Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists

M. Kopytek , M. Zabczyk , J. Natorska , J. Siudut , K.P. Malinowski , Paweł Ptaszek , A. Glajcar , T. Goralczyk , A. Undas

Abstract

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 – 217) ng/ml), 15 VTE patients taking VKA (INR: 2 – 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometer the storage (G') and loss (G'') moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G'' was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G'', patients taking rivaroxaban (–19% and –30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G''). G' and G'' correlated with plasma rivaroxaban concentrations (r = –0.67, P = 0.005 and r = –0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G'' showed no association with INR in patients on VKAs. G' or G'' were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G'' may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.
Author M. Kopytek
M. Kopytek,,
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, M. Zabczyk
M. Zabczyk,,
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, J. Natorska
J. Natorska,,
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, J. Siudut
J. Siudut,,
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, K.P. Malinowski
K.P. Malinowski,,
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, Paweł Ptaszek (FoFT / DoEaMiFI)
Paweł Ptaszek,,
- Department of Engineering and Machinery in Food Industry
, A. Glajcar
A. Glajcar,,
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, T. Goralczyk
T. Goralczyk,,
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, A. Undas
A. Undas,,
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Journal seriesJournal of Physiology and Pharmacology, ISSN 0867-5910, e-ISSN 1899-1505, (N/A 70 pkt)
Issue year2019
Vol70
No1
Pages79-85
Publication size in sheets0.5
Keywords in Englishfibrin clot, venous thromboembolism, anticoagulant therapy, rheology, scanning electron microscopy, vitamin K antagonist
ASJC Classification1314 Physiology; 3004 Pharmacology
DOIDOI:10.26402/jpp.2019.1.05
Internal identifierWTŻ/2019/55
Languageen angielski
Score (nominal)70
Score sourcejournalList
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.775; WoS Impact Factor: 2018 = 2.544 (2) - 2018=2.457 (5)
Citation count*
Additional fields
FinansowanieThe study was supported by the Polish National Science Center (DEC-2018/02/X/NZ5/00004, to TG).
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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