Thromb Haemost 2017; 117(09): 1739-1749
DOI: 10.1160/TH17-01-0060
Coagulation and Fibrinolysis
Schattauer GmbH

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban

Agnieszka Janion-Sadowska
1   Intensive Cardiac Care Unit, Świetokrzyskie Cardiology Centre, Kielce, Poland
,
Joanna Natorska
2   Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
3   Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
,
Jakub Siudut
2   Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
3   Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
,
Michal Zabczyk
2   Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
,
Andrzej Stanisz
4   Department of Bioinformatic and Telemedicine, Jagiellonian University Medical College, Krakow, Poland
,
Anetta Undas
2   Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
3   Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland
› Institutsangaben
Financial support: This work was supported by and the Polish National Science Centre (UMO-2013/09/B/NZ5/00254) (A. U.).
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Publikationsverlauf

Received: 30. Januar 2017

Accepted after major revision: 11. Juni 2017

Publikationsdatum:
28. November 2017 (online)

Summary

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.