scholarly journals Real-World Variability in ADAMTS13 Assay Methods May Impact upon Follow up for Patients with Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2085-2085
Author(s):  
Gavin Ling ◽  
Beth Brannan ◽  
Eleanor Foxton
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Conflicts Of Interest ◽  
Past History ◽  
Pearson Correlation ◽  
Positive Bias ◽  
Adamts13 Activity ◽  
International Consensus ◽  
History Of

Abstract Introduction ADAMTS13 activity (ADAMTS13:Ac) measurement is an important diagnostic marker in acute TTP (defined as a level of <10%). Increasing numbers of commercial assays have been developed (ELISA, FRET and chemiluminesence) for diagnostic purposes. The International Council for Standardization in Haematology have not made specific recommendations on ADAMTS13 assay selection in a recent publication in 2020. ADAMTS13:Ac has traditionally been used for diagnostic purposes but can also be useful for monitoring disease status and relapse risk. Patients between levels of 10-50% may require increased monitoring and subsequently treatment to avoid frank relapse, with an inverse relationship between ADAMTS13:Ac levels and intensity of clinical monitoring. We seek to compare the differences between different commercial assays available to measure the ADAMTS13:Ac in patients who have a history of TTP and whether this influences clinical practice. Methods Patients with an acute diagnosis of TTP as an inpatient or outpatient surveillance with past history of TTP were reviewed at Guy's and St Thomas' Hospital, London, UK, and samples were taken to measure ADAMTS13:Ac as part of disease monitoring between February and July 2021. A comparison was performed between an ELISA (Technozym ADAMTS13 activity, Technoclone) and FRET (Technofluor, Technoclone), with all samples processed in parallel. With no international consensus, broadly, levels of <10% were defined as either active TTP or relapse; patients with 10-30% required more intensive outpatient monitoring to detect for relapse and >50% was defined as within the normal range. Results 47 samples from 31 known or newly diagnosed TTP patients were processed over a six month period. Intra- and inter-assay CV for both ELISA and FRET on laboratory testing was as expected from manufacturers guidelines. Figure 1 plots the ADAMTS13:Ac ELISA vs FRET, with a Pearson correlation of p=0.949 across all samples. Ranges were for ELISA (0 - 109.3) and FRET (1.6 - 130.3). Mean ADAMTS13:Ac difference was 16±13.5%, with consistent positive bias in favour of the FRET assay. Higher levels demonstrated greater variability as demonstrated in Table 1, with the mean difference between ELISA and FRET increasing with increasing levels. Based on the above definitions as in the methods, there were 14/47 (29%) samples which had discordant results between the ELISA and FRET methods: 3 discordant samples on diagnosis of relapse, 8 discordant for where the ELISA detected levels <30% and FRET >30%; and 2 discordant for where ELISA <50% and FRET >50%. Conclusion Real-world clinical testing demonstrates substantial variability within a single manufacturer between two separate methods and demonstrates an impact on patient follow up and implications in decisions on follow-up intervals and treatment. There was a consistent positive bias in ADAMTS13:Ac by FRET measurement as compared with the ELISA. Greater consistency was demonstrated at the lower end of testing, where there was good concordance at levels of <10%, confirming that both assays were effective at determining a diagnosis or relapse of TTP. Further interrogation of other commercial platforms is warranted to establish the variability of results to inform on clinical practice in the monitoring of patients with TTP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Imatinib (IM) Treatment In Chronic Myeloid Leukemia (CML). Clinical Practice Limitations

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4454-4454
Author(s):  
Alicia Inés Enrico ◽  
Georgina Bendek ◽  
Maria Virginia Prates ◽  
Virginia Guerrero ◽  
Juan Jose Napal ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Trisomy 8 ◽  
History Of ◽  
One Year

