Relationship between Biological Activity and Concentration of a Low-Molecular-Weight Heparin (PK 10169) and Unfractionated Heparin after Intravenous and Subcutaneous Administration

1986 ◽  
Vol 16 (2) ◽  
pp. 116-122 ◽  
Author(s):  
J. Dawes ◽  
L. Bara ◽  
E. Billaud ◽  
M. Samama
Keyword(s):  
Molecular Weight ◽  
Biological Activity ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Subcutaneous Administration ◽  
Low Molecular Weight

Effect of Low-Molecular-Weight Heparin (Tinzaparin) and Unfractionated Heparin on Platelet Aggregation

1996 ◽  
Vol 2 (3) ◽  
pp. 209-212 ◽  
Author(s):  
Hanne B. Ravn ◽  
Claus Bregengaard ◽  
Henrik Vissinger ◽  
Per Østergaard ◽  
Jan Holst ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Aggregation ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Ex Vivo ◽  
Subcutaneous Administration ◽  
Low Molecular Weight ◽  
Pronounced Difference ◽  
Dose Dependent

A low-molecular-weight heparin (LMWH), when anti-IIa activity was compared. In the ex vivo part Tinzaparin, was compared with unfractionated heparin of the study, a significant enhancement of ADP-induced (UFH) for their effects on platelet aggregation in vitro and platelet aggregation was observed after i.v. administra ex vivo. Both heparins showed a dose-dependent proag- tion of both Tinzaparin and UFH with no difference in gregatory effect on ADP- and collagen-induced platelet potency. Subcutaneous administration of Tinzaparin in aggregation in vitro, but LMWH was less potent. The two different doses did not have any effect on platelet differences in potency between Tinzaparin and UFH de- activity. In conclusion, Tinzaparin appears, like other pended on how the compounds were compared. The most LMWHs, to have less proaggregatory effect on platelets pronounced difference was found when molar concentra- than UFH both in vitro and ex vivo.

Pharmacodynamic Properties of Long Lasting Butyryl Heparin Derivatives in the Rabbit

1992 ◽  
Vol 67 (05) ◽  
pp. 550-555 ◽  
Author(s):  
S Saivin ◽  
C Caranobe ◽  
M Petitou ◽  
J C Lormeau ◽  
G Houin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Intravenous Injection ◽  
Low Molecular Weight Heparin ◽  
Subcutaneous Administration ◽  
Constant Infusion ◽  
Daily Injection ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
Bolus Intravenous Injection

SummaryThis paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.

Fibrinolytic and Anticoagulant Activity After a Single Subcutaneous Administration of a Low Dose of Heparin or a Low Molecular Weight Heparin-Dihydroergotamine Combination

1988 ◽  
Vol 59 (03) ◽  
pp. 388-391 ◽  
Author(s):  
V Grimaudo ◽  
A Omri ◽  
E K O Kruithof ◽  
J Hauert ◽  
F Bachmann
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Fibrinolytic Activity ◽  
Low Molecular Weight Heparin ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Clot Lysis ◽  
Low Molecular Weight ◽  
Plate Assay ◽  
Fibrin Plate

SummaryThe anticoagulant and potential profibrinolytic effect of a combination of low molecular weight heparin with dihydroergotamine (LMWH-DHE) and of unfractionated heparin was studied in eight healthy volunteers. Each volunteer received a subcutaneous injection of either LMWH-DHE (1,500 U anti-Xa of LMWH + 0.5 mg DHE), unfractionated heparin (5,000 IU) or of placebo (saline) between 7 and 8 h in the morning on three different occasions. Anti-Xa activity, and fibrinolytic activity measured by the euglobulin clot lysis time (ECLT) and by the fibrin plate assay were determined before and at different times after administration of the three substances. Anti-Xa activity in plasma reached a maximum four hours after injection of both LMWH-DHE and unfractionated heparin. LMWH-DHE showed a better bioavailability when compared to unfractionated heparin; the anti-Xa activity peak was two and a half fold higher after LMWH-DHE despite injection of a three fold lower dose of anti-Xa units. The half-life of anti-Xa activity was approximately 4 hours for LMWH-DHE but only 90 min for unfractionated heparin. The fibrinolytic activity measured by ECLT as well as by fibrin plate assay, showed a significant increase during the day reaching a peak 8–12 h after injection regardless of the product administered (including the placebo). The profile of the diurnal fibrinolytic activity curve was identical for all three substances. The increase in fibrinolytic activity, observed after administration of LMWH-DHE or unfractionated heparin, was therefore not due to these drugs but reflected the circadian physiological fluctuation of fibrinolysis.

Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  
Keyword(s):  
Molecular Weight ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Dose Adaptation ◽  
Heparin Treatment ◽  
Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Comparison of the Non-Specific Binding of Unfractionated Heparin and Low Molecular Weight Heparin (Enoxaparin) to Plasma Proteins

1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
Author(s):  
Edward Young ◽  
Benilde Cosmi ◽  
Jeffrey Weitz ◽  
Jack Hirsh
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Plasma Proteins ◽  
Low Molecular Weight Heparin ◽  
Specific Binding ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
Fixed Amount

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.

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