Agnès Veyradier

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (93)400.91 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (i.e., after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence after or not preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1: 1 [11 patients], 2 [2 patients] or 4 [17 patients] infusions/course); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 (IQR, 0.46-0.7) to 0 (IQR, 0-0.81) episode/year (P<.01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. Five patients failed to increase durably ADAMTS13 activity. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 [IQR, 0.12-0.5] relapse/year, P<.01). Relapse-free survival was longer in group 1 (P=.049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses.
    Blood 05/2014; · 9.78 Impact Factor
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    ABSTRACT: BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP.
    Transfusion 02/2014; 54(2):389-397. · 3.53 Impact Factor
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    ABSTRACT: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.
    Critical care (London, England) 11/2013; 17(6):R273. · 4.72 Impact Factor
  • Thrombosis and Haemostasis 07/2013; 110(3). · 5.76 Impact Factor
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    ABSTRACT: INTRODUCTION: The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments. PATIENTS AND METHODS: In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %). RESULTS: Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62). CONCLUSION: Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.
    European Journal of Intensive Care Medicine 04/2013; · 5.17 Impact Factor
  • Chantal Loirat, Paul Coppo, Agnès Veyradier
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    ABSTRACT: PURPOSE OF REVIEW: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease in children, due to a severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13), inherited in congenital TTP or secondary to anti-ADAMTS13 antibodies in acquired TTP. Rapid techniques for ADAMTS 13 assays, long-term follow-up of patients, phenotype-genotype analysis, improved therapeutic schedules, and new therapies have emerged. RECENT FINDINGS: Rapid techniques for ADAMTS13 assays now permit rapid confirmation of diagnosis. In congenital TTP, mutations affecting the N-terminal domains of ADAMTS13 are associated with lower residual ADAMTS13 activity and more severe phenotype. Early initiation of plasma infusion treatment and lifelong prophylactic plasma infusion have decreased mortality and sequels and prevent relapses. In acquired TTP, a disease of adolescents but also of children less than 2, adding rituximab to plasma exchange is beneficial. Recombinant ADAMTS13 ought to be soon available for congenital TTP, while acquired TTP children might benefit from its administration, alone or in association with rituximab, to avoid or limit plasma exchange duration. SUMMARY: Progress in the understanding of TTP has boosted physicians' awareness that diagnosis and treatment are medical emergencies. New therapies hopefully will decrease treatment burden and improve prognosis.
    Current opinion in pediatrics 02/2013; · 2.01 Impact Factor
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    ABSTRACT: Thrombotic microangiopathies (TMA) encompass various diseases characterized by a microangiopathic hemolytic anemia, platelet clumping, and organ failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) is a particularly severe form of TMA characterized by systemic organ failure which results from a severe defect in ADAMTS13, a plasma enzyme specifically involved in the cleavage of highly hemostatic unusually large (UL) von Willebrand factor (VWF) multimers into smaller and less adhesive VWF forms. Failure to degrade these UL-VWF multimers leads to excessive platelet aggregates and capillary occlusion. Hemolytic uremic syndrome (HUS) is characterized prominently by a renal failure. In most cases, HUS is caused by entero-hemorrhagic Escherichia coli strains which secrete a shiga-like toxin (STX). STX-negative HUS, termed atypical HUS, was associated with a dysfunction in complement pathway. The major improvement in our understanding of TMA pathophysiology allows now a more accurate molecular classification of TMA syndromes, which opens fascinating perspectives of targeted therapies.
    La Revue du praticien 02/2013; 63(2):163-70.
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    ABSTRACT: Two unrelated families were recruited in the French Reference Center for von Willebrand disease with moderate bleeding symptoms associated with low von Willebrand factor (VWF) antigen levels, decreased collagen binding assay and no or partial response to desmopressin. Genetic analysis showed the presence of heterozygous mutations in the A3 domain away from the collagen-binding surface: one never reported previously (p.L1696R) and another (p.P1824H) described in a Spanish family. The mutations were reproduced by site-directed mutagenesis and mutant VWF was expressed in different expression systems, COS-7 cells, BHK cells and in VWF-deficient mice through hydrodynamic injection. p.L1696R and p.P1824H were associated with very low expression levels both in vitro and in vivo, with intracellular retention for p.P1824H. Both homozygous mutants displayed decreased binding to collagen types I and III but also decreased binding to platelet glycoproteins Ib and IIbIIIa. Co-transfections with wild-type VWF partially corrected these defects, except that collagen binding remained abnormal. The in vivo thrombosis response was severely reduced for both heterozygous mutants. In conclusion, we report two VWF A3 domain mutations that induce a combined qualitative and quantitative defect.
