Characterization of Two Patient Groups with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura, Defined by ADAMTS13 (n=195) and/or Classic Pentad (n=89).
Authors: Matsumoto Masanori , Isonishi Ayami , Kato Seiji , Ishizashi Hiromichi , Yagi Hideo , Fujimura Yoshihiro 
Published: October 2019

Abstract
Abstract 3505
Poster Board III-442

[Aims]
Thrombotic thrombocytopenic purpura (TTP) is a phenotype of thrombotic microangiopathies (TMAs), and now well defined by the congenital or acquired deficiency of ADAMTS13 activity (ADAMTS13:AC). But, it is also true that clinical diagnosis of TTP exists and can be made by classic “pentad”; the four clinical features mentioned below and fever. However, the comprehensive analyses on these two phenotypes of acquired idiopathic (ai-) TTP have not been done.

[Patients and Methods]
Nara Medical University is a Japan-wide referral center for TMAs via assaying ADAMTS13:AC. During July 1998 and December 2008, a database of registered 919 patients with TMAs was made (in press). TMAs were defined as having all of the followings: (i) microangiopathic hemolytic anemia (hemoglobin ≤12g/dL), (ii) thrombocytopenia (platelet count ≤100 × 109/L); and (iii) a variable severity of organ dysfunction (renal or neurological involvement) devoid of the stigmata of disseminated intravascular coagulation. Assays of ADAMTS13:AC and its inhibitor (ADAMTS13:INH) were performed by commercially available chromogenic act-ELISA (Tokyo-Vienna).
In our database, 284 patients with ai-TTP were enrolled, in which 195 patients (group A) were diagnosed by severe deficiency (<3% of the normal) of ADAMTS13:AC due to the presence of ADAMTS13:INH, and 89 patients (group B) by classic pentad, whose ADAMTS13:AC was not severely deficient without ADAMTS13:INH; 72 patients in group B had moderate deficiency of ADAMTS13:AC (3∼<25 %), 14 mild deficiency (25∼<50%), and 3 normal activity (≥50%).

[Results] (1) Age
The age and number of ai-TTP patients, when the initial TTP-bouts developed, are shown in Figure. It is interesting to note a tremendously wide range of the age (from 8 mo. to 87 y.o.) at TTP-bouts in both the groups A and B. The largest incident peak was seen at the age of around 60 y.o., and the 2nd one at around 45 y.o. The patients of under 30 y.o. were far less common, but present with consistent proportions. Particularly, it was a surprise to note the presence of 5 young infants (2 female and 3 males) under 2 y.o., who belonged to group A. (2) Deficient or detectable ADAMTS13:AC vs age: Higher population of group A patients was found in those after 70 y.o. than before. (3) Gender: Number of female patients in group A was 105 (/195, 54%), and that of group B was 48 (/89, 54%). Male patients were more common after 55 y.o. (4) Laboratory data: Platelet counts in group A appeared to be lower than in group B (14.7 ± 14.7 vs 28.8 ± 23.5 × 109/uL, mean ± SD), and serum creatinine levels tended to be lower in group A than group B (1.3±1.3 vs 3.2 ± 3.4 mg/dL).

[Conclusion]
We characterized two phenotypes of ai-TTP (n=284); group A (195/284, 69%) closely associated with deficient ADAMTS13, and group B (89/284, 31%) without. Patients with group A were commonly found in under 65 y.o., and those with group B in above 70 y.o. Further, a large-scale analysis revealed the presence of 5 young infants with ai-TTP belonged to group A, a hitherto not well-characterized clinical entity.

Disclosures:
Fujimura: Baxter BioScience: Consultancy, Membership on an entity's Board of Directors or advisory committees.