Abstract Abstract 4454 Introduction: CML represents 15% all of oncohematologic diseases in adults. IM changed the history of the disease. At one year of treatment, the emblematic IRIS study showed Major Cytogenetic Responses (MCyR) of approximately 87% and Complete Cytogenetic Responses (CCyR) of around 76%, with PFS to accelerated phase or blast crisis of 97.7% and 91.5%, respectively. Objective: To assess treatment characteristics and responses in a group of patients treated with IM in clinical practice. Materials and Method: 113 medical records of patients with CML diagnosed between 1998–2011 from two institutions in the Argentine Republic were retrospectively analyzed. Result: Mean population age was 46 years old (r 18–73) 65 male, 48 female. 97% in chronic phase, the rest in accelerated phase. 31% presented comorbidities at diagnosis. Cytogenetic abnormalities at diagnosis, in addition to the classic t(9:22), included: trisomy 8 and double Philadelphia chromosome in 4 tests. Only 7 patients had qualitative BCR/ABL determined at diagnosis. 25% had received interferon, patients received IM 400 mg and only 2% received 300 or 600 mg doses. 2.6% of patients did not achieve CHR. Cytogenetic responses assessed at any time of treatment were: Major: 12%, Minor 20%, Complete 51%, None 3%, 14% were not assessed. With a mean follow-up time of 46 months, the overall survival was 75%. 10% of patients progressed to BC/AP, 11 % of patients died due to disease-related causes or comorbidities. Conclusions: With a mean follow-up time of 46 months for chronic phase CML, treatment with IM achieved complete cytogenetic responses in 51% of patients, and progression occurred in 10% of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real-World Clinical Practice: Data from a Belgian Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1744-1744 ◽  
Author(s):  
Timothy Devos ◽  
Koen Theunissen ◽  
Fleur Samantha Benghiat ◽  
Alain Gadisseur ◽  
Stef Meers ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Median Time ◽  
Real World ◽  
Research Funding ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Best Response ◽  
History Of ◽  
T315i Mutation

Abstract Background Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for adult patients with resistant or intolerant chronic phase (CP), accelerated phase, or blast phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), or those with the T315I mutation. In Belgium, ponatinib has been commercially available since March 2016. The goal of this registry was to collect efficacy and safety data in CML and Ph+ ALL patients and to evaluate ponatinib in routine clinical practice in Belgium. Methods This ongoing, prospective, multi-center registry includes patients ≥18 years of age with CML or Ph+ ALL, who have initiated ponatinib treatment. Demographic, efficacy and safety data were collected for patients enrolled from March 2016 (day 0) onwards. Results up to study month 24 are presented. Data were analyzed by descriptive statistics. Ethics Committee approval was obtained and all patients provided informed consent. Results At time of data analysis, 34 patients (21 CP-CML and 13 Ph+ ALL) were enrolled. The median age of CP-CML and Ph+ ALL patients was 57 and 55 years, respectively. Patients were heavily pretreated: 90% of CML and 92% of Ph+ ALL patients had received ≥2 prior TKIs. Several patients had one or more risk factors for TKI cardiovascular toxicity: hypertension (10), history of cardiovascular disease (11), smoker (10), hypercholesterolemia (5), and diabetes (4). Median follow-up was 539 days for CML and 135 days for Ph+ ALL patients. The reasons for starting ponatinib therapy were related to refractoriness to previous TKIs (36%), progression (18%), presence of the T315I mutation (18%) or intolerance (29%). Eighty percent (8/10) of the patients who started ponatinib due to intolerance to previous TKIs had received ≥3 prior TKIs. At entry, 17 of the 34 patients (50%) had a confirmed BCR-ABL mutation. Of these 17, 10 (59%; 5 CML and 5 Ph+ ALL) had the T315I mutation. Starting doses of ponatinib in CML patients were 45 mg (76%), 30 mg (10%) and 15 mg (14%) once daily. Starting doses in Ph+ ALL patients were 45 mg (85%), 30 mg (8%) and 15 mg (8%). At latest follow up, the median treatment duration for the 21 CML patients was 531 days (range 15 - 2483) and for the 13 Ph+ ALL patients it was 123 days (range 13 - 1945). Best response was a major molecular response (MMR), which was obtained in 71% of CML patients and 38% of Ph+ ALL patients. The median time-to-best response was 175 days in CML and 35 days in Ph+ ALL patients. In the 10 patients (7 CML and 3 Ph+ ALL) who started ponatinib because of intolerance to several previous TKIs, 80% achieved MMR. The median time to achieve best response in these patients was 192 days for CML and 31 days for Ph+ ALL patients. Treatment-related adverse events (AEs) were reported in 20 patients (59%); the most common were rash (26%), dry skin (9%) and constipation (9%). Three patients reported ≥1 treatment-related serious AE (SAE): thrombocytopenia (n=1), cholecystitis (n=1) and hepatocellular injury (n=1). Three serious cardiovascular events were observed in 1 patient, who had a history of congenital cardiomyopathy and aortic prosthesis. They were scored as not related to ponatinib. Dose reductions or interruptions occurred in 33 cases (20 in CML and 13 in Ph+ ALL patients), with the following reasons most frequently mentioned: AEs (76%), to prevent AEs (18%) and other (6%). Dose increases occurred in 12 cases (10 in CML and 2 in Ph+ ALL patients), for the following reasons: good tolerance of treatment (58%), no or low response (33%) or other (8%). At time of analysis, 19 patients (9 CML and 10 Ph+ ALL) had discontinued treatment, of which 32% due to AEs, 5% due to an SAE, 21% due to planned allogeneic transplant, 16% due to disease progression and 26% due to other reasons. [Note: Percentages may not total 100 due to rounding] Conclusion Real-world evidence from this Belgian registry shows that ponatinib has a favorable efficacy and safety profile in, and supports its use in CML and Ph+ ALL patients who are resistant or intolerant to previous therapies or those with the T315I mutation. Deep molecular responses were obtained in the majority of patients. No new safety signals emerged with ponatinib treatment than those previously reported. Funding: Incyte Biosciences Benelux BV Disclosures Devos: Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Theunissen:Incyte: Honoraria. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Kuipers:Incyte Biosciences Benelux BV: Employment.

