Clinical and Laboratory Features of Patients with Acquired Thrombotic Thrombocytopenic Purpura: Fourteen Years of the Milan TTP Registry

2019 ◽  
Vol 119 (05) ◽  
pp. 695-704 ◽  
Author(s):  
Ilaria Mancini ◽  
Silvia Pontiggia ◽  
Roberta Palla ◽  
Andrea Artoni ◽  
Carla Valsecchi ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Age At Onset ◽  
Signs And Symptoms ◽  
Median Number ◽  
Cross Sectional Study ◽  
Interquartile Range ◽  
Cross Sectional ◽  
Thrombocytopenic Purpura

AbstractAcquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by the immune-mediated severe deficiency of ADAMTS13. We hereby report the demographic and disease-related data of acquired TTP patients recorded in the Milan TTP Registry (www.ttpdatabase.org). We performed a cross-sectional study of 302 individuals enrolled in our registry for an acute episode of acquired TTP occurred between 2002 and 2015 (female 77%; median age at onset 40 years, interquartile range: 30–50). Twenty per cent of patients had concomitant autoimmune disorders. Among potential triggers of acute episodes, infections were the most prevalent (27%), followed by estroprogestinics use and pregnancy (5 and 4% of women, respectively). At presentation, systemic (72%), bleeding (68%) and neurological (43%) symptoms were the most frequent, whereas a lower prevalence of renal (18%) and cardiovascular (10%) signs and symptoms was observed. Almost all acute events were treated by plasma exchange and steroids, and 15% by rituximab. Exacerbation of acute TTP occurred in 15% of events. The TTP-related mortality was 5%. In survivors, the median number of plasma exchange procedures to remission was 9 (interquartile range: 6–14), longer for first events than relapses (median difference 3, 95% confidence interval: 2–4). Of 251 survivors of the first TTP episode with at least a 6-month follow-up, 55% had a relapse. In conclusion, acquired TTP is a severe disease with highly variable clinical presentation, usually requiring a long hospitalization. The Milan TTP Registry represents a powerful tool to improve our knowledge and management of acquired TTP.

scholarly journals Evaluation of the Academic Vascular Surgeons in the Southern United States on Physician Rating Websites: Cross-sectional Study (Preprint)

2020 ◽  
Author(s):  
Qi Yan ◽  
Katherine J. Jensen ◽  
Rose Thomas ◽  
Alyssa R. Langley ◽  
Jiang Zheng ◽  
...  
Keyword(s):  
Social Media ◽  
Median Number ◽  
Cross Sectional Study ◽  
Interquartile Range ◽  
Average Score ◽  
Cross Sectional ◽  
Web Presence ◽  
Digital Footprint ◽  
Physician Rating ◽  
Google Search

BACKGROUND The Internet has become a popular platform for patients to obtain information and review the providers they interact with. However, little is known on the digital footprint of vascular surgeons and their interactivity with patients on social media. OBJECTIVE This study aims to understand the activity of academic vascular surgeons on physician rating websites. METHODS Information on attending vascular surgeons affiliated with vascular residency or fellowships in the Southern Association for Vascular Surgery was collected from public sources. A listing of websites containing physician rating was obtained via literature review and google search. Open access websites that contain either qualitative or quantitative evaluation of vascular surgeons were included. Closed access websites were excluded. Ranking scores from each website were converted to a standard 5-point scale for comparison. RESULTS A total of 6238 quantitative and 967 qualitative reviews were written for 287 physicians (236 males, 82%) across 16 websites that met inclusion criteria out of 62 websites screened. Surgeons in the SAVS region had a median of 8 (interquartile range; 7-10) profiles across 16 websites with only one surgeon having no web presence on any sites. The median number of quantitative ratings for each physician was 17 (interquartile range; 6-34, range; 1-137) and the median number of narrative reviews was 3 (interquartile range; 2-6, range; 1-28). Vitals, WebMD and Healthgrades were the only three websites where over a quarter of the physicians were rated, and those rated had more than 5 ratings on average. The median score for quantitative reviews was 4.4 (interquartile range; 4.0-4.9). Most narrative reviews (78.4%, 758/967) were positive, but 20.2% were considered negative, only 1.4% were considered equivocal. No statistical difference was found in the number of quantitative reviews or overall average score in physicians with versus without social media profiles. CONCLUSIONS Vascular representation on physician rating websites is varied with the majority of vascular surgeons only represented on the top half of the physician rating websites. The number of quantitative and qualitative reviews are low. No surgeons responded to reviews. The activity of vascular surgeons in this area of social media is low and reflects a small digital footprint that patients can reach and review.

