A STUDY OF THE ANTI-THROMBOTIC POTENTIAL OF LOW MOLECULAR WEIGHT HEPARIN LHN-1 (NOVO) IN NORMAL VOLUNTEERS

1987 ◽  
Author(s):  
R V Johnston ◽  
M Orr ◽  
A Rumley ◽  
J McLachalan ◽  
C D Forbes
Keyword(s):  
Molecular Weight ◽  
Platelet Function ◽  
Subcutaneous Injection ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Once Daily ◽  
Normal Volunteers ◽  
Fibrin Plate ◽  
Significant Measure

Studies of low molecular weight heparin have shown a molecular sized dependency of the anti-coagulant activity. We studied the effects of a low molecular weight heparin LHN-1 (Novo) with a mean molecular weight of 5-7000 daltons on the coagulation mechanism and platelet function of normal volunteers. The heparin was given for 5 days on a once daily dose of 2500, 5000 or 7500 anti-Xa units to 3 groups of volunteers and in a twice daily regime of 2500 and 5000 anti-Xa units in 2 further groups of volunteers. After subcutaneous injection LHN-1 produced a significant (p<0.01) increase in anti-Xa activity which peaked between 3-4 hours after subcutaneous injection on both once and twice daily regime. On once daily regime there was no significant measure able anti-Xa activity 24 hours after the last injection. There was a small but significant increase in both KCCT and thrombin time (p<0.01) following injection, which was also dose related. Bleeding time did not change and there was no effect on platelet function. There was a significant (p<0.01) increase in fibrinolysis as measured by the fibrin plate method. There were no bleeding problems. These findings would suggest that LHN-1 merits further clinical evaluation to confirm its anti-thrombotic and profibrinolytic potential.

Chrono-Pharmacological Study of Once Daily Curative Dose of a Low Molecular Weight Heparin (200IU antiXa/kg of Dalteparin) in Ten Healthy Volunteers

1995 ◽  
Vol 74 (02) ◽  
pp. 660-666 ◽  
Author(s):  
P Mismetti ◽  
J Reynaud ◽  
B Tardy-Poncet ◽  
S Laporte-Simitsidis ◽  
M Scully ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Healthy Volunteers ◽  
Low Molecular Weight Heparin ◽  
Pharmacological Study ◽  
Area Under The Curve ◽  
Factor Xa ◽  
Similar Efficacy ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Once Daily

SummaryLow molecular weight heparin (LMWH) is currently prescribed for the treatment of deep vein thrombosis at the dose of 100 IU antiXa/kg twice daily or at a dose of 175 IU antiXa/kg once daily with a similar efficacy. We decided to study the chrono-pharmacology of curative dose of LMWH once daily administrated according to the one previously described with unfractionated heparin (UFH).Ten healthy volunteers participated in an open three-period crossover study according to three 24 h cycles, separated by a wash-out interval lasting 7 days: one control cycle without injection, two cycles with subcutaneous injection of 200 IU antiXa/kg of Dalteparin (Fragmin®) at 8 a.m. or at 8 p.m. Parameters of heparin activity were analysed as maximal values and area under the curve.Activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and tissue factor pathway inhibitor (TFPI) were higher after 8 p.m. injection than after 8 a.m. injection (p <0.05) while no chrono-pharmacological variation of anti factor Xa (AXa) activity was observed. Thus the biological anticoagulant effect of 200 IU antiXa/kg of Dalteparin seems to be higher after an evening injection than after a morning injection.A chrono-therapeutic approach with LMWH, as prescribed once daily, deserves further investigation since our results suggest that a preferential injection time may optimise the clinical efficacy of these LMWH.

Comparison of a once Daily with a twice Daily Subcutaneous Low Molecular Weight Heparin Regimen in the Treatment of Deep Vein Thrombosis

1998 ◽  
Vol 79 (05) ◽  
pp. 897-901 ◽  
Author(s):  
Bernard A. Charbonnier ◽  
Jean-Noël Fiessinger ◽  
J. D. Banga ◽  
Ernst Wenzel ◽  
Pascal d’Azemar ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Daily Regimen ◽  
Once Daily ◽  
Daily Group ◽  
Vein Thrombosis ◽  
Deep Vein

SummaryBackground: Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation.Methods: Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens.Results: Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively.Conclusions: A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.