scholarly journals Potential cardiovascular risk reduction with evolocumab in the real world: a simulation in patients with a history of myocardial infarction from the HEYMANS register

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Ray ◽  
I Bridges ◽  
E Bruckert ◽  
P Perrone-Filardi ◽  
L Annemans ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Practice ◽  
Risk Reduction ◽  
Real World ◽  
Lipid Lowering ◽  
Number Needed To Treat ◽  
Lipid Lowering Therapy ◽  
Private Company ◽  
History Of

Abstract Background/Introduction FOURIER included 22,351 patients with a history of myocardial infarction (MI) and a median low-density lipoprotein cholesterol (LDL-C) of 2.4 mmol/L. Reducing LDL-C with evolocumab reduced the risk of major cardiovascular (CV) events by 1.3%, in absolute terms, over 2.2 years. Whether similar benefits might be observed in real-world evidence from evolocumab use is unknown. Purpose Simulate CV risk and assess the potential CV risk reduction among a large European cohort of evolocumab users with a history of MI. Methods We used interim data from HEYMANS, a register of patients initiating evolocumab in routine clinical practice across 12 European countries, from August 2015 with follow-up through July 2020. Demographic and clinical characteristics, lipid-lowering therapy (LLT), and lipid values were collected from routine medical records (6 months prior to evolocumab initiation through 30 months post initiation). Patients with a history of MI were considered and two sub-cohorts were created: recent MI (MI ≤1 year before evolocumab initiation) and remote MI (MI >1 year before evolocumab initiation). For each patient, we 1) simulated their CV risk using three different sources, correcting for age and LDL-C: i) the REACH equation, ii) FOURIER, iii) an observational study including FOURIER-like patients; 2) calculated their absolute LDL-C reduction on evolocumab; 3) simulated their relative risk reduction (RRR) by randomly sampling from the inverse probability distribution of the rate ratio per 1 mmol/L from the key secondary endpoint in the FOURIER landmark analysis; 4) calculated their absolute risk reduction (ARR) and number needed to treat (NNT) over 2 years (recent MI) or 10 years (remote MI). Results Our analysis included 90 recent MI and 489 remote MI patients initiating evolocumab in clinical practice per local reimbursement criteria, with up to 24 months follow-up. Median (inter-quartile range) age was 59 (53–67) and 61 (53–68) years in recent MI and remote MI patients, respectively. LDL-C before evolocumab was 3.8 (3.2–4.6) and 3.6 (3.0–4.5) mmol/L. Absolute LDL-C reduction on evolocumab was 2.2 (1.4–2.8) and 2.2 (1.6–2.8) mmol/L, meaning relative LDL-C reduction of 60% (44%-73%) and 62% (47%-72%), respectively. Predicted ARR with evolocumab was substantial, whether over 2 years (recent MI) or over 10 years (remote MI). See Table 1. Conclusions This cohort of evolocumab users in clinical practice had a higher baseline LDL-C and CV risk than patients enrolled in FOURIER. LDL-C reduction and RRR were very similar in recent MI and remote MI patients. However, patients with a recent MI had a higher short-term CV risk and therefore showed a larger ARR on evolocumab. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen

