Outcome Of Thrombotic Thrombocytopenic Purpura Research Articles

100 Years of Thrombotic Thrombocytopenic Purpura: A Story of Death and Life.

One hundred years ago, in 1924, the first description of a patient with a disease, now known as thrombotic thrombocytopenic purpura (TTP) was published by Dr. Eli Moschcowitz. In honor of this report, this article, written by distinguished specialists in TTP, reviews the increase in scientific knowledge on this disease during the last 100 years. It covers the scientific progress from plasma therapy, the first beneficial treatment for TTP, to the elucidation of the pathophysiology, the discovery of ADAMTS13, the development of assays and targeted therapies up to the modern treatment concepts, that improved the outcome of TTP from an incurable disease to a well understood and treatable disorder.

Clinical characteristics, treatments, and outcomes of thrombotic thrombocytopenic purpura treated with plasma exchange in Japan: a nationwide inpatient database study

BackgroundPlasma exchange (PEX) has been the primary treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) since the 1990s. Daily PEX is recommended in international guidelines, but PEX was only reimbursed up to three times weekly under the Japanese national health insurance system until March 2018. This study was conducted to analyze practice patterns and outcomes in patients with TTP in Japan.MethodsWe used the Japanese Diagnosis Procedure Combination inpatient database, including data from approximately 1,200 acute care hospitals. We identified all hospitalized adult patients who were diagnosed with TTP on admission from July 2010 to March 2017 and who received at least one PEX during hospitalization, which we defined as TTP treated with PEX. We revealed patient characteristics, treatment patterns, and outcomes.ResultsThere were 1,559 patients with TTP treated with PEX. The median age was 64 (interquartile range [IQR] 46–74) years. There were slightly more women (59%) than men enrolled into this study. The median PEX frequency within 7 days of the initial PEX was three (IQR 2–5) times. The median total PEX number during hospitalization was six (IQR 3–10), while the median PEX duration was 10 (IQR 4–22) days. The median time from admission to the initial PEX was 4 (IQR 2–11) days. Overall, in-hospital mortality was 32%. Thirty-three percent (144/437) of hospitals reported only one case of TTP during the study period.ConclusionsOur data demonstrated that clinical practice in Japan considerably varied and its standardization is warranted.

Frontiers in pathophysiology and management of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Hereditary or congenital TTP (cTTP) is caused by ADAMTS13 gene mutations. In acquired or immune TTP (iTTP), ADAMTS13 activity is reduced by anti-ADAMTS13 autoantibodies. TTP is characterized by thrombocytopenia, hemolytic anemia, fever, renal dysfunction, and neuropsychiatric symptoms. Therapeutic plasma exchange (TPE) and immunosuppressive therapy are the mainstays of treatment. As untreated TTP has a high mortality rate, immediate initiation of TPE is recommended when TTP is suspected. Conventionally, corticosteroids have been used for immunosuppressive therapy. Current drug therapies include rituximab, an anti-CD20 antibody that is effective in newly diagnosed cases and refractory cases, as well as for relapse prevention, and caplacizumab, an anti- von Willebrand factor (VWF) nanobody that inhibits the binding of platelets to VWF and prevents microthrombi formation. Recombinant human ADAMTS13 is a promising treatment for cTTP. Although these therapeutic advances have improved the outcomes of TTP, early diagnosis and prompt initiation of appropriate therapy are necessary to achieve these outcomes.

Epidemiology and Administration outcomes of Thrombotic Thrombocytopenic Purpura (TTP): Review article

Background: Fever, thrombocytopenia, hemolysis, pentad failing kidneys, anaemia, and neurological impairment has historically been used to describe bleeding as the blood syndrome “thrombotic thrombocytopenic purpura” (TTP), a type of hemolytic anaemia caused by microangiopathy. TTP is an uncommon condition, and it is unclear exactly how often it is? According to studies, incidence per million depends on where individuals live. TTP can occur in youth with congenital forms, however it mostly strikes adults over the age of 40. The two organ systems most frequently impacted by TTP are the nerve system of the body (CNS) and kidneys. Because TTP is a serious medical condition with a 90% fatality grad if untreated, prompt diagnosis is crucial. Initial therapy is effective in around 80% of patients, and post-treatment mortality is between 10% and 15%. Objectives: The study aimed to summarize current evidences regarding epidemiology and outcomes of Thrombotic Thrombocytopenic Purpura therapy (TTP). Methods: For article selection, the PubMed database and EBSCO Information Services were used. All articles relevant with our topic and other articles were used in our review. Other articles that were not related to this field were excluded. The data was extracted in a specific format that was reviewed by the group members. Conclusion: Older patients had longer Immune thrombotic thrombocytopenic purpura (iTTP) episodes and died at higher rates than younger patients. iTTP patients have a considerable increase in chance of illness and demise, while receiving TPE and immunosuppressants, which necessitate the need for more potent treatments. Moreover, they are more likely to have secondary thrombotic microangiopathies than primary microangiopathies due to several causes. Depending on the origin of thrombotic microangiopathies, there are different risks associated with dialysis, neurologic and cardiac issues, and mortality. Mortality rate are low for patients who received hospital care with low rate of complications.

