ADAMTS13 in Thrombotic Thrombocytopenic Purpura

NCT00426686 | Completed DMC

• 1 other identifier: PO51064
• Study Type: observational
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy defined by the spontaneous formation of platelet thrombi in the microvessels. These platelet microthrombi are responsible for a mechanical hemolytic anemia, a thrombocytopenia and a multivisceral ischemia. TTP is a rare but life-threatening disease in the absence of appropriate treatment (PLASMATHERAPY). The onset of the disease usually occurs in adulthood (MOSCHCOVITZ syndrome) and rarely in childhood (UPSHAW-SCHULMAN syndrome). TTP is either sporadic or recurrent with multiple unpredictable relapses. TTP pathophysiology has remained obscure until a new metalloprotease, ADAMTS13, has been demonstrated to be involved in about 90% of all cases. Physiologically, ADAMTS13 function consists in limiting the size of von Willebrand factor (VWF) multimers and consequently, their hemostatic capacity. A large majority of TTP is associated with a severe deficiency of ADAMTS13. In most cases, ADAMTS13 severe deficiency is acquired via auto-antibodies to ADAMTS13; more rarely, ADAMTS13 deficiency is hereditary via ADAMTS13 gene mutations. ADAMTS13 auto-antibodies are either inhibitory of the catalytic activity or non inhibitory. ADAMTS13 mutations are spread all over the gene. TTP prognosis is quite heterogeneous. Indeed, in about one third of the patients, TTP is refractory to PLASMATHERAPY and/or chronic relapsing. Until now, TTP prognosis factors are not known. Their identification is however crucial both to adapt the curative treatment of an acute episode (addition of first intention immunosuppressive agents to PLASMATHERAPY) and to prevent relapses. In this context, the aim of the current project is to identify some ADAMTS13 related prognosis factors in TTP. A national prospective multicenter study including both adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency will be designed over a three-year period. This study will involve our group as the French reference center for ADAMTS13 and 10 clinical departments from various French hospitals. Patients will be tested for ADAMTS13 activity and antigen, ADAMTS13 antibodies and ADAMTS13 gene sequencing. Our main hypothesis is that the inactivation of the ADAMTS13 domains crucial for its catalytic activity, either by inhibitory auto-antibodies (acquired TTP) or by genetic mutations (hereditary TTP) is a major bad prognosis factor.

Conditions

Thrombotic Thrombocytopenic Purpura

Keywords

thrombotic thrombocytopenic purpura; prognostic factors; ADAMTS13

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency.

You may qualify if:

• clinical suspicion of TTP
• Hemoglobin level \< 10 g/dl (adult) or \< 12 g/dl (child)
• Platelet level \< 150 giga/l
• ADAMTS13 activity \< 5%

You may not qualify if:

• Cancer
• Organ graft
• HIV infection

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Antoine Béclère

Clamart, 92140, France

Location

Related Publications (15)

• Veyradier A, Obert B, Houllier A, Meyer D, Girma JP. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood. 2001 Sep 15;98(6):1765-72. doi: 10.1182/blood.v98.6.1765.

  PMID: 11535510 BACKGROUND

• Veyradier A, Obert B, Haddad E, Cloarec S, Nivet H, Foulard M, Lesure F, Delattre P, Lakhdari M, Meyer D, Girma JP, Loirat C. Severe deficiency of the specific von Willebrand factor-cleaving protease (ADAMTS 13) activity in a subgroup of children with atypical hemolytic uremic syndrome. J Pediatr. 2003 Mar;142(3):310-7. doi: 10.1067/mpd.2003.79.

  PMID: 12640381 BACKGROUND

• Veyradier A, Lavergne JM, Ribba AS, Obert B, Loirat C, Meyer D, Girma JP. Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). J Thromb Haemost. 2004 Mar;2(3):424-9. doi: 10.1111/j.1538-7933.2004.00623.x.

