Evaluation of intravenous direct thrombin inhibitor monitoring tests: Correlation with plasma concentrations and clinical outcomes in hospitalized patients.

The parenterally administered direct thrombin inhibitors (DTIs) argatroban and bivalirudin are effective anticoagulants for acute heparin-induced thrombocytopenia (HIT) treatment. The activated partial thromboplastin time (aPTT) has classically been used as the monitoring test to assess degree of anticoagulation, however concerns exist with using aPTT to monitor DTI therapy. In this observational study plasma samples from DTI treated patients were analyzed by aPTT, dilute thrombin time (dTT) and ecarin chromogenic assay (ECA) to delineate results into concordant and discordant groups. Discordant samples were further analyzed via liquid chromatography with tandem mass spectrometry (LC MS/MS). In total 101 patients with 198 samples were evaluated. Discordance between tests were frequent (59% of DTI treated patients). Bivalirudin aPTT vs dTT discordance was observed in 45% (57/126) of samples. Amongst bivalirudin samples with test discordance dTT results were more likely to be concordant with LC MS/MS than the aPTT (77% vs 9%, p < 0.0001). Argatroban aPTT vs dTT discordance was observed in 43% (31/72) and aPTT vs ECA discordance was observed in 40% (29/72) of samples. Amongst argatroban samples with test discordance both the dTT and ECA tests were more likely to have concordant results with LC MS/MS than the aPTT (88% vs 9%, p < 0.0001 for both dTT and ECA tests). There were no differences between discordant and concordant patient groups in a composite outcome of bleeding/thrombosis rate (23% vs 27%, p = 0.689). Further investigation is warranted to elucidate the effect of suitable monitoring assays on patient outcomes in the setting of DTI therapy.

Hydroxocobalamin Versus Methylene Blue for Vasoplegic Syndrome in Cardiothoracic Surgery: A Retrospective Cohort.

OBJECTIVE: To compare methylene blue with hydroxocobalamin as a rescue therapy for vasoplegic syndrome. DESIGN: Retrospective cohort. SETTING: Academic medical center. PARTICIPANTS: Patients undergoing cardiothoracic surgery treated for vasoplegic syndrome. INTERVENTIONS: Thirty-five patients were treated with methylene blue (n = 16) or hydroxocobalamin (n = 19). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, systemic vascular resistance, and vasopressor exposures were recorded before and after medication administration. Change in time-averaged norepinephrine equivalents in the hour after administration was the primary outcome. The average norepinephrine equivalent observed at baseline in this cohort was 0.347 µg/kg/min. Methylene blue patients had greater Acute Physiological Assessment and Chronic Health Evaluation II scores (29.8 v 22.2; p = 0.01) and trended toward greater European System for Cardiac Operative Risk Evaluation II values (26.8% v 15.1%; p = 0.07). Methylene blue and hydroxocobalamin were associated with increased mean arterial pressure and systemic vascular resistance 1 hour after administration (10.6 mmHg and 192 dyn*sec/cm5; p = 0.01 and p = 0.01, respectively; 11.8 mmHg and 254 dyn*sec/cm5; p = 0.002 and p = 0.015, respectively). Hemodynamic changes were not different between the rescue therapy groups (p = 0.79 and p = 0.53, respectively). No significant differences were observed within the 1-hour change in time-averaged norepinephrine equivalents for either agent or when methylene blue and hydroxocobalamin were compared (0.012 ± 0.218 µg/kg/min v -0.037 ± 0.027 µg/kg/min; p = 0.46, respectively). When compared with baseline time-averaged norepinephrine equivalent (0.326 ± 0.106 µg/kg/min), only hydroxocobalamin was associated with decreased vasopressor requirements at the 1-hour (0.255 ± 0.129 µg/kg/min; p = 0.03) and 4-hour time points (0.247 ± 0.180 µg/kg/min; p = 0.04) post-administration. CONCLUSION: Methylene blue and hydroxocobalamin increased mean arterial pressures and systemic vascular resistance without significantly decreasing time-averaged norepinephrine exposure in the hour after administration.

Antithrombin Administration During Intravenous Heparin Anticoagulation in the Intensive Care Unit: A Single-Center Matched Retrospective Cohort Study.

Unfractionated heparin (UFH) is a frequently utilized indirect anticoagulant that induces therapeutic effect by enhancing antithrombin (AT)-mediated procoagulant enzyme inhibition. In suspected heparin resistance (HR) during cardiopulmonary bypass, AT activity may be decreased and AT supplementation helps restore UFH responsiveness. The benefit of AT supplementation in HR over longer durations of UFH therapy is unclear. The objective of this study was to describe and evaluate the use of AT III concentrate in the intensive care units (ICUs) at our institution for improving UFH therapy response over 72 hours. A total of 44 critically ill patients were included in the analysis-22 patients received at least 1 dose of AT and 22 patients received no AT. Thirty (68.2%) of the 44 patients were receiving mechanical circulatory support. Baseline characteristics were similar between groups. The average AT activity prior to AT supplementation was 57.9% in the treatment group, and the median cumulative dose of AT was 786.5 U (9.26 U/kg) per patient. There were no significant differences observed in proportion of time spent in therapeutic range (31.9% vs 35.2%, P = .65), time to therapeutic goal (16.5 vs 15.5 hours, P = .97), or patients who experienced a bleeding event (5 vs 5, P = .99) between groups. In conclusion, AT supplementation had minimal impact on anticoagulant response in this cohort of ICU patients with mild to moderate HR receiving a prolonged UFH infusion. Additional research is needed to define AT activity targets and to standardize AT supplementation practices in patients receiving prolonged heparin infusion.