A Descriptive Analysis of Immune Thrombotic Thrombocytopenic Purpura (iTTP) Patients with Fatal Outcomes in the U.S. Thrombotic Microangiopathy (USTMA) TTP Registry

Abstract Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy (TMA) occurring due to an acquired deficiency in ADAMTS13. Mortality due to iTTP is estimated at 10% with current standard treatment that consists of plasma exchange (PLEX) and corticosteroids. The United States TMA (USTMA) registry incorporates 15 large US referral centers across the nation, and includes patients diagnosed with iTTP between 1985 and 2019. We sought to perform a descriptive analysis on the patients with fatal outcomes attributable to acute iTTP episodes in the registry. Methods: We utilized the USTMA registry (n=771) and analyzed twenty-two baseline patient demographics, presenting symptoms, and laboratory findings. The study cohort included participants with iTTP diagnosis based on the presence of thrombocytopenia (platelet count <100 /µL), microangiopathic hemolyic anemia (hemoglobin less than the lower limit of normal with schistocytes on the peripheral blood smear), and either ADAMTS13 activity <10% or ADAMTS13 activity <20% with an anti-ADAMTS13 inhibitor or antibody. For participants diagnosed before the ADAMTS13 assay was developed (2006), the iTTP diagnosis was based on the clinical course and absence of alternative causes. iTTP exacerbation was defined as clinical disease recurrence within 30 days of PLEX discontinuation, and clinical relapse was defined as disease recurrence after 30 days of last PLEX, as per the international working group definitions 1. Results: A total of 33 patients (4.28%) in the USTMA cohort died during acute iTTP episodes. The patient demographics and initial presenting lab values are summarized in Table 1. Time of death (Figure 1): 22 patients (66.7%) died during the initial iTTP episode, and within 30 days of presentation. 3 patients (9.0%) died during disease exacerbation of the initial episode. 8 patients (24.2%) died due to disease relapse. Median time to death at initial presentation/exacerbation (n=25) = 8 days [IQR: 4-19] Median time to death due to relapse = 1.6 years [IQR: 1.1-5.7] Patient demographics and presenting features (Table 1): Median age = 51 years [IQR: 27.8-60] Sex = 54.5% female, 45.5% male Presence of neurologic symptoms on presentation: 22 (66.7%) Presence of any symptoms on presentation: 32 (97%) Conclusion: Patients with fatal outcomes due to acute iTTP episodes presented with variable symptoms and baseline characteristics. While the vast majority of deaths occurred during the initial acute episode, death also occurred during exacerbation of the initial episode or subsequent disease relapse. Vigilant laboratory and clinical monitoring both after achieving initial remission and during long-term follow-up are necessary, to allow detection of disease exacerbation and relapse, and potentially prevent iTTP-related deaths. 1. Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855-1861. Figure 1 Figure 1. Disclosures Mazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Lim: Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria; Dova Pharmaceuticals: Honoraria.

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ADAMS-TS13 Inhibitor Level and Risk of Relapse in Acquired Idiopathic Thrombotic Thrombocytopenic Purpura

Blood ◽

10.1182/blood-2021-149338 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1012-1012

Author(s):

Annum Faisal ◽

Darla Liles ◽

Yara Park ◽

Meera Sridharan

Keyword(s):

North Carolina ◽

Platelet Count ◽

Thrombotic Microangiopathy ◽

Final Analysis ◽

Refractory Disease ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Inhibitor Level ◽

