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P B Ostergaard

Publications and source records attributed to P B Ostergaard.

At least 19 recordsLinked to original sources
PubMed2000

The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein.

Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples were collected. The high-fat test was associated with an increase in plasma triglyceride and kallikrein concentrations and postprandial FVII activation (p<0.001). Plasma kallikrein was strongly associated with triglycerides in fasting and non-fasting samples (r2=0.74-0.87, p<0.0001), suggesting that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride-rich lipoproteins activate prokallikrein postprandially, which might form an important initial event in FVII activation after consumption of high-fat meals.

Adult↗
PubMed1997

An enzyme linked immunosorption assay for tissue factor pathway inhibitor.

An assay for the quantification of full-length and carboxy-terminus truncated tissue factor pathway inhibitor (TFPI) has been developed. The assay is a classical two-antibody sandwich assay with a monoclonal capture antibody directed against the third Kunitz-type domain of human TFPI and a polyclonal rabbit peroxidase-labelled anti-human TFPI detecting antibody. The assay is sensitive to full-length and carboxy-terminus truncated TFPI with intact third Kunitz-type domain, but not to two-domain TFPI. TFPI associated with lipoproteins is not or only sparsely detected and TFPI in complex with factor Xa only partially measured. The assays gives linear reference curves in the dose range of 5 to 100 ng/ml in a double logarithmic plot. The normal range assessed from analyses on citrated plasma from 81 normal human donors is 7.8 to 26.0 ng/ml (average +/- 2 SD, log-normal distribution). There is no statistically significant difference between TFPI levels measured in 10 fasting and 10 non-fasting individuals. The reproducibility of the assay is about 5.6-5.9% (relative standard error) and the within-days and between-day reproducibilities are 4.7-5.1% and 5.9-8.5%, respectively. The assay is in very good agreement with a commercial ELISA assay recently marketed. A robust, reproducible and convenient ELISA assay for the determination of full-length and three-domain TFPI has been developed.

Animals↗
PubMed1997

Proteoglycan expression in the normal rat kidney.

Proteoglycans constitute a heterogenous group of complex macromolecules, consisting of a backbone core protein and a variable number of sulfated polysaccharide side chains covalently linked to the core. A dual function for these polyanionic glycosaminoglycans in kidney physiology has been proposed: to maintain a fixed negative charge in the glomerular filtration barrier, and to bind and sequester cytokines essential for renal development and function. With the aim of identifying proteoglycan genes expressed in kidney glomeruli, we have performed in situ hybridization for selected proteoglycan core proteins in the normal rat kidney. Syndecan-4, glypican-1 and biglycan were all expressed in normal glomeruli, whereas syndecan-1, perlecan and versican mRNAs were confined to the papillary area. Decorin mRNA was detected in interstitial cells found between tubuli and surrounding larger vessels. No signal for betaglycan mRNA could be detected. By hybridizing adjacent sections with a probe for the podocyte-specific PTPase GLEPP-1, the glomerular cells containing mRNA for syndecan-4 and glypican-1 could be identified as podocytes, whereas the cells expressing biglycan were identified as mesangial cells. These results demonstrate that seven out of the eight proteoglycans investigated are expressed in the normal kidney in detectable amounts and, importantly, that each proteoglycan gene shows a unique pattern of expression. The constitutive expression of syndecan-4, glypican-1 and biglycan in glomerular cells points to a role for these polyanionic molecules in maintaining the integrity of the glomerular filtration barrier.

Amino Acid Sequence↗
PubMed1996

Pharmacokinetics and delayed experimental anti-thrombotic effect of two domain non-glycosylated tissue factor pathway inhibitor.

