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ADAMTS-13

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https://www.readbyqxmd.com/read/28981194/elevated-preoperative-von-willebrand-factor-is-associated-with-perioperative-thrombosis-in-infants-and-neonates-with-congenital-heart-disease
#1
Ryan Hunt, Corey M Hoffman, Sirisha Emani, Cameron C Trenor, Sitaram M Emani, David Faraoni, Chava Kimchi-Sarfaty, Juan C Ibla
BACKGROUND: The surgical repair of congenital heart lesions is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand Factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. OBJECTIVES: To describe perioperative changes to VWF, ADAMTS-13 and NETosis and evaluate clinical and biochemical associations with postoperative thrombosis. METHODS: Neonates and infants undergoing palliation or definitive repair of congenital heart disease (CHD) were recruited (n =133)...
October 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28942075/clinical-and-in-vitro-evidence-that-subclinical-hemolysis-contributes-to-lvad-thrombosis
#2
Carlo R Bartoli, David Zhang, Jooeun Kang, Samson Hennessy-Strahs, David Restle, Jessica Howard, Gretchen Redline, Christian Bermudez, Pavan Atluri, Michael A Acker
BACKGROUND: Recent data suggest that hemolysis contributes to left ventricular assist device (LVAD) thrombosis, but the mechanism is unknown. In a clinical study, we measured plasma free hemoglobin (pfHgb) and the incidence of LVAD thrombosis. In an in vitro study, we examined biophysical relationships between shear stress, pfHgb and von Willebrand factor (vWF) metabolism toward understanding mechanisms of LVAD thrombosis. METHODS: In the clinical study, blood samples were obtained from continuous-flow LVAD patients (n = 30)...
September 21, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28927148/association-of-abo-blood-groups-with-von-willebrand-factor-factor-viii-and-adamts-13-in-patients-with-lung-cancer
#3
Xia Liu, Xiaogang Chen, Jiezuan Yang, Renyong Guo
Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28912376/a-recombinant-human-adamts-13-first-in-human-study-evaluating-pharmacokinetics-safety-and-tolerability-in-cttp-patients
#4
Marie Scully, Paul Knöbl, Karim Kentouche, Lawrence Rice, Jerzy Windyga, Reinhard Schneppenheim, Johanna A Kremer Hovinga, Michiko Kajiwara, Yoshihiro Fujimura, Caterina Maggiore, Jennifer Doralt, Christopher Hibbard, Leah Martell, Bruce Ewenstein
Safety, tolerability and pharmacokinetics of recombinant ADAMTS-13 (rADAMTS-13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity < 6%) in a prospective phase 1, first-in-human, multicenter dose escalation study. BAX 930 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed. Following single dose administration of BAX 930 at 5, 20, or 40 U/kg body weight to adolescents and adults, there was approximate dose proportionality with respect to Cmax and AUC...
September 14, 2017: Blood
https://www.readbyqxmd.com/read/28843665/balanced-haemostasis-with-both-hypo-and-hyper-coagulable-features-in-critically-ill-patients-with-acute-on-chronic-liver-failure
#5
Caleb Fisher, Vishal C Patel, Sidsel Hyldgaard Stoy, Arjuna Singanayagam, Jelle Adelmeijer, Julia Wendon, Debbie L Shawcross, Ton Lisman, William Bernal
BACKGROUND: Cirrhotic patients have complex haemostatic abnormalities. Current evidence suggests stable cirrhotic (SC) patients have a "re-balanced" haemostatic state. However, limited data exists in acute decompensated (AD) or acute on chronic liver failure (ACLF) patients. METHODS: We utilised thrombin generation analysis, fibrinolysis assessment, and evaluation of haemostatic parameters to assess haemostasis in liver disease of progressive severity. RESULTS: The study cohorts were comprised of: SC, n=8; AD n=44; ACLF, n=17; and Healthy Control (HC), n=35...
