Journal of thrombosis and thrombolysis
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J. Thromb. Thrombolysis · Aug 2011
Randomized Controlled Trial Multicenter StudyChromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban--an oral, direct and selective factor Xa inhibitor.
An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. ⋯ The correlations for each method were equally strong at low (<100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100-200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (>200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.
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J. Thromb. Thrombolysis · Aug 2011
Clinical TrialEvaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series.
Our purpose was to describe anti-Xa levels, dosage requirements, and complications associated with enoxaparin treatment doses in patients with morbid obesity. Inpatients with a BMI >40 kg/m(2) at an academic medical center prescribed therapeutic enoxaparin from 2004 to 2010 who also had an associated anti-Xa level were included in this retrospective evaluation. Twenty-six patients were identified having median weight of 162 kg (range 106-243), median BMI of 49.5 kg/m(2) (range 40.1-98.1), and median enoxaparin duration of 4 days (range 1-32). ⋯ No thrombotic events occurred while on therapy. The majority in this cohort with morbid obesity achieved anti-Xa levels at or above goal at doses less than the recommended 1 mg/kg every 12 h. Bleeding events were more frequent among patients with anti-Xa levels above goal, despite similar PSCr values.
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J. Thromb. Thrombolysis · Aug 2011
The incidence of deep vein thrombosis detected by routine surveillance ultrasound in neurosurgery patients receiving dual modality prophylaxis.
The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. ⋯ The median hospital length of stay for DVT patients was 18 days. Institutional control data demonstrated non-ruptured aneurysm and cerebrovascular anomalies to be the leading reason for admission, followed closely by subarachnoid hemorrhage. The hospital protocol of biweekly screening ultrasound and dual modality prophylaxis for neurosurgery patients resulted in a proximal DVT incidence consistent with that demonstrated by previous studies of standardized dual modality prophylaxis, and higher than that demonstrated in previous studies that employed ultrasound screening protocols.
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Therapeutic hypothermia has been found to improve hemodynamic and metabolic parameters in cardiogenic shock. Tissue plasminogen activator (t-PA) is a pro-thrombolytic enzyme, which also possesses pro-inflammatory properties. Interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) are pro-inflammatory cytokines; interleukin 10 (IL-10) and transforming growth factor beta 1 (TGF-β1) are anti-inflammatory cytokines. ⋯ Hypothermia did not alter the inflammatory response. In conclusion, mild hypothermia improves hemodynamic and metabolic parameters in cardiogenic shock. This is associated with a reduction in basal t-PA levels and t-PA release from the peripheral vascular bed, but not with an altered inflammatory response.
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J. Thromb. Thrombolysis · May 2011
Randomized Controlled Trial Multicenter StudyExtended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol.
Patients with acute medical illnesses are at increased risk of venous thromboembolism (VTE), a significant cause of morbidity and mortality. Thromboprophylaxis is recommended in these patients but questions remain regarding the optimal duration of therapy. The aim of this study is to determine whether oral rivaroxaban is non-inferior to standard-duration (approximately 10 days) subcutaneous (s.c.) enoxaparin for the prevention of VTE in acutely ill medical patients, and whether extended-duration (approximately 5 weeks) rivaroxaban is superior to standard-duration enoxaparin. ⋯ As of July 2010, 8,101 patients from 52 countries have been randomized. These patients have a broad range of medical conditions: approximately one-third were diagnosed with acute heart failure, just under one-third were diagnosed with acute infectious disease, and just under one-quarter were diagnosed with acute respiratory insufficiency. MAGELLAN will determine the efficacy, safety, and pharmacological profile of oral rivaroxaban for the prevention of VTE in a diverse population of medically ill patients and the potential of extended-duration therapy to reduce incidence of VTE.