Survival and relapse in patients with thrombotic thrombocytopenic purpura

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1500-1511 ◽  
Author(s):  
Johanna A. Kremer Hovinga ◽  
Sara K. Vesely ◽  
Deirdra R. Terrell ◽  
Bernhard Lämmle ◽  
James N. George
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Signs And Symptoms ◽  
Population Based ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Estimated Risk ◽  
Subsequent Relapse ◽  
Organ Dysfunctions

AbstractSurvival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%, P = .83) and for patients with idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261 (93%) of 282 patients since 1995. Survival was not different between patients with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136 of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor titer of 2 or more Bethesda units/mL was associated with lower survival (P = .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16 of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.

scholarly journals US Food and Drug Administration utilization of postmarketing requirements and postmarketing commitments, 2009–2018

2021 ◽  
pp. 174077452110050
Author(s):  
Joshua J Skydel ◽  
Audrey D Zhang ◽  
Sanket S Dhruva ◽  
Joseph S Ross ◽  
Joshua D Wallach
Keyword(s):  
Drug Administration ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Food And Drug Administration ◽  
Median Number ◽  
Cross Sectional Study ◽  
Interquartile Range ◽  
New Drugs ◽  
Cross Sectional ◽  
The Us

Background/Aims The US Food and Drug Administration outlines clinical studies as postmarketing requirements and commitments to be fulfilled following approval of new drugs and biologics (“therapeutics”). Regulators have increasingly emphasized lifecycle evaluation of approved therapeutics, and postmarketing studies are intended to advance our understanding of therapeutic safety and efficacy. However, little is known about the indications that clinical studies outlined in postmarketing requirements and commitments investigate, including whether they are intended to generate evidence for approved or other clinical indications. Therefore, we characterized US Food and Drug Administration postmarketing requirements and commitments for new therapeutics approved from 2009 to 2018. Methods We conducted a cross-sectional study of all novel therapeutics, including small-molecule drugs and biologics, receiving original US Food and Drug Administration approval from 2009 to 2018, using approval letters accessed through the Drug@FDA database. Outcomes included the number and characteristics of US Food and Drug Administration postmarketing requirements and commitments for new therapeutics at original approval, including the types of studies outlined, the indications to be investigated, and the clinical evidence to be generated. Results From 2009 to 2018, the US Food and Drug Administration approved 343 new therapeutics with 1978 postmarketing requirements and commitments. Overall, 750 (37.9%) postmarketing requirements and commitments outlined clinical studies. For 71 of 343 (20.7%) therapeutics, no postmarketing requirements or commitments for clinical studies were outlined, while at least 1 was outlined for 272 (79.3%; median 2 (interquartile range: 1–4)). Among these 272 therapeutics, the number of postmarketing requirements and commitments for clinical studies per therapeutic did not change from 2009 (median: 2 (interquartile range: 1–4)) to 2018 (median: 2 (interquartile range: 1–3)). Among the 750 postmarketing requirements and commitments for clinical studies, 448 (59.7%) outlined new prospective cohort studies, registries, or clinical trials, while the remainder outlined retrospective studies, secondary analyses, or completion of ongoing studies. Although 455 (60.7%) clinical studies investigated only original approved therapeutic indications, 123 (16.4%) enrolled from an expansion of the approved disease population and 61 (8.1%) investigated diseases unrelated to approved indications. Conclusions The US Food and Drug Administration approves most new therapeutics with at least 1 postmarketing requirement or commitment for a clinical study, and outlines investigations of safety or efficacy for both approved and unapproved indications. The median number of 2 clinical studies outlined has remained relatively constant over the last decade. Given increasing emphasis by the US Food and Drug Administration on faster approval and lifecycle evaluation of therapeutics, these findings suggest that more postmarketing requirements and commitments may be necessary to address gaps in the clinical evidence available for therapeutics at approval.

