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James N. George - One of the best experts on this subject based on the ideXlab platform.
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Hereditary Thrombotic Thrombocytopenic Purpura.
The New England journal of medicine, 2019Co-Authors: Johanna A. Kremer Hovinga, James N. GeorgeAbstract:Hereditary Thrombotic Thrombocytopenic Purpura Hereditary Thrombotic thrombocytopenic purpura is an autosomal recessive disorder caused by the absence of a functional protease (ADAMTS13) that proce...
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Thrombotic thrombocytopenic purpura
The New England Journal of Medicine, 2006Co-Authors: James N. GeorgeAbstract:A 40-year-old obese black woman has had weakness and epigastric pain for several weeks and diarrhea and vomiting for four days. She does not appear acutely ill; the physical examination is normal except for abdominal tenderness. Her hematocrit is 25 percent. The platelet count is 10,000 per cubic millimeter. The peripheral-blood smear shows occasional fragmented and polychromatophilic red cells. The serum creatinine level is 1.1 mg per deciliter (97.2 μmol per liter), bilirubin 2.5 mg per deciliter (42.8 μmol per liter), and lactate dehydrogenase 722 U per liter (normal, <250). How should this case be managed?
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The association of pregnancy with Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
Current opinion in hematology, 2003Co-Authors: James N. GeorgeAbstract:Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome occurs more commonly in women and among women is commonly associated with pregnancy. Case series of Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome from 1964 to 2002 were reviewed (1) to document the reports of occurrence of Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy and (2) to search for reports of women with congenital or familial Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome who were initially diagnosed during their first pregnancy. The time during pregnancy with greatest risk for development of Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is near term and during the postpartum period. This is also the time of greatest risk for Thrombotic events and for the occurrence of other pregnancy-related syndromes: preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. These other syndromes may also be associated with thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal insufficiency, making their distinction from Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome difficult or impossible. The occurrence of preeclampsia and related syndromes, the hypercoaguable state that occurs in late pregnancy and postpartum, and the progressively decreasing concentration of ADAMTS13 that occurs during late pregnancy may combine to increase the risk for occurrence of Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
Adrian J Stanley - One of the best experts on this subject based on the ideXlab platform.
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previous use of antiThrombotic agents reduces mortality and length of hospital stay in patients with high risk upper gastrointestinal bleeding
Clinical Gastroenterology and Hepatology, 2019Co-Authors: Philip Dunne, Stig Borbjerg Laursen, Loren Laine, Harry R Dalton, Jing Hieng Ngu, Michael Schultz, Adam Rahman, Andrea Anderloni, Iain A Murray, Adrian J StanleyAbstract:Abstract Background and Aims Anti-Thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti-Thrombotic agents on outcomes of patients with high-risk UGIB. Methods We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee-ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti-Thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow-Blatchford Score, and full Rockall scores. We also collected and analyzed data on co-morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. Results Of the 619 patients who required endoscopic therapy, data on use of anti-Thrombotic agents was available for 568; 253 of these patients (44%) used anti-Thrombotic agents. Compared to patients not taking anti-Thrombotic agents, patients treated with anti-Thrombotics were older ( P P P P P P =.002); this was due to lower bleeding-related mortality in patients taking anti-Thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) ( P =.003). Patients taking anti-Thrombotic drugs had mean hospital stays of 6.9 days (95%, CI 2–23 days) compared to 7.9 days for non-users of anti-Thrombotic agents (95% CI, 2–26 days) ( P =.04). Conclusions Despite being older, with higher American Society of Anesthesiologists classification, AIMS65, and Rockall scores, patients who have UGIB that requires endoscopic therapy and take anti-Thrombotic drugs have lower mortality due to GI bleeding and shorter hospital stays, with similar rates of rebleeding, surgery, and transfusions, compared with those not taking anti-Thrombotic drugs.
Edward J. Testa - One of the best experts on this subject based on the ideXlab platform.
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Nonbacterial Thrombotic Endocarditis.
The New England journal of medicine, 2019Co-Authors: John Fournier, Edward J. TestaAbstract:Nonbacterial Thrombotic Endocarditis A 48-year-old man presented with pain in both flanks and weight loss. Numerous splinter hemorrhages were observed on the fingernails. A diagnosis of nonbacteria...
Véronique Frémeaux-bacchi - One of the best experts on this subject based on the ideXlab platform.
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Obstetric Nephrology: AKI and Thrombotic Microangiopathies in Pregnancy
Clinical Journal of the American Society of Nephrology, 2012Co-Authors: Fadi Fakhouri, Caroline Vercel, Véronique Frémeaux-bacchiAbstract:AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antian-giogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying Thrombotic microangiopathy, including throm-botic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or Thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related Thrombotic microangiopathy, complement alternative pathway dysregulation-related Thrombotic microangiopathy, secondary Thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and Thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for Thrombotic microangiopathy. Treatment of Thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of Thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).
