Haemostasis最新文献

Atherothrombosis is a systemic disease, hence it is difficult to prove the specificity of haemostasis abnormality for any single vascular phenotype. Associations between haemostatic variables and any given phenotype, e.g. (vascular) dementia, should be interpreted with caution, given the overlaps of vascular disease phenotypes, risk factors, and haemostatic variables.

The apolipoprotein E (APOE) gene is strongly associated to the risk of Alzheimer's disease (AD). More specifically, it seems undisputed that the APOE*4 allele plays an important role in the pathogenesis of AD. However, does this imply that it is ApoE4 which causes the increased susceptibility for AD? Empirical findings in non-Caucasians leave space for at least one alternative hypothesis: not the ApoE4 polymorphism but other defects in, or close to the APOE gene, could be responsible. We discuss this hypothesis, based on population and evolutionary genetic evidence.

Dementia is one of the most frequent and devastating disorders in the elderly. Due to the increased longevity and the increasing number of elderly people in our society, it is emerging more and more as a major health problem. We quantified the frequency and lifetime risk of dementia, and of subtypes of dementia, in the Rotterdam Study, a population-based prospective cohort study among 7, 983 subjects over the age of 55 years. The overall prevalence was 6. 4% and the overall incidence 1 per 100 person-years. Both prevalence and incidence increased strongly with age. Typical incidence estimates for age 65, 75 and 95 are 1 per 1,000, 1 per 100 and 1 per 10 person-years. One in 6 men, and almost 1 in 3 women, will suffer at least some of their lifetime from dementia.

Although apolipoprotein E4 (ApoE4) is a well-established risk factor for the development of Alzheimer's disease (AD), it is unclear how ApoE affects the progression of the disease. beta-amyloid (Abeta) is a major constituent of cerebrovascular amyloid deposits in brains of subjects with Alzheimer's disease. In cerebrospinal fluid and in plasma, Abeta is normally present in association with high density lipoproteins (HDL). These lipoproteins may play a role in the removal of excess cholesterol from the brain through interaction with ApoE and heparan sulphate proteoglycans (HSPG) in the subendothelial space of cerebral microvessels. At the same time, HDL may have a role in maintaining Abeta soluble and in mediating its clearance. Therefore, similar factors, e.g. HDL, ApoE and HSPG, may be involved in the regulation of reverse cholesterol transport in the brain and in the processing of Abeta. Alterations in the process of cholesterol secretion from the brain may contribute to the deposition of Abeta in the vascular wall.

Although epidemiological studies are limited by diagnostic uncertainties, they suggest that stroke increases the risk of dementia. The mortality rate is higher in vascular dementia (VaD) than in Alzheimer's disease (AD). Community-based studies have provided several consistent findings: (i) age dependence with prevalence rates doubling every 5 years, (ii) a higher frequency in men and (iii) nation-to-nation differences. The prevalence of VaD ranges from 2.2% in 70- to 79-year-old women, to 16.3% in men >80 years. One sixth of acute stroke patients have preexisting dementia. The incidence of VaD has been studied much less extensively than that of AD, and substantial variations in the incidence rates have been observed: annual incidence rates (per 100,000) range from 20 to 40 between 60 and 69 years of age and from 200 to 700 over 80. The incidence rate of VaD declined over the last 2 decades, probably as a consequence of effective stroke prevention. It is generally assumed that risk factors for VaD are those of stroke, with arterial hypertension as leading factor, followed by atherosclerotic disease, low education level, alcohol abuse and heart disease. Stroke characteristics, such as lacunar infarction and left-sided hemispheric lesions, are major determinants of VaD. The cerebrovascular lesions are likely to be the only cause of dementia in strategic infarcts, in lacunar state, in hereditary cystatin C amyloid angiopathy and in CADASIL. However, white matter changes, and associated Alzheimer pathology, which are both frequent in this age category, may also contribute to the cognitive decline.