scholarly journals Is the use of two versus one long-acting bronchodilator by patients with COPD associated with a higher risk of acute coronary syndrome in real-world clinical practice?

2021 ◽  
Vol 8 (1) ◽  
pp. e000840
Author(s):  
Lianne Parkin ◽  
Sheila Williams ◽  
David Barson ◽  
Katrina Sharples ◽  
Simon Horsburgh ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Clinical Practice ◽  
Real World ◽  
Chronic Obstructive ◽  
Treatment Intensification ◽  
Cardiovascular Comorbidity ◽  
Coronary Syndrome ◽  
Long Acting ◽  
The Impact

BackgroundCardiovascular comorbidity is common among patients with chronic obstructive pulmonary disease (COPD) and there is concern that long-acting bronchodilators (long-acting muscarinic antagonists (LAMAs) and long-acting beta2 agonists (LABAs)) may further increase the risk of acute coronary events. Information about the impact of treatment intensification on acute coronary syndrome (ACS) risk in real-world settings is limited. We undertook a nationwide nested case–control study to estimate the risk of ACS in users of both a LAMA and a LABA relative to users of a LAMA.MethodsWe used routinely collected national health and pharmaceutical dispensing data to establish a cohort of patients aged >45 years who initiated long-acting bronchodilator therapy for COPD between 1 February 2006 and 30 December 2013. Fatal and non-fatal ACS events during follow-up were identified using hospital discharge and mortality records. For each case we used risk set sampling to randomly select up to 10 controls, matched by date of birth, sex, date of cohort entry (first LAMA and/or LABA dispensing), and COPD severity.ResultsFrom the cohort (n=83 417), we identified 5399 ACS cases during 281 292 person-years of follow-up. Compared with current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a higher risk of ACS (OR 1.28 (95% CI 1.13 to 1.44)). The OR in an analysis restricted to fatal cases was 1.46 (95% CI 1.12 to 1.91).ConclusionIn real-world clinical practice, use of two versus one long-acting bronchodilator by people with COPD is associated with a higher risk of ACS.

scholarly journals Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain

2021 ◽  
Vol 11 ◽  
Author(s):  
Angel P. Sempere ◽  
Leticia Berenguer-Ruiz ◽  
Ines Borrego-Soriano ◽  
Amparo Burgos-San Jose ◽  
Luis Concepcion-Aramendia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Real World ◽  
Median Number ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Clinical Practice Setting ◽  
Number Of Treatment ◽  
Relapsing Multiple Sclerosis

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting.Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded.Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4–6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious.Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

scholarly journals Oral Antithrombotic Use Among Myocardial Infarction Patients

2003 ◽  
Vol 37 (1) ◽  
pp. 143-146 ◽  
Author(s):  
Menno E van der Elst ◽  
Nelly Cisneros-Gonzalez ◽  
Cornelis J de Blaey ◽  
Henk Buurma ◽  
Anthonius de Boer
Keyword(s):  
Myocardial Infarction ◽  
Record Linkage ◽  
Antithrombotic Therapy ◽  
Past History ◽  
Oral Anticoagulants ◽  
Antiplatelet Agents ◽  
Antithrombotic Treatment ◽  
History Of ◽  
Using Data

