1.[Argatroban, Aspirin, and Clopidogrel Combination Therapy for Acute Penetrating Artery Infarction: A Pilot Study].
Nishi R1, Mano T, Kobayashi Y, Matsuo K, Kobayashi Y. Brain Nerve. 2016 Feb;68(2):181-9. doi: 10.11477/mf.1416200370.
Treatment to prevent progressive neurological deficits in acute penetrating artery infarction (API) is clinically important, but has not yet been established. This study aims to investigate the efficacy and safety of argatroban, aspirin, and clopidogrel combination therapy for API. Patients with API (lacunar infarcts or branch atheromatous disease) admitted within 48 hours after onset were enrolled. We assigned them to argatroban, aspirin, and clopidogrel (AAC) group or argatroban and aspirin (AA) group. In both groups, blood pressure was controlled to near or below 180/105 mmHg in the admission period. We defined progressing stroke as a worsening of two or more points in the National Institutes of Health Stroke Scale score on the seventh day of admission. Fifty-four patients were enrolled. We assigned 28 patients to the AAC group, and 26 patients to the AA group. There were no significant differences in background factors between the two groups.
2.Argatroban pharmacokinetics and pharmacodynamics in critically ill cardiac surgical patients with suspected heparin-induced thrombocytopenia.
Keyl C1, Zimmer E, Bek MJ, Wiessner M, Trenk D. Thromb Haemost. 2016 Jan 21;115(5). [Epub ahead of print]
Only limited data are available on the pharmacokinetic and pharmacodynamic properties of argatroban in critically ill patients under clinical conditions. We determined plasma concentrations of argatroban, and its main metabolite M1, within a time period of 48 hours in 25 critically ill cardiac surgical patients, who were suspected of heparin-induced thrombocytopenia and had the clinical need for anticoagulation. Argatroban infusion was started at 0.5 µg/kg/minute, and adjusted in 0.1-0.25 µg/kg/minute increments when the activated partial thromboplastin time (aPTT) was not within the target range. Median argatroban plasma half-life was 2.7 hours (interquartile range 1.8 to 7.3). Linear regression analysis revealed that argatroban half-life was significantly related to the total bilirubin concentration (R² = 0.66, p< 0.001), as well as to the metabolism of argatroban, which was assessed by the ratio of the areas under the concentration time curves (AUC) of argatroban and M1 (R² = 0.
3.Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.
Harenberg J1. Thromb Res. 2016 Apr;140 Suppl 1:S165-7. doi: 10.1016/S0049-3848(16)30117-7.
A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs.