Study of anticoagulant mechanism of low molecular weight heparin

The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and ATIII was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and ATIII with stronger affinity to ATIII than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and ATIII with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, ATIII did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between ATIII and FR-860, but not that between ATIII and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, ATIII and thrombin.     

Subcutaneous treatment of deep venous thrombosis with low molecular weight heparin. A dose finding study with LMWH-Novo

Treatment of deep venous thrombosis with low molecular weight heparin (LMWH-Novo, Logiparin) was carried out with two different doses of Logiparin, 75 XaI U/kg b.w. twice daily and 150 XaI U/kg b.w. once daily subcutaneously for 5 days. Simultaneously warfarin was given from the first day of heparin treatment. Mean age of the twenty patients was 65 years and one third was females. No serious side effects, hematomas, pulmonary emboli or signs of recurrent thrombosis occurred during treatment with either dose regime. Venografic assessment with Marder scoring one week after initiation of Logiparin treatment showed a slight not significant improvement apparent in 40 % of the patients. The activities of F-IIaI and F-XaI in the blood plasma were found to increase after injection of Logiparin. These two parameters seem to be the most suitable for monitoring the effect during treatment. For future studies on the therapeutic effect of Logiparin in deep venous thrombosis a single dose of 150 to 200 F-XaI activity per 24 hours seems to be most suitable.     

Prevention of catheter thrombosis increases survival,but does not modify lung injury in rats receiving long-term parenteral nutrition

It has previously been shown that rats receiving total parenteral nutrition (TPN) or each component of TPN die within 40 days of treatment. Central catheter thrombosis and lung injury were constant findings. The aim of the present study was to examine the impact of central thrombosis on lung injury and survival in rats receiving long-term parenteral nutrition. In the first part of the study TPN was infused via the jugular vein and incidence of central venous thrombosis and rate of survival were recorded. Addition of low molecular weight heparin (LMWH) reduced central thrombosis from 6 out of 7 animals to 2 out of 7 animals (p=0.027) and increased survival from 17.1±4.5 days to 32.4±4.9 days (p=0.04). In the second part of the study four infusion groups were established. Group 1 (controls) received saline 100?mL/kg/day via the jugular vein (n=6). Group 2 received Intralipid&;lt;formula&;gt;^®&;lt;/formula&;gt; 40?mL/kg/day via the jugular vein (n=7). Group 3 received Intralipid 40?mL/kg/day via the portal vein (n=7). Group 4 received Intralipid 40?mL/kg/day with added LMWH 70?U/kg/day (n=7). Lung injury and occurrence of central thrombosis were investigated. Lung injury was assessed by measuring pulmonary arterial pressure (Ppa), clearance of serotonin by the vascular endothelium and the capillary filtration coefficient (CFC). Either infusion via the portal vein or the addition of LMWH to the infusion via the jugular vein prevented central thrombus formation, but the lung injury was not modified by this method compared with infusing Intralipid via the jugular vein without LMWH. In conclusion, central thrombus formation contributes to death in rats receiving parenteral nutrition. The mechanism of the injurious effect of central thrombosis remains unknown, but central thrombus formation seems not to increase lung injury caused by Intralipid.     

Influence of thromboembolism prophylaxis by low molecular weight heparin CY 216 (fraxiparine®) on several parameters of haemostasis in patients under dialysis and receiving either unfractionated heparin or CY 216

The hemorragic risk of an association of the low molecular weight (LMWH), Fraxiparine® injected intravenously at the dose of 7.500 AXaICU or of unfractionated heparin (UFH) injected intravenously at the usual dose used during hemodialysis (3.750 ± 1.280 IU + 1.000 IU after 2 hours of dialysis) to the subcutaneous administration once daily of a thromboembolism preventive dose of Fraxiparine (7.500 AXaICU) was evaluated on the modification of the following hemostasis parameters : thrombin time, activated partial thromboplastin time (APTT), anti Xa activity, in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevented efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induced a significant increase of the thrombin time and of the APTT, so explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the potential hemorrhagic risk. Nevertheless the association of SC and IV Fraxiparine 7 500 AXaIC u seems preferable to the association of SC Fraxiparine with UFH.