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      Pembrolizumab-induced acute thrombosis : A case report

      case-report
      , MD, PhD , , MD, PhD, , MD, , MD, , MD, , MD, PhD, , MD, PhD
      Medicine
      Wolters Kluwer Health
      acute thrombosis, pembrolizumab, pulmonary artery thromboembolism

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Rationale:

          Acute thrombosis has not been reported in the literature so far in lung cancer patients as an immune-related adverse event (irAE) associated with PD-1 pathway inhibitors.

          Patients concerns:

          Here, we for the first time present two NSCLC (non-small cell lung cancer) patients suffering from acute thrombosis as a pembrolizumab-induced irAE. Immediate treatment with continuous heparin infusion improved their symptoms and enabled them to continue pembrolizumab administration.

          Methods:

          Ethical approval was given by the ethics committee of Osaka International Cancer Institute and the informed consents were given by the patients.

          Diagnosis:

          Serum D-dimer level testing, venous ultrasonography, enhanced computed tomography (CT).

          Interventions:

          Continuous heparin infusion, direct oral anticoagulants (DOAC).

          Outcomes:

          Immediate continuous heparin infusion improved their symptoms and continuing pembrolizumab with direct oral anticoagulant successfully induced tumor shrinkage.

          Lessons:

          Reinvigoration of exhausted T cells by pembrolizumab induced systemic inflammation possibly resulting in development of thrombosis. Although acute thrombosis is a rare irAE, it may lead to cessation of treatment and can be lethal.

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          Most cited references6

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          Deep vein thrombosis and pulmonary embolism

          Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism, constitute a major global burden of disease. The diagnostic work-up of suspected deep vein thrombosis or pulmonary embolism includes the sequential application of a clinical decision rule and D-dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer. All other patients should undergo ultrasonography in case of suspected deep vein thrombosis and CT in case of suspected pulmonary embolism. Direct oral anticoagulants are first-line treatment options for venous thromboembolism because they are associated with a lower risk of bleeding than vitamin K antagonists and are easier to use. Use of thrombolysis should be limited to pulmonary embolism associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When venous thromboembolism is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding.
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            Trousseau's syndrome: multiple definitions and multiple mechanisms.

            Ajit Varki (2007)
            In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.
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              Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis

              J H Levy, T Iba (2018)
              The inflammatory response and the activation of coagulation are two important responses in a host's defense against infection. These mechanisms do not work independently, but cooperate in a complex and synchronous manner. Recent research has also shed light on the critical role of thrombus formation, which prevents the dissemination of microorganisms. The cellular components of blood vessels, i.e. leukocytes, platelets, erythrocytes, and vascular endothelial cells, play significant roles in the development of thrombi in combination with activation of the coagulation system. In addition to the cellular components, alarmins such as histones and high-mobility group box 1, microparticles and secreted granule proteins are all important for clot formation. In this summary, we review the pathophysiology of sepsis-induced coagulopathy and the role of cellular components and critical factors released from damaged cells. In addition, we review important therapeutic approaches that have been developed, are under investigation and are currently available in certain countries, including antithrombin, recombinant thrombomodulin, anti-Toll-like receptor 4 therapy, anti-damage associated molecular pattern therapy, and hemoadsorption with a polymyxin B-immobilized fiber column.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                May 2018
                18 May 2018
                : 97
                : 20
                : e10772
                Affiliations
                Department of Thoracic Oncology, Osaka International Cancer Institute, Otemae Chuoku, Osaka City, Japan.
                Author notes
                []Correspondence: Kei Kunimasa, Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae Chuoku, Osaka City, Osaka, 541-8567, Japan (e-mail: kunimasa-ke@ 123456mc.pref.osaka.jp ).
                Article
                MD-D-18-00336 10772
                10.1097/MD.0000000000010772
                5976311
                29768369
                7187b9b6-abb3-421a-8925-e22835f806ef
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 15 January 2018
                : 23 April 2018
                Categories
                5700
                Research Article
                Clinical Case Report
                Custom metadata
                TRUE

                acute thrombosis,pembrolizumab,pulmonary artery thromboembolism

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