Inhibitor Titer ◽

Risk Of Relapse

Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy due to reduced activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13). This disorder can be due to a congenital deficiency state or be acquired (immune TTP (iTTP)) due to an antibody which either inhibits or causes clearance of ADAMTS13. The aim of our study was to determine whether ADAMTS13 inhibitor titer at initial presentation could serve as a predictor of refractory disease and relapse in iTTP. We also measured clinical outcomes across different gender and racial subgroups. Methods: The United States Thrombotic Microangiopathy (USTMA) iTTP registry was used to extract patient information for two academic institutions in Eastern North Carolina. Descriptive statistics were used to analyze the data. The first iTTP episode recorded in the data base was used as the index episode. All patients included in the final analysis had an ADAMTS13 activity of <10%. An inhibitor level of 5 Bethesda units was arbitrarily chosen as the cutoff between low (<5) and high (>/5) inhibitor level. Response time was defined as the number of days of plasma exchange (PEX) required to achieve a platelet count of 150,000 for two consecutive days. Relapse was defined as occurrence of a new episode of iTTP 30 days after achievement of response. Refractory disease was defined as persistence of thrombocytopenia or absence of a sustained platelet count increment or platelet counts of < 50,000 despite 4-7 days of plasma exchanges and steroid treatment. Rituximab resistance was defined as lack of platelet recovery to more than 150,000 within 11 to 14 days of administration of the first dose of Rituximab. Results: A total of 161 patients with iTTP were identified. Ten patients had ADAMTS13 activity >10% and 15 patients did not have a reported inhibitor level. These subjects were not included in the final analysis. The cohort had 28% male (n =38/136) and 72% (n=98/136) female patients. There were more African American patients 73% (n=99/136) than Caucasians 24% (n=32/136). There were also 2 Hispanic, 1 Native American and 2 patients with unidentified race. Median ADAMTS3 inhibitor titer was 1.05 (Range 0-87). Forty three patients with ADAMTS13 activity <10 % had an inhibitor level of 0 (i.e undetectable).They were included in the low inhibitor group. Overall, 88% patients (n=120/136) had low inhibitor level and only 12% (n=16/136) had a high inhibitor. Thirteen percent females (n=13/98) and 8% (n=3/38) males had a high inhibitor level (p=0.387). Fourteen percent (n=14/99) African Americans and 6 % (n=2/32) Caucasians had a high inhibitor, p=0.23. In the low inhibitor group 30% (n=36/120) patients suffered at least one episode of relapse whereas 31% (n=5/16) had relapsed in the high inhibitor group. The median time to response was 6 days (range 1-76) in the low inhibitor group and 7 days (range 4-20) in the high inhibitor group (p=0.61). While looking at the various subgroups, median time to response for males was 6 days (range 4-21), females 6 days (range 1-76) , African Americans 6 days (range 3-29) , and Caucasians 6 days (range 1-76). The frequency of refractory disease was 31 % (n=5/16) in the high inhibitor group and 29% (n=34/119) in the low inhibitor group. At the time of enrollment in the registry, Rituximab was not a part of first line therapy. Only 26 out of 136 patients had received Rituximab. In the low inhibitor group 5 patients displayed Rituximab resistance whereas there were no patients in the high inhibitor group with Rituximab resistance. Conclusion: When evaluating patients presenting with iTTP in two centers in North Carolina, no correlation was found between a high inhibitor levels of >/ 5 Bethesda units and risk of relapse or refractory disease. A larger study is needed to evaluate this further. Disclosures No relevant conflicts of interest to declare.

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Haemolytic uraemic syndrome

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0496 ◽

2020 ◽

pp. 5027-5032

Author(s):

Edwin K.S. Wong ◽

David Kavanagh

Keyword(s):

Escherichia Coli ◽

Acute Kidney Injury ◽

Complement System ◽

Shiga Toxin ◽

Thrombotic Microangiopathy ◽

Initial Treatment ◽

Haemolytic Uraemic Syndrome ◽

Kidney Injury ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy characterized by the triad of thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. It is most often caused by Shiga toxin-producing Escherichia coli (STEC-HUS), and any HUS not caused by this is often termed atypical HUS (aHUS). aHUS may be caused by an underlying complement system abnormality (primary aHUS) or by a range of precipitating events, such as infections or drugs (secondary aHUS). Management of STEC-HUS is supportive. In aHUS, plasma exchange is the initial treatment of choice until ADAMTS13 activity is available to exclude thrombotic thrombocytopenic purpura as a diagnosis. Once this has been done, eculizumab should be instigated as soon as possible.

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Risk Factors for Recurrence of Thrombotic Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v108.11.1060.1060 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1060-1060 ◽

Cited By ~ 1

Author(s):

Flora Peyvandi ◽

Silvia Lavoretano ◽

Roberta Palla ◽

Hendrik B. Feys ◽

Tullia Battaglioli ◽

...