  PMID: 15009458 BACKGROUND

• Fakhouri F, Vernant JP, Veyradier A, Wolf M, Kaplanski G, Binaut R, Rieger M, Scheiflinger F, Poullin P, Deroure B, Delarue R, Lesavre P, Vanhille P, Hermine O, Remuzzi G, Grunfeld JP. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood. 2005 Sep 15;106(6):1932-7. doi: 10.1182/blood-2005-03-0848. Epub 2005 Jun 2.

  PMID: 15933059 BACKGROUND

• Ferrari S, Scheiflinger F, Rieger M, Mudde G, Wolf M, Coppo P, Girma JP, Azoulay E, Brun-Buisson C, Fakhouri F, Mira JP, Oksenhendler E, Poullin P, Rondeau E, Schleinitz N, Schlemmer B, Teboul JL, Vanhille P, Vernant JP, Meyer D, Veyradier A; French Clinical and Biological Network on Adult Thrombotic Microangiopathies. Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood. 2007 Apr 1;109(7):2815-22. doi: 10.1182/blood-2006-02-006064.

  PMID: 17164349 RESULT

• Malak S, Wolf M, Millot GA, Mariotte E, Veyradier A, Meynard JL, Korach JM, Malot S, Bussel A, Azoulay E, Boulanger E, Galicier L, Devaux E, Eschwege V, Gallien S, Adrie C, Schlemmer B, Rondeau E, Coppo P; Reseau d'Etude des Microangiopathies Thrombotiques (TMA-Rare Diseases Reference Center). Human immunodeficiency virus-associated thrombotic microangiopathies: clinical characteristics and outcome according to ADAMTS13 activity. Scand J Immunol. 2008 Sep;68(3):337-44. doi: 10.1111/j.1365-3083.2008.02143.x.

  PMID: 18782260 RESULT

• Loirat C, Girma JP, Desconclois C, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. Pediatr Nephrol. 2009 Jan;24(1):19-29. doi: 10.1007/s00467-008-0863-5. Epub 2008 Jun 24.

  PMID: 18574602 RESULT

• Hommais A, Rayes J, Houllier A, Obert B, Legendre P, Veyradier A, Girma JP, Ribba AS. Molecular characterization of four ADAMTS13 mutations responsible for congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). Thromb Haemost. 2007 Sep;98(3):593-9.

  PMID: 17849048 RESULT

• Weisinger J, Bouzid R, Fadlallah J, Provot F, Poullin P, Le Guern V, Ribes D, Martis N, Delmas Y, Chantepie S, Rieu V, Benhamou Y, Choukroun G, Marie M, Dana R, Veyradier A, Joly BS, Coppo P. Immune-mediated thrombotic thrombocytopenic purpura with systemic lupus erythematosus: clinical features and outcome. Lupus Sci Med. 2025 Jul 28;12(2):e001691. doi: 10.1136/lupus-2025-001691.

  PMID: 40730415 DERIVED

• Beranger N, Coppo P, Tsatsaris V, Boisseau P, Provot F, Delmas Y, Poullin P, Vanhoorelbeke K, Veyradier A, Joly BS. Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience. Blood Adv. 2024 Jan 9;8(1):183-193. doi: 10.1182/bloodadvances.2023011972.

  PMID: 38039511 DERIVED

• Beranger N, Tsatsaris V, Coppo P, Veyradier A, Joly BS. High sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio in Pregnancy-Onset Thrombotic Thrombocytopenic Purpura. Hypertension. 2023 Sep;80(9):e140-e142. doi: 10.1161/HYPERTENSIONAHA.123.20987. Epub 2023 May 12. No abstract available.

  PMID: 37170814 DERIVED

• Joly BS, Stepanian A, Leblanc T, Hajage D, Chambost H, Harambat J, Fouyssac F, Guigonis V, Leverger G, Ulinski T, Kwon T, Loirat C, Coppo P, Veyradier A; French Reference Center for Thrombotic Microangiopathies. Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency: a cohort study of the French national registry for thrombotic microangiopathy. Lancet Haematol. 2016 Nov;3(11):e537-e546. doi: 10.1016/S2352-3026(16)30125-9. Epub 2016 Oct 3.

