Development and Validation of a Predictive Model for Death in Acquired Severe ADAMTS13 Deficiency-Associated Idiopathic Thrombotic Thrombocytopenic Purpura: The French TMA Reference Center Experience

Abstract

2229 Background: Acquired thrombotic thrombocytopenic purpura (TTP) is still associated with a 10–20% death rate, which did not significantly improve for more than 20 years despite a better awareness about this diagnosis. Usually, death occurs within the first days of management and so far, early prognostic factors of death could not be clearly identified. In this context, the accurate understanding of factors associated with a fatal outcome at the acute phase of the disease would help to better tailor initial treatment and further improve these results. Objective: To identify prognostic factors associated with 1-month death in TTP patients with acquired severe (< 10% of normal activity) ADAMTS13 deficiency. Design: Prospective national cohort of adult (≥ 18 year-old) patients included between October, 2000, and December, 2008. A validation cohort of patients was set up from January, 2009 to March, 2010. Participants: 248 (analysis cohort) and 39 (validation cohort) consecutive adult TTP patients with acquired severe ADAMTS13 deficiency from 39 French centers. Measurements: 30-day mortality after treatment initiation according to characteristics at inclusion. Results: When compared to survivors, non-survivors (11%) were older (54.0 ± 19.4 versus 39.0 ± 15.5 year-old, respectively, P <.001) and had more frequently a past history of arterial hypertension (37% versus 10%, respectively, P <.001) and ischemic heart disease (19% versus 4%, respectively, P =.002). Prognosis was increasingly poor with age (p <.004), particularly in patients ≥ 60 year-old. On presentation, cerebral manifestations were more frequent in non-survivors (81% versus 55%, respectively, P =.009) and serum creatinine level was higher (172 ± 123 versus 117 ± 91 μmol/L, respectively, P =.037). Death occurred after a few days (mean 7 days, interquartile range = [3, 12]), in a context of one or multiple organ failure in relation with an uncontrolled TTP. Platelet count between diagnosis and death did not significantly increase (20 ± 25×109/L versus 28 ± 46×109/L, respectively, P =.44). The most significant independent variables for determining death were age (P <.001), cerebral involvement (stupor and seizure) and LDH level > 10 times normal value (P <.04 for both). After computing the risk scores using these 3 variables (Table), patients were stratified into 3 distinctive risk groups regarding death: low, 0 and 1; intermediate, 2; and high, 3 and 4. The proportion of positive predictive value for 30-day death was 11–13% in the low risk group, 20% in the intermediate group, and 39–50% in the high risk group. This score was confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death (P <.01). Conclusions: A risk score for early death was defined in patients with TTP and validated on an independent cohort. This score should help to stratify early treatment and intensify patients with a worse prognosis. Importantly, we provide clear evidence that age is an important prognostic factor of TTP. Consequently, old patients with a diagnosis of TTP should benefit from more intensive supportive care and should be monitored more closely in intensive care units with more aggressive attention to cardiac and renal function. Disclosures: Rottensteiner: Baxter Innovations GmbH: Employment.

Prognostic risk‐stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: nationally representative data from 2007 to 2012

“…Increasing age was an important predictor of survival with older patients showing worse outcomes. In particular, patients with age of 60 years or more were most susceptible to increased mortality even after adjusting for other comorbidities, as also shown in other studies . PLT transfusions were also an independent risk factor for mortality.…”

“…Renal failure (acute or chronic and with dialysis dependence) was also associated with worse outcome in TTP patients and higher adjusted odds of death. Varying degrees of renal dysfunction ranging from elevated creatinine to renal failure warranting dialysis have previously been reported as being associated with adverse outcomes in TTP patients but not death . In our data, renal failure was seen in the sickest TTP patients with more than three‐quarters of the subjects being in the highest grade of severity of illness by the APR‐DRG severity scoring and was identified as a significant independent predictor of death.…”

“…Using data from the Canadian Apheresis Group registry, Wyllie and colleagues proposed a new index predicting 6‐month mortality based on clinical variables at presentation including fever, low PLT count, low hemoglobin, and advanced age. Recognizing the need for a predictive model for mortality in TTP, a French group recently proposed that individuals who were older and had arterial hypertension, ischemic heart disease, cerebral manifestations, increased creatinine levels, and increased lactate dehydrogenase levels were more likely to die among a cohort of about 30 deaths in TTP patients with confirmed severe ADAMTS13 deficiency . The primary predictors of mortality identified from our model included increasing age especially 60 years or more, PLT transfusions, CNS bleeding, renal failure, arterial thrombosis, acute myocardial infarction, and ischemic stroke.…”

“…While it is widely recognized and accepted that TTP still has a high risk for in‐hospital morbidity and mortality, recent estimates of all‐cause mortality in hospitalized TTP patients are not available. Additionally, survivors of TTP hospitalizations have been proposed to be at higher risk for long‐term poor clinical outcomes and eventual premature death . The French TMA group proposed predictors of mortality in the subgroup of TTP patients with severe ADAMTS13 deficiency .…”

“…Additionally, survivors of TTP hospitalizations have been proposed to be at higher risk for long‐term poor clinical outcomes and eventual premature death . The French TMA group proposed predictors of mortality in the subgroup of TTP patients with severe ADAMTS13 deficiency . However, a comprehensive prognostic risk predictive score of all‐cause mortality in hospitalized patients with TTP remains elusive.…”