Keyword(s):

Risk Factors ◽

Relative Risk ◽

Thrombotic Thrombocytopenic Purpura ◽

Disease Recurrence ◽

Acute Episode ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Neutralizing Activity ◽

Adamts13 Deficiency

Abstract The introduction of plasma exchange therapy in early 1970s significantly reduced the rate of mortality in patients affected by thrombotic thrombocytopenic purpura (TTP), a disease characterized by thrombocytopenia and microangiopathic hemolytic anemia. A similar improvement was never achieved in the prevention of the disease recurrence. Still, 20–50% of patients, who survived the fatal disease, experience a relapse one month or even years after the acute episode of TTP. There is no pathognomic marker or laboratory test that can be used for the surveillance of TTP during remission and predict which patients will relapse. We have retrospectively analyzed for the first time at remission the role of ADAMTS13, anti-ADAMTS13 autoantibodies and von Willebrand Factor (VWF) in 109 patients who survived the acute episode of TTP. ADAMTS13 activity and ADAMTS13 antigen levels were measured as described by Gerritsen et al (TH 1999) and Feys HB et al. (JTH 2006), respectively. The total anti-ADAMTS13 autoantibodies (with and without neutralizing activity) were measured by western blot analysis and the presence of neutralizing anti-ADAMTS13 autoantibodies was checked according to Gerritsen et al (TH 1999). VWF antigen was measured using an ELISA assay and VWF multimers analysis was carried out using low-resolution SDS-agarose gel electrophoresis and exposing gels to human anti-VWF antibodies labeled with I125 for autoradiography (Ruggeri & Zimmerman, Blood 1981). All variables have been statistically analyzed in 2 subgroups of patients with or without TTP recurrence, in order to understand the role of each variable as a potential predictor marker for recurrence. Univariate and multivariate analysis were carried out to evaluate adjusted and unadjusted odds ratios (Ors) with 95% confidence intervals (CI) as a measure of the relative risk of relapse associated with the risk factors under investigation. Our data showed that the median value of ADAMTS13 activity and antigen levels at remission were significantly lower in patients with recurrent TTP than in patients with no relapse (ADAMTS13 activity: 12% vs. 41%; p=0.007; ADAMTS13 antigen: 36% vs 58%; p=0.003). Furthermore, the prevalence of patients with severe ADAMTS13 deficiency (≤10%) was significantly higher in the group of patients who relapsed (OR=2.9 CI95% 1.3–6.8, p=0.01). The prevalence of anti-ADAMTS13 autoantibodies (with or without neutralizing activity) resulted to be significantly higher in patients with recurrent TTP (OR= 3.1 CI 95% 1.4–7.3, p=0.006). A higher VWF antigen levels or the presence of ultralarge VWF (ULVWF) multimers at remission did not increase the risk of recurrence (p=0.4 for VWF:Ag and p=0.7 for ULVWF multimers). In conclusion, our data showed that the association of severe ADAMTS13 deficiency and the presence of anti-ADAMTS13 autoantibodies is a negative prognostic marker at remission and increases the relative risk of TTP recurrence by 3.6 times (OR=3.6 CI95% 1.4–9). Therefore our results would suggest that our efforts should go in the direction of maintenance therapy which aims at reducing or abolishing the presence of antibodies during remission and increasing the level of ADAMTS13 in plasma in order to prevent the recurrence of TTP.

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Longitudinal assessments of plasma ADAMTS13 biomarkers predict recurrence of immune thrombotic thrombocytopenic purpura

Blood Advances ◽

10.1182/bloodadvances.2019000939 ◽

2019 ◽

Vol 3 (24) ◽

pp. 4177-4186 ◽

Cited By ~ 2

Author(s):

Jingrui Sui ◽

Wenjing Cao ◽

Konstantine Halkidis ◽

Mohammad S. Abdelgawwad ◽

Nicole K. Kocher ◽

...