Recent Trends in the Incidence and Outcomes of Thrombotic Thrombocytopenic Purpura in the United States: Data from the 2009-2014 National Inpatient Sample

BackgroundThrombotic Thrombocytopenic Purpura (TTP) is a hematological emergency that can be fatal if not promptly recognized and treated. Given its rarity, there is paucity of data regarding the disease burden and outcomes. We used a large administrative database to examine recent incidence and outcomes of TTP in the United States.MethodsWe used the 2009-2014 National Inpatient Sample database, which is the largest publicly available all-payer inpatient database in the US, to identify patients ≥18 years with primary and secondary diagnoses of TTP (International Classification of Diseases, 9th Revision, Clinical-Modifications [ICD-9-CM] code 277.88) who underwent plasmapheresis (ICD-9-CM procedure code 99.71). We only included patients who received therapeutic plasmapheresis (ICD-9-CM procedure code 99.71) during hospitalization to capture active cases of TTP and improve coding accuracy. We calculated annual incidence of TTP specific hospitalizations by dividing the total number of TTP related hospitalizations in each year by the corresponding total all-cause hospitalizations recorded in the database in the same year. Annual incidence, mortality, length of stay (LOS), costs were calculated for each year 2009-2014, fitted into a log-linear model and compared using Monte Carlo permutation test to study the changes in trend. Statistical analyses were done using STATA version 13.0 and Joinpoint Regression Program version 4.5.0.1.ResultsA total of 32,609 cases of TTP were identified among 219,490,468 hospitalizations during the study period. Average annual incidence of TTP was 14.89 per 100,000 hospitalizations with an annual percent change (APC) of 0.99 which was statistically not significant (95% CI -3.2 to 5.4, p=0.6) (Figure 1). There was no significant change in the rate of plasmapheresis use from 2009 (40.11%) to 2014 (37.68%) (Figure 2). Similarly, there was no significant annual change in the in-hospital mortality (mean 10.2%), LOS (mean 13.1 days) and total hospital charge (mean $160,574; cost adjusted for yearly inflation using Consumer Price Index, Bureau of Labor Statistics) (Table 1).DiscussionOur study shows that the annual incidence of TTP has remained unchanged (14.89 per 100,000 adult hospitalizations) in the recent years. Similarly, the outcomes in terms of in-hospital mortality, LOS and total cost of hospitalization have not improved. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Lysine-Histone Triggers Thrombotic Thrombocytopenic Purpura in Zebrafish and Mice

