SummaryErythromelalgia, a characteristic aspirin-responsive microvascular thrombotic complication in essential thrombocythemia (ET), may develop despite oral anticoagulant treatment or treatment with heparin, suggesting that the generation of thrombin is not a prerequisite for its development. To study this, a cross-sectional comparison of the plasma levels of thrombomodulin (TM), platelet factor 4 (PF4), β-thrombo-globulin (β-TG), prothrombin fragment 1+2 (F1+2) and total degradation products of fibrin(ogen) (TDP) was made between 5 ET patients suffering from erythromelalgia, 16 asymptomatic ET patients and 20 control subjects, and after treatment with aspirin, respectively. Furthermore, 2 ET patients with a history of erythromelalgia were studied at regular time intervals after discontinuation of aspirin until erythromelalgia recurred. As compared with asymptomatic ET patients and control subjects erythromelalgia was characterized by significantly higher β-TG and TM levels but no significant differences were detected in either F1+2 or TDP levels. Treatment of erythromelalgia with aspirin resulted in disappearance of erythromelalgic signs and symptoms, which was paralleled by a significant decrease of β-TG and TM levels. Histopathologic and immunohistochemical analysis of biopsies derived from erythromelalgic skin areas of 2ET patients showed that erythromelalgic thrombi stained positively for von Wille-brand factor opposed to only a weak fibrin staining. Our data suggest that erythromelalgia is caused by the intravascular activation and aggregation of platelets with subsequent sludging or occlusion of the acral arterial microvasculature. The generation of thrombin appears not to be essential for the formation of these platelet thrombi, thereby giving a plausible explanantion for the inefficacy of coumadin derivatives and heparin in the prevention and treatment of erythromelalgia in essential thrombocythemia.
We have investigated the relationship between platelet count and large VWF (von Willebrand factor) multimers in the plasma of 36 patients with essential thrombocythaemia (ET) and 26 patients with reactive thrombocytosis (RT). In both ET and RT patients an inverse relationship could be established between platelet count and large VWF multimers in plasma as well in relatively decreased ristocetin cofactor/von Willebrand factor antigen and collagen binding activity/von Willebrand factor antigen ratios. A normalization of the platelet count was accompanied by restoration of a normal plasma VWF multimeric distribution. Our data suggest that increasing numbers of platelets circulating in blood result in increased removal of large VWF multimers from plasma.
Based on data from the Dutch Central Bureau of Statistics, the impact of influenza on mortality in The Netherlands was estimated for a 22.5-year period (1967-1989) in four age groups and three entities of disease, using Poisson regression techniques. Our analysis suggests that, on average, more than 2000 people died from influenza in The Netherlands each year, but in only a fraction of these deaths was influenza recognized as the cause of death. For each case of death registered as caused by influenza (registered influenza mortality), 2.6 additional cases of death registered as due to causes other than influenza, nevertheless, were influenza-related (non-registered influenza mortality). Therefore, the overall impact of influenza on mortality is estimated to be greater than registered influenza mortality by a factor of 3.6. Those under 60 years of age accounted for 5% of all non-registered influenza deaths, whereas people aged 60-69, 70-79 years and > 80 years accounted for 12%, 29% and 54% of such deaths, respectively. When extrapolating the figures for the Dutch population of 1989, we could attribute, on average per season-year, 82 deaths per 100,000 people > 60 years, 143 in people > 70 years, and 280 in people > 80 years. Of all non-registered influenza cases of death, 47% were estimated to occur in people with heart disease as a primarily reported cause of death, 23% in those with lung disease, and 30% in those with other diseases. This study stresses the serious effects of influenza, mainly in the elderly (95% of non-registered influenza mortality).(ABSTRACT TRUNCATED AT 250 WORDS)
Dexamethasone given before cardiac surgery changes circulating cytokines in an anti-inflammatory direction. Postoperative outcome may be improved by inhibition of the systemic inflammatory response.
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