Pharmacokinetics of low-molecular-weight heparin and unfractionated heparin during elective aortobifemoral bypass grafting

Abstract

Perioperative monitoring has demonstrated that administration of heparin on an empirical basis is associated with a wide variation in patient response and elimination rate. This problem may be overcome by intervention on the basis of perioperative monitoring or by using forms of heparin with different pharmacokinetic properties. When compared with unfractionated heparin, low-molecular-weight heparin has a higher bioavailability after subcutaneous administration, a linear clearance mechanism with a prolonged half-life, and is at least as effective in preventing postoperative vein thrombosis. Theoretically these characteristics of low-molecular-weight heparin could lead to more predictable levels of heparin activity. In this study we compared the pharmacokinetics of low-molecular-weight heparin and unfractionated heparin after an intravenous injection in patients undergoing aortic graft surgery. Heparin activity was measured before heparin administration and at 5, 20, 35, 50, 65, 80, 95, and 110 minutes after administration. The anti-Xa activity in the low-molecular-weight heparin group showed less variation and was more sustained when compared to the unfractionated heparin group. Fibrin degradation products were moderately correlated with the anti-factor Xa levels of the low-molecular-weight heparin group, but no correlation was found in the unfractionated heparin group. The anti-factor Xa activity of low-molecular-weight heparin was, in contrast to that of unfractionated heparin, not completely reversible by protamine administration. The blood loss was comparable in both groups. In contrast to what was expected, the pharmacokinetic profiles of low-molecular-weight heparin and unfractionated heparin showed a similarity after intravenous injection in patients undergoing aortobifemoral bypass grafting. Factors that could have influenced the pharmacokinetic behavior of heparin are discussed.

Prophylactic Perioperative Anti-Thrombotics in Open and Endovascular Abdominal Aortic Aneurysm (AAA) Surgery: A Systematic Review

“…Heparin has no linear doseeresponse and elimination curve after the administration of a standard dose. 4 This phenomenon is enhanced by the deregulated coagulation cascade 5,6 in vascular surgical patients. For this reason, monitoring the level of anti-coagulation produced by heparin is recommended.…”

“…For this reason, monitoring the level of anti-coagulation produced by heparin is recommended. 4,7 The preferred method is to measure the activated clotting time (ACT), which correlates with the anti-thrombotic effect of heparin better than the activated partial thromboplastin time (APTT). 8 Nevertheless, measuring heparin activity perioperatively has not gained widespread use.…”

Low molecular weight heparin: An evaluation of current and potential clinical utility in surgery

“…In studies of patients undergoing arterial bypass surgery of the lower limb [91,92], and in aortic and carotid surgery [93], LMWH and UFH have been similarly effective and safe. However, in a small study, LMWH was shown to have less interindividual variation in response and had a prolonged anticoagulant effect compared with UFH [94]. Large-scale randomized trials are warranted to examine the potential benefits of LMWH in this application.…”

Conventional and near-patient tests of coagulation

“…Conversely, LMWHs have predictable pharmacokinetics such that they can be given without close monitoring of anticoagulant effect. 31 Several pharmacologically distinct agents are commercially available. However, their anti-IIa and anti-Xa activities are sufficiently different that they are not considered interchangeable.…”