a function of the pathophysiology for ADAMTS13 deficiency.

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Laboratory testing for ADAMTS13: Utility for TTP diagnosis/exclusion and beyond

et al. 2021

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The metalloproteinase ADAMTS13 (a disintegrin with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterizes TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. Although prompt identification/exclusion of TTP can be facilitated by rapid ADAMTS13 testing, the most commonly utilized assays are based on ELISA (enzyme linked immunosorbent assay) and require long turnaround time and have relatively limited throughput. Nevertheless, several rapid ADAMTS13 assays are now available, at least in select geographies. The current mini-review discusses these issues, as well as the potential utility of ADAMTS13 testing in a range of other conditions, including coronavirus disease 2019 (COVID-19). | A SHORT EARLY HISTORY OF TTP AND ADAMTS13Thrombotic thrombocytopenic purpura was first characterized by Karl Singer and colleagues in 1947, 4 following pathological findings of thrombotic microangiopathy (TMA) by Eli Moschowitz in 1924. 5 Also key to understanding the pathophysiology of TTP and the involvement of ADAMTS13/VWF was the pioneering work of Moake et al. in 1982, 6 and Tsai et al. in 1996. 7,8 3 | BRIEF OVERVIEW OF TTP Note, TTP occurs either congenitally (ie, Upshaw Schulman Syndrome), or (more commonly) as an acquired event, typically due to development of anti-ADAMTS13 antibodies (commonly known as Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; BU, Bethesda Unit (inhibitor); CLIA, chemiluminescence immunoassay; COVID-19, coronavirus disease 2019; ELISA, enzyme linked immunosorbent assay; FRET, fluorescence resonance energy transfer; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura.

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Von Willebrand Factor and ADAMTS13

Cited by 73 publications

References 50 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

ADAMTS, Thrombotic Thrombocytopenic Purpura and Pregnancy

Laboratory testing for ADAMTS13: Utility for TTP diagnosis/exclusion and beyond

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