Thrombosis research
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Thrombosis research · May 2013
Fibrinogen concentrate and cryoprecipitate but not fresh frozen plasma correct low fibrinogen concentrations following in vitro haemodilution.
Fibrinogen deficiency often develops during massive bleeding due to e.g. fluid resuscitation with colloid plasma expanders like hydroxyethyl starch. This study investigates the haemostatic effect of various sources of fibrinogen: fibrinogen concentrates (Haemocomplettan® (FC 1), CSL Behring and Clottagen® (FC 2), LFB Biomedicaments), fresh frozen plasma (FFP), and Cryoprecipitate (CP). ⋯ Fibrinogen concentrates investigated dose dependently and equally corrected the MCF and caused no increase in thrombin generation. Cryoprecipitate also corrected the MCF, but also increased thrombin generation. FFP failed to improve MCF, but increased thrombin generation.
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Thrombosis research · May 2013
Darexaban: anticoagulant effects in mice and human plasma in vitro, antithrombotic effects in thrombosis and bleeding models in mice and effects of anti-inhibitor coagulant complex and recombinant factor VIIa.
Here, we investigated the anticoagulant effects of darexaban in mice and human plasma in vitro, effects of darexaban in thrombosis and bleeding models in mice, and reversal effects of anti-inhibitor coagulant complex (ACC) and recombinant factor VIIa (rFVIIa) on anticoagulant effects of darexaban. In mice, darexaban inhibited FXa activity in plasma with an ED50 value of 24.8 mg/kg. Both darexaban and warfarin prolonged prothrombin time (PT) at 3 mg/kg and 0.3 mg/kg/day, respectively. ⋯ In a tail-transection mouse model, darexaban had no significant effect on the amount of blood loss at doses up to 10 mg/kg, while warfarin showed a dose-dependent increase in blood loss, significantly so from 1 mg/kg/day. Darexaban and its metabolite darexaban glucuronide significantly prolonged PT and aPTT in human plasma in vitro, and while rFVIIa concentration-dependently reversed the prolonged PT in this plasma, ACC dose-dependently reversed both PT and aPTT changes prolonged by darexaban. Taken together, these results suggest that darexaban has a potential to be an oral anticoagulant with a better safety profile than warfarin, and that rFVIIa and ACC may be useful as antidotes to darexaban in cases of overdose.
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Thrombosis research · May 2013
ReviewThe anticoagulant therapy for sepsis-associated disseminated intravascular coagulation.
Sepsis is a leading cause of death in critically ill patients and it requires multidisciplinary treatment. The effects of anticoagulant therapy for sepsis-associated disseminated intravascular coagulation have been long discussed and intensively studied. The recent topics in this area are 1) withdrawal of recombinant activated protein C(rAPC) from the market, 2) potential efficacy of the supplement-dose of antithrombin, 3) success of the recombinant thrombomodulin in a Phase 2B trial. rAPC had been the only anticoagulant recommended in the global guideline for the treatment of severe sepsis (Surviving Sepsis Campaign guidelines (SSCG) 2008). ⋯ Nonetheless, a recent clinical study reported the potential efficacy of supplement-dose antithrombin in septic DIC. Recombinant thrombomodulin has been newly developed and its efficacy for DIC was reported. A recent multinational randomized controlled trial has also demonstrated the potential efficacy of this therapeutic agent for septic DIC and a Phase 3 study is currently underway.
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Thrombosis research · Apr 2013
Anticoagulation management in patients with mechanical heart valves having pacemaker or defibrillator insertion.
In patients with a high risk for stroke and having invasive procedures with a high risk for bleeding it is unclear how anticoagulant therapy should be managed. ⋯ We found a low risk for stroke in the absence of postoperative bridging. For patients with device replacement surgery reversal of the anticoagulant effect at the time of procedure might reduce the risk for pocket hematoma, but this requires prospective evaluation including the risk of thromboembolism.
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Thrombosis research · Apr 2013
High-dose aspirin in dogs increases vascular resistance with limited additional anti-platelet effect when combined with potent P2Y12 inhibition.
With the arrival of the potent P2Y12 antagonists, ticagrelor and prasugrel, the need for co-treatment with aspirin in acute coronary syndromes must be re-examined. This study assessed whether high-dose aspirin: a) provides additional anti-platelet efficacy, assessed in vivo and ex vivo, when combined with P2Y12 inhibition; and/or b) has a negative effect on vascular function. ⋯ In the dog, P2Y12 antagonists inhibit TXA2-mediated platelet-aggregation independently of aspirin. Aspirin provides less additional anti-platelet effects during maximal compared with sub-maximal P2Y12 inhibition but increases vascular resistance.