Johanna A. Kremer Hovinga - One of the best experts on this subject based on the ideXlab platform.
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Hereditary Thrombotic Thrombocytopenic Purpura.
The New England journal of medicine, 2019Co-Authors: Johanna A. Kremer Hovinga, James N. GeorgeAbstract:Hereditary Thrombotic Thrombocytopenic Purpura Hereditary Thrombotic thrombocytopenic purpura is an autosomal recessive disorder caused by the absence of a functional protease (ADAMTS13) that proce...
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Thrombotic thrombocytopenic purpura
Nature reviews. Disease primers, 2017Co-Authors: Johanna A. Kremer Hovinga, Joel L Moake, Toshiyuki Miyata, Paul Coppo, Bernhard Lammle, Karen VanhoorelbekeAbstract:Thrombotic thrombocytopenic purpura (TTP; also known as Moschcowitz disease) is characterized by the concomitant occurrence of often severe thrombocytopenia, microangiopathic haemolytic anaemia and a variable degree of ischaemic organ damage, particularly affecting the brain, heart and kidneys. Acute TTP was almost universally fatal until the introduction of plasma therapy, which improved survival from <10% to 80-90%. However, patients who survive an acute episode are at high risk of relapse and of long-term morbidity. A timely diagnosis is vital but challenging, as TTP shares symptoms and clinical presentation with numerous conditions, including, for example, haemolytic uraemic syndrome and other Thrombotic microangiopathies. The underlying pathophysiology is a severe deficiency of the activity of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), the protease that cleaves von Willebrand factor (vWF) multimeric strings. Ultra-large vWF strings remain uncleaved after endothelial cell secretion and anchorage, bind to platelets and form microthrombi, leading to the clinical manifestations of TTP. Congenital TTP (Upshaw-Schulman syndrome) is the result of homozygous or compound heterozygous mutations in ADAMTS13, whereas acquired TTP is an autoimmune disorder caused by circulating anti-ADAMTS13 autoantibodies, which inhibit the enzyme or increase its clearance. Consequently, immunosuppressive drugs, such as corticosteroids and often rituximab, supplement plasma exchange therapy in patients with acquired TTP.
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Thrombotic thrombocytopenic purpura
Journal of Thrombosis and Haemostasis, 2005Co-Authors: Bernhard Lammle, Johanna A. Kremer Hovinga, Lorenzo AlberioAbstract:Summary. This overview summarizes the history of Thrombotic thrombocytopenic purpura (TTP) from its initial recognition in 1924 as a most often fatal disease to the discovery in 1997 of ADAMTS-13 deficiency as a major risk factor for acute disease manifestation. The cloning of the metalloprotease, ADAMTS-13, an essential regulator of the extremely adhesive unusually large von Willebrand factor (VWF) multimers secreted by endothelial cells, as well as ADAMTS-13 structure and function are reviewed. The complex, initially devised assays for ADAMTS-13 activity and the possible limitations of static in vitro assays are described. A new, simple assay using a recombinant 73-amino acid VWF peptide as substrate will hopefully be useful. Hereditary TTP caused by homozygous or double heterozygous ADAMTS-13 mutations and the nature of the mutations so far identified are discussed. Recognition of this condition by clinicians is of utmost importance, because it can be easily treated and – if untreated – frequently results in death. Acquired TTP is often but not always associated with severe, autoantibody-mediated ADAMTS-13 deficiency. The pathogenesis of cases without severe deficiency of the VWF-cleaving protease remains unknown, affected patients cannot be distinguished clinically from those with severely decreased ADAMTS-13 activity. Survivors of acute TTP, especially those with autoantibody-induced ADAMTS-13 deficiency, are at a high risk for relapse, as are patients with hereditary TTP. Patients with Thrombotic microangiopathies (TMA) associated with hematopoietic stem cell transplantation, neo-plasia and several drugs, usually have normal or only moderately reduced ADAMTS-13 activity, with the exception of ticlopidine-induced TMA. Diarrhea-positive-hemolytic uremic syndrome (D+ HUS), mainly occurring in children is due to enterohemorrhagic Escherichia coli infection, and cases with atypical, D− HUS may be associated with factor H abnormalities. Treatment of acquired idiopathic TTP involves plasma exchange with fresh frozen plasma (FFP), and probably immunosuppression with corticosteroids is indicated. We believe that, at present, patients without severe acquired ADAMTS-13 deficiency should be treated with plasma exchange as well, until better strategies become available. Constitutional TTP can be treated by simple FFP infusion that rapidly reverses acute disease and – given prophylactically every 2–3 weeks – prevents relapses. There remains a large research agenda to improve diagnosis of TMA, gain further insight into the pathophysiology of the various TMA and to improve and possibly tailor the management of affected patients.
