AbstractOral cholecystography is considered by the patient and the physician to be the most tolerable way of verifying gallbladder disease; nevertheless, several and serious reactions to contrast media, including renal, cardiac, and hepatic damage, have been described [1-4]Haematological reactions are very rare. A severe thrombocytopenia following cholecystography with sodium ipodate has been reported [5]. Two cases of severe thrombocytopenia following ingestion of iopanoic acid, a widely used contrast medium, have been published [6, 7]. We wish to report a further case; to our knowledge, the first observed outside the United States
Background Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Aim We investigated whether type 2 VHD (other than moderate-severe rheumatic mitral stenosis or mechanical heart valve) influences the prescription of anticoagulants in AF. Methods Umbria-Fibrillazione Atriale is a prospective multicenter registry in patients with AF. For the purpose of this study, type 2 VHD patients were propensity matched with non-VHD counterparts in a 1:1 ratio. Patients with type 1 VHD (moderate-severe mitral stenosis or mechanical heart valve) were excluded. Results We identified 2,212 patients with AF and excluded 46 because data on VHD were unavailable. Type 2 VHD was present in 426 patients (19.7%). Before registry entry visit, 77.1% of type 2 VHD and 66.8% of non-VHD patients were on anticoagulants. At discharge, 90.8 and 85.2% of patients, respectively, were on anticoagulants. After propensity-score matching, 386 patient-pairs were created. In the matched sample, the likelihood of being on anticoagulants before (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02–2.01, p = 0.036) and after (1.63, 95% CI: 1.04–2.57, p = 0.034) the entry visit was higher in type 2 VHD than in non-VHD patients. Patients with type 2 VHD were 70% more likely to receive vitamin K antagonists (VKAs) (OR: 1.70, 95% CI: 1.28–2.27, p < 0.001), and 32% less likely to receive non–vitamin K oral anticoagulants (NOACs; OR: 0.68, 95% CI: 049–0.94, p = 0.011) than non-VHD patients. Conclusion VKAs consistently outperformed NOACs as preferred treatment option in patients with type 2 VHD. This could potentially deny to these patients the well-established benefits of NOACs observed in phase III trials.
Stroke is the third cause of mortality and one of most frequent causes of long-term neurological disability, as well as a complex disease that results from the interaction of environmental and genetic factors. The focus on genetics has produced a large number of studies with the objective of revealing the genetic basis of cerebrovascular diseases. Furthermore, pharmacogenetic research has investigated the relation between genetic variability and drug effectiveness/toxicity. This review will examine the implications of pharmacogenetics of stroke; data on antihypertensives, statins, antiplatelets, anticoagulants, and recombinant tissue plasminogen activator will be illustrated. Several polymorphisms have been studied and some have been associated with positive drug-gene interaction on stroke, but the superiority of the genotype-guided approach over the clinical approach has not been proved yet; for this reason, it is not routinely recommended.
Three factors are related with the pathogenesis of venous thrombosis: (1) blood stasis, (2) hypercoagulability, and (3) vessel damage. Local and systemic factors are implicated in blood stasis. Remarkable advances have been recently achieved regarding the understanding of the concept of hypercoagulability, with special emphasis to thrombophilic molecular abnormalities. Increased thromboembolic risk has been described in patients with antithrombin III, protein C, or protein S deficiencies as well as factor V Leiden, prothrombin mutation G20210A, or hyperhomocystinemia. Vessel wall has a remarkable role in protecting against and in promoting thrombosis. The role of inflammation on venous thrombosis is under investigation.