Background: Thrombotic thrombocytopenic purpura (TTP) is a potentially fatal syndrome, primarily resulting from a severe deficiency of plasma ADAMTS13 activity due to mutations in ADAMTS13 gene or autoantibodies against ADAMTS13. However, severe deficiency of plasma ADAMTS13 activity alone is often not sufficient to cause an acute episode; additional environmental and/or genetic factors may be required to trigger acute TTP.Objectives: To address the potential triggers and identify novel therapeutic targets for TTP, we established and characterized a novel Adamts13-/- zebrafish line and determined the pathogenic role of lysine-histone in triggering TTP in both zebrafish and mice.Methods and Results:CRISPR/Cas9 was employed to create an 8-nt deletion mutation in the signal peptide region of zebrafish Adamts13, resulting in complete deficiency of Adamts13 protein. Adamts13-/- zebrafish on the double transgenic (fli1-eGFP/gata1-dsRed) background showed normal size, morphology, and fertility except for the consistent appearance of a branching interseptal vessel. Adamts13-/- zebrafish larvae exhibited a significantly increased response to oxidative stress with an increased mortality rate and an accelerated rate of thrombus formation in microvasculature and caudal vessels after oxidative injury. Additionally, Adamts13-/- zebrafish demonstrated a significantly reduced number of circulating mature thrombocytes (thrombocytopenia) and an increased number of fragmented red blood cells (schistocytosis), consistent with the clinical phenotype of a spontaneous TTP. Moreover, plasma levels of histone/DNA complexes were found to be highly elevated in patients with acute TTP, but their pathogenic role is not known. Wild-Type and Adamts13-/- zebrafish and mice were challenged with a lysine rich-histone (H5505) intraperitoneally (200 μg/g body weight) and intravenously (20, 60, and 120 μg/g body weight), respectively. Complete blood counts were determined over a period of 14 and 3 days, respectively. We showed a more severe and persistent thrombocytopenia, increased fragmentation of red blood cells, as well as increased mortality rate in Adamts13-/- compared to Wild-Type zebrafish (Figure). Similar dose-dependent and profound thrombocytopenia was observed in Adamts13-/- but not in Wild-Type mice. Histological analysis of the organ tissues from Adamts13-/- zebrafish that died after histone challenge revealed the presence of microvascular thrombosis, supporting the diagnosis of TTP in these zebrafish.Conclusions: These results demonstrate for the first time the success in establishing a zebrafish model of Adamts13-/- and TTP. Such a novel animal model enables us to rapidly evaluate the role of lysine-histone and many other potential environmental or genetic factors in the onset, progression, and outcome of TTP. This model may also help to identify novel therapeutic targets for both hereditary and acquired TTP in at an unprecedented pace. [Display omitted] DisclosuresZheng:Alexion: Speakers Bureau; Ablynx: Consultancy.

Clinical characteristics and outcomes of adult patients with acquired thrombotic thrombocytopenic purpura: a single center retrospective study.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease and a potentially life-threatening thrombotic microangiopathy. Although the diagnostic and therapeutic techniques have improved, it is still difficult for clinicians to identify early due to different initial clinical manifestations and the incidence and survival rate are reported inconsistently. This study investigated the clinical characteristics, treatment strategies, and treatment outcomes of adult patients with acquired TTP. A retrospective analysis of 55 patients (35 females and 20 males) treated for acquired TTP from January 1, 2013 to December 31, 2017 was conducted. The analysis included clinical manifestations at onset, treatment efficacy measures, survival, cause of death, and the APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (sequential organ failure assessment) scores. At onset, in addition to thrombocytopenia and hemolysis, 50 patients (90.91%) presented with neurological abnormalities, but only 19 (34.55%) showed the classic TTP pentad of symptoms. The overall mortality rate was 34.55%. Plasma exchange (PEX) was performed in 49 patients. The most effective treatment was PEX with a normal dose of corticosteroid and rituximab which showed a response rate of 81.25%. The main cause of death was cerebral hemorrhage. The APACHE II and SOFA scores were higher in non-survivors compared to survivors (APACHE II: 20.12±7.83 vs. 11.50±4.49, P<0.05; SOFA: 12.06±3.27 vs. 7.74±2.10, P<0.05). Non-survivors had higher levels of lactic dehydrogenase (LDH; 1,646.94±1,269.48 vs. 942.76±740.58 IU/L, P=0.015), and higher numbers of schistocytes (6.18%±4.69% vs. 3.44%±3.13%, P=0.035) compared to survivors. TTP progressed rapidly, and its clinical manifestations varied between patients. The diagnosis depended on the clinical features and laboratory tests. Combination therapy with PEX, immunosuppressive therapy, and rituximab may be useful. Higher APACHE II and SOFA scores, higher LDH levels, and a greater degree of schistocytosis were associated with the severity and outcome of TTP.

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

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 &amp;gt; 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&amp;lt;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&amp;lt;0.001) but discharge to facilities increased (8.9% in 2007 to 14.4% in 2017; pTrend&amp;lt;0.001). Furthermore, in multivariable regression analysis, increasing age (OR 1.4; 95%CI 1.3-1.5; p&amp;lt;0.001), Caucasians (OR 1.4; 95%CI 1.2-1.7; p&amp;lt;0.001), pneumonia (OR 1.8; 95%CI 1.4-2.5; p&amp;lt;0.001), septicemia (OR 3.4; 95%CI 2.6-4.5; p&amp;lt;0.001), cardiovascular events (OR 2.2; 95%CI 1.5-3.2; p&amp;lt;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.

