von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women

Sánchez‐Luceros, Analía; Farías, Cristina Elena; Amaral, María Marta; Kempfer, Ana C.; Votta, Roberto; Marchese, Carlos; Salviú, María J.; Woods, Adriana Inés; Meschengieser, Susana S.; Lazzari, M.A.

doi:10.1160/th03-11-0683

Cited by 101 publications

(18 citation statements)

References 34 publications

(33 reference statements)

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“…6 In contrast, a review of 23 previously published cases of pregnancy-related TMA associated with ADAMTS13 deficiency [21][22][23][24][25][26][27][28][29][30] clearly shows this type of TMA occurs predominantly in the late second and third trimesters. This is in accordance with a recent review of 166 pregnancyrelated TTP cases in which the median time of TTP occurrence was 23 weeks.…”

Section: Discussionmentioning

confidence: 98%

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Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Fakhouri¹,

Roumenina²,

François³

et al. 2010

Journal of the American Society of Nephrology

396

395

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In contrast to pregnancy-associated thrombotic thrombocytopenic purpura, the pathogenesis and presentation of pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) remain ill-defined. We conducted a retrospective study to assess the presentation and outcomes of patients presenting with P-aHUS and the prevalence of alternative C3 convertase dysregulation. P-aHUS occurred in 21 of the 100 adult female patients with atypical HUS, with 79% presenting postpartum. We detected complement abnormalities in 18 of the 21 patients. The outcomes were poor: 62% reached ESRD by 1 month and 76% by last follow-up. The risk for P-aHUS was highest during a second pregnancy. Thirty-five women, 26 (74%) of whom had complement abnormalities, had at least one pregnancy before the onset of a non-pregnancy-related aHUS. Outcomes did not differ between patients with pregnancy-related and non-pregnancy-related aHUS. Mutations in the SCR19-20 domains of factor H were less frequent in P-aHUS patients compared with non-pregnancy-related aHUS. Pregnancies in female patients with complement abnormalities (n ϭ 44) were complicated by fetal loss and preeclampsia in 4.8% and 7.7%, respectively. Better understanding of complement dysregulation in pregnancy complications is essential, especially to guide development of pharmacologic agents to modulate this system.

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Section: Discussionmentioning

confidence: 98%

“…Pregnancy may trigger the onset or subsequent relapses of ADAMTS-13 deficiency-related TTP 6 as well as complement dysregulation associated-aHUS. More recently, complement dysregulation was also associated with another pregnancy disorder, HELLP (Hemolysis Elevated Liver enzymes and Low Platelet count) syndrome, which shares several features with P-TMA.…”

mentioning

confidence: 99%

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Fakhouri¹,

Roumenina²,

François³

et al. 2010

Journal of the American Society of Nephrology

396

395

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“…The low level of ADAMTS13 has also been found in patients with chronic renal disease including diabetic nephropathy [38]. Other conditions such as pregnancy [39] and thrombotic and bleeding disorders [40] were excluded as there is evidence that these conditions may influence estimation of ADAMTS13 levels.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

Azfar

Khan

Habib

et al. 2017

CIM

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Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock Abstract Purpose: ADAMTS13 level was evaluated as a predictor of mortality in patients with severe sepsis and septic shock, and compared with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.Methods: This prospective observational study was conducted in the Medical and Surgical Intensive Care Units of King Khalid University Hospital. Detailed clinical evaluations were performed on 84 patients (56.08±18.18 years of age) with severe sepsis and septic shock. ADAMTS13 levels were determined (three blood samples at 24 hours intervals) and APACHE II scores, hematological profiles, indices of organ hypo-perfusion, renal functions and coagulation profiles were recorded. Primary outcome was 30 days ICU mortality and secondary outcomes were its comparison with APACHE II score, length of ICU stay and use of vasopressor agents.Results: Hypertension (53.6%) and diabetic mellitus (45.2%) were the commonest comorbidities. The median ADAMTS13 levels were 336.65, 339.35 and 313.9, respectively. ROC analysis showed maximum area under the curve for second ADAMTS13 (AUC=0.760) compared with first (AUC=0.660) and third samples (AUC=0.707) and APACHE II scores (AUC=0.662). Patients were divided into low and high ADAMTS13 groups according to the best cut-off point. Mortality was high in the low ADAMTS13 level group [OR=4.5]and was significantly associated with age, DBP, ADAMTS13, APACHE II score, DIC score and platelet count. ADAMTS13 (OR=5.3), APACHE II (OR=4.13) and DIC scores (OR=7.32) were significant risk factors for mortality.Conclusions: Low ADAMTS13 was associated with increased mortality in patients with severe sepsis and septic shock and was comparable to APACHE II scores for predicting mortality.

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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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von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women

Cited by 101 publications

References 34 publications

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

ADAMTS, Thrombotic Thrombocytopenic Purpura and Pregnancy

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