Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura

Scully, Marie; Starke, Richard; Lee, Richard; Mackie, Ian; Machin, Samuel J.; Cohen, Hannah

doi:10.1097/01.mbc.0000240918.65306.20

Cited by 103 publications

(120 citation statements)

References 22 publications

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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: 94%

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

407

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: 94%

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

407

395

View full text Add to dashboard Cite

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“…For instance, the usefulness of the monitoring of ADAMTS13 activity and/or autoantibodies titer in patients with acquired ADAMTS13 deficiency is still a matter of debate, most particularly during pregnancy. Preliminary data suggest that the monitoring of ADAMTS13 levels during pregnancy may help identify patients at high risk of TMA relapse (49,50). Some authors have even advocated the use, early in pregnancy, of plasma exchanges in pregnant women with ADAMTS13 deficiency to maintain an enzymatic activity .10% (50).…”

Section: Tma In Pregnancy: the Great Paradigm Shiftmentioning

confidence: 99%

Obstetric Nephrology

Fakhouri

Vercel

Frémeaux‐Bacchi

2012

Clinical Journal of the American Society of Nephrology

147

121

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Summary AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).

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“…In TTP, which is an acute onset and quite fatal disease, there are hyaline thromboses in a great deal of tissue and organs (42). Although it is a rare disease, its incidence increases during pregnancy (43,44). In the pathogenesis of the disease, ultralarge von Willebrand factor multimers, which must be degraded by ADAMTS13 (vWFCP) in circulation, have an essential role (42).…”

Section: Adamts In the Pathogenesis Of Obstetrics And Gynecology Disementioning

confidence: 99%

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

Demircan

Cömertoğlu

Akyol

et al. 2014

J Turkish German Gynecol Assoc

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Review 250Introduction A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (ADAMTS) proteinases, which are released outside the cell (soluble), have very critical roles in damage and repair of extracellular matrix (ECM) processes (remodeling) (1). The ADAMTS family, which degrades ECM structural substrates, such as collagen, aggrecan and versican, has 19 family members (2). These enzymes, which are associated with a great deal of vital physiological processes in the ECM, are inhibited by tissue inhibitors of metalloproteinases (TIMPs) (3, 4). Family members of this group are divided into various subgroups according to their tasks in the ECM (Figure 1). ADAMTS1 (METH-1), which was identified for the first time in colon adenocarcinoma, is associated with inflammation (5) and shows anti-angiogenic properties with ADAMTS8 (METH-2) (6, 7). Especially in the physiology of ovulation, there is interest in these proteases. ADAMTS1 also takes important roles in the process of normal growth, fertility, and organogenesis (8). ADAMTS 2, 3, and 14, also known pro-collagen N-proteinases, have important roles in collagen synthesis in the ECM. Various connective tissue diseases are seen in ADAMTS2 deficiency in this group (9). ADAMTS1, -4, -5, -8, -9, -15, -16, and -18 degrade aggrecan, which is the one of the main components of the ECM; so, they are called as aggrecanases (1). ADAMTS1, -4, and -5 degrade brevican and versican, other structural ECM components (10). Versican helps hyaluronan, which is the basic element of the ECM, to stabilize the matrix (11). ADAMTS5 and -6, expressed specifically in the placenta, are thought to be responsible for implantation (12). ADAMTS7 and -12 degrade Cartilage oligomeric matrix protein (COMP), which is an essential glycoprotein in cartilage matrix (13). ADAMTS10 has important roles in the development of tissues of skin and lens. In ADAMTS10 mutations, autosomal recessive Weill-Marchesani syndrome is seen (14). Known as von Willebrand cleaving protease, ADAMTS13 has effects on coagulation and homeostasis. This protease degrades ultralarge VWF multimers that are localized in endothelial surfaces; so, it prevents thrombus formation (9). Thrombotic thrombocytopenic purpura (TTP), a serious problem during pregnancy, occurs in ADAMTS13 deficiency (15). Increased by follicle-stimulating hormone (FSH) and luteinizing hormone (LH), ADAMTS16 degrades a-2 macroglobulin in the ECM (16). ADAMTS17 is involved in estrogen-induced apoptosis in cancer cells (16). ADAMTS9 and -20 are known Playing a key role in the pathophysiology of many diseases, A Disintegrin-like and Metalloproteinase with Thrombospondin type-1 motif (AD-AMTS) proteinases have been attracted more attention in obstetrics and gynecology. First discovered in 1997, this zinc-dependent proteinase family has 19 members today. These enzymes, which are located in the extracellular matrix (ECM), have a lot of very important functions, like matrix formation and resorption, angiogenesis, ovulation, and coagulation. In additio...

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Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura

Cited by 103 publications

References 22 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

Obstetric Nephrology

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

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