Survival in TTP improved dramatically with the advent of plasma exchange but plateaued after that, with no difference in survival for the two 10 year periods (68 vs 69%).
The advent of plasma exchange and the need for early treatment reduced diagnostic stringency. In the pre-exchange era almost all patients exhibited the pentad. Now, only microangiopathic hemolytic anemia and thrombocytopenia (without other explanation) are required as the threshold for starting treatment. This early treatment has reduced expression of the other clinical features, with the result that the pentad is less often seen. Early treatment with a less stringent threshold has also increased the heterogeneity of the disease.
TTP may be idiopathic or secondary. Clinical profiles, survival and relapse rates in relation to these two categories and to ADAMTS 13 levels are detailed in the text.
The distinction between TTP and HUS is not always clear, particularly given the less stringent diagnostic criteria and early treatment, which may commence before ADAMTS 13 levels are available. From the paper:
Because standard practice in this region is to treat all adults who are diagnosed with either TTP or HUS and all children who are diagnosed with TTP with PEX, the Registry is a population-based inception cohort of consecutive patients in whom a diagnosis of TTP or HUS is made and PEX is requested. Children with typical (diarrhea-associated) HUS are not typically treated with PEX; therefore, most of these children are not included in the Registry...
Because these syndromes in adults, with or without renal failure or neurologic abnormalities, are commonly known as TTP, because Registry patients are almost all adults, and because patient descriptions focus on clinical presentations and levels of ADAMTS13 activity without testing for abnormalities of complement regulation, we describe patients in this report as having TTP. We recognize that some of our patients may be appropriately described as HUS, rather than TTP, particularly if complement regulatory abnormalities had been recognized or if a Shiga-like toxin-associated infection had been identified.
Categories of patients with TTP were: (1) allogeneic HSCT, (2) pregnancy/postpartum, (3) drug association, (4) bloody diarrhea prodrome, (5) additional or alternative disorder, and (6) idiopathic.
Patients within category 5 were further subdivided. The subdivisions included systemic infection, malignancy and autoimmune disorder (see Table 1).
TTP is more heterogeneous than commonly appreciated, such that the classification of patients into idiopathic and secondary TTP is simplistic. From the discussion section of the paper:
Patients defined as idiopathic were also heterogeneous. Although these patients were not recognized to have any of the conditions defining the other established clinical categories, some had preceding or concurrent conditions, such as pancreatitis, infections, or surgery which may have triggered the onset of TTP, reflecting the current arbitrary definition of "idiopathic" TTP. Only 46 (47%) of the 98 patients defined as idiopathic had ADAMTS13 activity below 10%.
Even patients who presented with ADAMTS13 levels below 10% were heterogeneous, initially presenting in multiple clinical categories (HSCT, postpartum, bloody diarrhea prodrome, additional or alternative disorders, as well as idiopathic). This experience suggests that dichotomous descriptions of TTP as either idiopathic or secondary do not accurately represent the heterogeneity among patients who are diagnosed and treated for TTP.
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