Tissue Factor Pathway Inhibitor (TFPI) is a naturally occurring inhibitor of the TF-FVIIa induced coagulation in the presence of FXa. Recombinant two domain TFPI, where Asn 117 on the FXa-inhibitory domain was exchanged to a Gln yielding non-glycosylated TFPI (117QTFPI1-161), was evaluated regarding pharmacokinetics and delayed antithrombotic potential in the rabbit. Pharmacokinetic study; 117QTFPI1-161 vs glycosylated TFPI1-161. Three rabbits/group were used and received 1,0 mg/kg a bolus iv injection. Plasma-TFPI was measured for three hours. The alpha-phase half-life was similar, the beta-phase half-life was close to four times longer for 117QTFPI1-161 (37 vs 10 min). Clearance of 117QTFPI1-161 was nearly two times lower (45 vs 21 ml/kg/min). Delayed anti-thrombotic study; 10 rabbits/group were used. 5 Groups; placebo + placebo, placebo + LMWH60 anti-Xa IU/kg, placebo + 117QTFPI1-161 0,25 mg/kg, 117QTFPI1-161 1,0 and 4,0 mg/kg + placebo. First injection 60 min prior to the second one, which coincided with the thrombus induction. The experimental thrombosis used combines a chemical destruction of the endothelium with a partial restriction of the bloodflow in the jugular veins. The thrombusweight was significantly reduced in LMWH and 117QTFPI1-161 1,0 and 4,0 mg/kg groups (0,6-2,6 vs 11,8 mg). Frequency of occlusive thrombosis was significantly reduced in the LMWH and 117QTFPI1-161 4,0 mg groups. All groups significantly effected the aXa-assay, the LMWH-group the most (0,85 IU/ml). LMWH was the only substance to prolong the dilute-PT-assay at the different timepoints. Absence of glycosylation increases the beta-phase half-life and decreases clearance of two domain TFPI. 117QTFPI1-161 (1,0 and 4,0 mg) has an antithrombotic effect indistinguishable from LMWH even though given 60 min before the thrombusinduction but with a considerable less effect on anti-Xa, APTT and no effect on dilute-PT. Glycosylation of TFPI influences the pharmacokinetics but not the antithrombotic capacity in this experimental setting.

Animals↗
PubMed1996

Increased tissue factor pathway inhibitor activity in IDDM patients with nephropathy.

OBJECTIVE: Tissue factor pathway inhibitor (TFPI) is bound to vascular endothelium (presumably to heparan sulfate) and circulates in complex with plasma lipoproteins. It directly binds and inhibits factor Xa. The purpose of the study is to investigate whether plasma TFPI activity is altered in IDDM and nephropathy and to evaluate the possible determinants of the alteration. RESEARCH DESIGN AND METHODS: We assessed plasma concentration of TFPI (total, truncated, and domain 3 TFPI) and plasma activity of factor Xa inhibition in nondiabetic control subjects (n = 22) and in IDDM patients with normoalbuminuria (urinary albumin excretion rate [UAE] < 30 mg/24h, n = 17), incipient nephropathy (UAE 30-300 mg/24 h, n = 17), clinical nephropathy (UAE > 300 mg/24h, n = 25). RESULTS: Total, truncated, and domain 3 TFPI concentrations were increased in IDDm patients compared with those in control subjects and were more pronounced in IDDM patients with nephropathy. Plasma activity of factor Xa inhibition measured by HEPTEST (Haemachem, St. Louis, MO) assay was increased in IDDM patients, especially in those with nephropathy. TFPI-dependent factor Xa inhibition, obtained as the difference in clotting time with and without adding activity-neutralizing anti-TFPI antibody to samples, was increased in IDDm patients with nephropathy. This was, however, not sufficient to inhibit the biological activity of factor Xa as demonstrated by increased levels of prothrombin fragment 1 + 2. LDL cholesterol and HbA1c were independently correlated to plasma TFPI. CONCLUSIONS: Inhibition of factor Xa activity is increased in IDDM patients with nephropathy, mainly because of increased plasma TFPI activity. The increased plasma TFPI activity in these patients may be associated with and regulated by LDL in plasma and metabolic control. The anticoagulant activity of TFPI may attenuate the hypercoagulable state in diabetes but does not seem to be able to normalize hemostasis.

Adult↗
PubMed1996

Experimental haemorrhagic effect of two-domain non-glycosylated tissue factor pathway inhibitor compared to low molecular weight heparin.