Favourable outcome of thrombotic thrombocytopenic purpura despite delayed presentation

Favourable outcome of thrombotic thrombocytopenic purpura despite delayed presentation

Thrombotic thrombocytopenic purpura: A 5-year tertiary care centre experience.

Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality if not managed timeously with therapeutic plasma exchange (TPE). TTP secondary to human immunodeficiency virus (HIV) infection is unique to sub-Saharan Africa. The management and outcome of TTP in the era of improved access to therapy has not been described. The present study describes the clinical presentation, treatment, therapeutic endpoints, and outcome of TTP patients at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa. The inpatient and outpatient records of 41 consecutive adults with TTP were reviewed between 2012 and 2016. Patients were classified according to aetiology and treatment response. TTP was the initial presenting feature of HIV infection in 78.0%, and 12.5% were noncompliant with antiretroviral therapy (ART). Most study patients were of black ethnicity (95%) and female gender (78.1%). Treatment included initial TPE (87.8%), plasma infusion (78.1%), antiretroviral therapy (78.3%), corticosteroids (61.0%) intensive care admission (41.5%), renal dialysis (12.2%), and other immunosuppressive agents (4.9%). The median (range) number of TPEs was 10.0 (7.0-15.0). A high rate of refractory disease (63.4%) was reported. Haemoglobin, platelet count, lactate dehydrogenase, red cell distribution width, and creatinine were reliable therapeutic end-points (P < .05). The relapse rate was 9.8% and the mortality rate was 29.3%. The high mortality rate emphasises the importance of early diagnosis, referral, and appropriate management of TTP. Anti-retroviral therapy and adherence monitoring are essential to TTP management associated with HIV. Future studies to identify patients at risk for refractory disease are indicated.

Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

AbstractImmune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10.3% (n = 32); 68% of patients had a raised troponin at presentation conferring a sixfold increase in mortality compared with those with normal troponin levels (12.1% vs 2.0%, P = .04). Twenty-four percent had a reduced Glasgow Coma Score (GCS) at presentation with a ninefold increase in mortality (20% vs 2.2% for normal GCS at presentation, P < .0001). Mortality increased with higher anti-ADAMTS13 antibody levels and lower ADAMTS13 antigen levels. Those with antibody levels in the upper quartile (antibody >77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody <20%) (P = .004). Those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for the highest quartile (antigen >11%) (P = .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality.

Advance in management of refractory/relapsing thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a kind of thrombotic microangiopathies which has low incidence but highly mortality. The outcome of TTP has been improved significantly since last decade due to the application of plasma exchange, however, early relapse occurs in some patients, and for relapsed/refractory patients the prognosis is still poor. This article reviews the recent progress in treatment and relevant influencing factors of TTP. Key words: Thrombotic thrombocytopenic purpura; Treatment

Evaluating the impact of the ABO blood group on the clinical outcome of thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency.

Thrombotic thrombocytopenic purpura (TTP) is caused by the decrease of ADAMTS13, leading to the accumulation of ultra large von Willebrand factor (ULVWF). It was proposed that the distribution of blood group O among TTP patients may be potentially lower than expected because of the lower levels of VWF. The aim of this study was to explore the relationship between various blood groups and the clinical outcome in TTP. Thirty-three patients with TTP with severe ADAMTS13 deficiency were studied. Data on blood group, relapse, number of plasma exchange sessions, replacement fluid and mortality were analysed. Mortality rate was 15·2% and it was not impacted by blood group. The distribution of group O among patients with idiopathic TTP was lower (12%) than expected (30%). Patients with blood group O required more sessions to achieve remission than did those with group B (P = 0·02). Cryo-supernatant was used in three refractory patients with group O, who failed to respond to fresh-frozen plasma and complete remission was achieved. The overall number of relapsing episodes was 7 of 33 (21·2%), and it was not impacted by blood group. Although blood group O appeared to provide protection against TTP, more sessions were required to achieve remission. Cryo-supernatant improved the clinical outcome in refractory patients with group O. Future studies may be warranted to determine whether higher baseline VWF can be a trigger for TTP, or can confer protection by competing with a newly secreted ULVWF for platelet binding.

