Heparin LMWH

The multiple effects of UFH on the coagulation cascade may increase its potential to cause hemorrhage." Anticoagulants with more specific sites of action may confer a better safety profile. Two such anticoagulants are low-molecular-weight heparin (LMWH) and heparinoids. 

The most extensively studied drugs for the prevention of VTE are unfractionated heparin (UFH), the low-molecular-weight heparins (LMWHs dalteparin, enoxaparin, and tinza-parin), fondaparinux, and warfarin.2 The LMWHs and fondaparinux provide superior protection against VTE when... 

Mechanism of action of unfractionated heparin, low-molecular-weight heparin (LMWH), and fondaparinux. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy ... 

Initiate unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) or fondaparinux by injection (see Table 7-3 for dosing guidelines)... 

Low-molecular-weight heparins (LMWHs) may be an alternative to UFH in STE ACS. Enoxaparin may produce a modest benefit over UFH in reducing the risk of death or nonfatal MI. Enoxaparin has not been studied in the setting of primary PCI. 

Low-molecular-weight heparins (LMWHs) are fragments of UFH that are heterogeneous mixtures of sulfated glycosaminoglycans with approximately one-third the molecular weight of UFH. 

Antitrombotics and Anticoagulants (warfarin, heparin, LMWH, Factor Xa inhibitors, direct trombin inhibitors, thrombolytics, and glycoprotein... 

When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients who are anticoagulated or scheduled to be anticoagulated with low molecular weight heparins (LMWHs) or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. 

Interchangeability with heparin LMWHs cannot be used interchangeably (unit for unit) with unfractionated heparin or other LMWHs. 

Interchangeability Do not use interchangeably (unit for unit) with heparin, LMWHs, or heparinoids, as they differ in manufacturing process, anti-Xa and anti-lla activity, units, and dosage. 

Given to patients with a history of typical angina accompanied by either a past medical history of coronary artery disease or ECG/cardiac enzyme changes, low molecular weight heparins (LMWH) were more efficacious in reducing MI and revascularization, but not mortality, with fewer serious side-effects than unfractionated heparin (UFH) (see Magee et al., 2003). 

Two types of heparin are used clinically. The first and older of the two, standard (unfractionated) heparin, is an animal extract. The second and newer type, called low-molecular-weight heparin (LMWH), is derived from unfractionated heparin. The two classes are similar but not identical in their actions and pharmacokinetic characteristics. 

Low-molecular-weight fragments produced by chemical depolymerization and extraction of standard heparin consist of heterogeneous polysaccharide chains of molecular weight 2,000 to 9,000. The LMWH molecules contain the pentasaccharide sequence necessary for binding to antithrombin III but not the 18-saccharide sequence needed for binding to thrombin. Compared to standard heparin, LMWH has a 2- to 4-fold greater antifactor Xa activity than antithrombin activity. 

LMWH have higher bioavailability after subcutaneous injection than standard, heparin. LMWH binds less than heparin to plasma proteins. The clearance of LMWH is mainly renal, independent of dose and slower than metabolic clearance of heparin. 

Figure 17.2 Schematic representation of the molecular weight distribution of unfractionated heparin (UH) and of low molecular weight heparin (LMWH). In the lower part of the figure, the polysaccharide chain of heparin, the pentasaccharide sequence, and the interaction between heparin, antithrombin (AT), thrombin, and factor Xa is represented. (Reproduced from Boneu B.Thrombosis Research 2000 100 V113-20, with permission from Elsevier Science.)...

Table 17.1 Anti-factor Xa/anti-factor Ha ratio for marketed low molecular weight heparins (LMWHs)...

In contrast to unfractionated heparin, LMWHs bind weakly to endothelial cells and are cleared mainly by renal excretion. A consequence of this is that their pharmacokinetics and pharmacodynamics are linear and the pharmacodynamics effect is proportional to the dose. This makes them more predictable than standard heparin, and is the main reason why routine monitoring is not needed. Because of the predominantly renal excretion there is a risk of accumulation in patients with reduced renal function. In this group of patients it may be advisable to monitor the anti-Xa activity. 

The indirect thrombin inhibitors are so-named because their antithrombotic effect is exerted by their interaction with a separate protein, antithrombin. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the... 

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