Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children.
Thrombotic thrombocytopenic purpura (TTP) related to a severely deficient activity of the von Willebrand factor cleaving protease, ADAMTS (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats) 13, is a life-threatening event, the onset of which may occur as early as childhood. TTP is either inherited (Upshaw-Schulman syndrome) via ADAMTS13 gene mutations (neonatal onset) or acquired via anti-ADAMTS13 autoantibodies (childhood onset). TTP is due to platelet- and von-Willebrand-factor-rich thrombi of the microvasculature, inducing mechanical hemolytic anemia, consumption thrombocytopenia, and multivisceral ischemia. Clinical course consists of relapsing acute events triggered mostly by infections, associated icterus and hyperbilirubinemia, severe hemolytic anemia with schistocytosis and a negative Coombs test, severe thrombocytopenia, and sometimes symptoms related to visceral ischemia (renal failure, central nervous system vascular events, other organ failure). The recently available ADAMTS13 laboratory investigation combining measurement of ADAMTS13 activity in plasma, search for an ADAMTS13 circulating inhibitor, and anti-ADAMTS13 IgG and ADAMTS13 gene sequencing is a crucial addition to TTP diagnosis. Plasma exchanges are first-line treatment of acquired TTP, combined with steroids and immunosuppressive drugs. Curative treatment of acute events in Upshaw-Schulman syndrome relies on plasma infusions (provider of active ADAMTS13). Guidelines for preventive treatment of relapses are not clearly established but should associate plasmatherapy and caution to triggers of relapses. Therapeutic perspectives are focused on the development of concentrated plasma-derived ADAMTS13 or recombinant ADAMTS13.
Service de Néphrologie, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Université Paris VII, 48 Boulevard Sérurier, 75019, Paris, France. chantal.loirat@rdb.aphp.fr
Chantal
C
Loirat
Jean-Pierre
JP
Girma
Céline
C
Desconclois
Paul
P
Coppo
Agnès
A
Veyradier
D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics; D000071120:ADAMTS13 Protein; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010951:Plasma Exchange; D010956:Plasmapheresis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human