Characterization of Two Patient Groups with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura, Defined by ADAMTS13 (n=195) and/or Classic Pentad (n=89).

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.

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%).

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 2^nd 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).

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.

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