Thrombelastography Detects the Anticoagulant Effect of Rivaroxaban in Patients With Stroke

Bowry, Ritvij; Fraser, Stuart; Archeval-Lao, Joancy; Parker, Stephanie; Cai, Chunyan; Rahbar, Mohammad Hossein; Grotta, James C.

doi:10.1161/strokeaha.113.004016

Cited by 27 publications

(25 citation statements)

References 6 publications

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“…These settings include cardiac surgery [67–70], liver transplantations [71], sepsis [72], trauma [73–79], obstetrics [80], psychophysiological stress [81]. These systems have also been utilized to evaluate anticoagulant activity [82, 83] and determine what the critical threshold value is for the initiation of antifibrinolytic therapy in trauma [84]. The platelet mapping assay system, used to measure platelet aggregation, is more frequently being used in the clinical setting [85], including in patients undergoing cardiac surgery and cardiopulmonary bypass, in which their TEG findings as measured using collagen were correlated with postoperative bleeding [86].…”

Section: Thrombin Generation Assaysmentioning

confidence: 99%

Global assays of hemostasis

Brummel‐Ziedins

Wolberg

2014

Current Opinion in Hematology

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Purpose of review There exists an imbalance between our understanding of the physiology of the blood coagulation process and the translation of this understanding into useful assays for clinical application. As technology advances, the capabilities for merging the two areas have become more attainable. Global assays have advanced our understanding of the dynamics of the blood coagulation process beyond end point assays and are at the forefront of implementation in the clinic. Recent findings We will review recent advances in the main global assays with a focus on thrombin generation that have potential for clinical utility. These assays include direct (thrombogram, whole blood, purified systems) and indirect empirical measures of thrombin generation (thromboelastography) and mechanism-based computational models that use plasma composition data from individuals to generate thrombin generation profiles. Summary Empirical thrombin generation assays (direct and indirect) and computational modeling of thrombin generation have greatly advanced our understanding of the hemostatic balance. Implementation of these types of assays and visualization approaches in the clinic potentially will provide a basis for the development of individualized patient care. Advances in both empirical and computational global assays have made the goal of predicting pre-crisis changes in an individual’s hemostatic state one step closer.

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Section: Thrombin Generation Assaysmentioning

confidence: 99%

Global assays of hemostasis

Brummel‐Ziedins

Wolberg

2014

Current Opinion in Hematology

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“…TEG, an ex vivo technique that measures thrombodynamic properties of blood under low–shear conditions, has been approved by the FDA for diagnosis and management of coagulation disorders. It is also used during surgery . In contrast, HAS is an ex vivo technique that elucidates forces generated by platelets within a clot .…”

Section: Resultsmentioning

confidence: 99%

“…TEG and HAS assays were performed as reported in the literature . For both studies, CaCl 2 was used to initiate clotting of citrated human blood containing varying levels of SCI or enoxaparin.…”

Section: Methodsmentioning

confidence: 99%

A synthetic heparin mimetic that allosterically inhibits factor XIa and reduces thrombosis in vivo without enhanced risk of bleeding

Al‐Horani

Abdelfadiel

Afosah

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Human factor XIa (FXIa) is an actively pursued target for development of safer anticoagulants. Our long‐standing hypothesis has been that allosterism originating from heparin‐binding site(s) on coagulation enzymes is a promising approach to yield safer agents. Objectives To develop a synthetic heparin mimetic as an inhibitor of FXIa so as to reduce clot formation in vivo but not carry high bleeding risk. Methods We employed a gamut of methods involving synthetic chemistry, biophysical biochemistry, enzyme assays, blood and plasma coagulation assays, and in vivo thrombosis models in this work. Results Sulfated chiro‐inositol (SCI), a non‐saccharide mimetic of heparin, was synthesized in three steps in overall yields of >50%. SCI inhibited FXIa with potency of 280 nmol/L and preferentially engaged FXIa's heparin‐binding site to conformationally alter its active site. SCI inhibition of FXIa could be rapidly reversed by common antidotes, such as protamine. SCI preferentially prolonged plasma clotting initiated with recalcification, rather than thromboplastin, alluding to its intrinsic pathway‐based mechanism. Human blood thromboelastography indicated good ex vivo anticoagulation properties of SCI. Rat tail bleeding and maximum‐dose‐tolerated studies indicated that no major bleeding or toxicity concerns for SCI suggesting a potentially safer anticoagulation outcome. FeCl3‐induced arterial and thromboplastin‐induced venous thrombosis model studies in the rat showed reduced thrombus formation by SCI at 250 μg/animal, which matched enoxaparin at 2500 μg/animal. Conclusions Overall, SCI is a highly promising, allosteric inhibitor of FXIa that induces potent anticoagulation in vivo. Further studies are necessary to assess SCI in animal models mimicking human clinical indications.

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“…) and another study found a significant change in TEG parameters in 10 people receiving RIV compared to their baseline values (Bowry et al . ). Power calculation to determine sample size was not performed.…”

Section: Methodsmentioning

confidence: 97%

“…) which is contrary to humans receiving therapeutic levels of RIV where increased R and K values and significantly decreased G, maximum amplitude, alpha angle and LY30 compared to baseline have been reported (Bowry et al . ).…”

Section: Introductionmentioning

confidence: 97%

A prospective evaluation of rivaroxaban on haemostatic parameters in apparently healthy dogs

Evans

Tansey

Wiebe

et al. 2019

Veterinary Medicine & Sci

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The purpose of this study was to determine the effect of rivaroxaban (RIV) on haemostatic parameters assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT) and kaolin‐activated thromboelastography (TEG) in apparently healthy dogs administered 1 mg kg−1 orally once daily for 1 week. Eleven dogs had a baseline complete blood count (CBC), fibrinogen, platelet count, serum chemistry profile, PT, aPTT, and TEG performed. Each dog was then administered approximately 1.0 mg kg−1 of RIV orally once daily for 1 week and the CBC, fibrinogen, platelet count, serum chemistry profile, PT, aPTT, and TEG was re‐evaluated. Any side effects attributed to RIV were noted at this time. One dog was excluded due to identification of a macrocytic thrombocytopenia on pre‐treatment blood work. The remaining 10 enrolled dogs completed the study. Dogs received a median dose of 1.02 mg kg−1 (range 0.94–1.17 mg kg−1) of RIV once daily and was associated with a significant increase in pulse, packed cell volume, total solids, platelet count, fibrinogen and a significant decrease in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. There was no significant change in PT, aPTT or any TEG parameters. The RIV appeared well tolerated with one dog having one episode of vomiting on day 4 but otherwise no other side effects were identified clinically or on recheck blood work. The results of this study suggests that RIV at a dose of 1 mg kg−1 orally once daily is safe and well tolerated but does not cause a significant prolongation of PT, aPTT or TEG parameters.

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Thrombelastography Detects the Anticoagulant Effect of Rivaroxaban in Patients With Stroke

Cited by 27 publications

References 6 publications

Global assays of hemostasis

Global assays of hemostasis

A synthetic heparin mimetic that allosterically inhibits factor XIa and reduces thrombosis in vivo without enhanced risk of bleeding

A prospective evaluation of rivaroxaban on haemostatic parameters in apparently healthy dogs

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