Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening condition, characterized by thrombotic microangiopathy (TMA) that results in microangiopathic hemolytic anemia (MAHA), thrombocytopenia and clinical symptoms including altered mental status, renal impairment and fever. Diagnosing TTP in acute setting continues to be a challenge, since the clinical pentad is not consistently present in TTP, making it difficult to differentiate from other conditions with TMA. The initial clinical decision for plasma exchange (PEX) is supported if there are MAHA and thrombocytopenia without a clear alternative cause. Acquired autoimmune deficiency of ADAMTS13 is known to cause idiopathic TTP and forms a basis for success of PEX in many patients by replenishing ADAMTS13 in addition to immunosuppressive therapy. However, low levels of ADAMTS13 alone are known to be neither sufficiently sensitive nor specific for diagnosis of TTP in acute setting. The aims of this retrospective study were to evaluate: (i) the utilization of ADAMTS13 testing in suspected TTP; (ii) the utilization of PEX in patients with TTP diagnosis; (iii) the association of low ADAMTS13 activity with early mortality in TTP; and (iv) the incidence of ADAMTS13 deficiency in non-TTP diagnoses. Methods After IRB approval, we identified 49 adult patients at a single tertiary medical center, who had ADAMTS13 testing between 2005 and June 2013 for suspected TTP. We searched the final diagnosis, either TTP or non-TTP. The results of ADAMTS13 testing and use of PEX were reviewed in the TTP and non-TTP patients. We identified the final diagnosis of the non-TTP patients. We assessed association of severely low ADAMTS13 activity (<10%) with early mortality defined as death within 3 months of diagnosis in patients with TTP diagnosis. Results Of the 49 patients who had ADAMTS13 testing 18 (37%) were male. The median age was 51years (range 20-81). All patients with TTP had PEX except one who could not initiate PEX due to early death. Twenty-five of the 30 patients (83%) with TTP had low ADAMTS13 activity and 17 of the 30 patients (57%) had severe deficiency (<10%). Five of the 30 patients with TTP suffered early mortality. The relative risk of death among TTP patients with severely low ADAMTS13 activity (<10%) was 1.15 (95% CI 0.22-5.90) compared to TTP patients with low to normal ADAMTS13 activity. Nineteen of the 49 patients who had ADAMTS13 testing subsequently had non-TTP diagnosis. Eight of these 19 patients with non-TTP diagnoses were found to have low ADAMTS13 activity: two patients with DIC secondary to sepsis; two patients with thrombocytopenia associated with primary presentation of hemophagocytic lymphohistiocytosis (HLH); one patient each with malignancy associated with TMA, vasculitis due to autoimmune disease, hematopoietic stem cell transplantation associated TMA and sepsis with renal failure; None of the eight patients with non-TTP diagnosis had severe deficiency. Four patients with non-TTP diagnosis underwent PEX and all had normal ADAMTS13 activity. Three of the 4 patients were subsequently diagnosed with drug induced TMA after oral opioid injection and one with hemolytic uremic syndrome. Conclusions Patients with a strong suspicion of TTP should be treated with PEX. ADAMTS13 activity is found to be relatively specific for TTP, being supportive of the clinical diagnosis in majority of cases. There was no statistically significant correlation between death and severely low ADAMTS13 activity in the cohort of TTP patients studied. ADAMTS13 activity can be low in a variety of non-TTP conditions. Its utility in diagnosis and prognosis of non-TTP conditions, especially HLH, needs further evaluation. Disclosures: No relevant conflicts of interest to declare.

Background Thrombocytopenic thrombotic purpura (TTP) and hemolytic uremic syndrome (HUS) form a group of diseases distinguishable by the development of thrombotic microangiopathy. Both are life-threatening disorders classically described by a pentad of symptoms: microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure and altered mental status. Early initiation of plasma exchange (PEX) is vital when TTP/HUS is suspected. However, diagnostic criteria are imprecise and clinical judgment remains the primary impetus for initiation of treatment. ADAMTS13 levels have not proven to be highly specific or sensitive for diagnosis of outcomes in TTP/HUS, and the delay in laboratory reporting limits its use in the acute setting. There may be other data available that more closely correlates with prognosis. The goal of this single institution retrospective study is to assess (i) the association of easily available clinical and laboratory factors with early death in patients with clinically diagnosed TTP/HUS, and (ii) the association of these factors among survivors with the length of stay (LOS) during the initial hospitalization with TTP/HUS. Design and methods After IRB approval, medical record review of adult patients at a single tertiary medical center treated with plasma exchange (PEX) for presumed TTP/HUS between 1999 and May 2013 was performed. For the 62 discrete cases identified, demographic and clinical data was obtained from the medical center and pertinent information was collected. Descriptive analysis was used to evaluate clinical symptoms and laboratory biomarkers with respect to their associations with survival. Episodes of TTP/HUS in the same patient were considered discrete if they occurred greater than 3 months apart. Survival was defined by hospital discharge without readmission for TTP/HUS or their sequelae for 3 months following discharge. The association of demographic factors (age, gender), symptoms (fever, neurologic changes, abdominal pain), and laboratory factors (hemoglobin [Hb], white blood cell count [WBC], platelet count, acute kidney injury [AKI] based on creatinine, AST, ALT, lactate dehydrogenase (LDH), indirect bilirubin, prothrombin time (PT), partial thromboplastin time (PTT), reticulocyte count) with survival during the first 3 months was studied using univariate analysis. ADAMTS13 levels were not included in analysis as the decision to treat with PEX was made in all cases prior to knowledge of any deficiency. All factors that attained a p value of, <= 0.1 were analyzed collectively using logistic regression with backward model selection. For survivors (n=49), the association with length of stay was compared with each of the above factors and was similarly studied using univariate analysis and multiple linear regression. Results In our sample (n=62), median age was 48 years and 26 (42%) were male. Of these, 79% (n=49) survived to discharge and did not have relapse or known death until 3 months afterwards. Thirteen (21%) died during hospitalization or within 3 months after discharge. There were 55 TTP and 7 HUS patients included in this retrospective cohort. Acute kidney injury (AKI) was diagnosed in 44 (71%) patients. On univariate analysis, factors associated with death included: AST (p=0.009) and AKI (p=0.045) with trends noted for hemoglobin (p=0.080) and PT (p=0.078). On multiple logistic regression, association with death was observed with AKI (OR: 0.093, 95% CI 0.009 – 0.950, p= 0.04) and hemoglobin (OR: 0.65, 95% CI 0.434 – 0.975, p=0.037). Among the 49 survivors (median age 45.1, range 12-81 years; 28 (57%) were female), correlation of the LOS in hospital with all variables was assessed. On linear regression analysis, elevated white blood cell count (WBC) (p=0.027) and prolonged prothrombin time (PT) (p=0.035) were independently associated with prolonged hospitalization. Conclusion Clinical and laboratory markers found to have an independent association with death are AKI and low hemoglobin. It may be possible to risk stratify patients more accurately with clinical algorithms based on this evidence even before ADAMTS13 levels are available. Increased WBC count and prolonged PT are independently associated with increased length of stay. The application of our results could therefore be used for further risk stratification in prospective studies of outcomes in patients diagnosed with TTP/HUS. Disclosures: No relevant conflicts of interest to declare.