Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy

Mariotte, Éric; Azoulay, Élie; Galicier, Lionel; Rondeau, Éric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; Maistre, Emmanuel de; François, Patrice; Delmas, Yahsou; Perez, Pierre; Benhamou, Y.; Stépanian, Alain; Coppo, Paul; Veyradier, Agnès

doi:10.1016/s2352-3026(16)30018-7

Cited by 260 publications

(317 citation statements)

References 31 publications

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“…Our estimated current prevalence of patients in remission is 19 per 1 000 000, similar to the estimated 13 patients per 1 000 000 in France. 20 These patients are at risk not only for relapse, but also for hypertension, depression, minor cognitive impairment, and premature death. 8,9,21 Fifty years ago, before the era of effective treatment, TTP was defined and diagnosed by a pentad of clinical features (fever, thrombocytopenia, anemia, neurologic abnormalities, and kidney function abnormalities).…”

Section: Discussionmentioning

confidence: 99%

Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015

Page

Hovinga

Terrell³

et al. 2017

Blood Advances

236

289

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Key Points• The diagnosis of TTP requires clinical judgment in addition to measurement of ADAMTS13 activity.• Patients with TTP may not seem to be seriously ill; they may have no or only mild neurologic and kidney function abnormalities. inhibitor titers were not associated with presenting features or outcomes. Microangiopathic hemolytic anemia and thrombocytopenia were not severe in all patients. Forty-seven percent of patients had no or minor neurologic abnormalities; 95% had no or minor serum creatinine abnormalities. Ten patients (13%) died, 2 before completing 1 plasma exchange (PEX); 3 deaths were attributed to PEX complications. For patients presenting after we began using rituximab in some patients (December 2003), fewer PEX treatments were required and fewer relapses occurred. Patients with their first relapse presented with higher platelet counts and hematocrits and lower lactate dehydrogenase levels and required fewer PEX treatments compared with their initial episodes.

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Section: Discussionmentioning

confidence: 99%

Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015

Page

Hovinga

Terrell³

et al. 2017

Blood Advances

236

289

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“…Thrombotic thrombocytopenic purpura (TTP) is a rare, life threatening disorder with a reported incidence of between 4 and 13 cases per million per year, [1][2][3][4] at least 3 times more common in women, 2,5 and with an untreated mortality of up to 90%. 3,6 Severe deficiency of the metalloprotease ADAMTS13 results in the abnormal presence of circulating ultra large von Willebrand factor (VWF) multimers.…”

Section: Introductionmentioning

confidence: 99%

Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

Alwan¹,

Vendramin

Vanhoorelbeke

et al. 2017

Blood

101

103

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Key Points• High anti-ADAMTS13 antibody and low ADAMTS13 antigen levels adversely affect outcome in immunemediated TTP with greater mortality seen.• A raised troponin at presentation confers a sixfold increase and reduced GCS a nine-fold increase in mortality in acute TTP.Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10.3% (n 5 32); 68% of patients had a raised troponin at presentation conferring a sixfold increase in mortality compared with those with normal troponin levels (12.1% vs 2.0%, P 5 .04). Twenty-four percent had a reduced Glasgow Coma Score (GCS) at presentation with a ninefold increase in mortality (20% vs 2.2% for normal GCS at presentation, P < .0001). Mortality increased with higher anti-ADAMTS13 antibody levels and lower ADAMTS13 antigen levels. Those with antibody levels in the upper quartile (antibody >77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody <20%) (P 5 .004). Those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for the highest quartile (antigen >11%) (P 5 .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality. (Blood. 2017;130(4):466-471)

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“…Serologically documented acquired, antibody-induced TTP (aTTP) is estimated to occur in 1 in 200 000 pregnancies. 35,36 Approximately 10% of women with aTTP 24,37 and a quarter to half of those with congenital TTP (cTTP) 35,38,39 present for the first time during pregnancy, often the first pregnancy, 36 or postpartum. 35,40 This predisposition may reflect the fall in ADAMTS13 and rise in von Willebrand factor that occurs normally during gestation.…”

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confidence: 99%

Thrombocytopenia in pregnancy

Cines¹,

Levine

2017

Blood

134

137

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Thrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions.

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Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy

Cited by 260 publications

References 31 publications

Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015

Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015

Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

Thrombocytopenia in pregnancy

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