The ADAMTS13 Family: In-Patient Trends and Outcomes of Thrombotic Thrombocytopenic Purpura

Abstract

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal dysfunction and other end organ failure. It is associated with inherited or acquired antibody-mediated deficiency of ADAMTS13 resulting in an inability to cleave von Willebrand factor. It occurs in approximately 3 in 1 million adults and 1 in 10 million children annually. First line therapy is plasmapheresis, typically coupled with steroids. Patients recovering from TTP may demonstrate persistent or intermittent ADAMTS13 deficiency without symptoms or thrombocytopenia. Most relapses of acquired TTP occur in the first week after stopping plasma exchange. There are multiple factors contributing to relapses, which include age > 60, severe neurological symptoms at presentation and a persistently elevated lactate dehydrogenase. Thus young patients with low ADAMTS13 activity are appropriate candidates for prophylactic treatment. The early initiation of immune-modulatory therapy targeting the antibody inhibitor of ADAMTS13 could potentially reduce the number of plasma exchange procedures required to achieve remission, increase the response rate and decrease the incidence of relapses in patients with TTP. Since TTP is a rare disease, the aim of our study was to outline the trends and outcomes of hospitalizations due to TTP using the nationally representative database for future use in risk stratification and treatment protocols. Methods: We performed retrospective study using the National Inpatient Sample database, a part of the Healthcare Cost and Utilization Project (HCUP) of the agency for Healthcare Research and Quality (AHRQ). We extracted the study cohort of adult admissions with TTP from 2007-2017 by using International Classification of Diseases (9th/10th editions) Clinical Modification diagnosis codes. In the final study cohort we only included patients who received plasmapheresis to restrict patient population with active TTP disease. This approach has been validated in prior publications from administrative databases. Other diagnosis of interests and other comorbidities were identified by ICD-9/10-CM codes and Elixhauser comorbidity software. We utilized Cochran Armitage trend test and survey logistic multivariable regression modeling to analyze trends and predictors of outcomes with weighted analysis. Statistical analyses were performed using SAS software, version 9.4. Results: There were a total 22,054 hospitalizations due to TTP, which increased from 1,620 in 2007 to 1,870 in 2017. The median age was 47-years (IQR:33-60) with 25% hospitalizations among the age group of 18-34 years, 66.1% were females, 46.7% were Caucasians followed by 39.2% African American race. The overall length of stay was 16-days which declined from 17-days in 2007 to 15-days is 2017 (pTrend<0.001). In the study cohort, 14.5% were discharged to a facility, and 9.8% died during the hospitalization. In trend analysis, in-hospital mortality decreased (13.4% in 2007 to 8.02% in 2017; pTrend<0.001) but discharge to facilities increased (8.9% in 2007 to 14.4% in 2017; pTrend<0.001). Furthermore, in multivariable regression analysis, increasing age (OR 1.4; 95%CI 1.3-1.5; p<0.001), Caucasians (OR 1.4; 95%CI 1.2-1.7; p<0.001), pneumonia (OR 1.8; 95%CI 1.4-2.5; p<0.001), septicemia (OR 3.4; 95%CI 2.6-4.5; p<0.001), cardiovascular events (OR 2.2; 95%CI 1.5-3.2; p<0.0001), electrolytes imbalance (OR 1.4; 95%CI 1.1-1.9; p=0.005), and liver disorders (OR 1.7; 95%CI 1.1-2.6; p=0.02) were associated with higher odds of in-hospital mortality. Conclusion: In this study, we described national trends of hospitalizations and outcomes of TTP. We observed in-hospital mortality has decreased coupled with an increase in discharge to facilities over the past decade. We also identified risk factors for poorer outcomes, including advanced age, caucasian background and associated sepsis, revealing higher odds of in-hospital mortality. Early identifications of these potential risk stratifiers may play a crucial role in initiating early treatment in addition to identifying populations who may benefit from immune-modulatory therapy along with prophylactic plasma exchange. Disclosures No relevant conflicts of interest to declare.

A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura

“…Treatment with therapeutic plasma exchange (TPE) and immunosuppression significantly lowers iTTP-related mortality rates [ 3 , 5 ]. Yet, despite improvements in diagnosis and treatment of iTTP, the most recent mortality rate estimates remain around 5% to 10% in the past decade [ [6] , [7] , [8] , [9] , [10] ].…”

A descriptive analysis of fatal outcomes in immune thrombotic thrombocytopenic purpura in the USTMA TTP Registry

“…The overall acute iTTP-related mortality rate of 6.6% in our cohort was similar to other recent reports. 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 The overwhelming majority (73%) of deaths occurred during the first episode, two-thirds of which occurred before achieving a clinical response. This is consistent with previous findings that suggest the highest risk of mortality at the first presentation.…”

“…Modern estimates of mortality are lacking, particularly in the United States, where, until recently, there were no multi-institutional registries on which to base their estimates. There are also few data reports on how mortality from iTTP has improved over time as a result of advances in the earlier recognition, diagnosis, and management of iTTP, including the development of clinical diagnostic scores, [2][3][4] clinical guidelines, [5][6][7] and education programs. 8 The United States Thrombotic Microangiopathies (USTMA) iTTP registry contains data on 770 patients with iTTP from 15 high-volume centers across the United States between 1985 and 2019.…”