{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:26:06Z","timestamp":1780075566481,"version":"3.54.0"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"01","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Endowment foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Various reactions are involved in the phases of activation and further propagation of coagulation in space. The effects of different anticoagulants on these phases are unknown. Our aim was to study how different anticoagulants affect the activation and propagation phases of coagulation.<\/jats:p>\n                  <jats:p>Coagulation in the presence of low-molecular-weight heparin (nadroparin), and direct oral thrombin or factor Xa inhibitors (dabigatran and rivaroxaban, respectively) was studied in vitro and ex vivo via a global blood coagulation assay (Thrombodynamics-4D), which allows simultaneous analysis of thrombin activity in space and the clot growth rate. The ex vivo measurements were carried out in dynamics (8\u20139 days). The presence of asymptomatic thrombosis after 7 to 8 days of treatment was determined for each group of patients via ultrasound of the lower extremities.<\/jats:p>\n                  <jats:p>All the tested anticoagulants inhibited thrombin generation but resulted in different patterns of thrombin spatial distribution and clot growth. The reversible inhibitors\u2014dabigatran and rivaroxaban\u2014inhibited the initiation phase of coagulation, while further clot growth was altered moderately. Irreversible nadroparin weakly affected the initiation phase of thrombin generation, but unlike dabigatran and rivaroxaban, it could completely suppress spatial thrombin propagation. Asymptomatic thrombosis was observed in 0%, 11%, and 29% of the patients in the nadroparin, dabigatran, and rivaroxaban groups, respectively.<\/jats:p>\n                  <jats:p>Antithrombin-dependent and independent inhibitors act differently on different phases of coagulation. High concentrations of dabigatran or rivaroxaban are insufficient to completely prevent fibrin clot growth, but even small amounts of heparin completely suppress this growth, due to factor IXa inhibition.<\/jats:p>","DOI":"10.1055\/a-2516-7384","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T19:09:46Z","timestamp":1739819386000},"page":"062-077","source":"Crossref","is-referenced-by-count":2,"title":["Heparin and Direct Oral Anticoagulants have Different Effects on the Phases of Activation and Spatial Spread of Blood Coagulation"],"prefix":"10.1055","volume":"126","author":[{"given":"Fazoil I.","family":"Ataullakhanov","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Biophysics of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Physiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya M.","family":"Dashkevich","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Hemostasis Mechanisms, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruzanna A.","family":"Ovsepyan","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Hemostasis Mechanisms, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana A.","family":"Vuimo","sequence":"additional","affiliation":[{"name":"Scientific Department, Hematological Corporation HemaCore LLC, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Balandina","sequence":"additional","affiliation":[{"name":"Laboratory of Blood Coagulation Regulation and Integral Phenotyping, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Laboratory of Cell Hemostasis and Thrombosis, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Healthcare, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna D.","family":"Kuprash","sequence":"additional","affiliation":[{"name":"Laboratory of Blood Coagulation Regulation and Integral Phenotyping, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Laboratory of Cell Hemostasis and Thrombosis, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Healthcare, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorzo-Cyren B.","family":"Ayusheev","sequence":"additional","affiliation":[{"name":"Department of Large Vessel Endoprosthetics, N.N. Priorov National Medical Research Center for Traumatology and Orthopedics, Ministry of Healthcare, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey I.","family":"Bernakevich","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Laboratory, N.N. Priorov National Medical Research Center for Traumatology and Orthopedics, Ministry of Healthcare, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Sinauridze","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Biophysics of the Cell, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"},{"name":"Laboratory of Biophysics, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Healthcare, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.thromres.2015.07.025","article-title":"Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion","volume":"136","author":"M A 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