  PMID: 27720178 DERIVED

• Mariotte E, Azoulay E, Galicier L, Rondeau E, Zouiti F, Boisseau P, Poullin P, de Maistre E, Provot F, Delmas Y, Perez P, Benhamou Y, Stepanian A, Coppo P, Veyradier A; French Reference Center for Thrombotic Microangiopathies. 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. Lancet Haematol. 2016 May;3(5):e237-45. doi: 10.1016/S2352-3026(16)30018-7. Epub 2016 Apr 16.

  PMID: 27132698 DERIVED

• Thouzeau S, Capdenat S, Stepanian A, Coppo P, Veyradier A. Evaluation of a commercial assay for ADAMTS13 activity measurement. Thromb Haemost. 2013 Oct;110(4):852-3. doi: 10.1160/TH13-05-0393. Epub 2013 Jul 11. No abstract available.

  PMID: 23846249 DERIVED

• Moatti-Cohen M, Garrec C, Wolf M, Boisseau P, Galicier L, Azoulay E, Stepanian A, Delmas Y, Rondeau E, Bezieau S, Coppo P, Veyradier A; French Reference Center for Thrombotic Microangiopathies. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood. 2012 Jun 14;119(24):5888-97. doi: 10.1182/blood-2012-02-408914. Epub 2012 Apr 30.

