Heparin molecular weight dependence

Maximum labelling of heparin with F-D was achieved at 5 hours at 25 °C, pH 8.4. In the case of heparin, the efficiency of labelling was not dependent on molecular weight, but solely a function of the ratio of the concentrations of labelling reagent to monosaccharide subunit in the reaction mixture. Similar results were encountered in the labelling of dextrans of different molecular weight (9). 

In vitro platelet activation is dependent on the anticoagulant that is used for blood collection. In one study it was demonstrated that PF4 levels in platelet-poor plasma isolated after incubation without any stimuli for 1 hour at 37°C were as follows conventional heparin, 1180 ng/ml hirudin, 469 ng/ml citrate, 440 ng/ml and EDTA, 217 ng/ml (110). EDTA appears to suppress platelet degranulation. PF4 levels obtained with a low-molecular-weight heparin preparation called Frag-min were, however, comparable to those obtained with hirudin (110). 

Nesheim M., Blackburn M. N., Lawler C. M., Mann K. G. Dependence of antithrombin III and thrombin binding stoichiometries and catalytic activity on the molecular weight of affinity purified heparin. J Biol Chem 1986 261,3214-21. 

The general drawback of the Wessler model is the static nature of the venous thrombus development. To overcome this problem some investigators have developed more dynamic models with reperfusion of the occluded vessel segments after clot development. Depending on the time of test compound administration (pre- or post-thrombus initiation), the effect on thrombus growth and fibrinolysis can be evaluated. Levi et al. (1992) have used this model to assess the effects of a murine monoclonal anti-human PAI-1 antibody and Biemond et al. (1996) compared the effect of thrombin and factor Xa inhibitors with a low molecular weight heparin. 

The effects of the low molecular weight heparin enoxaparin in combination with levobupivacaine on coagulation have been studied in vitro (6). Whole blood from 10 patients treated with enoxaparin was mixed with levobupivacaine to concentrations of 2.5 gg/ml and 2.5 mg/ml, followed by thromboelastography. Levobupivacaine produced a dose-dependent reduction in clotting. The clinical implications of these findings are yet to be acknowledged larger, in vivo studies are required. 

Heparin possesses an affinity for many molecules, among which is a phospholipid-binding protein, an-nexin V. Affinity chromatography evidenced the dependence of the binding mechanism [10] von Wille-brand factors with high and low molecular weights have been separated using their different affinities toward heparin [11]. 

Unfractionated Heparin Yes Low-Molecular-Weight Heparins (LMWHs) Extracted from porcine gut mucosa or beef lung f 15,000 30-90 min (dose dependent) 1 1 SC 30-70% (dose dependent)... 

---