We have previously demonstrated that therapeutic concentrations of unfractionated heparin (UFH) impair fibrin polymerization leading to the formation of clots which are more sensitive to lysis induced by tissue plasminogen activator (t-PA). The aim of this study was to compare the effect of UFH with that of three different low molecular weight heparins (LMWHs) on clot sensitivity to t-PA-induced lysis. Labelled fibrin clots, prepared from plasma containing UFH, Fraxiparine, Reviparine, Enoxaparine or saline, were incubated in phosphate buffer containing t-PA (0.1 and 0.5 microgram/ml) and plasminogen (20 micrograms/ml). The extent of clot lysis was quantified by counting the residual radioactivity of the clots and by measuring D-dimer levels released into the medium. Fibrin polymerization and clot structure were evaluated by means of a turbidimetric assay and by electron microscopic scanning. Pre-incubation of plasma with 0.5 or 1.0 U/ml UFH resulted in a marked dose-dependent acceleration of lysis induced by 0.1 or 0.5 microgram/ml t-PA. In contrast, lysis rates induced by 0.5 microgram/ml t-PA were not modified by pre-incubation of plasma with LMWHs. When exposed to 0.1 microgram/ml t-PA clots formed from plasma containing 0.5-2 IU/ml of Fraxiparine, Reviparine and Enoxaparine showed only a minor increase in lysis rates compared to control clots. There was not a clear dose-response curve with LMWHs. Furthermore, lysis rates obtained with UFH-treated clots were always significantly higher than those seen with LMWHs-treated clots.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical characteristics and management of acute deep vein thrombosis and pulmonary embolism (PE) have been reported to be different in patients with and without cancer. The aim of this paper was to provide information on clinical characteristics and management of acute venous thromboembolism in patients with cancer by means of a large prospective registry.MASTER is a multicenter registry of consecutively recruited patients with symptomatic, objectively confirmed, acute venous thromboembolism. Information about clinical characteristics and management was collected by an electronic data network at the time of the index event.A total of 2119 patients were enrolled, of whom 424 (20%) had cancer. The incidence of bilateral lower limb deep vein thrombosis was significantly higher in patients with cancer than in patients without cancer (8.5% versus 4.6%; p<0.01), as were the rates of iliocaval thrombosis (22.6% versus 14%; p<0.001), and upper limb deep vein thrombosis (9.9% versus 4.8%; p<0.001). Major bleeding (3.3% versus 1.1%; p=0.001), in-hospital treatment (73.3% versus 66.6%; p=0.02) and inferior vena cava filter implantation (7.3% versus 4.1%; p=0.005) were significantly more frequent in patients with cancer, in whom oral anticoagulants were less often used (64.2% versus 82%; p<0.0001).The clinical presentation of acute venous thromboembolism is different and often more extensive in cancer patients than in patients free from malignancy. Moreover, the management of the acute phase of venous thromboembolism is more problematic in cancer patients, especially because of a higher rate of major bleeding and the need for implantation of inferior vena cava filters.
Ischemic penumbra was first defined by Astrup in 1981 as perfused brain tissue at a level within the thresholds of functional impairment and morphological integrity, which has the capacity to recover if perfusion is improved. It exists, even for a short period of time in the center of ischemia, from which irreversible necrosis propagates to the neighboring tissues over time. Penumbra has become the focus of intense imaging research to differentiate it from infarction. Accurate detection of this ‘tissue at risk’ could be used to identify patients who would benefit most from acute treatment. Currently, recombinant tissue plasminogen activator (rtPA) is the only approved drug that has shown significant benefits in acute stroke patients when administered intravenously less than 4.5 h after stroke. However, its use is limited. Discrimination between infarct core and the surrounding potentially salvageable tissue is useful to better identify patients suitable for treatment. This can be achieved by positron emission tomography, single-photon-emission computed tomography, computed tomography perfusion scan and perfusion-weighted and diffusion-weighted magnetic resonance imaging. Identification of the penumbra might enable selective rtPA use in patients with large penumbras and small infarct cores, even beyond the 4.5-hour time window, where the penumbra may persist for more than 12 h. The purpose of this review was to describe neuroimaging modalities capable of identifying penumbra tissue so as to provide surrogate markers for new trials in acute ischemic stroke patients.
Previous and recent reports have suggested a fibrinolysis-enhancing property of standard heparin (SH) and low molecular weight heparin (LMWH) but these observations have never been confirmed in a clinical study fulfilling appropriate methodological criteria.Aim of this study was to evaluate in a cross-over double blind placebo-controlled study the effect of SH and LMWH (K 2165) on fibrinolysis. Six healthy volunteers (age 22-30) received a bolus dose of the following treatments: l)Placebo, 2)Kabi SH,5000 I.U., 3) Kabi 2165,5000 anti Xa U, 4)Kabi 2165, 10000 anti Xa U. A 4 day wash-out period was adopted.The volunteers had been fasting for at least 12 hours before the infusion and were sitting during the experiment.Before starting the infusion and at 1,2,5,10,15,30,60,120 minutes thereafter, blood samples were collected for the assay of t-PA activity, PA inhibitor activity, plasminogen, alfa2-antiplasmin, fibrinplate lysis area (FPLA), fibrinogen, aPTT, antithrombin III and anti-Xa activity. Placebo and Kabi 2165,5000 U had no effect on t-PA plasma level, however both SH and Kabi 2165,10000 U produced a statistically significant increase of t-PA level at 1 hour after the infusion. The t-PA increase lasted for at least 2 hours after the infusion; at that time the average t-PA activity was 0.14 U/ml for SH and 0.09 U/ml for Kabi 2165,10000 U (p<0.05, AN0VA,average pre-infusion level and placebo at 2 hours:0.01 U/ml).At that time plasma anti-Xa was 0.11 U/ml for SH and 1.05 U/ml for Kabi 2165,10000 U. SH and Kabi,10000 produced no effect on PA inhibitor.No effect of any treatment on fibrinogen,alfa2-antiplasmin,plasminogen, FPLA and antithrombin III was observed. We conclude that in this study both SH and Kabi 2165 produced a delayed and sustained increase of t-PA. The relevance of this effect remains to be established.
