No major differences in outcomes between the initial and relapse episodes in patients with thrombotic thrombocytopenic purpura: The experience from the Ohio State University Registry
Authors: Camila Masias, Haiwa Wu, Michael McGookey, Lauren Jay, Spero Cataland, Shangbin Yang
Journal: American Journal of Hematology (2017)

Patients with immune mediated TTP (iTTP) are diagnosed when they present with microangiopathic hemolytic anemia and consumptive thrombocytopenia without an alternative explanation, confirmed by severely reduced ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) of less than 10%.1 Once the patient has recovered from their initial episode, they have a 50% chance of an exacerbation in the next 30 days and a 30%-50% chance of relapse in the future.2-4 It is presumed that patients presenting with a iTTP relapse recover faster and have a milder course due to their earlier presentation, however the evidence behind this is limited. We present a retrospective cohort study to evaluate the difference between initial and relapse iTTP episodes in terms of clinical presentation and outcomes in patients treated at a single institution with a standard treatment protocol. Data was obtained from patients enrolled in the TTP registry at The Ohio State University between 2003 and 2016. The diagnosis of TTP was made by the presence of thrombocytopenia (<100 × 109/ul) and a microangiopathic hemolytic anemia without an alternative explanation, and confirmed by the finding of severely deficient ADAMTS13 activity (<10%). ADAMTS13 activity and inhibitor titers were measured at the Biomarker Reference Laboratory at Ohio State University using a Surface Enhanced Laser Desorption/Ionization Time-of-flight Mass Spectrometry (SELDI-TOF-MS) as reported previously.5 This assay has been validated and standardized to meet the requirements set forth by the College of American Pathologists (CAP) for clinical testing. Clinical information regarding the initial clinical presentation including the presence of petechiae and ecchymosis, neurological and gastrointestinal symptoms were obtained. Laboratory information regarding initial hemoglobin, platelet count, lactate dehydrogenase (LDH), and creatinine were also noted. Patients were considered to have a clinical response when they had achieved a normal platelet count (>150 × 109/L), normal LDH and a stabilization or improvement of any neurologic or renal injury present. PEX procedures for each episode were calculated as the number of PEX sessions that occurred since diagnosis until clinical response or death. Remission was defined by a stable clinical response for 30 days after their last PEX procedure. Exacerbations were defined as the need to restart PEX therapy within 30 days after the last PEX procedure. iTTP relapse were recurrences that occurred beyond 30 days after their last PEX procedure. Descriptive analysis was done using medians and proportions. We divided the patients in two groups; those with an initial episode and those with relapses, and compared major clinical outcomes between the two groups. To account for same patient variation, comparisons were made using the Generalized Estimating Equation. All analysis were conducted using IBM® SPSS Statistics® software. P values <.05 were considered significant. One hundred twenty-five iTTP episodes (42 initial and 83 relapses) from 57 patients were identified and included in the analysis. Forty-two patients presented to our institution with their initial episode and 15 at the time of their second episode. During the study period, 22 patients had only one episode, 11 had two episodes, 12 had three episodes, 5 had four episodes, and 5 had five episodes. The time between episodes varied greatly, from 2 months to 8 years. There was no difference in the age and proportion of women on both groups; there was however a significant higher number of African American patients in the initial group compared to the relapse group (P = .018) Patients on their initial episode presented more commonly with neurologic symptoms (P = .049), significantly lower platelet counts (P = .002), higher LDH (P < .0001), and lower ADAMTS13 activity (P = .033), compared to those patients presented as a relapse (Table 1). Treatment details were available for 35 initial episodes and for 76 relapse episodes. Patients in their initial episode required a median of 10 PEX procedures to achieve a clinical response, compared to five needed for the relapse episodes (P = .927). While the difference was not statistically significant, more patients in the initial presentation required five or more PEX compared to patients in the relapse cohort (P ≤ .0001). Despite these differences in duration of treatment, there were no significant differences in the main clinical outcomes between the initial and relapse groups regarding clinical response (P = .267), exacerbation (P = .483), refractory iTTP (P = .075) or death (P = .066) (Table 1). There is little evidence to support the general hypothesis that patients will have a milder course and better outcomes in their relapse episodes when compared their initial iTTP episode. We report a single institution experience of 125 iTTP episodes, in which patients on their initial and relapse episodes have similar clinical response, exacerbation, refractoriness and mortality rates. We compared the initial episodes with the relapses in our registry as opposed to comparing initial and relapse episodes from the same patient as done before, as this may more accurately reflect clinical practice, in which a patient may present to different institutions for their initial and relapse episodes.6 These results support the hypothesis that patients will present with more severe laboratory markers of their disease and neurologic symptoms on their initial episode when compared to relapse episodes. As published before, we also saw a trend toward patients requiring more PEX during the initial episodes compared to relapse episodes.3, 6 However, we did not find any differences in outcomes. The series reported before included all patients referred for PEX in different regions of Europe and Canada, including patients with HUS and thrombotic microangiopathy due to other etiologies. Our registry includes only patients with a clinical diagnosis if TTP confirmed by a severely deficient ADAMTS13. In summary, our findings show that while patients may have a less severe presentation in terms of symptoms, laboratory data and the number of PEX required in their relapse episodes compared to their initial diagnosis, this did not translate into differences in clinical outcomes. We propose that both in clinical practice and research, patients in their initial episode and relapse episodes should be viewed as comparable events in terms of the urgency to start PEX, as well as for enrollment in clinical trials.