The glycosylated multivalent three-domain Kunitz inhibitor TFPI is a natural inhibitor of tissue factor-FVIIa complex in the presence of FXa. TFPI has an experimental antithrombotic capacity indistinguishable from LMWH in a prophylactic dose, regardless of glycosylation and of the third domain. An inherited equilibrium between antithrombosis and haemorrhage exists. The aim of the study was to evaluate whether a two-domain non-glycosylated TFPI (117QTFPI1-161) has a bleeding potential in a rat gastric mucosa model. Groups; placebo, LMWH (tinzaparin) 60 and 250 anti-Xa IU/kg and 117 QTFPI1-161 1.0 and 10.0 mg/kg, given i.v. (bolus injection), randomised double dummy design. All actively treated groups significantly prolonged both the bleeding volume (493-984 microliters) and the bleeding time (10-20 min) compared to placebo (41 microliters, 2 min). It was not possible to distinguish a difference between the lower dose of LMWH and 117QTFPI1-161 in either parameter (p = 0.23-0.71). The two doses of 117QTFPI1-161 caused elevation of plasma-TFPI, 18 and 150 times baseline value. Both LMWH doses (0.6-3.2 anti-Xa IU/ml) and both 117QTFPI1-161 doses (0.2-2.7 anti-Xa IU/ml), caused significant effect in the anti-Xa assay, however 117QTFPI1-161 significantly less. Only the largest dose of 117QTFPI1-161 caused significant prolongation in the APTT assay (34 s). Both doses of LMWH caused significant prolongation (60-300 s). LMWH was the only substance to prolong the dilute-PT assay. Non-glycosylated two-domain 1.0 mg/kg TFPI, yielding supraphysiological plasma concentration, has an experimental haemorrhagic potential indistinguishable from LMWH in a prophylactic dose. The effect mediated by this type of TFPI could primarily be due to an inhibition of FXa.

Animals↗
PubMed1995

Structure of heparin fragments with high affinity for lipoprotein lipase and inhibition of lipoprotein lipase binding to alpha 2-macroglobulin-receptor/low-density-lipoprotein-receptor-related protein by heparin fragments.

Heparin-derived deca- and octa-saccharides were subjected to affinity chromatography on lipoprotein lipase-Sepharose and the fractions eluted at high salt concentration were analysed by strong-anion-exchange chromatography. Two high-affinity decasaccharides were isolated and the structure determined by one- and two-dimensional 1H-n.m.r. spectroscopy. The affinities of 3H-labelled low-molecular-mass heparin and size-fractionated deca-, octa-, and hexa-saccharides for lipoprotein lipase immobilized on microtitre plates were determined from saturation curves. From competition experiments the affinities of unlabelled heparins and pure deca- and hexa-saccharide fragments were determined. The binding was size- and charge-dependent, but structural dependency was also indicated. Thus substitution of a 2-O-sulphated L-iduronic acid with D-glucuronic acid was less important than the sulphation pattern of the D-glucosamine residue for affinity for lipoprotein lipase. Heparin inhibits binding of lipoprotein lipase to alpha 2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein. The effects of size, charge and structure for this inhibition were studied. The ability of the heparin fragments to inhibit binding correlated with their affinity for lipoprotein lipase. This indicates that the inhibition of the binding of lipoprotein lipase to alpha 2-macroglobulin-receptor/low-density-lipoprotein receptor-related protein by heparin is exclusively mediated by binding of heparin to lipoprotein lipase.

Amino Acid Sequence↗
PubMed1995

Isolation and characterization of hexasaccharides derived from heparin. Analysis by HPLC and elucidation of structure by 1H NMR.

Four hexasaccharides representing major structural sequences of heparin were isolated and characterized after degradation of heparin by heparinase. The structures were determined from two-dimensional 1H NMR spectroscopy including TOCSY (total correlated spectroscopy), COSY (correlated spectroscopy), and ROESY (rotating frame nuclear Overhauser enhancement spectroscopy) methods, providing new data on hexasaccharides. One of the hexasaccharides, the last eluting component from anion exchange chromatography, was derived from the tri-sulfated repeating disaccharide, alpha-L-idopyranosyluronic acid 2-sulfate-(1-->4)-2-amino-2-deoxy-D-glucopyranose 6,N-disulfate, and having the structure delta UAp2S-(1)-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L- IdoAp2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L- IdoAp2S-(1-->4)-alpha-D-GlcNp2S6S. The second hexasaccharide contained a nonsulfated D-glucuronic acid unit instead of the L-iduronic acid adjacent to the reducing end, and having the structure delta UAp2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L- IdoAp2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-beta-D- GlcAp-(1-->4)-alpha-D-GlcNp2S6S. The last two hexasaccharides were obtained in lower yield and they have not been isolated and characterized before. The structure of the third saccharide corresponded to a trimer of the repeating disaccharide except for the lack of a 6-O-sulfate group at the reducing end glucosamine residue; deltaUAp2S-(1-->4)-alpha-D-Glcnp2S6S-(1-->4)-alpha-L- IdoAp2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L-IdoAp2S -(1-->4)-alpha- D-GlcNp2S. The fourth and last hexasaccharide were less sulfated and the following structure was established delta UAp2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L- Idop2S-(1-->4)-alpha-D-GlcNp2S6S-(1-->4)-alpha-L- IdoAp-(1-->4)-alpha-D-GlcNpAc6S. Analysis of the ROESY spectra revealed conformational difference of the glucosidic linkage alpha-L-IdoAp-(1-->4)-alpha-D-GlcNp between the hexasaccharides and longer heparin chains.

