Browsing by Author "Welsby, IJ"

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    Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation
    (Expert review of hematology, 2016-01) Ghadimi, K; Welsby, IJ; Levy, JH; Dombrowski, KE
    Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.
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    Perioperative management of the bleeding patient.
    (British journal of anaesthesia, 2016-12) Ghadimi, K; Levy, JH; Welsby, IJ
    Perioperative bleeding remains a major complication during and after surgery, resulting in increased morbidity and mortality. The principal causes of non-vascular sources of haemostatic perioperative bleeding are a preexisting undetected bleeding disorder, the nature of the operation itself, or acquired coagulation abnormalities secondary to haemorrhage, haemodilution, or haemostatic factor consumption. In the bleeding patient, standard therapeutic approaches include allogeneic blood product administration, concomitant pharmacologic agents, and increasing application of purified and recombinant haemostatic factors. Multiple haemostatic changes occur perioperatively after trauma and complex surgical procedures including cardiac surgery and liver transplantation. Novel strategies for both prophylaxis and therapy of perioperative bleeding include tranexamic acid, desmopressin, fibrinogen and prothrombin complex concentrates. Point-of-care patient testing using thromboelastography, rotational thromboelastometry, and platelet function assays has allowed for more detailed assessment of specific targeted therapy for haemostasis. Strategic multimodal management is needed to improve management, reduce allogeneic blood product administration, and minimize associated risks related to transfusion.
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    Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?
    (J Neonatal Perinatal Med, 2017-03-16) Ahmadzia, HK; Lockhart, EL; Thomas, SM; Welsby, IJ; Hoffman, MR; James, AH; Murtha, AP; Swamy, GK; Grotegut, CA
    INTRODUCTION: Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid on in vitro clotting properties in pregnancy. METHODS: Blood samples was obtained from healthy pregnant, obese, and preeclamptic pregnant women (n = 10 in each group) prior to delivery as well as from healthy non-pregnant controls (n = 10). Maximum clot firmness (MCF) and clotting time (CT) were measured using rotation thromboelastometry in the presence of tranexamic acid (3, 30, or 300 μg/mL) or ɛ-aminocaproic acid (30, 300, or 3000 μg/mL). ANOVA and regression analyses were performed. RESULTS: Mean whole blood MCF was significantly higher in healthy pregnant vs. non-pregnant women (66.5 vs. 57.5 mm, p < 0.001). Among healthy pregnant women, there was no significant difference between mean MCF (whole blood alone, and with increasing tranexamic acid doses = 66.5, 66.1, 66.4, 66.3 mm, respectively; p = 0.25) or mean CT (409, 412, 420, 424 sec; p = 0.30) after addition of tranexamic acid. Similar results were found using ɛ-aminocaproic acid. Preeclamptic women had a higher mean MCF after the addition of ɛ-aminocaproic acid and tranexamic acid (p = 0.05 and p = 0.04, respectively) compared to whole blood alone. CONCLUSIONS: Pregnancy is a hypercoagulable state, as reflected by an increased MCF compared to non-pregnant women. Addition of antifibrinolytic therapy in vitro does not appear to increase MCF or CT for non-pregnant, pregnant, and obese women. Whether antifibrinolytics are safe in preeclampsia may require further study.