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H K Breddin

Publications and source records attributed to H K Breddin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Regression of deep vein thrombosis by i.v.-administration of a low molecular weight heparin--results of a pilot study.

Twenty-five patients with phlebographically confirmed deep vein thrombosis of the lower limb were treated with intravenous infusions of low molecular weight heparin for 7 to 29 days. The mean dosage was 15.2 +/- 3.0 Uanti-Xa (equivalent 7.6 +/- 1.5 U-aPTT). Phlebograms were taken before, during and after the treatment with low molecular weight heparin and evaluated using the score system of Marder. Nearly complete recanalization of the occluded veins was found in six (24%) patients, improvement of the Marder score of 60 to 90% was found in four patients and of 30 to 60% in seven patients, while eight patients remained unchanged. With an average dose of 15.2 I.U./kg/h the heptest was prolonged to 70 to 120 seconds while the aPTT-level did not significantly increase. tPA-antigen-levels increased significantly in most of the patients after the third day of treatment, while PAI-activity remained unchanged. A positive conclusion between the decrease of the Marder score and the duration of treatment was found. Thus the low molecular weight heparin used in this investigation proved to be effective and safe in treating deep vein thrombosis.

Adult↗
PubMed1994

Laboratory monitoring of new antithrombotic drugs.

This article examines laboratory methods that are used or may be used to monitor newly developed heparins, low-dose vitamin K antagonists, new thrombin inhibitors such as recombinant hirudin, and oligopeptide thrombin inhibitors (some of which it is hoped will be orally active), thromboxane receptor antagonists, glycoprotein IIb-IIIa inhibitors, and ticlopidine-like structures.

Blood Coagulation Tests↗
PubMed1994

The antithrombotic effect of thromboxane receptor antagonist HN 11500 on thrombus formation in laser thrombosis model and platelet function tests.

The effect of thromboxane receptor antagonist HN 11500 (Chemie Linz AG, Austria) on thrombus formation in laser thrombosis model and platelet function test has been studied. In this study HN 11500 was a potent antithrombotic agent significantly inhibiting thrombus formation in venules in doses higher than 5 mg/kg after i.v. and 10 mg/kg after oral administration. Lower doses were needed to obtain the same antithrombotic effect when arterioles were investigated. The antithrombotic effect of minimal effective doses of HN 11500 lasted longer than 8 hours in venules and more than 12 hours in arterioles. After oral feeding of this thromboxane receptor antagonist in doses 5 mg/kg, antithrombotic effect in investigated arterioles lasted longer than 16 hours but less than 20 hours. When different doses of HN 11500 were injected i.v. together with r-Hirudin or LMWH CY 216 the inhibitory effect on thrombus formation in venules was stronger and observed with lower doses of HN 11500. In vitro study HN 11500 inhibited platelet adhesion to the siliconized glass, bovine extracellular matrix as well as ADP and collagen mediated platelet aggregation. Lower concentration of this agent were needed to inhibited platelet adhesion to the extracellular matrix than platelet adhesion to the siliconised glass, and ADP and collagen induced aggregation.

Animals↗
PubMed1994

[Antithrombotic properties of heparin independent of its anticoagulant activity].

Antithrombotic effects of two glycosaminoglycans: LMWH-Fraxiparin (Sanofi) and UFH Heparinum (Polfa) have been studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats. Thrombus formation was induced in small mesenteric venules 25-30 microns in diameter using argon laser. An interference contrast system based on a Leitz Orthoplan microscope was used for the evaluation of thrombus formation. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis model. Fraxiparin and UFH showed doses dependent antithrombotic effect in the laser model. Fraxiparin in minimal dose 16 aXa/kg and UFH in minimal dose 15 IU/kg 30 min after i.v. injection to the rats markedly inhibited thrombus formation in small mesenteric venules. Antithrombotic effect of the administration of minimal effective doses of both glycosaminoglycans lasted longer than 4 hours but less than 6 hours. Protamine injected in a dose 1 ml per 5000 U/heparin neutralized anticoagulant activity of both heparins in rat plasma but did not inhibit the antithrombotic effect in laser thrombosis model. After the injection of protamine antithrombotic effect of the investigated glycosaminoglycans was weaker but still observed. Further studies are needed to clarify the factors which are responsible for the antithrombotic effect of heparins after neutralization of their anticoagulant activity (inhibition factors: IIa and Xa).