Higher Incidence of TTP in African Americans and Females: An Analysis of Demographics, Cost and Length of Stay in Teaching and Nonteaching Hospitals for Thrombotic Thrombocytopenic Purpura Between 1999 and 2013

Background: Limited studies compare the differences in care for Thrombotic Thrombocytopenic Purpura (TTP) patients in teaching versus nonteaching hospitals. TTP is a rare, life-threatening disease marked by widespread aggregation of platelets throughout the body, resulting in multi-organ sequelae including neurological dysfunction and renal insufficiency: a timely diagnosis is imperative for successful treatment. Academic centers generally have more individuals involved in each patient's care. This was considered in the evaluation of demographics, cost, length of stay, and disposition at discharge in the different settings.Methods: Adult admissions with a primary diagnosis of TTP for a 15-year period between 1999 and 2013 were extracted from the National Inpatient Sample database using the ICD-9 code 446.2 during a 15 year period between 1999 and 2013 (N=6,292, for a weighted N=30,011). The sample was weighted to approximate the full inpatient population of the U.S. over the time period. Teaching and nonteaching hospitals were compared within the parameters of gender, race, total cost, insurance, length of stay, mortality, and disposition. Chi square analysis was performed to examine differences in the categorical variables. Total cost was adjusted for inflation using data from the U.S. Bureau of Labor Statistics.Results: The total number of admission for TTP was weighted N=28,058, divided between 20,426 for teaching and 8,082 for nonteaching hospitals. 67.6% of TTP admissions were female in both categories but a greater percentage of African Americans with TTP were admitted to teaching (N=6,842; 33.50%) than nonteaching hospitals (N=1,962; 24.28%) (p < 0.0001). More Caucasians with TTP were admitted to non-teaching (N=2,707; 33.50%) than teaching hospitals (N=6,834; 32.46%) (p <0.0001).The overall length of stay for TTP hospitalizations was 12.30 days +/- 0.16, with teaching hospitals being found to have a shorter length of stay at 11.26 +/- 0.28 days compared to nonteaching hospitals with 13.15 +/- 0.20 days (p < 0.0001). There was a slightly higher mortality rate in nonteaching hospitals: 8.92% in teaching hospitals versus 9.32% in nonteaching hospitals (p <0.6232). Overall hospital mortality decreased from 12.1% in 1999 to 6.0% in 2013. At discharge, more patients from nonteaching hospitals were transferred to short term facilities than those from teaching: 1,877 (23.23%) non-teaching patients versus 2,038 (9.98%) teaching patients (p = 0.0001).The overall cost of a TTP hospitalization was $106,184.94 +/- $1,762.57. Nonteaching hospitals had more costly hospitalizations at $113,437.87 +/- $2247.78 than teaching hospitals, which cost $99,481.35 +/- $3093.53 (p <0.0001). Medicare paid 26.23% of TTP hospitalizations in nonteaching hospitals and 22.91% in teaching hospitals (p <0.0006). Medicaid paid for 18.12% of TTP hospitalizations in teaching hospitals and 12.89% in nonteaching hospitals (p <0.0006).An increase in the cost for admissions for TTP was noted from 1999 to 2013. While the total charge of TTP admission was $58,437 in 1999, it was found to be $153,643 in 2013, or $109,878 when adjusted for inflation. This amounted to an adjusted 88% increase despite an essentially unchanged average length of stay, 12.5 days in 1999 and 12.6 days in 2013.Conclusion: In comparing TTP hospitalizations, teaching hospitals had a shorter length of stay, lesser cost of stay, and sent fewer patients to short term facilities upon discharge. However, these factors did not play a statistically significant role in decreasing mortality. Additionally, a trend of increasing total charges was noted from 1999 to 2013 despite an unchanged length of hospitalization and a decrease in mortality. Advanced age is associated with worse outcome in TTP and this is reflected by the higher mortality and higher percentage of Medicare payment in nonteaching hospitals. Medicaid was responsible for a higher percentage of payment in teaching hospitals and correlated with an improved mortality. Both African Americans and females were found to have more admissions regardless of hospital type, with African Americans being admitted more often to teaching than nonteaching hospitals. Further studies are necessary to determine the etiology of this significant rise in the cost of TTP treatment and to investigate the disproportionately higher incidence of TTP in African Americans and females. DisclosuresNo relevant conflicts of interest to declare.

