Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass.

BACKGROUND: Trauma is followed by an increased plasma clearance and oxidation of exogenous fat but the underlying mechanism is not fully understood. AIM: To examine the influence of a surgical trauma on the plasma elimination of exogenous triglycerides (TG) and its relationship with lipoprotein lipase (LPL) activity and LPL mass. METHODS: Nine patients underwent a hypertriglyceridaemic clamp and a lipolytic capacity test before and after open abdominal surgery. The infusion rate was adjusted to maintain a stable TG concentration of 4 mmol x l(-1) during 180 min. The lipolytic capacity was determined as the change in LPL activity and mass following a bolus dose of 100 IU x kg BW(-1) heparin sodium. RESULTS: Postoperatively, the plasma elimination rate of fat was 2.6 times higher (P<0.001). Infusion of lipids in the postoperative state was followed by a smaller rise in free fatty acids (P<0.05) in comparison with the preoperative situation. The postoperative basal fasting LPL activity was half of that in the preoperative state and the LPL activity rose almost two-fold during the clamp. The heparin-induced rises in LPL activity and LPL mass were similar (n.s.) before and after surgery. CONCLUSIONS: A moderate surgical trauma is accompanied by a greater than two-fold rise in plasma elimination rate of exogenous fat despite a lower basal LPL activity and a virtually unchanged LPL pattern during infusion of lipids. Our study demonstrates that although trauma may substantially enhance the fat elimination capacity a significant proportion of the infused fat is not utilized for metabolic purposes.

Long-term clinical follow-up in 265 patients with deep venous thrombosis initially treated with either unfractionated heparin or dalteparin: a retrospective analysis.

The primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i.v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the postthrombotic score was significantly higher among patients with initial proximal DVT (p = 0.0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29.4% of the patients treated with dalteparin and in 23.5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40.7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the intravenous treatment of deep venous thrombosis.

In order to study whether a low molecular weight heparin (LMWH) of mw 4000 D is effective in the treatment of deep venous thrombosis (DVT), patients with DVT verified by phlebography were randomized to treatment by continuous intravenous infusion of either unfractionated heparin (UFH) or LMWH. The initial dose was 240 U (anti F Xa)/kg/12 h. This study (study I) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated. The heparin activity measured as F Xa inhibition assayed in retrospect, was found to be much higher in the LMWH group (mean 1.6-2.0 anti F Xa U/ml) than in the UFH group (mean 0.5-0.8 anti F Xa U/ml). A second study was therefore initiated in which the DVT patients were randomly given UFH (240 U/kg/12 h) or LMWH only 120 U (anti F Xa)/kg/12 h, as initial doses (study II). In this study 27 patients could be evaluated, the mean heparin activity still being higher in the LMWH group (0.9-1.2 anti F Xa U/ml) than in the UFH group (0.5-0.7 anti F Xa U/ml). A second phlebographic investigation showed progression of thrombus size in 3 (11%) of the UFH patients of studies I and II (n = 29) and improvement in 14 (48%). There was no progression in any LMWH patient, 6 (50%) had improved in study I and 10 (77%) in study II. The mean decrease of thrombus size score (according to Marder) during treatment did not differ between the 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT).

In a prospective, randomized, open study 119 consecutive patients with phlebographically verified deep venous thrombosis (DVT) of the leg (36% distal and 64% proximal) were treated either with a low molecular weight heparin (Fragmin, Kabi-Vitrum) subcutaneously (120 anti-FXa U/kg) twice daily or standard heparin (SH) as continuous intravenous infusion (480 IU kg-1 day-1). The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2-0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection. The SH dose was modified to prolong the APTT 2-3 times. Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 +/- 12.1 to 15.7 +/- 12.7 in the Fragmin group and from 16.9 +/- 12.0 to 14.4 +/- 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings. After 22 +/- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups. We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.

Pharmacokinetics of intravenously and subcutaneously administered Fragmin in healthy volunteers.

Studies in 8 healthy volunteers showed that the low molecular weight heparin Fragmin KabiVitrum is eliminated according to first order kinetics without dose dependency after intravenous injection of doses between 40 and 120 anti-Xa U/kg. Fragmin remains in the circulation more than twice as long as unfractionated heparin (UFH). Fragmin administered subcutaneously has a bioavailability which is much greater than that of UFH. Fragmin administered subcutaneously twice a day results in a significant anti-Xa activity and provides an alternative to intravenous infusions.

Clinical experiences in the administration of a low molecular weight heparin (Fragmin, Kabi-Vitrum) to healthy volunteers and in the treatment of established deep venous thrombosis.

A low molecular weight heparin (Fragmin, Kabi-Vitrum) with a mean molecular weight of 4,000-5,000 D has been investigated in healthy volunteers and in patients with DVT. We found a T 1/2 of 4 hours and a high bioavailability after subcutaneous injection in volunteers. In a randomised study, patients with phlebographically verified DVT, 120 U(anti-FXa)/kg Fragmin injected twice daily was found to be as effective as 240 U/kg, 12 h standard heparin as continuous infusion in preventing DVT progress. No major bleedings were seen in the Fragmin group. We conclude that Fragmin administered subcutaneously twice daily results in adequate anticoagulation and is safe and practical in the treatment of DVT.

Intravenous and subcutaneous administration of Fragmin in deep venous thrombosis.

54 patients with venographically verified deep venous thrombosis (DVT) were randomized to treatment with either intravenous infusions of 240 anti-Xa U/kg/12 h unfractionated heparin (UFH) or 240 or 120 anti-Xa U/kg/12 h of the low molecular weight heparin Fragmin. Repeated venographies showed improvement in 48% of the UFH-treated patients and 50 and 77%, respectively, in the Fragmin-treated patients. Progression was seen only in the UFH-treated patients and was observed in 11%. Two bleeding complications were seen in the Fragmin group in 2 patients receiving the very high dose of 240 anti-Xa U/kg/12 h. Anti-Xa activity in plasma and activated partial thromboplastin time (APTT) does not correlate in the Fragmin-treated patients. Fragmin was as effective as UFH in preventing the progress of thrombosis in DVT. In another study 120 anti-Xa U/kg Fragmin given subcutaneously 2 times daily to 13 patients with DVT resulted in adequate anti-Xa activity but with a tendency for accumulation of the Fragmin-induced activity. Subcutaneous injections of Fragmin 2 times daily also appears to prevent the progression of thrombosis effectively.