OBJECTIVE To examine the use of oral antithrombotics (i.e., antiplatelet agents, oral anticoagulants) after myocardial infarction (MI) in the Netherlands from 1988 to 1998. METHODS Retrospective follow-up of 3800 patients with MI, using data from the PHARMO Record Linkage System. RESULTS From 1988 to 1998, oral antithrombotic treatment increased significantly from 54.0% to 88.9%. In 1998, only 75.8% of patients who experienced a MI in the late 1980s received oral antithrombotic treatment compared with 94.4% of those who experienced a recent MI. CONCLUSIONS Oral antithrombotics were considerably underused in patients with a past history of MI. Therefore, these patients should be reviewed for antithrombotic therapy to assess whether their failure to use oral antithrombotics was right or wrong, and whether treatment should be initiated if possible.

scholarly journals Audit of safety, efficacy, and cost-effectiveness of local anaesthetic cystodiathermy

2010 ◽  
Vol 92 (8) ◽  
pp. 706-709 ◽  
Author(s):  
Kim Davenport ◽  
Francis X Keeley ◽  
Anthony G Timoney
Keyword(s):  
Cost Effectiveness ◽  
Local Anaesthetic ◽  
Past History ◽  
Transitional Cell ◽  
General Anaesthetic ◽  
Patient Anxiety ◽  
Bladder Transitional Cell Carcinoma ◽  
Flexible Cystoscopy ◽  
History Of

INTRODUCTION The aim of this study was to audit our experience of cystodiathermy under local anaesthetic (LA) at the time of flexible cystoscopy for recurrent superficial bladder transitional cell carcinoma (TCC). PATIENTS AND METHODS A total of 264 flexible cystoscopies were performed on patients with a past history of TCC. The number and site of recurrences were recorded and selected patients were offered cystodiathermy. Patient tolerability was noted. At follow-up, any recurrence was recorded. RESULTS Eighty patients (30%) had 91 procedures showing one or more recurrences. Fifty-one of the 80 patients (64%) were treated with cystodiathermy under LA. All completed treatment. Forty-five (88%) tolerated the procedure well. Forty-seven (92%) treatments were completed within 5 min. At a median follow-up of 15 weeks, 30 (59%) treated patients had no recurrence and three (6%) had recurrence at the site of treatment. CONCLUSIONS LA cystodiathermy is an effective and well-tolerated alternative to general anaesthetic cystodiathermy that enables treatment at the time of detection and may, thereby, reduce patient anxiety.

scholarly journals Patients with History of Myocardial Infarction and Acute Cerebrovascular Accidentin Clinical Practice: Demographic, Clinical Characteristics, Drug Treatment and Outcomes (Data of Outpatient and Hospital Registry REGION)

2019 ◽  
Vol 15 (5) ◽  
pp. 656-662 ◽  
Author(s):  
E. Yu. Okshina ◽  
M. M. Loukianov ◽  
S. Yu. Martsevich ◽  
S. S. Yakushin ◽  
N. P. Kutishenko ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Practice ◽  
Family History ◽  
Drug Treatment ◽  
Clinical Characteristics ◽  
Beta Blockers ◽  
All Cause Mortality ◽  
History Of ◽  
Hospital Registry

