摘要:

In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily subcutaneous administration of LMW heparin plus 2 placebo injections or 3 × 5,000 IU unfractionated (UF) heparin was given for 10 (8-11) days. The primary end point was the incidence of proximal deep-vein thrombosis or pulmonary embolism. Patients were assessed during the study period for development of proximal deep-vein thrombosis by compression sonography at days 1 and 10 and for pulmonary embolism by scintigraphy in symptomatic patients. Aim of the study was to demonstrate the equivalence of both treatment regimens. A total of 1,968 patients were randomized to receive UF or LMW heparin. Of these, 378 patients were excluded during the study period, so that 780 patients on UF and 810 on LMW heparin were included in the efficacy analysis. Four primary end points were observed with UF and 6 with LMW heparin, demonstrating the equivalence of treatments (p = 0.012). Additionally, pulmonary embolism was suspected as the cause of death in 6 patients who died during the study (3 per treatment group). A higher frequency of death (n = 32) was observed in the LMW-heparin group (p = 0.02) particularly documented in a part of the centers. Safety analysis showed a higher frequency of local pruritus, local erythema and subcutaneous hematoma, a higher increase in plasma levels of triglycerides, total cholesterol, alanine aminotransferase and aspartate aminotransferase, and a decrease of antithrombin III in patients receiving UF heparin. A decrease in platelet count (values ranging between 40,000 and 80,000/μl) was observed in 4 patients with UF and in none with LMW heparin. No severe thrombocytopenia was observed. Subcutaneous LMW heparin is as effective as UF heparin for prophylaxis of thromboembolism in bedridden, hospitalized medical patient

ISSN:1424-8832    

DOI:10.1159/000217198

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The pharmacodynamic effects of different intravenous and subcutaneous doses of a recombinant hirudin (r-hirudin; IK-HIR02) on clotting parameters and bleeding time were investigated in 24 healthy volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2 and 0.3 mg/ kg IK-HIR02 caused a prolongation of thrombin time (TT) and aPTT in a dose-dependent manner and led to an increase in hirudin plasma levels& > 6 μg/ml. The plasma half-life of IK-HIR02 was calculated as 1.3 h. A continuous infusion of 0.03 mg/kg/h of IK-HIR02 for 4 h significantly prolonged TT and aPTT. At the end of the hirudin infusion, a mean plasma level of 0.19 ± 0.13 μg/ml was measured. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg markedly prolonged the coagulation tests. The highest increase in hirudin plasma levels was found 2 h after injection. At this time the aPTT was doubled after 0.5 mg/kg. After repeat subcutaneous injections of 0.3 mg/kg b.i.d., aPTT was doubled, and TT increased to about 200 s, 2 h after the injections. At this time the mean plasma level was 0.5-0.6 μg/ml. There was no cumulative effect after multiple injections. Bleeding time was not changed after the 4-hour intravenous infusion and after repeat subcutaneous injections of 0.3 mg/kg IK-HIR02. Bleeding time was moderately but significantly prolonged after the highest single intravenous and subcutaneous hirudin doses tested. Other than very minor local bleeding in some volunteers, IK-HIR02 was well tolerated. Biochemical blood and urine parameters did not change. In conclusion, r-hirudin (IK-HIR02) obtained by a new technique was well tolerated in healthy volunteers after single intravenous and subcutaneous injections, after repeat subcutaneous doses and during continuous intravenous infusion. Measurement of aPTT and anti-IIa activity, using a chromogenic substrate test, can be used to monitor hirudin effects if doses similar to those tested here are administe

ISSN:1424-8832    

DOI:10.1159/000217199

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000317920

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The protective effects of ticlopidine and d, l-lysine acetylsalicylate (L-ASA), used alone and in combination, on the pathogen-esis of thrombosis in cerebral blood vessels were investigated in a rat animal model using a He-Ne laser method. Ticlopidine and L-ASA, given orally at a concentration from 100 mg/kg, inhibited thrombus formation in a dose-dependent manner. Ticlopidine (300 mg/kg p.o.) inhibited thrombosis in arterioles and venules for 3 days after administration. The inhibitory activity of L-ASA (300 mg/kg p.o.) was less prolonged than that of ticlopidine and was observed for only approximately 24 h. Combined administration of ticlopidine and L-ASA significantly enhanced and prolonged the antithrombotic effects of either drug given alone. The results demonstrate that ticlopidine and L-ASA have potent antithrombotic properties in rat cerebral blood vessels in vivo.

