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

Abstract

Introduction Deep 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. Methods AFXa 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. Results Four 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. Conclusion Standard 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.

Inadequate prophylaxis in patients with trauma: anti-Xa-guided enoxaparin dosing management in critically ill patients with trauma

“…Anti-Xa levels <0.2 are considered below target, those between 0.2 and 0.5 are considered on-target, and levels >0.5 are considered above target. [19][20][21] In patients with below target anti-Xa levels, the enoxaparin dose should be increased to the next syringe size. Those with above target anti-Xa levels should have the enoxaparin dose decreased to the next syringe size.…”

“…As more work is completed on this topic, it becomes clear that the true anti-Xa level at which patients receive a true prophylactic benefit remains somewhat unknown. [19][20][21] In conclusion, VTE remains a significant cause of morbidity in the critically ill trauma population. Though enoxaparin has been shown to be the superior agent for VTE prophylaxis in the trauma population, the ideal dose and titration regimen have not yet been settled on.…”

The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

“…Enoxaparin (Clexane R, Aventis Pharma, Frankfurt, Germany), which is a LMWH (4500 Da) isolated from porcine intestinal mucosa and used as sodium salt, was injected subcutaneously at a dose of 0.5 mg/kg in the thighs of all eligible patients after obtaining the baseline blood samples within 1 h of the diagnosis of sepsis [20,21]. …”

“…Nevertheless, failure of deep vein thrombosis prophylaxis in critically ill patients has been well described [17,19]. The reason for this is thought to be multifactorial and one possible proposed explanation could be related to lower anticoagulant effect (as assessed by anti-FXa activity) in these patients, despite appropriate LMWH dosage [20]. …”

S3-Leitlinie Sepsis – Prävention, Diagnose, Therapie und Nachsorge

“…Vergleichbare Ergebnisse sind auch für andere NMH, wie z. B. Certoparin oder Dalteparin, beschrieben [517,689]. Durch die höherdosierte Applikation von NMH (z.…”