Aim. To assess the demographic and clinical characteristics, drug treatment and outcomes in patients with a history of acute cerebrovascular accident (ACVA) and with concomitant history of myocardial infarction (MI) in clinical practice based on outpatient and hospital parts of REGION registry.Material and methods. The total 1886 patients with a history of ACVA (aged of 70.6±12.5 years, 41.9% men) were enrolled into the outpatient registry REGION (Ryazan) and the hospital registry REGION (Moscow). 356 patients had ACVA and a history of MI (group “ACVA+MI” and 1530 patients had ACVA without history of MI (group “ACVA without MI”). The incidence of cardiovascular diseases (CVD), non-CVD comorbidities, drug therapy and outcomes were analyzed.Results. In the group ACVA+MI compared with group ACVA without MI the significantly higher proportions of patients with the following conditions (diagnosis) were revealed: arterial hypertension (AH) – 99.1% and 94.2%; coronary heart disease (CHD) – 100% and 57%; chronic heart failure (CHF) – 61.5% and 41.8%; atrial fibrillation (AF) – 42.7% and 23.8%; repeated ACVA – 32.9% and 18.9%, respectively, p<0.0001 for all. In ACVA+MI and ACVA without MI groups the respective proportions of patients were smokers – 16.2% and 23.7% (p=0.10), had a family history of premature CVD – 3.2% and 1.2% (p=0.01), and had a hypercholesterolemia – 47% and 59.7% (p<0.001). The incidence of drug administration with proved positive prognostic effect was insufficient in both groups, but higher in the ACVA+MI group compared with ACVA without MI group (on average 47.1% and 40%, respectively), including: anticoagulants in AF – 19.1% and 21.4% (p=0.55); antiplatelets in CHD without AF – 69.4% and 42% (p<0.001); statins in CHD – 26.4% and 17.2% (p<0.001); beta-blockers in CHF – 39% and 23.8% (p=0.002), respectively. During 4- year follow-up in the group ACVA+MI compared with group ACVA without MI there were significantly higher all-cause mortality – 44.9% and 26.8% (p<0.001), nonfatal recurrent ACVA – 13.7% and 5.6% (p=0.0001), and nonfatal MI – 6.9% and 1.0% (p<0.0001), respectively.Conclusion. The proportion of patients with a history of MI was 18.9% among the patients with a history of ACVA. In patients of ACVA+MI group, compared with patients of ACVA without MI group a higher incidence of the following characteristics was revealed: a presence of AH, CHD, CHF, AF, repeated ACVA and a family history of premature CVD. The incidence of taking drug with proved positive effect on prognosis in patients of the compared groups was insufficient, especially of statins and anticoagulants in AF. During the follow-up period ACVA+MI group was characterized by a higher all-cause mortality and higher incidence of nonfatal ACVA and MI. In these patients the improvement of the quality of pharmacotherapy and of the secondary prevention effectiveness are the measures of especial importance. 

Thienopyridine-Associated Thrombotic Thrombocytopenia Purpura: Updated Antibody Results From the SERF-TTP Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 892-892
Author(s):  
Anaadriana Zakarija ◽  
Thanh Ha Luu ◽  
Hau C. Kwaan ◽  
June McKoy ◽  
Ivy Weiss ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Neutralizing Antibodies ◽  
Conflicts Of Interest ◽  
Therapeutic Plasma Exchange ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Laboratory Findings ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Drug Dependent

Abstract Abstract 892 Background: The thienopyridines, ticlopidine and clopidogrel, have been associated with thrombotic thrombocytopenia purpura (TTP). However, few studies have reported information on antibodies to ADAMTS13 among patients with thienopyridine-associated TTP. We previously reported on two mechanistic pathways of thienopyridine-associated TTP with some overlapping features. Evaluation of ADAMTS13 autoantibodies was undertaken to improve understanding of these syndromes. Methods: Clinical and laboratory findings were evaluated for 30 ticlopidine-, 10 clopidogrel-associated TTP cases, and 54 cases of idiopathic TTP. Results: Among patients with thienopyridine-induced TTP, those with a history of ticlopidine versus clopidogrel use were more likely to present with severe thrombocytopenia (platelet < 20,000) (90% versus 13%), severe ADAMTS13-deficiency (80% versus 0%), and neutralizing antibodies to ADAMTS13 (100% versus 0%), and were less likely to have less than a two week history of thienopyridine exposure (0% versus 50%) (p<0.05 for each comparison). They were also more likely to survive following therapeutic plasma exchange (TPE) (85% versus 50%). 2 patients exposed to clopidogrel later relapsed and had similar characteristics to idiopathic TTP patients with non-deficient ADAMTS13 activity. Conclusion: Ticlopidine causes TTP by a pathway involving a neutralizing autoantibody to ADAMTS13 while clopidogrel causes TTP by an ADAMTS13-independent pathway. Although ADAMTS13 autoantibodies are present in both idiopathic and ticlopidine-associated TTP, spontaneous relapses are not seen in ticlopidine-associaated TTP, suggesting that drug-dependent antibodies are present. Clopidogrel associated TTP is distinct from idiopathic TTP in that ADAMTS13 autoantibodies are absent and response to TPE is poor. Disclosures: No relevant conflicts of interest to declare.

