Haemostasis最新文献

High-dose intravenous immune globulin (IV IgG) is currently the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who undergo splenectomy; however, this treatment is extremely expensive. We report on 13 ITP patients with severe thrombocytopenia (<20 x 10(9)/l) who were prepared for laparoscopic splenectomy with a 4-day oral course of high-dose (40 mg/day) dexamethasone (DEX). Four patients had an excellent response with platelet counts that increased to above 150 x 10(9)/l. Seven patients had a good response with a platelet count that increased to between 50 and 150 x 10(9)/l (median 121 x 10(9)/l). Two patients were resistant both to DEX and IV IgG. The operation was uneventful in all the patients, including the 2 who had resistant ITP and were operated on while their platelet count was very low (5 x 10(9)/l). Thus, high-dose DEX, which is an easy, effective and inexpensive treatment, is recommended for the preparation of ITP patients prior to splenectomy.

Both bleeding and thrombosis are complications of uremia in patients on regular hemodialysis. An excessive endogenous formation of the vasodilator and platelet inhibitor nitric oxide (NO) has been proposed to contribute to the bleeding defect. Since exposure to pharmacological donors of NO, nitrovasodilators, can cause tolerance to NO, we investigated whether platelets from uremic patients on regular hemodialysis are influenced differently by NO donors than platelets from healthy subjects. A frequently used S-nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), was compared to a recently synthezised mesoionic oxatriazole derivate, GEA 3175, regarding its capacity to inhibit adenosine 5'-diphosphate (ADP)-induced platelet aggregation in vitro. The final products of NO production, nitrite + nitrate, were found to be significantly increased in uremic patients. The capacity to inhibit platelet aggregation by SNAP was only slightly different between the groups. However, GEA 3175 showed a significantly marked and reduced capacity to inhibit aggregation of uremic platelets compared to controls. Interactions of erythropoietin (EPO) with NO have earlier been reported. Addition of EPO to platelets from healthy donors in vitro did not significantly influence the NO donor capacity to inhibit platelet aggregation, but showed a tendency to enhance the effect of SNAP while the effect of GEA 3175 was inhibited. These results suggest compound-specific resistance to NO donors in uremic platelet activation.

We describe a previously healthy male patient, with severe immune thrombocytopenic purpura (ITP) following CMV infection which was refractory to steroids and intravenous immunoglobulin, who developed massive intracranial bleeding. Despite an extremely low platelet count (2x10(9)/liter) which was refractory to platelet transfusions, successful emergency splenectomy was performed, with rapid resolution of the thrombocytopenia. Bleeding complications are extremely rare in viral-associated ITP. Emergency splenectomy should be considered in the presence of life-threatening bleeding when other modalities fail to produce a rise in the platelet count. Infection with CMV should be ruled out in cases of severe, treatment-resistant ITP.

Background: The role of platelet activation and endothelial cell damage in the pathogenesis of atherosclerosis was investigated.

Methods: Flow-cytometric detection of platelet activity was accomplished by measuring the surface expression of activated platelet glycoprotein IIb/IIIa (activated CD41) and the lysosomal integral membrane protein (CD63). Levels of thrombomodulin (TM) and von Willebrand factor (vWF) were estimated by the ELISA technique as markers of endothelial cell damage. These procedures were performed in healthy male subjects without obvious signs of atherosclerosis. Also, the intima-media thickness of the carotid artery was measured with high-resolution B- mode ultrasound to quantitate the presence and/or the extent of carotid atherosclerosis.

Results: According to ultrasound findings patients were divided into those with apparent evidence of atherosclerosis (AS+) with intima-media thickness >1.1 mm (n = 19) and those without such evidence (AS-) with intima-media thickness <1.1 mm (n = 17). The percentages of activated CD41 and CD63 surface antigen expression were significantly increased in the AS+ compared to AS- subjects. TM levels were elevated in the former group compared to the latter, while vWF levels were not different in the two groups. Multivariate analysis indicated the independent association of carotid atherosclerosis with each of the expression of activated CD41, CD63 as well as TM levels after adjustment of other risk factors.

Conclusion: This study demonstrates that platelets circulate in an enhanced activation state in asymptomatic atherosclerosis, which is closely related to the degree of endothelial cell damage as expressed by increased plasma levels of TM. The detection of platelet activation can be used as a potential marker for oncoming atherosclerosis.

Twenty to 25% of stroke patients are demented after stroke, which makes stroke an important risk factor for dementia. However, the diagnosis of dementia is difficult and depends heavily on methodology. In this review, we describe pitfalls of diagnosis, the prevalence and incidence of dementia after stroke based on data from prospectively studied stroke cohorts, and the risk factors for post-stroke dementia that emerged from these studies. Finally, the course and prognosis of post-stroke dementia are described.

We performed a cross-sectional case-control study among 295 subjects with dementia and 406 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, to evaluate the association of the factor V Leiden mutation and activated protein C (APC) response with dementia and its subtypes. The risk of dementia was 2.11-fold increased among carriers of factor V Leiden mutation relative to subjects lacking factor V Leiden mutation (95% confidence interval, CI, 0.93-4.77). The increased risks of vascular dementia and of Alzheimer's disease were 4.28 (95% CI 1.26-14.5) and 2.15 (95% CI 0.82-5.63), respectively. No association was found for APC response. We showed a nonsignificant twofold increased risk of dementia among subjects with factor V Leiden. The association appeared to be stronger for vascular dementia.

Platelets play an important role in atherosclerosis, and increased platelet activation is associated with stroke. Stroke is an important risk factor for dementia, as approximately 25% of the patients are demented after stroke. In this review, we describe platelet activation studies in patients with stroke and with dementia. In addition, we review the few studies that have investigated the effect of antiplatelet medication such as aspirin and non-steroidal anti-inflammatory drugs on cognitive function and the occurrence of dementia. We conclude that further studies are needed to characterize the mechanisms and determinants of platelet activation in relation to the development of dementia. Furthermore, the efficacy and safety of antiplatelet intervention will have to be assessed in properly designed randomized trials.

We performed a cross-sectional case-control study among 277 subjects with dementia and 298 control subjects drawn from participants of the Rotterdam Study, a population-based cohort study among subjects aged 55 years or over, and from participants of the Rotterdam Stroke Databank, a hospital-based stroke registry, with the objective to evaluate the association of indicators of coagulability, fibrinogen, prothrombin fragments 1+2, thrombin-antithrombin complex (TAT), and indicators of fibrinolysis, plasmin-inhibitor complex, D-dimer and tissue-type plasminogen activator (t-PA) with dementia. Increased levels of TAT, D-dimer and t-PA activity were associated with an increased risk of dementia. Additional stratified analyses indicated that an increased TAT level was the primary factor related to dementia. The present study provides evidence that predominantly increased thrombin generation is associated with dementia.

Brief dementia screening instruments, or mental status tests are frequently used to screen for cognitive impairment. We discuss the strengths and weaknesses of existing mental status tests in dementia screening in general. Most screening instruments that are used in clinical practice are developed to detect dementia compatible with Alzheimer's disease, and their value in detecting dementia after stroke is less well known. A stroke may cause both cortical and subcortical deficits, and the clinical expression of post-stroke dementia is different from that of Alzheimer's disease. Existing brief mental status tests have limited value in this patient group because they tend to ignore specific problems which may occur in stroke patients. Some expanded screening instruments, like the CAMCOG, are more useful and have additional diagnostic value. With the growing interest in research for vascular factors in dementia over the past years, however, a specific screening instrument for post-stroke dementia would be a valuable contribution.

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.