August 17, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28839178/hypercoagulability-progresses-to-hypocoagulability-during-evolution-of-acetaminophen-induced-acute-liver-injury-in-pigs
#6
Karla Chui Luan Lee, Luisa Baker, Susan Mallett, Anne Riddell, Pratima Chowdary, Hatim Alibhai, Yu-Mei Chang, Simon Priestnall, Giacomo Stanzani, Nathan Davies, Rajeshwar Mookerjee, Rajiv Jalan, Banwari Agarwal
Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to 'ALF', defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats-13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775254/adamts-13-regulates-neutrophil-recruitment-in-a-mouse-model-of-invasive-pulmonary-aspergillosis
#7
Astrid Alflen, Steve Prüfer, Katharina Ebner, Sebastian Reuter, Pamela Aranda Lopez, Inge Scharrer, Fumiaki Banno, Michael Stassen, Hansjörg Schild, Kerstin Jurk, Markus Bosmann, Hendrik Beckert, Markus P Radsak
Von Willebrand factor (VWF) is secreted as an acute phase protein during inflammation. ADAMTS-13 regulates the size and prothrombotic activity of VWF by it's specific proteolytic activity. To determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (PMN), we employed a mouse model of invasive pulmonary aspergillosis (IPA) where PMN functionality is crucial for fungal clearance and survival. IPA was induced by intratracheal application of Aspergillus fumigatus (A...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743060/glucose-fluctuation-and-the-resultant-endothelial-injury-are-correlated-with-pancreatic-%C3%AE-cell-dysfunction-in-patients-with-coronary-artery-disease
#8
Makoto Murata, Hitoshi Adachi, Shigeru Oshima, Masahiko Kurabayashi
AIMS: We evaluated whether glucose fluctuation (GF) causes vascular endothelial injury and affects glucometabolic factors during lengthy oral glucose tolerance test (OGTT). METHODS: We enrolled consecutive 116 patients with coronary artery disease (CAD) who were performed coronary angiography and 4-h OGTT. Blood samples were collected before and 4h after glucose load to measure endothelial injury factor [von Willebrand factor (vWF) and vWF/a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) ratio]...
July 8, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28682993/quantification-of-von-willebrand-factor-cleavage-by-adamts-13-in-patients-supported-by-left-ventricular-assist-devices
#9
Yong Zhou, Shizhen Qin, Tristan Hilton, Li Tang, Miguel Cruz, Ruben Hernandez, Joel L Moake, Qiang Tian, O H Frazier, Jing-Fei Dong, Angelo Nascimbene
Patients supported by left ventricular assist devices (LVADs) often present with the loss of large von Willebrand factor (VWF) multimers. This VWF deficiency is believed to contribute to the bleeding diathesis of patients on LVAD support and is caused by excessive VWF cleavage by the metalloprotease ADAMTS-13 under high shear stress. However, only a small percentage of patients who have suffered the loss of large VWF multimers bleed. The actual rates of VWF cleavage in these patients have not been reported, primarily because of the lack of reliable detection methods...
July 1, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28651806/von-willebrand-factor-deposition-and-adamts-13-consumption-in-allograft-tissue-of-thrombotic-microangiopathy-like-disorder-after-living-donor-liver-transplantation-a-case-report
#10
S Nakanuma, T Miyashita, H Hayashi, Y Ohbatake, H Takamura, M Okazaki, T Yamaguchi, S Sakai, I Makino, K Oyama, H Tajima, I Ninomiya, S Fushida, T Ohta
BACKGROUND: Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation...
June 23, 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28650450/endothelial-damage-is-aggravated-in-acute-gvhd-and-could-predict-its-development
#11
E Mir, M Palomo, M Rovira, A Pereira, G Escolar, O Penack, E Holler, E Carreras, M Diaz-Ricart
The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n=31) and without (NoGvHD, n=13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins...
September 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28607779/thrombotic-microangiopathy-secondary-to-intravenous-abuse-of-opana%C3%A2-er
#12
Kamia Thakur, Vaibhav Agrawal, Ashley Kass, Lauren M Dimarino, R Patrick Dorion, Joseph Vadakara
Opana ER (oxymorphone) is an opioid drug available throughout the United States, and intravenous abuse of the crushed oral formulation has been associated with drug-induced thrombotic microangiopathy. In this abstract, we describe two young patients who lived together and used Opana ER intravenously. Both presented with microangiopathic hemolytic anemia that mimicked thrombotic thrombocytopenic purpura (TTP). Treating this condition poses a clinical challenge, as it is difficult to distinguish it from TTP. The role for plasma exchange is not clear but can be used while awaiting the results of the ADAMTS-13 activity, but ultimately supportive care with drug discontinuation is the recommended therapy of choice...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28546076/sirna-knockdown-of-adamts-13-modulates-endothelial-cell-angiogenesis
#13
Huiyuan Tang, Manfai Lee, Eun Ho Kim, Daniel Bishop, George M Rodgers
ADAMTS-13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a zinc-containing metalloprotease that cleaves von Willebrand factor (vWf). Previous publications by our laboratory have shown that ADAMTS-13 may also be involved in angiogenesis. For this study, we report the successful transient knockdown of endogenous ADAMTS-13 in human umbilical vein endothelial cells (HUVEC) via siRNA and the effects of reduced endogenous ADAMTS-13 on HUVEC angiogenesis functions. 15nM of ADAMTS-13 siRNA reduced HUVEC ADAMTS-13 protein levels by 90% after 24h incubation, whereas control siRNA did not affect endogenous ADAMTS-13 levels...