Animals↗
PubMed1994

Acetylsalicylic acid--reocclusion--prophylaxis after angioplasty (ARPA-study). A randomized double-blind trial of two different dosages of ASA in patients with peripheral occlusive arterial disease.

We report on a randomized controlled clinical trial in patients with peripheral occlusive arterial disease who have been successfully treated with angioplasty. The efficacy and the rate of side effects of two doses of ASA (300 mg vs. 1000 mg daily) have been compared during a treatment period of 6 months after angioplasty. It was planned to include a total of 600 patients in the trial. A predefined interim analysis of 200 patients which was performed after the actual inclusion of 218 patients showed identical reocclusions rates and a very similar frequency of side effects in both treatment groups. The study was then terminated since it was not expected that further continuation would lead to a relevant difference between the two treatment groups concerning efficacy or side effects. Patients already included in the trial at the interim evaluation were included in the final analysis, leading to a total number of 223 patients. Finally 112 patients had been randomized to receive a daily dose of 300 mg ASA and 111 patients to receive 1000 mg ASA. Reocclusions occurred in 18 patients (16%) on 300 mg of ASA/day and in 20 patients (18%) receiving 1000 mg ASA/day. The study was interrupted because of side effects in 27 patients (24%) in the 300 mg/day group and in 27 patients (24%) in the 1000 mg/day group. Mostly subjective gastric complaints were the cause of interruption in 17 patients (15%) in the 300 mg group and in 21 patients (19%) receiving the higher dose regimen. So the reocclusion rate was identical in both dosage-groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1993

Functional studies on platelets of a patient with an acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIB/IIIA complex.

Platelet functions have been studied of a 63 year old woman with a severe acquired thrombopathy. The platelets did not adhere to siliconized glass. Aggregation could not be induced by either ADP (1 microM) nor collagen (2 micrograms/ml), no release of serotonin was found under these conditions. Thrombin caused only a weak aggregation response. Quantitative analysis of platelet actin revealed a very low total actin content (473 micrograms/10(9) platelets) and an extremely low F-actin value (3% of total actin). Stimulation of platelets with 0.1 U/ml thrombin for 3 min resulted in an increase of only 5% F-actin, whereas ADP and collagen did not induce any actin polymerization. Ca2+ movement in the patient's platelets is severely impaired after ADP and collagen stimulation, whereas a normal Ca2+ movement was obtained by 0.1 U/ml thrombin. The inhibition of the functions of normal platelets (aggregation and actin polymerization) by addition of patient's serum (5-10% final concentration) points to receptor blockade by platelet autoantibodies in the patient's serum. The antibody was purified by adsorption on Protein-A-Sepharose. Addition of IgG-suspension (5% final concentration) to washed control platelets resulted in similar effects on aggregation and actin polymerization compared to the effects of patient's serum.

Actins↗
PubMed1993

Treatment of patients with peripheral arterial occlusive disease Fontaine stage IV with intravenous iloprost and PGE1: a randomized open controlled study.

In a randomized open controlled study the clinical effects and tolerability of prostaglandin E1 (PGE1) and the stable prostacyclin (PGI2) analogue, iloprost in the management of diabetic and non-diabetic patients with advanced peripheral arterial occlusive disease (PAOD Fontaine stage IV) were compared. 267 patients were enrolled in this multicentre study and treated for 21-28 days, either by daily infusions of 6 h with iloprost or 2 x 2 h with PGE1. At the end of treatment patients were assessed for evidence of improvement of trophic lesions, relief of rest pain and change of global clinical status. 228 patients were considered as evaluable for efficacy analysis, which revealed 52.7% responders in the iloprost group and 43.1% for PGE1 (p = 0.148). Whereas iloprost showed similar effects in diabetics and non-diabetics (53.3% and 51.4% response rates, respectively), the diabetics treated with PGE1 had a considerably poorer outcome (36.6% versus 53.3%). At 6 months follow-up 62.2% of patients in both groups were alive with a viable limb. Slightly more iloprost patients underwent major amputation (32.1% versus 27.2%), but the number of deaths was reduced by 50% in the iloprost group compared to the PGE1 group (7.5% versus 14.6%, p = 0.10). Side-effects such as headache, flushing and gastrointestinal symptoms were significantly more common in the iloprost group (73.9%) than in the PGE1 group (31.0%), particularly during the first 3 days of dose titration. No specific toxic or unexpected reactions were reported in either group.

