RESUMO
BACKGROUND: Andexanet alfa is a Gla-domainless mutant (S195A) factor Xa (GDXa) approved for acute reversal of oral factor Xa inhibitors. Cardiac surgery patients exposed to andexanet before cardiopulmonary bypass often exhibit severe heparin resistance. There is a paucity of data on the effectiveness and optimal dosage of antithrombin use in this setting. The objective of this study was to evaluate the in vitro effect of increased heparin with antithrombin levels on attenuating heparin resistance induced by GDXa. METHODS: Heparinised normal pooled plasma and cardiopulmonary bypass plasma were spiked with GDXa 4 µM. Tissue factor-activated thrombin generation was used to assess heparin reversal effects of GDXa and restoration of anticoagulation with additional heparin with and without antithrombin. Serum thrombin-antithrombin complex, antithrombin activity, and tissue factor pathway inhibitor were also measured in tissue factor-activated, recalcified cardiopulmonary bypass plasma spiked with GDXa. RESULTS: In normal pooled plasma, GDXa-induced heparin reversal was mitigated by maintaining a high heparin concentration (12 U ml-1) and supplementing antithrombin (1.5-4.5 µM) based on peak and velocity of thrombin generation. Heparin reversal by GDXa was also demonstrated in cardiopulmonary bypass plasma, but supplementing both heparin (8 U ml-1) and antithrombin (3 µM) attenuated GDXa-induced changes in peak and velocity of thrombin generation by 72.5% and 72.2%, respectively. High heparin and antithrombin levels attenuated thrombin-antithrombin complex formation in tissue factor-activated, GDXa-spiked cardiopulmonary bypass plasma by 85.7%, but tissue factor pathway inhibitor remained depleted compared with control cardiopulmonary bypass plasma. CONCLUSIONS: Simultaneous supplementation of heparin and antithrombin mitigate GDXa-induced heparin resistance by compensating for the loss of tissue factor pathway inhibitor.
Assuntos
Antitrombinas , Ponte Cardiopulmonar , Inibidores do Fator Xa , Fator Xa , Heparina , Humanos , Heparina/farmacologia , Fator Xa/metabolismo , Antitrombinas/farmacologia , Inibidores do Fator Xa/farmacologia , Resistência a Medicamentos , Anticoagulantes/farmacologiaRESUMO
BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.
Assuntos
Transfusão de Sangue , Registros Eletrônicos de Saúde , Humanos , Transfusão de Componentes Sanguíneos , América do Norte , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Transplante de Fígado , Criança , Humanos , Salas Cirúrgicas , Estudos Retrospectivos , Tempo de InternaçãoRESUMO
Ex vivo viscoelastic testing can be used to assess the concentration responses to tranexamic acid in blood samples obtained from pregnant women across the three trimesters and in non-pregnant controls. Minor variations in fibrinolysis across pregnancy suggest a target tranexamic acid blood concentration of 12.5 mg L-1 for complete inhibition of fibrinolysis. Although the data support the potential utility of viscoelastic testing using the ClotPro® TPA test in maintaining therapeutic tranexamic acid concentrations during postpartum haemorrhage, it might obscure potentially crucial endogenous fibrinolysis inhibitor interactions essential to the microcirculation.