Keyword(s):

Clinical Response ◽

Thrombotic Thrombocytopenic Purpura ◽

Medical Center ◽

Disease Recurrence ◽

Response To Therapy ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Aggressive Approach ◽

Increased Risk ◽

The University

Abstract Immune thrombotic thrombocytopenic purpura (iTTP) is primarily caused by immunoglobulin G (IgG)–type autoantibodies that bind and inhibit plasma ADAMTS13 activity and/or accelerate its clearance from circulation. Approximately 50% of patients with iTTP who achieve initial clinical response to therapy experience recurrence (ie, exacerbation and/or relapse); however, a reliable biomarker that predicts such an event is currently lacking. The present study determines the role of longitudinal assessments of plasma ADAMTS13 biomarkers in predicting iTTP exacerbation/recurrence. Eighty-three unique iTTP patients with 97 episodes from the University of Alabama at Birmingham Medical Center between April 2006 and June 2019 were enrolled. Plasma levels of ADAMTS13 activity, antigen, and anti-ADAMTS13 IgG on admission showed no significant value in predicting iTTP exacerbation or recurrence. However, persistently low plasma ADAMTS13 activity (<10 U/dL; hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.6-12.5; P = .005) or high anti-ADAMTS13 IgG (HR, 3.1; 95% CI, 1.2-7.8; P = .016) 3 to 7 days after the initiation of therapeutic plasma exchange was associated with an increased risk for exacerbation or recurrence. Furthermore, low plasma ADAMTS13 activity (<10 IU/dL; HR, 4.8; 95% CI, 1.8-12.8; P = .002) and low ADAMTS13 antigen (<25th percentile; HR, 3.3; 95% CI, 1.3-8.2; P = .01) or high anti-ADAMTS13 IgG (>75th percentile; HR, 2.6; 95% CI, 1.0-6.5; P = .047) at clinical response or remission was also predictive of exacerbation or recurrence. Our results suggest the potential need for a more aggressive approach to achieve biochemical remission (ie, normalization of plasma ADAMTS13 activity, ADAMTS13 antigen, and anti-ADAMTS13 IgG) in patients with iTTP to prevent the disease recurrence.

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Longitudinal Assessment of Plasma ADAMTS13 Biomarkers Helps Predict Recurrence of Immune Thrombotic Thrombocytopenic Purpura

Blood ◽

10.1182/blood-2019-126093 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2456-2456

Author(s):

Jingrui (Jean) Sui ◽

Wenjing Cao ◽

Mohammad S. Abdelgawwad ◽

Konstantine Halkidis ◽

Nicole K. Kocher ◽

...