A RANDOMIZED, DOUBLE BLIND STUDY OF A LOW MOLECULAR WEIGHT HEPARIN (KABI 2165) ONCE DAILY AND LOW DOSE STANDARD HEPARIN TWICE DAILY, IN THE PREVENTION OF POST OPERATIVE DEEP VEIN THROMBOSIS IN GENERAL SURGERY. A French Multicenter Trial

1987 ◽  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Low Dose ◽  
Multicenter Trial ◽  
Low Molecular Weight ◽  
Double Blind ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Deep Vein

The efficacy and safety of a low molecular weight heparin (Kabi 2165) in preventing postoperative deep vein thrombosis (D.V.T.), was assessed in a double blind randomly allocated multicenter trial. 385 patients were included and analysed on a intention to treat basis. Kabi 2165 was given S.C. 24 hourly in 2 500 anti-factor Xa units and compared with standard low dose calcium heparin 5 000 i.u. S.C. 12 hourly in patients undergoing major abdominal or gynaecological surgery. The first dose was administered two hours before operation in both groups. The relevant characteristics of the patients in the two treatment groups were similar. The two groups were well matched for risk factors which could predispose to D.V.T.DVT was detected by the radioactive fibrinogen test. Venography was performed whenever a positive scan developed in a patient. Six (3,1 96) of 195 patients receiving Kabi 2165 and seven (3,7 96) of 190 patients in the standard heparin group developed D.V.T. No pulmonary embolism we re detected during the prophylactic regimens. There was no significant difference between the two groups in terms of blood loss during surgery, postoperative drainage, blood transfusion, wound haematoma. Mean hemoglobin levels and mean hematocrit values preoperatively and postoperatively (day 1 and 6) were :There were no statistically significant differences in both groups. No thrombocytopenia was reported in this study. The antifactor Xa activity was significantly higher in the Kabi 2165 group.In conclusion, Kabi 2165 once daily is as effective and safe as standard heparin twice daily in preventing postoperative D.V.T. in general surgery.

Pharmacodynamic Differences of An Anti-Xa Enriched Low Molecular Weight Heparin, AVE 5026 in Comparison to Enoxaparin and Unfractionated Heparin.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4171-4171
Author(s):  
Debra Hoppensteadt ◽  
Angel Gray ◽  
Evangelos Litinas ◽  
Brigitte Kaiser ◽  
Jawed Fareed
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Time Course ◽  
Fold Increase ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Primate Model

Abstract Abstract 4171 AVE5026 (Sanofi-Aventis, Paris, France) represents an anti-Factor (F) Xa enriched ultra low molecular weight heparin (ULMWH) (Mw=2.4 Kda; anti-FXa activity ∼160 U/mg). In comparison to Enoxaparin it has a lower anti-FIIa activity (∼2 U/mg). The oligosaccharide composition of AVE5026 also differs from Enoxaparin and other LMWHs. Besides the molecular and compositional differences, the biologic half-life of AVE5026 (18-20 hours) is significantly longer than Enoxaparin (4-6 hours). In order to compare the other pharmacodynamic differences between AVE5026, Enoxaparin and unfractionated heparin (UFH), a primate model (macaca mulatto) was used since its tissue factor pathway inhibitor (TFPI) profile is comparable to the human response. Individual groups of primates (n=6) were administered with 1 mg/kg SC of either AVE5026, Enoxaparin or UFH. Heptest and APTT measurements were determined on whole blood (WB) and plasma was analyzed for APTT, Heptest, thrombin time (TT), anti-FXa and anti-FIIa effects at varying periods up to 28 hours. TFPI antigen was measured using the assay from Stago (Parsipanny, NJ). Functional TFPI measurements were determined using the kit from American Diagnostica (Stamford, CT). In contrast to UFH, in the WB assays, neither the AVE5026 nor the Enoxaparin produced a strong effect on the APTT and TT, however both demonstrated a strong effect on the heptest assay. AVE5026 produced a much stronger effect with a longer half-life (T½=11 hrs) in comparison to Enoxaparin (T½=6 hrs). In the plasma based systems only UFH produced a measurable effect on the APTT and TT. However, in the heptest and anti-FXa assays, both AVE5026 and Enoxaparin produced a stronger effect, which was much longer with AVE5026 (2-3 fold increase). The plasma time course of TFPI antigen release was longer with AVE5026 in comparison to Enoxaparin and UFH. The ratios of immunologic to functional TFPI levels were also higher in the primates administered with AVE 5026. In the thrombin generation test, AVE5026 produced a sustained effect which lasted longer than Enoxaparin (T½ =16.8 hrs vs. 9.2 hrs.). These results show that AVE5026 produces stronger anti-FXa effects in primates which are associated with a higher circulating level of TFPI and more pronounced suppression of thrombin generation compared to Enoxaparin and UFH. Disclosures: Hoppensteadt: Sanofi-Aventis: Research Funding.

Heparin and Fibrinolysis - Comparison of Subcutaneous Administration of Unfractionated and Low Molecular Weight Heparin

1988 ◽  
Vol 59 (02) ◽  
pp. 284-288 ◽  
Author(s):  
E Eriksson ◽  
I M Wollter ◽  
B Christenson ◽  
L Stigendal ◽  
B Risberg
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Normal Saline ◽  
Low Molecular Weight Heparin ◽  
Bolus Injection ◽  
Subcutaneous Administration ◽  
Fibrinolytic System ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Diurnal Range

SummaryThe effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration.In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti- Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, ɑ2-antiplasmin, fibrinogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin.It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.

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