Carbohydrate Sequence↗
PubMed1994

Pharmacokinetics of tinzaparin (Logiparin)--a low molecular weight heparin--after single and repeated intravenous administration in rats.

After a single and repeated i.v. injections of 1 mg/kg 3H-radiolabelled tinzaparin once daily to rats for 7, 14, and 21 days, drug-related radioactivity in plasma, tissues, urine and faeces was measured by use of liquid scintillation counting. The decay in plasma could be described by a three-compartment model with half-lives of the two distributive phases and the terminal elimination phase of 15 min, 90 min, and 37 hrs, respectively. The peak plasma concentration did not change during repeated dosing, as opposed to the trough concentration which increased 3 fold. The decay in tissues was significantly different from that in plasma, and showed less fluctuations. Drug-related radioactivity accumulated gradually with repeated dosing, reaching accumulation ratios between 5 and 9, when based on trough concentrations. Slow elimination was observed from tissues, and significant amounts were still present 14 days after discontinuation of the repeated dosing. In the liver, the concentrations were almost constant during a dosing interval. After a single injection, 86% and 4% of the administered radioactive dose were excreted in urine and faeces over 7 days, respectively, the majority being recovered during the first 24 hrs, demonstrating that the major route of elimination was by renal excretion. The molecular mass distribution of radioactivity in urine was similar but not identical to the injected test substance. It was shifted slightly towards lower molecular mass and had no anti-factor Xa activity, suggesting that the heparin was either inactivated, presumably by desulphation, or that the antithrombin binding portion of the drug was cleared through a different route.

Animals↗
PubMed1994

Binding of low molecular weight heparin (Tinzaparin sodium) to bovine endothelial cells in vitro.

Heparinase depolymerized low molecular weight (LMW) heparin (Tinzaparin sodium, Logiparin) was radiolabelled by catalytic tritiation to high specific radioactivity and the binding to fetal bovine heart endothelial (FBHE) cells was studied at 4 degrees C and 37 degrees C. The binding was found to be time dependent and saturable. Two classes of binding sites could be distinguished from Scatchard analysis at both temperatures: One with high affinity (KD = 0.027 microM at 4 degrees C, KD = 0.012 microM at 37 degrees C) and another with very low affinity (KD = 69 microM at 4 degrees C and 37 microM at 37 degrees C). The binding reversibility was affected by the temperature indicating internalization of a fraction of the bound LMW heparin. At 4 degrees C only 11% of the specifically bound heparin was bound irreversibly. At 37 degrees C the non displaceable fraction accounted for 28% of the specifically bound LMW heparin. This work demonstrates that tinzaparin sodium binds specifically to endothelial cells. This binding may be useful in interpreting pharmacokinetic properties of this low molecular weight heparin.

Animals↗
PubMed1994

Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers.

The aim of the present study was to investigate whether tinzaparin sodium (a low-molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c., 175 anti-Xa IU tinzaparin/kg b.w. s.c., or 1 ml of saline s.c. PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0.5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-IIa activities were seen following i.v. tinzaparin. In the s.c. groups 60-65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65-75%), anti-IIa activity (55%) and aPTT activity (35-45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis--a comparison with low molecular weight heparin.

The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161), which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2: LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the anti-thrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.

Animals↗
PubMed1993

Antithrombotic properties of a truncated recombinant tissue factor pathway inhibitor in an experimental venous thrombosis model.

The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1-161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0-10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin.

Animals↗
PubMed1992

Effect of tissue factor pathway inhibitor (TFPI) in the HEPTEST assay and in an amidolytic anti factor Xa assay for LMW heparin.

