Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib

The third-generation tyrosine kinase inhibitor (TKI) ponatinib has been associated with high rates of acute ischemic events. The pathophysiology responsible for these events is unknown. We hypothesized that ponatinib produces an endothelial angiopathy involving excessive endothelial-associated von Willebrand factor (VWF) and secondary platelet adhesion. In wild-type mice and ApoE–/– mice on a Western diet, ultrasound molecular imaging of the thoracic aorta for VWF A1-domain and glycoprotein-Ibα was performed to quantify endothelial-associated VWF and platelet adhesion. After treatment of wild-type mice for 7 days, aortic molecular signal for endothelial-associated VWF and platelet adhesion were five- to sixfold higher in ponatinib vs sham therapy (P
Source: Blood - Category: Hematology Authors: Tags: Myeloid Neoplasia, Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Vascular Biology Source Type: research

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CONCLUSION: Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results. PMID: 31924102 [PubMed - as supplied by publisher]
Source: Interventional Neuroradiology - Category: Radiology Tags: Interv Neuroradiol Source Type: research
PMID: 31902309 [PubMed - as supplied by publisher]
Source: Vascular - Category: Surgery Authors: Tags: Vascular Source Type: research
This article comprehensively reviews the efficacy, safety, pharmacokinetics, and pharmacodynamics of vonicog alfa. These points will be discussed using institutional experiential data from the University of Virginia (UVA) Health System in relation to the clinical studies. The goal of this review article is to offer insights to clinical directions, discuss operational challenges, and offer guidance for future studies and formulary decisions.
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
CONCLUSIONS: Our data suggest a VWF-mediated role for MMP-13 in the recruitment of platelets to the site of vascular injury and may provide new insights into the association of MMP-13 in atherothrombotic and stroke pathologies. PMID: 31894636 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
This article gives an overview of the bleeding risks involved and therapeutic options to overcome them. [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
Semin Thromb Hemost DOI: 10.1055/s-0039-3402430Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 mutations and many disease-causing mechanisms have been described in the 35 years since the VWF gene was identified. Genetic testing in VWD patients is now available in many centers as a part of the VWD diagnostic algorithm. Molecular mechanisms leading to types 2...
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
CONCLUSIONS: AS patients exhibited quantitative and qualitative abnormalities of VWF including significantly increased VWF antigen, activity, and propeptide levels following surgery (p
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
Abstract von Willebrand factor (VWF) is a blood glycoprotein that plays an important role in platelet thrombus formation through interaction between its A1 domain and platelet glycoprotein Ib. ARC1779, an aptamer to the VWF A1 domain, was evaluated in a clinical trial for acquired thrombotic thrombocytopenic purpura (aTTP). Subsequently, caplacizumab, an anti-VWF A1 domain nanobody, was approved for aTTP in Europe and the United States. We recently developed a novel DNA aptamer, TAGX-0004, to the VWF A1 domain; it contains an artificial base and demonstrates high affinity for VWF. To compare the effects of these t...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
von Willebrand factor (VWF) and platelets are key mediators of normal hemostasis. At sites of vascular injury, VWF recruits platelets via binding to the platelet receptor glycoprotein Ibα (GPIbα). Over the past decades, it has become clear that many hemostatic factors, including VWF and platelets, are also involved in inflammatory processes, forming intriguing links between hemostasis, thrombosis, and inflammation. The so-called “thrombo-inflammatory” nature of the VWF-platelet axis becomes increasingly recognized in different cardiovascular pathologies, making it a potential therapeutic target to i...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Semin Thromb Hemost DOI: 10.1055/s-0039-3400273Cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) cause hemostatic derangements that can predispose patients to both bleeding and thrombotic complications. Often, patients present for urgent surgery while taking medications including antiplatelet agents, vitamin K antagonists, and direct oral anticoagulants, which must be recognized, monitored, and managed. During extracorporeal circulation, appropriate anticoagulation, most commonly with heparin, is required to maintain blood flow and avoid thrombotic complications. However, anticoagulation and other effec...
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
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