Rituximab for the Treatment of Recurrent Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4020-4020
Author(s):  
Teresa C. Bortolheiro ◽  
N. S. Castro ◽  
Cançado D. Rodolfo ◽  
Chiattone Carlos
Keyword(s):  
Complete Remission ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Randomized Clinical Trials ◽  
Severe Disease ◽  
Sustained Remission ◽  
Thrombocytopenic Purpura ◽  
Significant Toxicity ◽  
Clinically Significant ◽  
Von Willebrand

Abstract Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease, characterized by thrombocytopenia, microangiopathic anaemia, fever, renal failure, and neurological manifestation caused by deposition of von Willebrand factor - platelet rich hyaline thrombi in the arterioles and capillaries. Plasma exchange has decreased the mortality in TTP from almost 100% to 10–30%. However, relapses occur in more than one-third of patients, a subset of whom develop multiple relapses or chronic disease requiring numerous sessions of plasma exchange. This treatment is costly and associated with many adverse reactions. Case Report: We describe a female patient - diagnosed with TTP in 1996 - who did not achieve a sustained remission with plasma exchange, steroids and vincristine, but who remained in remission after a splenectomy performed in 1997. The patient underwent relapse in 2003 and restarted plasma exchange, with progressive improvement of cytopenias. Plasma exchange was reduced in frequency from daily sessions to every other day. There was a lowering of platelet levels and an increase in LDH levels - steroids and vincristine were re-initiated, but without response. The patient was treated with four, weekly doses (375 mg/m2) of rituximab. Plasma exchange was only required during the first 2 weeks of rituximab treatment, and was discontinued after the second dose of rituximab. The patient remained in complete remission for 9 months, but was then admitted to hospital with femoral thrombosis, and normal LDH and platelet levels. After 40 days of thrombosis therapy, the patient had a further relapse and refused plasma exchange. Treatment with rituximab was restarted as previously, and the patient achieved a complete remission within 2 weeks - now sustained for 11 months. Conclusion: In comparing this patient with eight previous cases not treated with rituximab, we conclude that rituximab is a very effective treatment for TTP, which is not associated with clinically significant toxicity. Randomized clinical trials are required to confirm these findings.

scholarly journals Thrombotic Thrombocytopenic Purpura: Etiopathogenesis, Diagnostics and Basic Principles of Treatment

2017 ◽  
Vol 18 (1) ◽  
pp. 61-68
Author(s):  
Željko Todorović ◽  
Milena Jovanovic ◽  
Dusan Todorovic ◽  
Dejan Petrovic ◽  
Predrag Djurdjevic
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Haemolytic Anaemia ◽  
Signs And Symptoms ◽  
Genetic Mutation ◽  
Clinical Syndrome ◽  
Main Function ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Microangiopathic Haemolytic Anaemia