    Blood 01/2013; · 9.78 Impact Factor
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    ABSTRACT: It is established that proplatelets are formed from mature megakaryocytes (MK) as intermediates before platelet production. Recently, the presence of proplatelets was described in blood incubated in static conditions. We have previously demonstrated that platelet and proplatelet formation is upregulated by MK exposure to high shear rates (1800 s(-1)) on immobilized von Willebrand factor (VWF). The purpose of the present study was to investigate whether VWF is involved in the regulation of terminal platelet production in blood. To this end, Vwf (-/-) mice, a model of severe von Willebrand disease, were used to create a situation in which blood cells circulate in a vascular tree that is completely devoid of VWF. Murine platelets were isolated from Vwf (-/-) and Vwf (+/+) blood, exposed to VWF at 1800 s(-1) in a microfluidic platform, and examined by means of videomicroscopy, as well as fluorescence and activation studies. Proplatelets became visible within 5 minutes, representing 38% of all platelets after 12 minutes and 46% after 28 min. The proportion of proplatelets was 1.8-fold higher in blood from Vwf(-/-) mice than from Vwf(+/+) mice, suggesting a role of VWF in vivo. Fragmentation of these proplatelets into smaller discoid platelets was also observed in real-time. Platelets remained fully activatable by thrombin. Compensation of plasmatic VWF following hydrodynamic gene transfer in Vwf(-/-) mice reduced the percentage of proplatelets to wild-type levels. A thrombocytopenic mouse model was studied in the flow system, 7 days after a single 5-FU injection. Compared to untreated mouse blood, a 2-fold increase in the percentage of proplatelets was detected following exposure to 1800 s(-1) on VWF of samples from mice treated with 5-FU. In conclusion, VWF and shear stress together appear to upregulate proplatelet reorganization and platelet formation. This suggests a new function for VWF in vivo as regulator of bloodstream thrombopoiesis.
    PLoS ONE 01/2013; 8(5):e63810. · 3.73 Impact Factor
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    ABSTRACT: The purpose of this study is to assess the incidence and describe the clinical and pathological features of macrovascular thrombosis during the course of thrombotic micro-angiopathy (TMA) in a 6 year retrospective study of all adults with TMA, admitted to a teaching-hospital ICU. Of the 55 patients identified, all had anaemia and thrombocytopenia and 45 (82 %) had renal or neurological impairment. All patients received plasmapheresis, steroids, and strict blood pressure control. Macrovascular venous or arterial thromboses were diagnosed in 28 (51 %) patients; among them, 7 had cerebral artery thrombosis and 21 (including 13 with central venous catheters) had deep vein thrombosis. Median time from plasmapheresis initiation to thrombosis was 7 (4-10) days. Clinical findings were suggestive of deep venous thrombosis in 7 of the 21 patients (33 %) and only one of the 7 patients with stroke had corresponding clinical signs. By multivariate analysis, factors independently associated with macrovascular thrombosis were undetectable ADAMTS13 activity (odds ratio 7.33, 95 % confidence interval 1.3-41.3), cardiac involvement with TMA (odds ratio, 3.46; 95 % confidence interval, 1.1-13.9) and TMA flare (odds ratio 9.03; 95 % confidence interval 1.03-79.4). In conclusion, half of the patients with TMA experience macrovascular thrombosis. Patients with TTP-related ADAMTS13 deficiency and those with cardiac manifestations of TMA are at higher risk for arterial or deep venous thrombosis.
    Internal and Emergency Medicine 10/2012; · 2.35 Impact Factor
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    ABSTRACT: Although plasma therapy of thrombotic micro-angiopathies (TMAs) has dramatically improved survival, the outcome remains fatal in up to 15 % of patients. We investigated the causes and risk factors of death in patients with TMA. Retrospective matched case-control national-registry study of 57 patients who died within 180 days of TMA diagnosis and 48 survivors matched on age, gender, and baseline platelet count and creatinine level. The study period was 1995-2007. Factors associated with mortality were identified using a conditional logistic regression model. Median time from TMA symptom onset to death was 7 (5-14) days. The leading causes of death were nosocomial infections, myocardial infarction, stroke, and pulmonary embolism. Cases and controls did not differ significantly regarding haemolysis parameters, ADAMTS13 activity, or neurological or gastrointestinal involvement. TMA was more frequently related to HIV or cancer in patients who died. Compared to survivors, non-survivors more often had cardiac involvement at diagnosis (38 vs. 6 %, p = 0.03) and less often received plasma exchange therapy (60 vs. 92 %, p = 0.004). Only two factors were independently associated with mortality by multivariate analysis: cardiac involvement at diagnosis (odds ratio, 5.96; 95 % confidence interval, 1.06-33.4) and plasma exchange therapy (odds ratio, 0.25; 95 % confidence interval, 0.06-0.99). Our data emphasise the adverse prognostic significance of cardiac abnormalities and support routine plasma exchange in patients with TMA. Given the high risk of cardiac and neurological complications, adequate monitoring should be proposed to these patients in appropriate hospital settings.