Are Patients Who Have Recovered From ADAMTS13-Deficient Thrombotic Thrombocytopenia Purpura (TTP) at Risk for Developing Systemic Lupus Erythematosus (SLE)?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2519-2519
Author(s):  
Deirdra R. Terrell ◽  
Zayd Al-Nouri ◽  
Judith A. James ◽  
Johanna A. Kremer Hovinga Strebel ◽  
Bernhard Lämmle ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Features ◽  
Lupus Erythematosus ◽  
Conflicts Of Interest ◽  
Population Data ◽  
First Episode ◽  
Adamts13 Activity ◽  
Acr Criteria ◽  
Adamts13 Deficiency

Abstract Abstract 2519 TTP associated with acquired, ADAMTS13-deficiency and SLE are both autoimmune disorders that occur preferentially in young, black women and they have many similar clinical features. TTP may occur in patients previously diagnosed with SLE, or patients may develop SLE following recovery from TTP. In addition, TTP may be quite difficult to distinguish from SLE patients with severe hematologic manifestations. We compared the prevalence of SLE-associated autoantibodies in TTP patients to published population data using 95% confidence intervals (CI). The Oklahoma TTP Registry enrolled 292 consecutive patients with their first episode of clinically diagnosed TTP from 11–13-1995 (date of our initial ADAMTS13 measurement) to 7–31-2009; ADAMTS13 activity was measured in 271 (93%) patients; 64 (24%) patients had ADAMTS13 activity <10%, 63 were evaluated for SLE-associated autoantibodies, including 2 patients with a previous diagnosis of SLE. Serum from the patient's acute initial episode was used for analysis. The prevalence of ANA, anti-dsDNA, anti-Ro, and aPL in TTP patients was significantly higher than published population data; prevalences of anti-nRNP, anti-Sm, and anti-La were not different. Autoantibody TTP (95% CI) Population % ANA  ≥1:40 89% (78%–95%) 0–27%  ≥1:120 56% (42%–68%) 0% Anti-dsDNA  ≥1:30 43% (30%–56%) 3% Anti-Ro  OD>0.350 17% (8%–29%) 3% aPL IgM  ≥20 PL units 15% (7%–26%) 2% Because of the increased prevalence of SLE-associated autoantibodies, we evaluated our TTP patients for the America College of Rheumatology (ACR) criteria for SLE (presence of ≥4 of 11 criteria suggests the diagnosis of lupus); abnormalities associated with any TTP episode were not counted in this evaluation of clinical criteria for SLE. By definition ACR criteria can be fulfilled serially or simultaneously over a lifetime. Evaluations were completed between 6-1-2007 and 5-1-2009 on 38/42 (90%) eligible patients (alive, non-institutionalized, no previous SLE diagnosis) consisting of physical examination, review of available lifetime medical records, and serial laboratory evaluations. Patients have been followed for a median of 8.3 years (range, 1–14 years). During this time, 3 (8%) developed clinically evident SLE requiring treatment 1, 5, and 70 months after their initial TTP episodes. Among the other 35 patients, 3 (8%) have ≥4 SLE classification criteria by medical record review (1 had pre-existing Sjögren's syndrome and receives treatment; 2 have minimal clinical features and are not actively treated for SLE); 9 (24%) have 3 criteria; 16 (42%) have 2 criteria; 6 (16%) have 1 criterion; and 1 (2%) patient has no ACR criteria for SLE. All patients continue to be followed and clinically evaluated for potential intervention. SLE diagnosis is a clinical designation and because of the lack of disease modifying drugs, routine follow-up is standard of care unless the patient is symptomatic. Conclusions: [1] A high prevalence of SLE-associated autoantibodies was present in a cohort of consecutive patients with TTP associated with acquired severe ADAMTS13 deficiency. [2] The presence of anti-dsDNA, anti-Ro, aPL and high titers of ANA suggest that patients with ADAMTS13-deficient TTP may be at risk for developing SLE. [3] During long-term follow-up, 6 (16%) of 38 patients have developed overt SLE or ACR criteria without an established diagnosis of SLE. Careful continuing evaluation following recovery from TTP is important. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document