1.
Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists.
Kopytek, M, Zabczyk, M, Natorska, J, Siudut, J, Malinowski, KP, Ptaszek, P, Glajcar, A, Goralczyk, T, Undas, A
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2019;(1)
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 rheometier 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.
2.
A protocol for the rapid normalization of INR in trauma patients with intracranial hemorrhage on prescribed warfarin therapy.
Kalina, M, Tinkoff, G, Gbadebo, A, Veneri, P, Fulda, G
The American surgeon. 2008;(9):858-61
Abstract
Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.