The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria are judged whether they contain criteria for both dementia and vascular disease as well as for the relationship between the two. We conclude that only the criteria of the State of California Alzheimer's Disease Diagnostic and Treatment Centers and of NINDS-AIREN provide sufficient operational criteria for dementia suitable for use in patients with vascular disease as well as for the diagnosis of cerebrovascular disease and for the establishment of a relationship between dementia and vascular disease. The latter criteria include also specific recommendations to the use of CT and MRI. However, the interpretation of the neuroimaging findings in the context of mixed vascular and degenerative dementia demands further study. Given the heterogeneous pathophysiology and pathology of vascular dementia and the modest reliability of the criteria, it seems plausible that the diagnosis of vascular dementia will become more reliable when specific diagnostic tests for the various degenerative diseases, from which vascular dementia has to be differentiated, become available.

Background: No consensus exists about the management of iatrogenically induced excessive hypocoagulability episodes.

Objective: To compare the two most common therapeutic approaches in such situations (discontinuation of the oral anticoagulant vs. low-dose subcutaneous vitamin K1) when acenocoumarol is the normally used anticoagulant.

Patients and methods: The study was retrospective and comparative. Patients received antithrombotic therapy using acenocoumarol. Anticoagulant plasmatic activity was assessed through the international normalized ratio (INR) recorded from December 1994 to December 1997 at two medical centers.

Results: INR is brought faster to a safe range in patients treated with low-dose vitamin K1 (p = 0.01). Their long-term behavior is also more stable and predictable and no resistance to the oral anticoagulant was found.

Conclusion: Low-dose vitamin K1 is a safer therapeutic option compared to simply withholding the oral anticoagulant. Its best scheme of administration, however, has yet to be defined.

Activated recombinant human coagulation factor VII (rFVIIa) is a promising new therapeutic agent for patients with hemophilia A or B with inhibitors who experience serious bleeding episodes or who need coverage during surgical procedures. This open-label, uncontrolled, emergency-use study evaluated the efficacy and safety of rFVIIa in 11 hemophiliac patients and 1 FVII-deficient patient with life-threatening intracranial hemorrhage previously unresponsive to one or more alternative therapies. rFVIIa effectively controlled intracranial hemorrhage in 10 of the 12 patients. Patients with hemophilia A or B received an average of 96.9 rFVIIa injections over 14.7 days with a mean total administration of 153.3 mg, corresponding to 8.1 mg/kg. Most reported adverse events were considered to be unrelated to rFVIIa therapy. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of central nervous system bleeding in patients with hemophilia A or B with inhibitors.

This study compares the extent of inhibition of thrombin generation and activity achieved in patients with acute myocardial infarction receiving fibrinolytic treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin treatment adjusted to the patients' weight with that achieved with the same heparin regimen but without fibrinolytic therapy. The study involved 90 patients, grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial thromboplastin time were measured. Patients treated with SK+heparin or rt-PA+heparin and higher F1+2 plasma levels than the patients treated with heparin alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were decreased in the three treatment groups at 24-48 h. There were no significant changes in TAT and FPA plasma levels among the three treatment groups at the different times. After thrombolytic therapy with both SK and rt-PA, there was an increase in thrombin generation, although high-dose intravenous heparin inhibited the different increases in thrombin associated with the thrombolytic agents to the same extent.

This study investigates the effect of enoxaparin (Lovenox, Klexane), a low-molecular-weight heparin, on edema following a photothrombotic lesion using rose bengal dye in the rat. An area of cerebral ischemia was provoked in the right hemisphere of rats. Edema developed over 24 h after the lesion, as seen comparing water content of a core sample from the right hemisphere to that of a similar sample from the left hemisphere of each rat. Enoxaparin at 0. 5 mg/kg i.v. plus 2 mg/kg s.c. reduced edema 24 h after lesion induction by 32% (p < 0.01) when the treatment was started 2 h after photothrombotic insult, with maintenance doses of 2 mg/kg s.c. enoxaparin at 6 and 18 h. When the same initial treatment with enoxaparin was started 18 h after insult, there was still a significant reduction of 20% (p < 0.01) in cerebral edema. Administration of enoxaparin 18 h after insult reduced cerebral edema in a dose-dependent manner. There was no evidence of intracranial hemorrhages in any of the animal groups and when the hemoglobin content of the brain samples was assayed by the method of Drabkin, no increase in hemoglobin content was seen compared to sham-operated animals.