Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008.
BACKGROUND
Thrombotic microangiopathies (TMAs) are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13: AC) is more specific for TTP, but not for HUS. Since 1998, our laboratory has functioned as a nationwide referral center for TMAs by analyzing ADAMTS13.


METHODS
Of 1,564 patients tested from 426 hospitals, 919 were positive for TMA. Levels of ADAMTS13: AC and the ADAMTS13 neutralizing autoantibody (ADAMTS13: INH) were determined by chromogenic act-ELISA and/or by classic von Willebrand factor multimer assay.


RESULTS
TMA patients consisted of two groups: severe (less than 3% of normal control) and non-severe deficiency of ADAMTS13: AC. Both groups were divided into congenital (n=65) and acquired (n=854) TMA. Of the former, 41 had congenital deficiency of ADAMTS13: AC, while the remaining 24 had disease of unknown etiology. The 854 patients with acquired TMA could be largely grouped into three categories: idiopathic TTP (n=284), idiopathic HUS (n=106), and secondary TMAs (n=464). The secondary TMAs were observed in heterogeneous patient groups and were associated with drugs, connective tissue diseases, malignancies, transplantation, pregnancy, E. coli O157: H7 infection, and other factors. All of the patients with acquired severe ADAMTS13: AC deficiency were positive for ADAMTS13: INH.


CONCLUSIONS
Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13: AC. Platelet transfusions to such patients are contraindicated. Rapid ADAMTS13: AC assays are therefore prerequisite to appropriately treat TMA patients.
Fujimura
Yoshihiro
Y
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan. malon@naramed-u.ac.jp
Matsumoto
Masanori
M
D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D000465:Algorithms; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007564:Japan; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000175:diagnosis*; D012042:Registries
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human