title: Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.
abstract: Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.
authors.affiliation: Service de Médecine Interne, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.|Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Maximilien
authors.identifier: http://orcid.org/0000-0002-2962-9828
authors.initials: M
authors.lastname: Grall
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Réanimation Médicale, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Immunologie Clinique, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Néphrologie, Hôpital Albert Calmette, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Provôt
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Néphrologie, Hôpital Maison Blanche, Reims, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Wynckel
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hémaphérèse, Hôpital de Marseille Conception, Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de réanimation médicale Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Grange
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Néphrologie, Centre Hospitalier Universitaire Bretonneau, Tours, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Réanimation médicale, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lautrette
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire Pellegrin, Bordeaux, France.
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Médecine Interne, Centre Hospitalier Universitaire d'Amiens Nord, Amiens, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service Médecine Interne, Hôpital Hôtel-Dieu, Nantes, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hématologie clinique, Centre Hospitalier Universitaire Dupuytren, Limoges, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Girault
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Réanimation Polyvalente, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pène
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Réanimation, Centre Hospitalier Universitaire Brabois, Nancy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Perez
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hématologie et Oncologie Médicale, Centre Hospitalier Universitaire St Eloi, Montpellier, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Kanouni
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Réanimation Médicale, Centre Hospitalier Universitaire de Caen, Caen, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Seguin
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service de Néphrologie, Centre Hospitalier Universitaire de Dijon, Dijon, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mousson
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Département de Néphrologie et Transplantation d'Organes, CHU Rangueil, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hématologie clinique, Centre Hospitalier Emile Muller, Mulhouse, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Ojeda-Uribe
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Unité d'Hémostase Vasculaire, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Barbay
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hématologie Biologique, Hôpital Lariboisière, AP-HP, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.|Service d'Hématologie, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.affiliation: Service de Médecine Interne, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.|Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Ygal
authors.initials: Y
authors.lastname: Benhamou
mesh_terms: D000071120:ADAMTS13 Protein / Q000172:deficiency; D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000175:diagnosis; D000974:Antibodies, Antinuclear / Q000032:analysis; D003298:Coombs Test; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000974:Antibodies, Antinuclear; D006454:Hemoglobins; D000071120:ADAMTS13 Protein