Adult↗
PubMed1993

Low molecular weight heparins--state-of-the-art and unsolved issues.

Low molecular weight heparins are well established in the prophylaxis of deep vein thrombosis in patients with general surgery, in high risk patients undergoing elective hip surgery or emergency surgery and also in patients with an enhanced risk of thrombosis who are treated in medical wards. There are, however, many possibilities for improving prophylaxis and treatment with LMWH. The mechanisms by which low molecular weight heparins and also unfractionated heparin inhibit thrombus formation are not fully understood. The inhibition of thrombin formation and local effects at the endothelial level may be more important than antithrombin-III mediated effects on factor IIa and on factor Xa. For most low molecular weight heparins the most effective dose regimens to be used in patients at high risk have not yet been established. Low molecular weight heparins may be more effective in the treatment of deep venous thrombosis than unfractionated heparin. In the therapeutic studies published so far the major intention was to show that low molecular weight heparins can prevent the progression of deep venous thrombosis and pulmonary embolism to the same extent as unfractionated heparin. Extended treatment regimens, however, may lead to a relevant thrombus reduction. Outpatient treatment for a longer period of time with results not far from those obtained with thrombolysis seem possible especially in elderly patients. Low molecular weight heparins in their present form or modified low molecular weight heparins may be useful for long-term treatment of patients with atherosclerosis with the aim of regression of atherosclerotic lesions. New forms of application, e.g. inhalation, may render long-term treatment more feasible.

Coronary Disease↗
PubMed1993

Effects of unfractionated and low molecular weight heparin on platelet-induced thrombin formation time and platelet adhesion.

Fraxiparin induced a significant inhibition of PITT 3 and 6 hours after the injection, and a nonsignificant moderate 25% prolongation after 9 hours. UFH inhibited PITT significantly 2 and 4 hours after the injection, and after 6 and 8 hours a nonsignificant 15 to 20% prolongation was observed. In hirudinized blood platelet adhesion was significantly prolonged 3 and 12 hours after the injection of Fraxiparin. If citrated blood was used to measure platelet adhesion a significant decrease was observed 3 to 18 hours after the Fraxiparin injection. UFH significantly inhibited platelet adhesion up to 8 hours after the injection. The long duration of the inhibition of platelet adhesion may possibly be correlated with the antithrombotic effect of heparin.

Adult↗
PubMed1992

Platelet-induced thrombin generation time: a new sensitive global assay for platelet function and coagulation. Method and first results.

A new sensitive test--platelet-induced thrombin generation time (PITT)--is described, in which the formation of thrombin in partially anticoagulated platelet-rich plasma (PRP) leads to aggregation immediately followed by coagulation of PRP. 0.6 ml PRP are rotated in a disk-shaped cuvette within the light beam of a photometer. In PITT, platelets stick to the cuvette wall and, mediated by a large PRP/surface/air interface at the cuvette wall, are activated and participate in thrombin formation which leads to aggregation and clotting. The times from onset of rotation until aggregation (Ta) and until coagulation (Tc) of the PRP samples are recorded. PITT was very sensitive and detected low concentrations of unfractionated heparin (0.01 IU/ml) in vitro. PITT parameters were significantly prolonged ex vivo 2 h after oral administration of acetylsalicylic acid (0.5 g) and after single subcutaneous injections of heparin (5,000 IU). Patients receiving phenprocoumon prophylaxis had markedly prolonged Ta and Tc values (longer than 20 min, n = 23). Patients with recent thrombotic episodes had markedly shorter values than healthy volunteers. PITT may become a very sensitive global test to detect mild hemorrhagic disorders, to monitor the effects of antithrombotic drugs and to detect patients with a risk of vascular occlusions.