Microangiopathic haemolytic anaemia resembling thrombotic thrombocytopenic purpura in systemic lupus erythematosus: the role of ADAMTS13

Thrombotic thrombocytopenic purpura (TTP) is a rare but frequently fatal complication of SLE. It occurs in the context of both active and inactive lupus and carries a worse overall prognosis than idiopathic acquired TTP. Recent advances in the knowledge and treatment of TTP do not seem to have brought similar improvements in the management and outcome of TTP in SLE. The illumination of the role of the von Willebrand factor multimer protease, ADAMTS13 in idiopathic TTP continues to enhance our comprehension of the pathogenesis of the disease and has contributed to improvements in diagnosis and management. We explore the overlap of TTP and SLE, and discuss the current understanding of the involvement of ADAMTS13 and its implications for patients with this uncommon form of microangiopathic haemolytic anaemia.

A comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus

To compare the clinical presentation, response to therapy and outcome of thrombotic thrombocytopenic purpura (TTP) in an inception cohort of patients with and without SLE. Medical records of patients diagnosed with TTP at Singapore General Hospital between January 2003 and December 2007 were reviewed. Ten idiopathic TTP (iTTP) and eight SLE-associated TTP (sTTP) patients were identified, with iTTP patients being older (mean 50.4 vs 34.5 yrs). Five iTTP patients were ANA positive but did not have any features of SLE. All sTTP patients had active SLE at TTP diagnosis and had more renal involvement than iTTP (87.5% vs 50%). The mean duration from the first symptom suggestive of TTP to diagnosis was 7.7 days and 19.5 days in iTTP and sTTP patients. All patients received high-dose corticosteroids. Cytotoxic and immunosuppressive drugs were used more commonly (87.5% vs 50%) and earlier (Day 2/3 vs after Day 7) in sTTP patients. Vincristine was the drug of choice in iTTP and cyclophosphamide in sTTP. Three SLE patients received rituximab. Mortality for iTTP and sTTP was 50% (95% CI 19%, 81%) and 62.5% (95% CI 29%, 96%), respectively. The mean (s.d.) time to complete remission was 31.3 (+/- 26.4) days in sTTP (n = 3) and 16.8 (+/- 6.1) days in iTTP (n = 5). Despite early and more aggressive therapy in sTTP, mortality was higher and the time to complete remission were longer, suggesting that sTTP is more severe. The tempo of development of TTP in SLE patients was slower.

Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: risk factors and clinical outcome: a single centre study

The study was undertaken to investigate clinical characteristics of thrombotic thrombocytopenic purpura (TTP) in patients with SLE and to determine risk factors and clinical outcome of TTP in patients with SLE. Among the 1203 patients with SLE admitted to catholic medical centre of the catholic university of Korea from January 1990 to December 2006, 26 patients with SLE were found to admit with TTP. TTP was defined if microangiopathic haemolytic anaemia, thrombocytopenia and negative Coombs' test were present and when at least one of the following signs was noted: renal impairment, neurologic deficit or fever. Eighty-seven patients with SLE who admitted with other manifestations, matched for age and sex, were included as disease controls. Data were retrospectively analysed based on medical records. There were no significant demographic characteristics between SLE patients with TTP and those with other manifestations. Multivariate analysis showed that independent risk factors for the development of TTP included high SLE disease activity index score (SLEDAI > 10, P = 0.006) and coexisting nephritis (P = 0.004). Among the 26 SLE patients with TTP, 12 died during admission period (in-hospital mortality rate: 46.1%). SLE patients with infection or neurologic manifestations had higher mortality rates. Multivariate analysis showed that infection is the only independent risk factor for mortality in SLE patients with TTP (P = 0.035). Patients with SLE who are in the active stage or who have renal involvement have the increased risk for TTP. Development of TTP in patients with SLE can be fatal. Therefore, intensive therapy will be needed especially in the presence of infection.

ADAMTS-13 Levels Do Not Predict Outcome in Thrombotic Thrombocytopenic Purpura: Protein S Levels Are Maintained during Plasma Exchange with Solvent Detergent Treated Plasma.

