| 1. |
- Casslén, B, et al.
(författare)
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Plasminogen activators in the human endometrium, cellular origin and hormonal regulation.
- 1992
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 3:2, s. 133-8
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial tissue explants in culture were found to release urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). In order to identify their cellular origin and possible hormonal regulation, enriched cultures of glandular epithelial cells and stromal cells were prepared from fresh endometrium, and the cultures treated with hormones. Both epithelial and stromal cell cultures were found to secrete u-PA and t-PA. Treatment of epithelial cell cultures with oestradiol, progesterone and DH-testosterone had no effect on the secretion of t-PA or u-PA. In stromal cell cultures, on the other hand, the secretion of u-PA was significantly reduced after treatment with progesterone, whereas oestradiol and DH-testosterone had no effect. This reduction of u-PA antigen in the tissue culture medium did not result from a reduction of the relative level of u-PA mRNA in the cells, suggesting that the synthesis of u-PA was not reduced. Alternatively, an increased clearance of u-PA by the cells from the medium may explain the reduction. This in vitro observation probably reflects the in vivo reduction of u-PA in endometrial secretion during the secretory phase.
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| 2. |
- Henriksson, Anders E., et al.
(författare)
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Time course of clotting and fibrinolytic markers in acute upper gastrointestinal bleeding : relation to diagnosis and blood transfusion treatment.
- 1993
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 4:6, s. 877-80
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Tidskriftsartikel (refereegranskat)abstract
- One hundred consecutive patients with acute upper gastrointestinal bleeding were investigated. Blood coagulation and fibrinolytic activity were monitored by levels of plasma thrombin-antithrombin III (TAT) complex and plasmin-alpha 2-antiplasmin (PAP) complex in samples obtained from patients at admission with haematemesis and/or melana and in samples obtained from patients the first day after admission. Blood was transfused according to a restrictive policy. Median plasma TAT complex was significantly elevated both at admission and on the first day after admission compared with a reference group. Plasma PAP complex levels were normal at admission but decreased on the first day after admission. This decrease was independent of blood transfusion. The results indicate hypercoagulability at admission among patients with upper gastrointestinal haemorrhage reinforced by the development of a hypofibrinolytic state during the first day after admission. Restricted blood transfusion was not associated with any detectable change in blood coagulation or fibrinolysis in these patients.
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| 3. |
- Brunkwall, J, et al.
(författare)
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The effect of unfractionated and low-molecular-weight heparin on the release of prostacyclin from the arterial wall
- 1990
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 1:6, s. 641-645
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Tidskriftsartikel (refereegranskat)abstract
- Heparin is widely used as an antithrombotic agent, but one reported complication is thrombocytopenia associated with platelet aggregation. The mechanism is not fully clear but heparin interference in the prostaglandin production has been proposed. To investigate if heparin interacts with the production of prostacyclin from the vessel wall, and if low-molecular-weight heparin differs from unfractionated heparin in this respect, excised rabbit aortas were studied in a perfusion model. The vessels were perfused ex vivo for 5 x 15 min and in the last period arachidonic acid was added. Unfragmented heparin (500 IU/kg body weight) or low-molecular-weight heparin (LMWH) (500 antifactor Xa units/kg body weight) were given either 15 min before harvesting the vessels or added directly to the perfusate. The stable degradation product for prostacyclin, 6-keto-PGF1 alpha was not altered by addition of these agents. It is concluded that heparin and LMWH per se do not interact with the prostacyclin system in normal rabbit aortas in the doses studied.
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| 4. |
- Holst, J., et al.
(författare)
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Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin(TM)). An experimental investigation in healthy volunteers
- 1994
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235. ; 5:5, s. 795-803
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Tidskriftsartikel (refereegranskat)abstract
- 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-Ila 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. A continuous absorption of tinzaparin from the s.c. depot is presumably the cause of the returned activity. PS caused an 8-27% transient drop in the platelet count in all groups. This study confirms that the anti-Xa activity following i.v. and s.c. administration of tinzaparin (a LMWH) is only partially neutralizable by protamine. This is not due to insufficient dosages of the antidote, as an excess of protamine could be demonstrated ex vivo immediately after the protamine infusion. The present results suggest that protamine neutralization of tinzaparin given s.c. should be obtained with intermittent injections or continuous infusion.
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| 5. |
- Mätzsch, Thomas, et al.
(författare)
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No transplacental passage of standard heparin or an enzymatically depolymerized low molecular weight heparin
- 1991
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 2:2, s. 273-278
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Tidskriftsartikel (refereegranskat)abstract
- In 21 women who had an abortion by hysterotomy between the 15th and 23rd week of pregnancy, the possibility that unfragmented heparin or low molecular weight heparin (LMWH) passed the placental barrier to the foetus was studied. Laboratory analyses included amidolytic assays of factor Xa inhibitory activity (XaI), antithrombin III (ATIII) and a direct measurement of heparin-like substances in plasma with a competitive binding assay. The ATIII concentration in foetal plasma was about 20% of that in normal human plasma and varied considerably between individuals (2-27%). The XaI activity did not differ between the two treated groups, but the mean XaI activity of the combined groups differed from zero (P less than 0.05). If the XaI activity was corrected for the ATIII concentration, the heparin activities no longer differed significantly from zero. As the concentration of heparin-like substances were above the detection limit (0.35 microgram/ml) in 6/16 analysable samples of foetal plasma, a further 15 women who had not received any heparin were included as controls. In 12/14 analysable foetal plasmas heparin-like substances in concentrations above 0.35 micrograms/ml could be detected. Determination of heparin activity in foetal plasma is thus difficult due to the influence of endogenous ATIII on heparin assays. In conclusion, this study did not demonstrate any evidence for the passage of heparin or LMWH across the placental barrier. No differences were detected whether unfragmented heparin or LMWH had been given to the mothers. Our results also indicate the presence of an endogenous glycosaminoglycan in foetal plasma.
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| 6. |
- Mätzsch, Thomas, et al.
(författare)
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The influence of surgical trauma on factor XaI and IIaI activity and heparin concentration after a single dose of low-molecular-weight heparin
- 1991
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 2:5, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- To study the influence of surgical trauma on the XaI and IIaI activity after injection of a low-molecular-weight heparin (LMWH) 24 patients undergoing elective cholecystectomy received one subcutaneous injection of the LMWH Fragmin. Each group of eight patients received either 2,500 or 5,000 XaI U 2 h before operation or 5,000 XaI U 10 h before surgery. For comparison an additional eight patients received 5,000 IU unfragmented heparin (UH) before operation. Laboratory analyses included amidolytically measured XaI- and IIaI-activities and direct measurements of heparin. Dose-dependent increase in the XaI- and IIaI-activity with maximal levels about 3-4 h after injection was seen. Patients given the LMWH 2 h before operation had lower levels of XaI-activity 2 h after injection than those receiving it 10 h before surgery, despite the same dose given. This correlated with the heparin concentrations, where the highest concentration was measured in patients given the LMWH 10 h before surgery. In conclusion, the surgical trauma of a cholecystectomy does not seem to have any major influence on the XaI- or IIaI-activity after administration of the studied LMWH. Alterations of the absorption and/or elimination rates cannot, however, be ruled out, but are related to factors other than the operative trauma per se, such as effects of premedication or circadian rhythmic variations.
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| 7. |
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