Adult↗
PubMed1992

Individual and combined effects of a thromboxane receptor antagonist and different antithrombotic agents in a rat microcirculatory thrombosis model.

The antithrombotic effect of a thromboxane A2 receptor antagonist (HN-11501:5-[2-(4-chlorophenylsulfonylamino)-ethyl]-2-thienylox y-acetic acid) alone and in combination with other antithrombotic agents has been studied in an experimental thrombosis model in which laser lesions are used to induce a defined thrombosis in rat mesenteric venules. The thromboxane receptor antagonist showed a significant and dose-dependent antithrombotic effect if given orally. The strongest additive thrombosis-inhibiting effect was observed after oral administration of HN-11501 at a dose of 2.5 mg/kg together with an intravenous infusion of 1 microgram/kg/h of a prostacyclin analogue (cicaprost). An additive antithrombotic effect was also observed after oral application of 2.5 mg/kg of HN-11501 and intravenous injection of 0.2 mg/kg of a low molecular weight heparin (Fraxiparine). The combination of 2.5 mg/kg of HN-11501 orally with an intravenous injection of 0.1 mg/kg molsidomine also had a significant additive effect. No significant additive effect was observed when 2.5 mg/kg of HN-11501 and 10 mg/kg of acetylsalicylic acid were orally administered simultaneously.

Animals↗
PubMed1992

[Evaluation of the antithrombotic effects of pentoxifylline, acetylsalicylic acid and low molecular weight heparin in the laser model of thrombosis].

Antithrombotic effects of different agents including acetylsalicylic acid (Asprocol/Polfa PL/), pentoxifylline (Agapurin/Spofa CS/) and low molecular weight heparin (Antixarin B. Braun, Melsungen, FRG) were studied in the laser-induced rat thrombosis model. The investigations were carried out on male Wistar rats weighing 200-300 g. Thrombus formation was induced in small mesenteric arteries 25-30 microns; using argon laser. An interference contrast system based on a Leitz Orthoplan microscope for the evaluation of thrombus formation was used. The number of laser injuries needed to induce a defined thrombus proved to be a useful way to quantitate the results in this thrombosis mode. All agents showed dose dependent antithrombotic effect in our laser model. Acetylsalicylic acid (ASA) 2 hours after oral administration markedly inhibited thrombus formation in minimal dose 50 mg/kg, pentoxifylline in dose 10 mg/kg 30 min after i.v. injection and low molecular weight heparin (Antixarin) in dose 0.1 mg/kg, 2 hours, after s.c. injection. Antithrombotic effect of administration of minimal effective doses of ASA (orally) and pentoxifylline (i.v.) lasted longer than 4 hours but less then 6 hours. LMW heparin (Antixarin) in minimal effective dose 0.1 mg/kg after s.c. injection inhibited thrombus formation in small mesenteric vessels for more than 12 hours but less than 24 hours.

Animals↗
PubMed1992

Effects of combinations of a prostacyclin analogue (Cicaprost) with different antithrombotic agents in a rat microcirculatory thrombosis model.

The antithrombotic effects of the stable PGI2-analogue Cicaprost, acetylsalicylic acid (Aspisol), the low molecular weight heparin CY 216 (Fraxiparin) and Molsidomin (Corvaton) have been investigated alone and in combinations in a thrombosis model in rats in which mesenteric venules with a diameter of 20-30 microns were injured by defined argon laser lesions. In this animal thrombosis model all agents showed a significant and dose-dependent antithrombotic effect. A strong additive effect was observed when Cicaprost was infused together with an i.v. dose of 0.1 mg/kg Molsidomin. A similar additive effect was observed after infusion of minimal effective doses of Cicaprost together with Fraxiparin. The combination of Cicaprost and Aspisol did not have any additive effect. Our results suggest that combinations of antithrombotic agents which show additive effects in animal thrombosis model may lead to a more effective prophylaxis and treatment of human venous or arterial thrombosis.

Animals↗