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Clinical Remission ◽

Medical Center ◽

Disease Process ◽

Disease Recurrence ◽

Adamts13 Activity ◽

Longitudinal Assessment ◽

Thrombocytopenic Purpura ◽

Kaplan Meier ◽

Increased Risk

Background: Severe deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13 is the primary cause of immune thrombotic thrombocytopenic purpura (iTTP). The anti-ADAMTS13 IgGs may bind and inhibit plasma ADAMTS13 activity and/or accelerate its clearance from circulation. Approximately 40% of iTTP patients who survived the initial episode may experience disease recurrence (e.g. exacerbation and/or relapse). However, a reliable biomarker that predicts disease recurrence is still lacking. The present study sought to determine the roles of plasma ADAMTS13 activity, antigen, inhibitors, and anti-ADAMTS13 IgG at various stages of the disease process in predicting recurrence (e.g. exacerbation and/or relapse) in adult patients with iTTP. Methods: 93 episodes from 83 unique iTTP patients who underwent therapeutic plasma exchange (TPE) therapy at UAB Medical center from April 2006 to December 2018 were enrolled into the study. Clinical and laboratory parameters were collected at diagnosis, and ADAMTS13 biomarkers (e.g. activity, inhibitors, antigen, and anti-ADAMTS13 IgG) were determined in samples collected on admission, 3-7 days following the first TPE, and at clinical response (prior to discharge). Various statistical analyses including Kaplan-Meier survival and Cox analyses were performed to assess the clinical relevance of each biomarker at various stages of the disease course. Results: We found that plasma ADAMTS13 activity and antigen on admission had no significant value in predicting iTTP exacerbation (disease recurrence within 30 days of discontinuation of TPE) or relapse (the disease recurrence after 30 days of discontinuation of TPE). However, high levels of anti-ADAMTS13 IgG on admission were associated with an increased risk of exacerbation (HR=2.1, 95% CI, 1.0-4.1, p=0.34) or recurrence within one year (HR=2.0, 95% CI 1.0-3.9, p=0.041). More interestingly, low plasma ADAMTS13 activity (<10 U/dL) 3 to 7 days after initiation of TPE (HR=3.8, 95% CI 1.3-11.0, p=0.015) or at clinical remission (median 7 days, IQC 6-10 days) when platelet counts and lactate dehydrogenase (LDH) levels had normalized (HR=4.3, 95% CI 1.6-11.8, p=0.004) and low levels of plasma ADAMTS13 antigen at clinical remission (HR=3.2, 95% CI 1.1-7.5), even when body mass index, race, and partial thromboplastin time (PTT) were all included as covariates for the analysis, were associated with the increased risks of iTTP recurrence. Conclusions: Longitudinal assessment of plasma ADAMTS13 biomarkers (e.g., activity, antigen and anti-ADAMTS13 IgG) is of a critical value for predicting iTTP recurrence. These results suggest the need for additional therapeutic coverage (such as the use of rituximab, corticosteroids, and caplacizumab) to prevent iTTP recurrence after discharge from the hospital and supports the concept for achieving the biochemical remission (e.g. the normalization of ADAMTS13 activity, antigen, and anti-ADAMTS13 IgG) for the long-term management of patients with iTTP. Disclosures Zheng: Shire/Takeda: Research Funding; Clotsolution: Other: Co-Founder; Ablynx/Sanofi: Consultancy, Speakers Bureau; Alexion: Speakers Bureau.

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Diagnosis of Hereditary TTP Caused by Homozygosity for a Rare Complex ADAMTS13 Allele After Salmonella Infection in a 43-Year-Old Asylum Seeker

Frontiers in Medicine ◽

10.3389/fmed.2021.639441 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ralph Wendt ◽

Sven Kalbitz ◽

Felix Otto ◽

Tanja Falter ◽

Joachim Beige ◽

...

Keyword(s):

Thrombotic Microangiopathy ◽

Half Life ◽

Clinical Course ◽

Adamts13 Activity ◽

Salmonella Infection ◽

Thrombocytopenic Purpura ◽

Plasma Infusion ◽

Congenital Thrombotic Thrombocytopenic Purpura ◽

Double Blinded ◽

Ergometric Exercise

A 43-year-old Armenian patient was diagnosed with salmonella infection and thrombotic microangiopathy (TMA). The clinical course was benign with resolution of all laboratory alterations after antibiotic treatment. Constantly deficient ADAMTS13 activity without ADAMTS13 inhibitors and evidence of homozygosity for a rare complex ADAMTS13 allele led to the diagnosis of congenital thrombotic thrombocytopenic purpura (cTTP). Half-life of ADAMTS13 after plasma infusion was calculated (27,6h) and double blinded plasma infusion as well as ergometric exercise with and without prior plasma infusion undertaken to investigate suspected smoldering TTP activity.

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Streptococcus pneumoniae-associated thrombotic microangiopathy in an immunosuppressed adult

Open Medicine ◽

10.1515/med-2020-0030 ◽

2020 ◽

Vol 15 (1) ◽

pp. 204-210 ◽

Cited By ~ 1

Author(s):

Yumi Ichikawa ◽

Masato Murata ◽

Makoto Aoki ◽

Jun Nakajima ◽

Yuta Isshiki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Streptococcus Pneumoniae ◽

Blood Culture ◽

Renal Dysfunction ◽

Hemolytic Anemia ◽

Thrombotic Microangiopathy ◽

Detailed Examination ◽

Adamts13 Activity ◽

Adult Case

AbstractA 62-year-old male who was receiving prednisolone and methotrexate for scleroderma and rheumatoid arthritis complained of diarrhea and vomiting, and was transferred to our hospital for detailed examination and treatment of renal dysfunction and thrombocytopenia. Hemolytic anemia and crushed erythrocytes were found during the patient’s course; therefore, we suspected thrombotic microangiopathy (TMA). His ADAMTS13 activity was 60.3% and his ADAMTS13 inhibitor was under 0.5. In addition, his blood culture was positive for Streptococcus pneumoniae, and we finally diagnosed Streptococcus pneumoniae-associated TMA (pTMA). The patient was treated with antibiotics and hemodialysis. The patient recovered and was discharged on the 45th hospital day. Adult pTMA cases are remarkably rare. We herein report a successfully treated adult case of pTMA.