    European Journal of Intensive Care Medicine 07/2012; 38(11):1810-7. · 5.17 Impact Factor
  • European Journal of Intensive Care Medicine 07/2012; 38(11):1908-10. · 5.17 Impact Factor
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    ABSTRACT: Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.
    Haematologica 05/2012; 97(8):1181-6. · 5.94 Impact Factor
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    ABSTRACT: Human immunodeficiency virus (HIV) infection represents a risk factor for thrombotic microangiopathy. HIV-associated thrombotic microangiopathies encompass two entities with distinct pathophysiology, clinical presentation, treatment and prognosis. Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus is typically characterized by a sudden onset in a patient with a moderate immune deficiency and a few events of opportunistic diseases, and a profound acquired deficiency in the von Willebrand factor cleaving protease ADAMTS13. This diagnosis requires a well-codified management including daily therapeutic plasma exchanges, a highly active antiretroviral therapy and eventually immunomodulatory drugs. The prognosis is good with a response rate and an overall survival comparable to that of HIV-negative thrombotic thrombocytopenic purpura. On the opposite, HIV-associated thrombotic microangiopathy with a progressive onset that occurs in profoundly immunocompromised patients with past history of multiple opportunistic diseases usually have a detectable ADAMTS13 activity and a worse prognosis. Usual treatment is poorly efficient. Forthcoming studies should assess the role of immunomodulatory drugs such as rituximab in the setting of HIV-associated thrombotic microangiopathy, and identify possible risk factors associated with the occurrence of these diseases.
    La Revue de Médecine Interne. 05/2012; 33(5):259–264.
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    ABSTRACT: Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.
    Blood 04/2012; 119(24):5888-97. · 9.78 Impact Factor
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    ABSTRACT: The quantification of residual plasmatic ADAMTS13 activity in congenital thrombotic thrombocytopenic purpura (TTP) patients is constrained by limitations in sensitivity and reproducibility of commonly used assays at low levels of ADAMTS13 activity, blunting efforts to establish genotype-phenotype correlations. In the present study, the residual plasmatic activity of ADAMTS13 was measured centrally by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (limit of detection = 0.5%) in 29 congenital TTP patients. The results were used to study correlations among ADAMTS13 genotype, residual plasmatic activity, and clinical phenotype severity. An ADAMTS13 activity above 0.5% was measured in 26 (90%) patients and lower levels of activity were associated with earlier age at first TTP episode requiring plasma infusion, more frequent recurrences, and prescription of fresh-frozen plasma prophylaxis. Receiver operating characteristic curve analysis showed that activity levels of less than 2.74% and 1.61% were discriminative of age at first TTP episode requiring plasma infusion < 18 years, annual rate of TTP episodes > 1, and use of prophylaxis. Mutations affecting the highly conserved N-terminal domains of the protein were associated with lower residual ADAMTS13 activity and a more severe phenotype in an allelic-dose dependent manner. The results of the present study show that residual ADAMTS13 activity is associated with the severity of clinical phenotype in congenital TTP and provide insights into genotype-phenotype correlations.
    Blood 04/2012; 120(2):440-8. · 9.78 Impact Factor
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    ABSTRACT: BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies.
