摘要:

The intraduodenal absorption of a new low-molecular-weight heparin (LMWH) diamine salt (ITF 1331) was compared with the parent compound ITF 1060 and with sodium LMWH, in anaesthetized rabbits. The administration of either salt, but not of sodium LMWH, resulted in a dose-related increase in plasma anti-Xa activity. In this respect ITF 1331 was slightly superior to ITF 1060, and in acute-toxicity studies the counterion itself (ITF 258) was less toxic than that in ITF 1060 (counterion No. 4). These data confirm that a tertiary diamine within the counterion is an important structural requirement for the bioavailability of heparin by the intraduodenal route, and suggest that ITF 1331 may represent an important advance in the search for an oral heparin.

ISSN:1424-8832    

DOI:10.1159/000216305

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p < 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p < 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p < 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.

ISSN:1424-8832    

DOI:10.1159/000216306

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

ISSN:1424-8832    

DOI:10.1159/000216307

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In a prospective, randomized clinical trial we compared the efficacy of subcutaneously (SC) administered (every 8 h) calcium heparin to intravenous (IV) sodium heparin in the treatment of proximal deep-vein thrombosis (DVT). A secondary objective was to give enough heparin to achieve a therapeutic anticoagulant effect by the end of the first 24 h. Five of 36 patients (14%) in the SC heparin group failed to achieve a therapeutic anticoagulant effect by the end of the first 24 h compared to 2 of 23 patients (9%) in the IV group (p = NS; 95% Cl for true difference = -11.7% to 22.1%). Two of 31 patients (6.5%) in the SC group had venographic evidence of clot propagation compared to 1 of 19 patients (5.3 %) in the IV group (p = NS; 95 % CI for true difference = -12.4% to 14.8 %). The rate of major hemorrhagic complications was similar in each group (∼ 15%). We conclude: (1) using a large initial dose of SC heparin, a therapeutic anticoagulant effect can be readily achieved within 24 h, and (2) combining the results of this trial with previous studies, the efficacy of SC administered calcium appears to be comparable to IV sodium heparin.

ISSN:1424-8832    

DOI:10.1159/000216308

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216309

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We studied the effect of emotional stress (mental arithmetic for 10 min) in 10 postinfarction patients and in 10 age-matched apparently healthy subjects as controls. Blood samples for platelet function studies and for the determination of epinephrine levels in serum were taken in basal conditions, at the end of mental stress and after 30 min of recovery. Patients were studied twice, in washout of medications and after oral administration of dipyridamole, 200 mg twice a day for 6 consecutive days. Mental stress induced in patients significant increments in different hemodynamic parameters (heart rate, systolic blood pressure and diastolic blood pressure) and in serum epinephrine levels. Concomitantly, the test produced a significant increase in platelet aggregation (induced by 3 μM ADP or 1 μg/ml collagen), the formation of circulating platelet aggregates and an increase in plasma thromboxane B2 levels. Hemodynamic parameters and platelet function tests returned to baseline values after 30 min. Similar activation of hemodynamic parameters, similar increase in epinephrine levels and lower increase in platelet function by emotional stress were observed in control subjects. Treatment of patients with dipyridamole had no effect on stress-induced increase in hemodynamic parameters and epinephrine levels, but decreased stress-related platelet activation. These data can contribute to a better understanding of the complex relationships between psychosocial factors, the hemostatic system and vascular disease.

ISSN:1424-8832    

DOI:10.1159/000216310

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The inhibitory effects of ticlopidine and acetylsalicylic acid (ASA) on thrombus formation in rat mesenteric microvessels were studied. The results were compared with the effect of the drugs on platelet aggregation in citrated whole blood. He-Ne laser-induced thrombus formation in arterioles and in venules was significantly inhibited by 100 mg/kg ticlopidine. In contrast, a higher dose of ASA (300 mg/kg) was needed to inhibit thrombus formation and the effects of ASA were observed only in arterioles and not in venules. In addition, although the inhibition by ASA in arterioles was not strong it followed a dose-dependent manner, suggesting that the differential effect of ASA on platelets and endothelium may not be evident in vivo. Ticlopidine and ASA strongly inhibited ADP-induced whole blood platelet aggregation, but not collagen- or thrombin-induced platelet aggregation.

ISSN:1424-8832    

DOI:10.1159/000216311

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Russell’s viper venom (RW) leads to a strong activation of the coagulation system with consumptive coagulopathy and thrombopenia. For better comprehension of the pathophysiologic process, the effect of RW was examined in an in vitro model of hemostasis. The stimulation of the coagulation system and of platelet activity can be discriminated by sequential measuring of fibrinopeptide A (FPA) generation and platelet factor 4 (PF 4) release, respectively. In coagulating whole blood both parameters show a parallel response curve in the control series (n = 6) with an initial slow phase followed by a rapid phase after 4.7 ± 0.8 min (FPA) and 6.0 ± 0.9 min (PF 4) of the incubation period. Varying concentrations of RW (15,50, 100 and 1,000 ng/ml; n = 6 each) cause a dose-dependent stimulation of FPA generation as well as of PF 4 secretion. Clot formation time shows a decrease from 9 min (controls) to 6.3 ± 2.0 min (100 ng/ml RW) and 2.7 ± 0.5 min (1,000 ng/ml), respectively. The concomitant addition of antithrombin III (AT III, 20 U/ml) and RW (100 ng/ml) leads to a nearly complete normalization of hemostasis in vitro. The beginning of the rapid activation phase is comparable to that of the control group, clot formation does not occur during the 10-min incubation period. Heparin (1 IU/ml) acts as an antagonist not only of the venom-induced FPA generation, but also of the PF 4 release. Prostaglandin E1 (PGE1 (150 ng/ml) does not inhibit the RW-stimulated FPA generation, but causes a moderate inhibition of PF 4 secretion, especially during the rapid phase. Clot formation time is prolonged to 7.3 ± 0.5 min, compared to 6.7 ± 2.0 min after RW alone. In conclusion, RW leads to a dose-dependent activation of hemostasis. PGE1 acts as an inhibitor of platelet activity without alteration of FPA generation, while heparin leads to the inhibition of both agents. At high concentrations AT III normalizes hemostasis and thus may become of therapeutic i

ISSN:1424-8832    

DOI:10.1159/000216312

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216313

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The slide test method of Velaskar and Chitre for determining platelet aggregation in whole blood after induction of aggregation was modified for spontaneous platelet aggregation and evaluated. The reproducibility was satisfactory (CV 1-3%). The results obtained with this method and the method of Velaskar were not significantly different. The Spearman rank correlation was 0.75 (p < 0.0001). We established reference values for the particle counter method and Velaskar’s method in pregnant and non-pregnant women; no significant change in spontaneous platelet aggregation was seen throughout pregnancy. In order to estimate the clinical value of the test in pregnancy, we followed up a number of pregnant patients with primary enhanced spontaneous whole-blood platelet aggregation before and after treatment with low-dose acetylsalicylic acid. The test was found to be suited for the detection of spontaneous whole-blood platelet aggregation and for the follow-up after treatment with acetylsalicylic acid. Further studies are necessary, however, to assess the predictive value of an aberrant test result during pregnanc

ISSN:1424-8832    

DOI:10.1159/000216314

出版商:S. Karger AG    

年代:1992

数据来源: Karger