Two hundred and seventy patients over 65 years were included in a placebo-controlled randomized double-blind trial to determine whether a small dose of a low molecular weight (LMW) heparin prevents the occurrence of deep vein leg thrombosis (DVT) diagnosed by ¹²⁵I fibrinogen scanning. LMW heparin (60 mg daily) significantly reduced the frequency of DVT from 9 to 3 percent (p = 0.03). Adverse drug reactions did not differ significantly between the 2 groups, except for the injection site hematomas that were more frequent in the LMW heparin group. In conclusion, LMW heparin appears of value in preventing the occurrence of DVT in an unselected elderly in-patient population.

The pharmacokinetics of enoxaparine, a low molecular weight heparin, was randomly studied in 12 healthy male volunteers. Doses of 20, 40, 60, and 80 mg were injected subcutaneously in randomized cross-over fashion. Anti-IIa and anti-Xa activities (using amidolytic methods), and calcium thrombin time, were measured over 36 hours. The maximum Amax of the anti-IIa and anti-Xa activities appeared 3 to 4 hours after administration. The terminal half-lives of anti-IIa and anti-Xa activities were approximately 2 and 4 hours, respectively, with no significant variation between the different doses. For the anti-Xa activity, there was a highly significant positive correlation between the dose injected and individual values of Amax (r = +0.915; P less than .001) and AUC (r = +0.913; P less than .001). Enoxaparine displays a relatively small apparent volume of distribution (about 7.0 L) and its total body clearance is about 1.25 L/hr. The mean residence time ranges from 4.6 to 7.6 hours. Thus, the pharmacokinetic profile of enoxaparine is characterized by a linear relationship between dose and absorption, a relatively low clearance and long elimination half-life, and a high anti-Xa/anti-IIa ratio.

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The depolymerized heparin fragment PK 10169 was compared with unfractioned mucosal sodium heparin. The inhibition of factors Xa and IXa by heparin and by PK 10169 was comparable on a weight base, whilst the inhibition of thrombin by PK 10169 was at least 5 times weaker than by heparin. Subcutaneous injection of PK 10169 was not followed by an increase of the thrombin time. The activated partial thromboplastin time was considerably less prolonged after PK 10169 than after heparin. Platelet count and platelet functions were not influenced by PK 10169. In vitro, the euglobulin lysis time (ELT) was shortened after addition of heparin to plasma but not after addition of PK 10169. After injection however, there was an equal shortening of the ELT by both substances. The half-life in circulation of PK 10169 was longer than the half-life of heparin. The advantages of PK 10169 over heparin are therefore the weaker influence on overall coagulation, the missing influence on platelet functions and the longer half-life in circulation.

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