    Transfusion 03/2012; · 3.53 Impact Factor
  • Paul Coppo, Agnès Veyradier
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    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by microangiopathic hemolytic anemia, profound peripheral thrombocytopenia, and a severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13 (acronym for A Disintegrin And Metalloproteinase with ThromboSpondin-1 motifs [13th member of the family]). ADAMTS13 deficiency is usually severe (<10% of normal activity) and results from autoantibodies directed to ADAMTS13 (acquired TTP) or from biallelic mutations of the encoding gene. In some cases, acquired TTP occurs in association with specific conditions that must be identified for appropriate management: a HIV infection, a connective tissue disease, a pregnancy, a cancer or a treatment with antiplatelet agents. TTP requires a rapid diagnosis and an adapted management in emergency, which allows current remission rates of 80 to 90%. Maximal measures of resuscitation may be required. Daily sessions of therapeutical plasma exchange (TPE) until durable platelet count recovery remain the basis of management of acquired TTP. In the last few years, the anti-CD20 monoclonal antibody rituximab has been increasingly used in patients with a suboptimal response to standard treatment, such as those with refractory disease (∼10% of cases) or an exacerbation of the disease despite intensive TPE (∼50% of cases). Rituximab prevents 1-year but not long-term relapses. Further studies should specify the optimal schedule of rituximab administration and its role as a prophylactic treatment in asymptomatic patients with severe acquired ADAMTS13 deficiency that persists even in disease remission. In hereditary TTP, also known as Upshaw-Schulman syndrome (USS), a diagnosis early in life is mandatory. Prophylactic infusions of plasma should be performed in chronic relapsing forms to prevent long-term organ complications, which have to be assessed accurately and regularly. In the upcoming years, new targeted therapies evaluated through international trials should further improve the management of these diseases. Consensual guidelines for the treatment of very specific and rare situations (such as management during pregnancy in USS patients and prevention of relapses in chronic relapsing acquired TTP) should arise from the shared experience of national groups.
    La Presse Médicale 03/2012; 41(3 Pt 2):e163-76. · 0.87 Impact Factor
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    ABSTRACT: Human immunodeficiency virus (HIV) infection represents a risk factor for thrombotic microangiopathy. HIV-associated thrombotic microangiopathies encompass two entities with distinct pathophysiology, clinical presentation, treatment and prognosis. Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus is typically characterized by a sudden onset in a patient with a moderate immune deficiency and a few events of opportunistic diseases, and a profound acquired deficiency in the von Willebrand factor cleaving protease ADAMTS13. This diagnosis requires a well-codified management including daily therapeutic plasma exchanges, a highly active antiretroviral therapy and eventually immunomodulatory drugs. The prognosis is good with a response rate and an overall survival comparable to that of HIV-negative thrombotic thrombocytopenic purpura. On the opposite, HIV-associated thrombotic microangiopathy with a progressive onset that occurs in profoundly immunocompromised patients with past history of multiple opportunistic diseases usually have a detectable ADAMTS13 activity and a worse prognosis. Usual treatment is poorly efficient. Forthcoming studies should assess the role of immunomodulatory drugs such as rituximab in the setting of HIV-associated thrombotic microangiopathy, and identify possible risk factors associated with the occurrence of these diseases.
    La Revue de Médecine Interne 01/2012; 33(5):259-64. · 0.90 Impact Factor
  • Agnès Veyradier, Paul Coppo
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    ABSTRACT: ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats) is the specific von Willebrand factor (VWF)-cleaving protease. ADAMTS13 was partially purified from human plasma in 1996 and its gene was cloned in 2001. In case of vascular injury, multimeric VWF is the mediator of both platelet adhesion to the sub-endothelium and platelet aggregation within the microvessels at high shear rates of blood flow. ADAMTS13 regulates VWF adhesive capacity by reducing the size of VWF multimers. A severe functional deficiency of ADAMTS13 (activity lower than 10%) is associated with most cases of thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy characterized by the spontaneous formation, within the microcirculation, of VWF-rich platelet thrombi responsible for a mechanical hemolytic anemia, a consumption thrombocytopenia and a multivisceral ishemia. TTP is a rare disease (4 cases/10(6)/year) with a life-threatening prognosis in the absence of an appropriate treatment in emergency (plasmatherapy). In 90% of cases, TTP is acquired and related to the development of auto-antibodies to ADAMTS13. In the other cases, TTP is inherited via bi-allelic autosomic recessive mutations of ADAMTS13 gene (Upshaw-Schulman syndrome). A better characterization of ADAMTS13 structure/function combined to clinical trials led in TTP patients is crucial to evaluate the relevance of either a -plasma-purified or a -recombinant ADAMTS13 as a therapeutic agent.
    Medecine sciences: M/S 12/2011; 27(12):1097-105. · 0.56 Impact Factor

Publication Stats

2k Citations
400.91 Total Impact Points

Institutions

  • 2014
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2011–2013
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Centre Hospitalier Universitaire Rouen
      • Service de Médecine Interne
      Rouen, Haute-Normandie, France
  • 2010–2012
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2009–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008–2012
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Hôpital Armand-Trousseau (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2001–2003
    • Unité Inserm U1077
      Caen, Lower Normandy, France