Abstract Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome that manifests with thrombocytopenia, microangiopathic haemolytic anaemia and symptoms and signs of kidney and brain damage, but it rarely involves other organs. The main pathophysiological cause of TTP is diminished metalloproteinase ADAMTS13 activity; the main function of ADAMTS13 is to degrade large multimers of the von Willebrand factor. Diminished activity of ADAMTS13 is caused either by a genetic mutation in the gene that codes ADAMTS13 (congenital TTP) or by antibodies that block ADAMTS13 enzyme activity or accelerate the degradation of ADAMTS13 (acquired TTP). Clinically, TTP presents most frequently with signs and symptoms of brain and kidney damage with concomitant haemorrhagic syndrome. TTP is suspected when a patient presents with a low platelet count, microangiopathic haemolytic anaemia (negative Coombs tests, low haptoglobine concentration, increased serum concentration of indirect bilirubin and lactate dehydrogenase, increased number of schysocytes in peripheral blood) and the typical clinical presentation. A definitive diagnose can be made only by measuring the ADAMTS13 activity. The differential diagnosis in such cases includes both typical and atypical haemolytic uremic syndrome, disseminated intravascular coagulation, HELLP syndrome in pregnant women and other thrombotic microangiopathies. The first line therapy for TTP is plasma exchange. In patients with acquired TTP, in addition to plasma exchange, immunosuppressive medications are used (corticosteroids and rituximab). In patients with hereditary TTP, the administration of fresh frozen plasma is sometimes required.

scholarly journals Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049967
Author(s):  
Karen Sól Saevarsdóttir ◽  
Hildur Ýr Hilmarsdóttir ◽  
Ingibjörg Magnúsdóttir ◽  
Arna Hauksdóttir ◽  
Edda Bjork Thordardottir ◽  
...  
Keyword(s):  
Severe Disease ◽  
Symptom Burden ◽  
Cross Sectional Study ◽  
Illness Severity ◽  
University Education ◽  
Adjusted Relative Risk ◽  
Sectional Study ◽  
Cross Sectional ◽  
Symptoms Of Depression ◽  
Increased Risk

ObjectiveTo test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

Response to Plasma Exchange and Steroids as Combined Therapy for Patients with Thrombotic Thrombocytopenic Purpura

1999 ◽  
Vol 102 (1) ◽  
pp. 12-16 ◽  
Author(s):  
Javier de la Rubia ◽  
Aurelio López ◽  
Francisco Arriaga ◽  
Ana Rosa Cid ◽  
Ana Isabel Vicente ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Combined Therapy ◽  
Thrombocytopenic Purpura

scholarly journals A Signet Ring Cell Carcinoma Presented as Refractory Acquired Thrombotic Thrombocytopenic Purpura

2020 ◽  
Vol 13 (3) ◽  
pp. 1368-1372
Author(s):  
Umit Yavuz Malkan ◽  
Murat Albayrak ◽  
Hacer Berna Ozturk ◽  
Merih Reis Aras ◽  
Bugra Saglam ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Unknown Origin ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Thrombocytopenic Purpura ◽  
Signet Ring ◽  
Gastric Endoscopy ◽  
Ring Cell

Microangiopathic hemolytic anemia (MAHA) can be observed as a paraneoplastic syndrome (PS) in certain tumors. MAHA-related signet ring cell carcinoma (SRCC) of an unknown origin is very infrequent. Herein we present a SRCC case presented with refractory acquired thrombotic thrombocytopenic purpura (TTP). A 35-year-old man applied to the emergency service with fatigue and headache. His laboratory tests resulted as white blood cell 9,020/µL, hemoglobin 3.5 g/dL, platelet 18,000/µL. Schistocytes, micro-spherocytes, and thrombocytopenia were observed in his blood smear. MAHA was present and he was considered as having TTP. Plasma exchange treatment was initiated; however, he was refractory to this treatment. Thorax and abdomen computerized tomography revealed thickening of minor curvature in stomach corpus with hepatogastric and paraceliac lymphadenopathy. Bone marrow (BM) investigation by our clinic resulted as the metastasis of adenocarcinoma. Ulceration and necrosis were observed by gastric endoscopy procedure. Biopsy was taken during endoscopic intervention, which resulted as SRCC. MAHA may be seen as a PS in some tumors, especially gastric cancers. Tumor-related MAHA is generally accompanied by BM metastases. As a result, BM investigation may be used as the main diagnostic method to find the underlying cancer. The clinical course of cases with tumor-related MAHA is usually poor, and these cases are usually refractory to plasma exchange treatment. In conclusion, physicians should suspect a malignancy and BM involvement when faced with a case of refractory TTP.

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