[New results on the influence of prostaglandin E 1 on blood platelet function and aggregation].
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Biomedical subjects
Publications and source records attributed to E Wenzel.
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Hydroxyethyl starch (HES) is a frequently used plasma substitute that is popular due to a high degree of therapeutic safety. However, the administration of large volumes of highly substituted, high-molecular-weight starch often leads to iatrogenic von Willebrand syndrome (vWS) with hemorrhagic complications. In patients with cerebral circulatory disturbances we carried out hemodilution therapy during 9-10 days, infusing HES 200/0.62. A von Willebrand factor (vWF) multimeric analysis was carried out in 6 patients using a modified western blot according to the sodium dodecyl sulfate agarose gel electrophoresis method. The vWF multimeric analysis showed that all multimers decreased to the same degree, corresponding to type-I vWS.
Hydroxyethyl starch (HES) with a high or medium molecular weight (MW) and a high degree of substitution is difficult to degrade and leads to an accumulation of large molecules. These molecules have a negative effect on hemostasiological parameters. In 10 patients with cerebrovascular diseases, a hemodilution therapy was carried out with low MW HES for 10 days. Due to the low MW of the HES used (56-61 kD), the rheological parameters erythrocyte aggregation and plasma viscosity were significantly lowered (p < 0.01). No coagulation parameters studied were affected beyond the dilution effect, which was measured using the decline in hematocrit. Low MW starch is a volume substitute that is well-suited for repeated infusion or hemodilution therapy, particularly for patients with increased hemorrhagic diathesis, because it does not affect hemostasis. The disadvantage of a relatively short volume effect can be compensated through a continuous infusion of a larger volume.
Hydroxyethyl starch (HES) is often used for volume therapy. Since bleeding complications have been reported repeatedly, a strict dose limitation of a maximum of 1,500 ml 6% solution per day is recommended. However, many indications require higher dosages. Bleeding complications are known to be caused by an acquired von Willebrand syndrome. It has been shown that the accumulation of large molecules and their impairment in the coagulation system can be avoided by using HES preparations with a low in vivo molecular weight. However, the effects of a high-dose therapy have not been studied yet. We have investigated, how a 4-day high-dose therapy, using 3,000 ml 6% HES 70/0.5 on the 1st day and 1,500 ml on days 2-4, affects the coagulation system and hemorheological parameters of acute stroke patients. Thromboplastin time, activated partial thromboplastin time and thrombin time showed no significant changes, except for a slight, clinically irrelevant change due to dilution. The subunits of von Willebrand factor VIII showed no significant change. Hematocrit decreased from 42.3 +/- 4.6 to 37.4 +/- 3.9% (p < 0.05) after day 1, reaching 35.3 +/- 4.2% (p < 0.01) at the end of the therapy, demonstrating a substantial volume effect. Plasma viscosity and erythrocyte aggregation decreased slightly, however not significantly. Our study shows that even a high-dose therapy with 6% HES 70/0.5 has no influence on the coagulation system.
Haemodilution is an efficient conservative therapy of peripheral arterial occlusive disease. Already a single isovolaemic haemodilution (replacement of 500 ml blood for Haes* 0.5, 10%) increases the pain-free walking distance by 85%. These effects can be maintained by a constant therapy over six weeks and following haemodilution once or twice per month. The haematocrit values should be between 38 and 42%. The haemodilution should be done hyper- or isovolaemically. Not more than 250 ml blood and 500 ml Haes should be infused during one session in order to avoid hypovolaemia. This means an infusion of 250 ml Haes, venesection of 250 ml blood via the same access and then infusion of the remaining 250 ml. The whole procedure should not last more than one hour. Blood pressure, heart rate, lung auscultation and percussion as well as creatinine values has to be controlled during an intensive therapy. If the hydroxyethyl starch concentration exceeds 150 g per week pruritus may occur in singular cases, if the concentration exceeds 700 g per week it is observed in 50% of the cases. Provided the preventive measures are observed haemodilution is an efficient and good therapy which also increases the compliance to practice vascular exercise.
During the treatment of two patients with Klippel-Trenaunay syndrome interesting observations of the efficacy and the side effects of DHE were made. This led to the decision to carry out a validity study in 12 patients suffering from chronic venous insufficiency (CVI). The patients were treated with 0.25 mg or 0.5 DHE intravenously, and after that with 7.5 mg orally for one week. Before and after treatment measurements of venous capacity, microcirculatory parameters and rheological parameters were performed. Following the i.v. injection of 0.25 to 0.5 mg DHE the venous capacity decreased significantly in a dose-dependent way. The flow of erythrocytes in capillaries measured under resting condition was significantly lower and peak flow of reactive hyperemia decreased. No relation was found between the dose of DHE administered and the particular side effects (stomach trouble, increase in diastolic blood pressure) in 2 of the 12 patients. After oral treatment patients showed signs of subjective improvement of their complaints. On the basis of the results, the validity of non-invasive angiological tests is discussed.
The efficacy of fibrinolysis in deep venous thrombosis (DVT) depends on the age and organization of the thrombus as well as its localization. Up to now, indication for lysis therapy is defined according to the duration of clinical symptoms (less than 7 days). Our lysis results in urokinase therapy (n = 87) with high-dose and long-term regimen (mean 7.8 days), however, have shown no correlation between the duration of clinical symptoms (up to six weeks) and lysis efficacy (p less than 0.05). Therefore phlebographic criteria were established to allow the differentiation of fibrinolytic therapy depending on the site of the thrombus, its localization and the formation of collateral veins. In order to determine the state of thrombus organization, we used a new ultrasound Duplex system device (ARTIS, 7.5 Mhz, Picker International). In vivo experiments with induced thrombosis in human vena saphena magna demonstrate that echodensity of thrombi in ultrasound starts at the 11th-15th day. These findings are in good agreement with pathological studies of thrombus formation. Recent results of 24 patients with DVT indicate that echodensity of thrombus in ultrasound correlates with the course of organization and the efficacy of later lysis therapy.
Congenital dysfibrinogenemia is based on different alterations in the structure of the fibrinogen molecule leading to a variety of disturbances in the clotting process. Clinical manifestations of the disorder are showing a wide range from asymptomatic states to mild bleeding diathesis as well as thrombotic complications. In this study two of the 14 patients with dysfibrinogenemia showed a history of mild bleeding while the others showed no clinical symptoms. As fibrinogen is also an important factor of the blood fluidity not only haemostatic but also rheological parameters were measured. Included in the study were 14 patients with ascertained dysfibrinogenemia in comparison to 11 non-affected relatives and a control group of 297 apparently healthy subjects. Plasma viscosity (p < 0.0001) and erythrocyte aggregation index (p < 0.00001) were significantly higher in the patients than in their healthy relatives and the control group. A pathologically increased erythrocyte aggregation was found in 10 of the 14 patients but only in 1 of the 10 relatives. The dysfunction of the fibrinogen molecule thus influences the aggregation process of the red blood cells to a greater extent than normal fibrinogen. Moreover, there seems to be a stronger influence of the dysfunctional fibrinogen molecule on the aggregation process than on plasma viscosity. To date the question if the enhanced erythrocyte aggregation in dysfibrinogenemic patients may be of any diagnostic interest and if there are significant differences between patients with bleeding diathesis and thrombophilia cannot be answered and remains to be cleared in further investigations.