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Nestin and cluster of differentiation 146 expression in breast cancer: Predicting early recurrence by targeting metastasis?

Tumor Biology ◽

10.1177/1010428317691181 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769118 ◽

Cited By ~ 4

Author(s):

Ekaterini Christina Tampaki ◽

Athanasios Tampakis ◽

Afroditi Nonni ◽

Konstantinos Kontzoglou ◽

Efstratios Patsouris ◽

...

Keyword(s):

Breast Cancer ◽

Disease Recurrence ◽

Prognostic Impact ◽

Stem Cell Markers ◽

Disease Relapse ◽

Nestin Expression ◽

Mesenchymal Transition ◽

Positive Group ◽

Cluster Of Differentiation ◽

Cd146 Expression

The purpose of this study was to investigate the relationship between the expression of stem-cell markers nestin and cluster of differentiation 146 with clinicopathological characteristics in breast cancer and to determine whether a prognostic impact of nestin and CD146 expression exists regarding occurrence of disease relapse in breast cancer. A total of 141 patients who were histologically diagnosed with breast cancer and underwent radical operations from November 2006 to October 2013 in Laiko General Hospital, National and Kapodistrian University of Athens, were enrolled in the study. CD146 and nestin protein expression were evaluated using immunohistochemistry. Nestin expression was observed in 18.4% (26/141) of the cases, while CD146 expression was observed in 35.5% (50/141) of the cases. Nestin expression is significantly higher in younger patients with breast cancer. Nestin and CD146 expression were not correlated with the tumor size and the presence of lymph node metastasis. On the contrary, a significantly higher expression of nestin and CD146 was observed with triple-negative cancers (p < 0.0001 for both markers), low differentiated tumors (p = 0.021 for nestin and p = 0.008 for CD146), and increased Ki-67 expression (p = 0.007 for nestin and p < 0.0001 for CD146). The nestin-positive group of patients and the CD146–positive group of patients presented significantly higher rates of disease recurrence (log-rank test, p = 0.022 for nestin and p = 0.003 for CD146) with a distant metastasis, 30 months after the primary treatment. CD146 but not nestin, however, predicted independently (p = 0.047) disease recurrence. Nestin and CD146 are expressed in breast cancer cells with highly aggressive potency. They might contribute to disease relapse in breast cancer by activating the epithelial–mesenchymal transition pathway and assist tumor neovascularization.

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Real-world data of thrombotic microangiopathy management: The key role of ADAMTS13 activity and complement testing

Thrombosis Update ◽

10.1016/j.tru.2021.100043 ◽

2021 ◽

Vol 3 ◽

pp. 100043

Author(s):

Eleni Gavriilaki ◽

Eudoxia-Evaggelia Koravou ◽

Thomas Chatziconstantinou ◽

Christina Kalpadaki ◽

Nikoleta Printza ◽

...

Keyword(s):

Real World ◽

Thrombotic Microangiopathy ◽

Adamts13 Activity ◽

Real World Data ◽

World Data

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Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies

Thrombosis and Haemostasis ◽

10.1160/th07-12-0753 ◽

2009 ◽

Vol 101 (02) ◽

pp. 233-238 ◽

Cited By ~ 62

Author(s):

Sara Gastoldi ◽

Erica Daina ◽

Daniela Belotti ◽

Enrico Pogliani ◽

Paolo Perseghin ◽

...

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Therapeutic Option ◽

Severe Disease ◽

Renal Involvement ◽

First Episode ◽

High Morbidity ◽

Sustained Remission ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Haemolytic Anemia

SummaryThrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.

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