ISSN:1424-8832    

DOI:10.1159/000217200

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000317921

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Procoagulant activity (PCA) of peripheral mononuclear cells (PMC) was evaluated in patients with primary thrombocythemia (PT, group A), polycythemia vera (PV), idiopathic myelofibrosis (IM) and myelodysplastic syndromes (group B), and in 15 healthy subjects as control group. PCA of PMC was assayed under basal conditions and after agonist-induced stimulation: bacterial lipopolysaccharide, glycosylated granu-locyte-macrophage colony-stimulating factor, recombinant α-interferon. PCA was similar in the control group and group A when no stimulation was used, while PCA was found significantly higher in group B patients in the same conditions. In group A patients and in the control group, but not in group B patients, a lower PCA expression was found when PMC were simultaneously coincubated with LPS and α-interferon with respect to LPS incubation alon

ISSN:1424-8832    

DOI:10.1159/000217201

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In a previous study we tried to assess the clinical usefulness of platelet count (PIC) to confirm whether postoperative pulmonary embolism could be suspected early. Unexpectedly, the 19 patients who subsequently developed pulmonary embolism had significantly lower mean PIC levels even before surgery. In an attempt to discover whether the preoperative PIC levels were associated with a different incidence of postoperative blood loss, we decided to retrospectively study the relationship between preoperative PIC levels and the consequences of blood loss. There were 459 consecutive patients undergoing hip surgery. After excluding 5 patients who died during the first 3 postoperative days, and 16 patients who bled from a definitive anatomic site, there were 438 patients. Blood loss was considered to be excessive when two or more of the following conditions were present: (1) total transfusion requirements exceeding 1,000 ml whole blood or 2 units of packed red cells; (2) a drop in hemoglobin level of 5 g/dl or more, and (3) a hemoglobin level below 8 g/dl at any moment during the first 8 postoperative days. Blood loss was considered to be excessive in 91 patients. Preoperative PIC levels were significantly lower in these patients as compared to patients without the condition (204 ± 52 vs. 236 ± 79 × 109 liter–1; p = 0.0002). When patients were classified according to the quartiles of preoperative PIC, the odds ratio of developing excessive blood loss was 0.69 (95% CI: 0.38-1.26) in patients in the second quartile; 0.57 (95% CI: 0.30-1.06) in the third quartile, and 0.27 (95% CI: 0.13-0.57) in patients in the highest quartile. After adjusting for age, sex, type of surgery and type of prophylaxis, the preoperative PIC levels maintained a statistically significant inverse correlation with postoperative blood

ISSN:1424-8832    

DOI:10.1159/000217202

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000317922

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Synovial fluids drawn from joints of patients suffering from rheumatoid arthritis were investigated for their concentrations of proteins and activation markers of the complement, coagulation and fibrinolytic systems. A broad spectrum of plasmatic inhibitors and other hemostatic proteins were detectable by immunologic assays. Compared to normal plasma concentration ranges, levels of α2-antiplasmin, antithrombin III, heparin-cofactor II, factor H, α2-macroglobulin, inter-α-trypsin inhibitor, fibrinogen and particularly high molecular weight kininogen were found to be decreased when corrected for total protein content. However, highly elevated levels of C-reactive protein, factor XIII, PMN-elastase, prothrombin fragment F1+2 thrombin-antithrombin III, plasmin-antiplas-min and terminal complement-complexes as well as C5a were determined. Eight and 24 hours after induction of chemical synoviorthesis, a general increase in most of the parameters was observed. Statistically significant alterations were found for C1-inhibitor, factor H, α1-antitrypsin, inter-α-trypsin inhibitor, factor XIII, protein C, thrombin-antithrombin III complexes and

ISSN:1424-8832    

DOI:10.1159/000217203

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217204

出版商:S. Karger AG    

年代:1996

数据来源: Karger