  PMID: 22547583 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

March 2010

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• paul COPPO, MD, PhD

  Hôpital Saint Antoire, PARIS

  PRINCIPAL INVESTIGATOR

• Elie AZOULAY, MD, PhD

  Hôpital Saint Louis Paris

  STUDY DIRECTOR

• Benoît SCHLEMMER, MD

  Hôpital Saint Louis Paris

  STUDY DIRECTOR

• Eric OKSENHENDLER, MD

  Hôpital Saint Louis Paris

  STUDY DIRECTOR

• Fadi FAKHOURI, MD

  Hôpital Necker, PARIS

  STUDY DIRECTOR

• Jean-Paul MIRA, MD, PhD

  Hôpital Cochin, PARIS

  STUDY DIRECTOR

• Eric RONDEAU, MD

  Hôpital Tenon, PARIS

  STUDY DIRECTOR

• Jean-paul VERNANT, MD

  Hôpital la Pitié Salpétrière, PARIS

  STUDY DIRECTOR

• Nicolas SCHLEINITZ, MD

  CHU Conception, MARSEILLE

  STUDY DIRECTOR

• Gilles KAPLANSKI, MD, PhD

  CHU Conception, MARSEILLE

  STUDY DIRECTOR

• Albert BENSMAN, MD

  Hôpital Trousseau, PARIS

  STUDY DIRECTOR

• Chantal LOIRAT, MD

  Hôpital Robert Debré, PARIS

  STUDY DIRECTOR

• Brigitte BADER-MEUNIER, MD

  Hôpital Robert Debré, PARIS

  STUDY DIRECTOR

• Christophe PIGUET, MD

  Hôpital Dupuytren, LIMOGES

  STUDY DIRECTOR

• Guy PUTET, MD

  Hospices civils de LYON, LYON

  STUDY DIRECTOR

• Béatrice DUCOT, MD

  INSERM U569 Kremlin Bicêtre, Paris

  STUDY DIRECTOR

• Agnes VEYRADIER, MD, PhD

  Hôpital Antoine Béclère, CLAMART

  STUDY DIRECTOR

• Thierry LEBLANC, MD

  Hôpital Saint Louis Paris

  STUDY DIRECTOR

• Patrick NIAUDET, MD, PhD

  Hôpital Necker, PARIS

  STUDY DIRECTOR

• Christophe RIDEL, MD

  Hôpital Tenon, PARIS

  STUDY DIRECTOR

• Pascale POULLIN, MD

  CHU de la Conception, MARSEILLE

  STUDY DIRECTOR

• arlos FRANGIE, MD

  Hôpital Bicêtre, LE KREMLIN BICETRE

  STUDY DIRECTOR

• Hélène FRANCOIS, MD

  Hôpital Bicêtre, LE KREMLIN BICETRE

  STUDY DIRECTOR

• Olivier LAMBOTTE, MD

  Hôpital Bicêtre, LE KREMLIN BICETRE

  STUDY DIRECTOR

• Dominique BORDESSOULE, MD, PhD

  Hôpital Dupytren, LIMOGES

  STUDY DIRECTOR

• Stéphane GIRAULT, MD

  Hôpital Dupytren, LIMOGES

  STUDY DIRECTOR

• Hervé CHAMBOST, MD

  Hôpital de la Timone Enfants, Marseilles

  STUDY DIRECTOR

• Pierre BORDOGONI, MD, PhD

  Hôpital de Brabois-Hôpital d'Enfants, Vandoeuvre-lès-Nancy

  STUDY DIRECTOR

• Alexandra SALMON, MD

  Hôpital de Brabois- hôpital d'enfants, Vandoeuvre-lès-Nancy

  STUDY DIRECTOR

• Laurence CLEMENT, MD

  Hôpital de Brabois-Hôpital d'enfants, Vandoeuvre-lès-Nancy

  STUDY DIRECTOR

• Christian COMBE, MD, PhD

  Hôpital Pellegrin, Bordeaux

  STUDY DIRECTOR

• Sandrine MEUNIER, MD

  Hôpital Edouard Heriot, Lyon

  STUDY DIRECTOR

• Gwenaêlle ROUSSEY, MD

  Hôpital Hotel Dieu, Nantes

  STUDY DIRECTOR

• Mohammed HAMIDOU, MD, PhD

  Hôpital Hotel Dieu, Nantes

  STUDY DIRECTOR

• Bernard BONNOTTE, MD, PhD

  Hôpital du Bocage, Dijon

  STUDY DIRECTOR

• Yves TANTER, MD

  Hôpital du Bocage, Dijon

  STUDY DIRECTOR

• Jacques POURRAT, MD, PhD

  Hôpital de Rangueil, Toulouse

  STUDY DIRECTOR

• Marie-Christine THOURET, MD

  CHU de l'Archet 2, Nice

  STUDY DIRECTOR

• Philippe VANHILLE, MD

  CH de Valenciennes, Valenciennes

  STUDY DIRECTOR

• Nicolas LIMAL, MD

  Hôpital Henri Mondor, Créteil

  STUDY DIRECTOR

• Philippe REMY, MD

  Hôpital Henri Mondor, Créteil

  STUDY DIRECTOR

• Jean-Michel KORACH, MD

  CHG Châlons-en-Champagne, Châlons-en-Champagne

  STUDY DIRECTOR

• Carine GREIB, MD

  Hôpital Haut-Lévêque, Pesac

  STUDY DIRECTOR