Both the HEPTEST and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) on these assays. The HEPTEST determinations were performed on an ACL 300 R Clottimer using the APTT program which resulted in a longer incubation time with factor Xa than recommended by the manufacturer. rTFPI added to plasma prolonged the HEPTEST clotting time markedly, but had only a little effect in the amidolytic assay. Antibodies against TFPI (anti-TFPI) abolished these effects. The effect of adding rTFPI and Logiparin was additive. When anti-TFPI IgG was added to samples of normal plasma, a statistically significant shortening of the HEPTEST clotting time was seen. When anti-TFPI was added to plasma samples from volunteers who had received Logiparin by subcutaneous or intravenous injection, then the HEPTEST clotting time was shortened considerably. For some samples the clotting time was halved. These experiments show that the HEPTEST clotting time is prolonged not only by heparin-antithrombin III, but also by TFPI released by heparin injection.

Amides↗
PubMed1991

Development and validation of a size exclusion chromatography method for determination of molecular masses and molecular mass distribution in low molecular weight heparin.

A precise and rugged high performance size exclusion chromatography (HPSEC) method for determination of peak maximum molecular mass (Mp), weight average molecular mass (Mw), number average molecular mass (Mn), and molecular mass distribution (MMD) in Low Molecular Weight heparin (LMW heparin) has been developed and validated on two Ultrahydrogel 250 (ID 7, 8 mm, length 30 cm) columns in series at three laboratories using different equipment. The calibration is based on four local laboratory heparin standards with relatively narrow molecular mass distribution and Mp covering the range from 3,000 to 17,000 Da. The calibration curve describing the logarithm of the molecular mass versus retention time is linear in the range 3,000 to 17,000 Da. The precision (relative standard deviation) within-run and between-run is better than 2%. The between-laboratory variation is below 5%, 3% and 8% for Mp, Mw and Mn, respectively. This method is reproducible, rugged, and fast and is suited for the determination of average molecular masses and molecular mass distribution of LMW heparins on a routine basis.

Calibration↗
PubMed1991

Pharmacokinetics of a low molecular weight heparin, logiparin, after intravenous and subcutaneous administration to healthy volunteers.

In six healthy volunteers we have estimated the pharmacokinetic parameters of the anti factor Xa (AXa) and anti factor IIa (AIIa) activities of a LMW heparin, Logiparin. For the AXa the following parameters were estimated in a 1-compartment model (mean and 95% confidence limits in brackets): elimination half life 82 minutes (60-127 min), absorption half life (s.c. inj.) 200 minutes (137-368 min), bioavailability 90% (24-156%), and apparent volume of distribution 3.9 l (3.1-5.2 l). The plasma activity was linearly correlated to the dose given and to the body weight of the volunteer. For the AIIa the parameters estimated in a 1-compartment model were: elimination half life 71 minutes (52-115 min), absorption half life 257 minutes (133-3442 min), bioavailability 67% (44-90%), and apparent volume of distribution 10.1 l (7.2-16.7 l). The plasma activity was dependent on dose and body weight but it also seemed to be influenced by individual factors. This study shows that the absorption rate is the rate limiting factor and the explanation for the long lasting effect of this LMW heparin after subcutaneous injection. The slow absorption rate and the high bioavailability are probably the major advantages of LMW heparins compared to conventional heparin.

Absorption↗
PubMed1987

The effect of low molecular weight heparin on experimental thrombosis and haemostasis--the influence of production method.

Three low molecular weight heparins prepared by enzymatic depolymerization, chemical degradation, and fractionation, respectively were studied in experimental thrombosis and haemostasis models in vivo and in biological assays in vitro. The three low molecular weight heparins, which had comparable molecular weight distributions, showed very similar activities both in vitro and in vivo. All three showed dose dependent thromboprophylactic effect. The antithrombotic effects of the low molecular weight heparins and conventional heparin administered in the same dose (30 XaI u/kg b.w.) did not differ. Neither LMW heparin nor conventional heparin (60 or 90 XaI u/kg b.w.) showed significant effects on the haemostatic plug formation time in the rabbit mesenteric microcirculation. These experiments confirm that low molecular weight heparins are potential antithrombotic drugs, which by intravenous administration have effects similar to those of standard heparin. The method of preparation seems to be of no or minor importance, at least if the molecular weight distributions of the products are similar.

Animals↗