Introduction The ultimate therapy for TTP is not yet defined. While approximately 85% of patients respond to plasma exchange with FFP, the use of alternative solutions such as cryosupernatant plasma, which is deficient in the high molecular weight forms of vWF. has not been proven by appropriate randomized prospective sample trials. However, it is intellectually appealing. Additionally, the use of the ADAMTS 13 level either to predict disease or outcome has not been resolved.Methods Cryosupernatant plasma (CSP) was compared to solvent detergent treated plasma (SDP) over one cycle (nine days) of plasma exchange (PE) and subsequent procedures as required. Throughout treatment, ADAMTS 13 and protein S levels were followed.Results At the primary end point of one month, 3 of 35 of the CSP and 1 of 27 of the SDP patients died. The average platelet count was 184 × 109 per litre for CSP and 209 × 109 per litre for SDP. While vWF and FVIII were elevated in all patients at entry, no unusually large vWF multimers were seen at any time. At entry 9 patients had ≤ 0–10% ADAMTS 13 and 14 of 62 had normal levels with the rest in between. At presentation only 9 patients had 100% inhibitor activity with no inhibitor in 18 patients. Of the four patients who died, two who received CSP, had 100% enzyme activity at presentation whereas one had no ADAMTS-13 and another had 10%. All 4 patients died within 10 days. Fifteen patients with less than 10% enzyme activity had >1.5 vWF. However, elevated (>3u/mL) vWF was seen in the presence of normal ADAMTS-13 levels. Six months after remission, and in the presence of a normal platelet count, ADAMTS13 remained low in 5 patients and normal in 15.Protein S levels in 41/62 patients studied showed little variation during therapy with values on day 3 and 5, similar to those seen on entry.Conclusion In idiopathic TTP, ADAMTS 13 levels do not correlate with disease, and are not predictive of outcome. While protein S levels in the SDP were lower than those found in FFP, this did not appear to have clinical significance.

Adjuvant Rituximab and/or Chemotherapy Improves Outcome of Thrombotic Thrombocytopenic Purpura: University of Cincinnati Experience.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but serious hematological disease. Immune therapy related to anti-ADAMTS13 antibodies has not been investigated systematically. Remission duration, morbidity and mortality with and without chemotherapy in addition to plasmapheresis have not been studied prospectively. A small number of case studies make treatment guidelines non-uniform and outcomes difficult to assess. Duration of plasmapheresis, the mainstay of therapy impacts heavily on the patient's quality of life and healthcare resources.Hypothesis: Rutuximab based chemotherapy in addition to plasmapheresis is better than plasmapheresis alone. Objectives of the study: To compare plasmapheresis alone (P) to plasmapheresis in combination with Rituximab based chemotherapy (P+R/RC) for the duration of plasmapheresis required for the achievement of remission.Methods: Retrospective chart review of all patients diagnosed with TTP at the University of Cincinnati Medical Center from 1997–2007. The variables reviewed were: Patient demographics, types of treatment received (i.e. P alone versus P+R/RC), duration of plasmapheresis, remission rate and duration of remission.Results: Eighteen patients were treated between 1997 and 2007. The mean age was 33 years (Range 17–61). Sixteen patients (88%) were females. Thirteen patients (72%) were African American. Six patients (33%) had elevated creatinine and ten patients (56%) had change in mental status at diagnosis. The etiology of TTP was idiopathic in 11 patients, drug related in 3 patients, HIV related in 1 patient and associated with pregnancy in 2 patients. All patients were treated with plasmapheresis, however eleven patients (61%) were in the first group (P) treated with plasmapheresis alone and seven patients (39%) were in the second group (P+R/RC) treated with plasmapheresis in addition to immunosuppressive therapy. As shown in Tables 1, and 2, the results trended towards a shorter duration of plasmapheresis required for remission following P+R/RC versus P alone, in the same patient (n=7), though the data did not reach statistical significance due to the small sample size. However when the duration of plasmapheresis after P+R/RC was compared to the total duration of plasmapheresis in TTP patients who did not receive Rutuximab based chemotherapy (P) (p=0.06), there was a statistical significance.Four patients (22%) relapsed in group 1 (P) and one patient (6%) relapsed in group 2 (P+R/RC).Conclusion: Plasmapheresis with immunosuppressive therapy trended towards a decreased duration of plasmapheresis, relapse rate, and increased duration of remission in patients with TTP. Prospective studies with immunosuppressive therapy upfront are needed to substantiate this.Median duration of plasmapharesis in patients with rituximab based therapyDurationMedian25%–75%p valuePre-immunosuppressive therapy168.539, 977.00.15Post-immunosuppressive therapy7132, 133.0Signed rank testMedian duration of plasmapharesis alone (group 1) versus plasmapharesis with rituximab-based therapyGroupMedian25%, 75%p-value1216.591.5, 564.00.0627132.0, 133.0Wilcoxon test

Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here?

Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here?