• Jean-Louis PALLOT, MD

  CHI André Grégoire, Montreuil

  STUDY DIRECTOR

• Alain WYNCKEL, MD

  CHU de Reims, Reims

  STUDY DIRECTOR

• Claire CAZALETS, MD

  Hôpital Sud, Rennes

  STUDY DIRECTOR

• Bertrand DE CAGNY, MD

  CHU d'Amiens, Amiens

  STUDY DIRECTOR

• Claire PRESNE, MD

  CHU D'Amiens, Amiens

  STUDY DIRECTOR

• Cécile FOHRER, MD

  Hôpital de Haute-Pierre, Strasbourg

  STUDY DIRECTOR

• Karin BILGER, MD

  Hôpital de Haute-Pierre, Strasbourg

  STUDY DIRECTOR

• Bruno LIOURE, MD

  Hôpital de Haute-Pierre, Strasbourg

  STUDY DIRECTOR

• Raoul HERBRECHT, MD, PhD

  Hôpital de Haute-Pierre, Strasbourg

  STUDY DIRECTOR

• Dominique PLANTAZ, MD, PhD

  Hôpital Nord, Grenoble

  STUDY DIRECTOR

• Hubert NIVET, MD, PhD

  Hôpital Gatien de Clovheville, Tours

  STUDY DIRECTOR

• Emmanuel FLECK, MD

  Hôpital Saint Louis, La Rochelle

  STUDY DIRECTOR

• Jean-Philippe COINDRE, PH

  Centre Hospitalier du Mans, LE MANS

  STUDY DIRECTOR

• François MAURIER, PH

  Hôpital Sainte-Blandine Service de Médecine Interne, METZ

  STUDY DIRECTOR

• Mario OJEDA-URIBE, PH

  Centre Hospitalier Régional de MULHOUSE Hôpital Edouard Muller, Département d'Hématologie, Unité de thérapie cellulaire et greffes, MULHOUSE

  STUDY DIRECTOR

• Christophe RIDEL, PH

  Hôpital Tenon, Service de Néphrologie et de Transplantation rénale, PARIS

  STUDY DIRECTOR

• François BRIVET, PH

  Hôpital Antoine Béclère, Service de réanimation médicale, CLAMART

  STUDY DIRECTOR

• Sylvain LAVOUÉ, PH

  CHU Pontchaillou, Service de maladies infectieuses et réanimation médicale, RENNES

  STUDY DIRECTOR

• Sébastien CANET, PH

  Centre Hospitalier de Perpignan, Hôpital Saint-Jean, Service de Néphrologie, Hémodialyse, PERPIGNAN

  STUDY DIRECTOR

• François PROVOT, PH

  Centre Hospitalier Régional Universitaire de Lille, Hôpital Calmette, Pôle de Néphrologie, LILLE

  STUDY DIRECTOR

• Claude GUYOT, PH

  CHU de Nantes, Hôpital de jour et d'Hémodialyse pédiatrique

  STUDY DIRECTOR

• Xavier BELENFANT, PH

  CHI André Grégoire de Montreuil, Service de Néphrologie, Diabète et Dialyse, MONTREUIL

  STUDY DIRECTOR

• Laurent PERARD, PH

  Hôpital Edouard Herriot, Service de Médecine Interne, LYON

  STUDY DIRECTOR

• Edouard DEVAUD, PH

  CHR de Pontoise Hôpital René Dubos, Service de Médecine Interne- Néphrologie- Dialyse, PONTOISE

  STUDY DIRECTOR

• Arnaud BUFFIN, PH

  CH CHAMBERY, Service de Pédiatrie, CHAMBERY

  STUDY DIRECTOR

• Tarik KANOUNI, PH

  CHU Montpellier Hôpital Lapeyronie, Service d'Hématologie et Oncologie médicale, MONTPELLIER

  STUDY DIRECTOR

• Nicolas GAMBIER, PH

  Hôpital Avicenne, Service de Médecine Interne, BOBIGNY

  STUDY DIRECTOR

• Alain DEVIDAS, PH

  CH Sud-Francilien- Hôpital Gilles de Corbeil, Service d'Hématologie Clinique, CORBEIL-ESSONNES

  STUDY DIRECTOR

• Laure FEDERICI, PH

  CH Colmar- Hôpital Pasteur, Service de Médecine Interne, COLMAR

  STUDY DIRECTOR

• Michel FOULARD, PH

  CHRU de Lille- Hôpital Jeanne de Flandre, Service de Néphrologie pédiatrique, LILLE

  STUDY DIRECTOR

• Serge BOLOGNA, PH

  Hôpital Brabois Adulte, Service d'Hématologie, VANDOEUVRE-LÈS-NANCYS

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2007
• First Posted: January 25, 2007
• Study Start: November 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: April 1, 2011
• Last Updated: December 12, 2012

Record last verified: 2011-04

Locations

FR (1)