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      Global hemostasis assays in acute myeloid leukemia: results of an observational prospective study

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          Abstract

          Background

          Acute myeloid leukemia (AML) is characterized by a complex spectrum of coagulopathy ranging from hemorrhagic to thrombotic symptoms. To date, platelet count (PLT) and conventional coagulation tests (CCTs) cannot predict hemorrhagic events and thrombotic risk. Thromboelastography (TEG) measures the viscoelastic properties of the clot, thus providing information on the entire process of blood coagulation. The primary aim of the study was to assess the hemostatic balance from AML diagnosis to the end of chemotherapy (CHT) by TEG.

          Material and methods

          Here we present the results of a prospective study enrolling newly diagnosed AML patients treated with chemotherapy. Patients had complete blood counts (CBCs), TEG and CCTs performed at three time points: 1) diagnosis (T 0); 2) during the first cycle of CHT (T 1); and 3) at the end of CHT (T 2). An algorithm of TEG indirectly calculated thrombin generation (TG). Patients underwent daily follow-up for bleeding and thrombotic episodes up to the time of hospital discharge or death.

          Results

          Eighty consecutive patients were evaluated; forty were eligible for the study, and 21 completed the entire study. At T 1, maximum amplitude (MA), TG and K-time were significantly shifted toward a hypocoagulability state compared to T 0 (p<0.05), while a hypercoagulable state at T 2 was shown by changes in α-angle, MA and TG values. Otherwise, there were no statistically significant differences in CCTs between the evaluated time points.

          Discussion

          Overall, TEG revealed complex and dynamic coagulation abnormalities in patients with AML according to both the course of disease and therapy. Further studies are needed to investigate more fully the role of TEG in defining the hemostatic profile in patients with AML.

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          Most cited references37

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          Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

          The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
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            TEG and ROTEM: technology and clinical applications.

            Initially described in 1948 by Hertert thromboelastography (TEG) provides a real-time assessment of viscoelastic clot strength in whole blood. Rotational thromboelastometry (ROTEM) evolved from TEG technology and both devices generate output by transducing changes in the viscoelastic strength of a small sample of clotting blood (300 µl) to which a constant rotational force is applied. These point of care devices allow visual assessment of blood coagulation from clot formation, through propagation, and stabilization, until clot dissolution. Computer analysis of the output allows sophisticated clot formation/dissolution kinetics and clot strength data to be generated. Activation of clot formation can be initiated with both intrinsic (kaolin, ellagic acid) and extrinsic (tissue factor) activators. In addition, the independent contributions of platelets and fibrinogen to final clot strength can be assessed using added platelet inhibitors (abciximab and cytochalasin D). Increasingly, ROTEM and TEG analysis is being incorporated in vertical algorithms to diagnose and treat bleeding in high-risk populations such as those undergoing cardiac surgery or suffering from blunt trauma. Some evidence suggests these algorithms might reduce transfusions, but further study is needed to assess patient outcomes.
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              Dose of prophylactic platelet transfusions and prevention of hemorrhage.

              We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1x10(11), 2.2x10(11), or 4.4x10(11) platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25x10(11)) than in the medium-dose group (11.25x10(11)) or the high-dose group (19.63x10(11)) (P=0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1x10(11) and 4.4x10(11) platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                Role: Formal analysisRole: Writing – original draftRole: Validation
                Role: Data curationRole: Validation
                Role: Data curationRole: Validation
                Role: Data curationRole: Validation
                Role: Data curationRole: Validation
                Role: Validation
                Role: InvestigationRole: Validation
                Role: Formal analysisRole: Validation
                Role: Data curationRole: Validation
                Role: Writing – review & editingRole: Validation
                Role: InvestigationRole: ConceptualizationRole: SupervisionRole: Writing – review & editingRole: Validation
                Journal
                Blood Transfus
                Blood Transfus
                SIMTI
                Blood Transfusion
                Edizioni SIMTI - SIMTI Servizi Srl
                1723-2007
                2385-2070
                January 2024
                12 June 2023
                : 22
                : 1
                : 65-74
                Affiliations
                [1 ]University of Palermo, Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), Palermo, Italy
                [2 ]Department of Hematology and Rare Diseases, V Cervello Hospital, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
                [3 ]Hematology Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
                [4 ]Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo and Policlinico Paolo Giaccone, Unit of Hematology, Palermo, Italy
                [5 ]Hematology Unit, Campus Bio-medico, University of Rome, Rome, Italy
                [6 ]Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo and Policlinico Cardiology Unit, Paolo Giaccone, Palermo, Italy
                [7 ]Department and U.O.C. Laboratory Medicine, “Paolo Giaccone” University Hospital, Palermo, Italy
                [8 ]Istituto di Statistica, ISTAT, Palermo, Italy
                [9 ]Division of Internal Medicine, Hematology Service, Regional Hospital “A. Cardarelli”, Campobasso, Italy
                Author notes
                Correspondence: Simona Raso, e-mail: simona.raso86@ 123456gmail.com
                Article
                blt-22-065
                10.2450/BloodTransfus.575
                10812886
                37458717
                823331b5-7145-41fd-bc56-c784ef35bfbb
                © SIMTI Servizi Srl

                Published under a CC BY-NC-ND license

                History
                : 27 October 2022
                : 24 March 2023
                Categories
                Hemostasis and Thrombosis
                Original Article

                thromboelastography,acute myeloid leukemia,thrombosis,hemorrhage

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