aFXa Levels Research Articles

Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial

IntroductionIntensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients.MethodsThe 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity.ResultsMedian peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02).ConclusionsOur study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients.Trial RegistrationISRCTN03037804

Anti-activated factor × response to enoxaparin in critically ill patients

Low molecular weight heparin (LMWH) dosing protocols for deep vein thrombosis prophylaxis in critically ill patients (CIPs) are not based on pharmacologic studies in these patients. Antithrombotic LMWH activity correlates with peak anti-activated factor × (aFXa) levels (4 hours post injection) of 0.1 to 0.2 IU/ml. The hypothesis of this study is that most CIPs do not achieve therapeutic levels for prevention of DVT.

Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study

IntroductionDeep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients.MethodsAFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin.ResultsFour hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels <0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels.ConclusionStandard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.

Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis with standard doses of enoxaparin

Background: Low-molecular-weight heparins (LMWHs) have become increasingly used to prevent thromboembolic complications in intensive care patients. Unlike in medical and surgical patients, no data on the anticoagulant effectiveness of standard LMWH dosages exist in intensive care patients. Therefore, we prospectively investigated antifactor Xa (aFXa) levels after subcutaneous administration of 40 mg of enoxaparin in 89 intensive care patients over a 24-h period. Methods: AFXa levels were measured before, 4, 12 and 24 h after subcutaneous administration of enoxaparin. Laboratory parameters including prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen as well as platelet count were collected at same intervals. Demographics included age, sex, height, weight, body mass index, admission diagnosis, a thromboembolic risk score and a modified Goris multiple organ dysfunction score. Results: At 4, 12 and 24 h, 56.5%, 39.3% and 12.6% of the study patients were within recommended antithrombotic aFXa levels (0.1–0.3 U ml −1). Presence of multiple organ dysfunction as well as high body weight were significantly correlated with low aFXa levels. Conclusion: European standard dosages of 40 mg of enoxaparin once daily proved to be ineffective in achieving recommended antithrombotic aFXa levels in intensive care patients. This was most pronounced in patients with high body weight and presence of multiple organ dysfunction.

Dose Finding Study of a Low Molecular Weight Heparin, Innohep, in Haemodialysis

A pilot investigation was performed with Innohep, a low molecular weight (LMWH) preparation (peak maximum molecular mass 3,000-6,000), to determine possible dose regimens for patients undergoing regular maintenance haemodialysis for chronic renal failure. Results from this study suggested that suppression of macroscopic clot formation and fibrinopeptide A (FPA), a marker of fibrin formation, could be achieved following bolus injections rather than bolus injections and an infusion. On the basis of these preliminary findings, a randomised crossover study was performed in eight patients undergoing regular maintenance haemodialysis for 5-7 h to determine the effective antithrombotic dose of this LMWH. Single i.v. bolus doses of 1,250 AFXa u, 2,500 AFXa u and 5,000 AFXa u (n = 7-8) were compared to an UFH regime of 5,000 iu + 1,500 iu/h. Excessive clot formation in the dialyser bubble trap, necessitating additional UFH to enable completion of a prolonged (up to 7 h) dialysis, was observed in all patients on the 1,250 AFXa u dose (mean duration of dialysis prior to UFH, 3 h) but in a single patient only receiving the other LMWH doses. A dose-related response in the AFXa activity, measured by chromogenic substrate (CS) assay was seen in the three LMWH groups, with levels declining significantly (p less than 0.05) from 1-7 h. This contrasted with the constant levels maintained during dialysis with UFH. FPA levels were significantly elevated after 2 h following the 1,250 AFXa u bolus and after 4 h following the 2,500 AFXa u bolus. There was no significant difference in FPA levels between the 5,000 AFXa u bolus and UFH.(ABSTRACT TRUNCATED AT 250 WORDS)