May 22, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28508977/thrombotic-microangiopathy-caused-by-interferon-%C3%AE-1b-for-multiple-sclerosis-a-case-report
#14
Haruomi Nishio, Tatsuo Tsukamoto, Takeshi Matsubara, Yoichiro Okada, Ryosuke Takahashi, Motoko Yanagita
A 41-year-old man with a history of multiple sclerosis (MS) developed thrombotic microangiopathy after taking interferon β-1b for 10 years. Although the relapse of his MS was well controlled under normal blood pressure, he had persistent nausea, anorexia, gait disturbance and visual disorder 1 month before admission. He showed lethargy and high blood pressure (180/102 mmHg). Laboratory test results revealed anemia and thrombocytopenia, elevated LDH and renal dysfunction. Urinary dipstick showed a 2+ result for proteinuria and 3+ for hematuria...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28457019/dynamics-of-von-willebrand-factor-reactivity-in-sickle-cell-disease-during-vaso-occlusive-crisis-and-steady-state
#15
J W R Sins, M Schimmel, B M Luken, E Nur, S S Zeerleder, C F J van Tuijn, D P M Brandjes, W F Kopatz, R T Urbanus, J C M Meijers, B J Biemond, K Fijnvandraat
Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil activation. Hyper-adhesive VWF may promote VOC in sickle cell disease. SUMMARY: Background Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells...
April 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28413093/-thrombotic-thrombocytopenia-purpura-in-martinique-retrospective-study-between-2008%C3%A2-and-2015
#16
M Patient, P Fuseau, C Deligny
INTRODUCTION: Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique. METHODS: We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st...
April 13, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28380082/heparin-induced-thrombocytopenia-as-a-cause-of-prolonged-low-platelet-count-in-a-patient-with-thrombotic-thrombocytopenic-purpura-treated-with-plasmapheresis
#17
Agata Winiarska, Norbert Kwella, Tomasz Stompór
Thrombotic thrombocytopenic purpura (TTP) is a rare disorder belonging to thrombotic microangiopathies (TMA) and is caused by functional deficiency of the ADAMTS-13 metalloproteinase. Plasma exchange (PE) remains the treatment of choice in this disease. Here, were describe the case of a patient who apparently recovered from TTP following multiple sessions of PE, but remained thrombocytopenic. Careful analysis revealed the development of heparin-induced thrombocytopenia (HIT) that precluded platelet count (PLT) normalization...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28374895/increased-von-willebrand-factor-over-decreased-adamts-13-activity-is-associated-with-poor-prognosis-in-patients-with-advanced-non-small-cell-lung-cancer
#18
Renyong Guo, Jiezuan Yang, Xia Liu, Jianping Wu, Yu Chen
BACKGROUND: Hypercoagulability induced by the imbalance between von Willebrand factor (VWF) secretion and its cleaving protease (ADAMTS-13) has been correlated with cancer metastasis. The aim of this study was to explore the prognostic significance of the VWF/ADAMTS-13 ratio in advanced non-small-cell lung cancer (NSCLC). METHODS: Pre-treatment sera/plasma levels of VWF, ADAMTS-13, VWF/ADAMTS-13 ratio, factor (F) VIII, and other clinical/laboratory parameters were measured in 119 patients with advanced NSCLC and 102 healthy controls...
April 4, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28325251/interferon-induced-thrombotic-microangiopathy-tma-analysis-and-concise-review
#19
REVIEW
Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28265287/pernicious-anemia-associated-cobalamin-deficiency-and-thrombotic-microangiopathy-case-report-and-review-of-the-literature
#20
Farhanah Yousaf, Bruce Spinowitz, Chaim Charytan, Marilyn Galler
A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam...
2017: Case Reports in Medicine
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