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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.
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.
Standard unfractionated heparin is a mixture of mucopolysaccharide chains of various length that may vary from 5000 to 30,000 daltons. Heparin is only effective as an anticoagulant in the presence of a plasma protein termed antithrombin III, with which it forms a complex. High- and low-affinity heparin are 2 types that readily bind or do not bind, respectively, to antithrombin III. The pharmacokinetics of unfractionated heparin are compatible with a model based on the combination of a saturable and a linear mechanism. The primary indication for intravenous infusion of conventional heparin is to prevent extension of an established arterial, venous or intracardiac thrombus. The average requirement is 400 U/kg/24h. Subcutaneous administration of 5000U of concentrated unfractionated heparin, administered every 8 or 12 hours, is effective and safe in the prevention of postoperative venous thrombosis and pulmonary embolism in patients at medium thrombotic risk. Adequate prophylaxis is also obtained in patients at high thrombotic risk if 5000U of heparin combined with 0.5mg dihydroergotamine is given subcutaneously 3 times daily, or by monitoring the 3 subcutaneous doses of heparin in order to maintain an adjusted activated partial thromboplastin time (APTT) of around 50 to 70 seconds. Low molecular weight heparins have been produced by a variety of techniques and their molecular weights range from 3000 to 9000 daltons. These preparations have a ratio of anti-factor Xa activity to anti-factor IIa activity of about 4, while the ratio for unfractionated heparin is 1. After intravenous administration of low molecular weight heparin, the half-life of the anti-factor Xa activity is considerably longer than for unfractionated heparin, while the anti-factor IIa half-lives are similar. In contrast to unfractionated heparin, low molecular weight heparin is completely absorbed after subcutaneous administration and its biological half-life is almost twice as long. In spite of certain differences with regard to the ratio between factor Xa and IIa inhibition, the various low molecular weight preparations show a rather similar absorption pattern. The bioavailability of all low molecular weight heparin fractions is substantially higher than that of unfractionated heparin, which renders their use more simple. Low molecular weight heparins less readily enhance platelet aggregation although there is no evidence that low molecular weight heparins are less antigenic or that they do not interact with platelet IgGFc receptor. A lower bleeding incidence for equivalent antithrombotic efficacy of fractionated heparins when compared to unfractionated heparins has yet to be established in humans.(ABSTRACT TRUNCATED AT 400 WORDS)
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