bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed-dose, Body Weight-independent Subcutaneous LMW Heparin versus Adjusted Dose Unfractionated Intravenous Heparin in the Initial Treatment of Proximal Venous Thrombosis
Authors: Schmidt J. A. , Koppenhagen K. , Tolle A. , Huisman M. V. , Büller H. R. , Harenberg J. ,   the EASTERN Investigators
Published: March 2018

SummaryBody weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism.Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee.The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02).Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis. With respect to the composite outcome of death, recurrent venous thromboembolism and major bleeding LMWH treatment performed significantly better both during initial therapy and at a six-month follow-up.
Incidence of Venous Thromboembolism: A Community-based Study in Western France
Authors: Oger Emmanuel ,   the EPI-GETBO Study Group
Published: March 2018

SummaryThe incidence of venous thromboembolism has been studied during one year in a defined population of 342,000 inhabitants. The overall incidence (95% confidence interval) of venous thromboembolism was found to be 1.83 per thousand per year (1.69 to 1.98). The incidences of deep venous thrombosis and pulmonary embolism were 1.24 per thousand per year (1.12 to 1.36) and 0.60 per thousand per year (0.52 to 0.69), respectively. The incidence of venous thromboembolism rose markedly with increasing age for both sexes; over the age of 75, the annual incidence reached 1 per 100. Sixty three percent of the patients were at home when venous thromboembolism occurred. Of these, sixteen percent had been previously hospitalised within three months. These results raise concerns on identification of medical patients at high risk and effective prophylaxis.
Outcome and One Year Follow-up of Intra-arterial Staphylokinase in 191 Patients with Peripheral Arterial Occlusion
Authors: Heymans Stephane , Vanderschueren Steven , Verhaeghe Raymond , Stockx Luc , Lacroix Hendrik , Nevelsteen André , Laroche Yves , Collen Désiré 
Published: March 2018

SummaryWild-type or equipotent variants of recombinant staphylokinase (rSak) were given intra-arterially (as a 2 mg bolus injection followed by an infusion of 1 mg/h or 0.5 mg/h overnight, with concomitant heparin [1000 IU/h]) to 191 patients of less than 80 years (62 ± 1 years, mean ± SEM), with a peripheral arterial occlusion (PAO) of less than 120 days (mean 14 ± 1 days, median 11 days, 5 to 95 percentiles 3 to 30 days). Ninety nine patients presented with acute or subacute ischemia, 57 with severe claudication, 33 with chronic rest pain and 2 with gangrene. Occlusion occurred in 122 native arteries and in 69 grafts. Revascularization was complete in 83 percent (158/191), partial in 13 percent (24/191) and absent in 4 percent (7/191) after administration of 12 ± 0.5 mg rSak over 14 ± 0.7 h. Complete revascularization of acute occlusions of popliteal or more distal arteries was less frequent (60 percent, 15/25) than of acute occlusions of more proximal native arteries (95 percent, 37/39, p <0.001) or grafts (89 percent, 50/56, p = 0.005). Additional endovascular procedures were performed in 47 percent and subsequent elective bypass surgery in 23 percent of patients. Major bleeding occurred in 12 percent (23/191), one month mortality was 3.1 percent (6/191) and one year mortality was 6.9 percent (12/174). However, four patients (2.1 percent) had an intracranial bleeding following therapy: a 85 year old woman with severe diabetic arteriopathy, who was included in violation of the protocol, a 79 and a 74-year-old woman and a 74-year-old man, all with severe hypertension and limb threatening ischemia; these four patients died within two months after treatment. Amputations were performed within the first year in 16 of 162 surviving patients (9.8 percent): in 7 percent (7/96) with an occluded native artery and 14 percent (9/66) with an occluded graft (p = 0.19). No significant difference in lysis rate, one month mortality or one year amputation-free survival was observed in occlusions of recent onset (<14 days, n = 126) as compared to occlusions of longer duration (<14 days, n = 65). Treatment was interrupted prematurely in 4 patients because of a suspected allergic reaction. Fibrinogen levels remained unaffected during treatment (3.3 ± 0.1 g/l before vs. 3.3 ± 0.1 g/l after infusion, n = 167).In conclusion, rSak appears to be a highly effective thrombolytic agent in patients with PAO, resulting in a low one month mortality (3.1 percent) and a high one year amputation free survival (84 percent), with an acceptable incidence of major bleedings, but with occasional fatal intracranial hemorrhages.
Pravastatin: An Antithrombotic Effect Independent of the Cholesterol-lowering Effect
Authors: Smith Donald , Unger Allen , Shao John , Meraj Perwaiz , Fier Carl , Cohen Adam , Fallon John , Badimon Juan , Ambrose John , Dangas George 
Published: March 2018

SummaryLipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy.We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) “adequate LDL-C reduction”: LDL-C reduction >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 ± 4 mg/dl; 6-month LDL-C 119 ± 5 mg/dl); (ii) “inadequate LDL-C reduction”: neither of the above criteria (n = 19; LDL-C reduction 31 ± 5 mg/dl; 6-month LDL-C 158 ± 6 mg/dl). Placebo patients were divided into those “with LDL-C reduction” (n = 17, mean reduction 21 ± 5 mg/dl) and those “without LDL reduction” (n = 19).The following parameters were altered at 6 months in both patients with “adequate” and “inadequate” LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 ± 0.4 and 1.5 ± 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 ± 2.0 and 10.1 ± 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 ± 0.9 and 2.8 ± 1.2 µm2 × 103 respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity.Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.
Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats
Authors: Noguchi Takanori , Seki Junji , Giddings J. C. , Yamamoto Junichiro , Sasaki Yasuto 
Published: March 2018

SummaryInhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, NG
- nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.
Fibrinogen and Fibrin Protect Fibroblast Growth Factor-2 from Proteolytic Degradation
Authors: Sahni Abha , Baker Christopher , Sporn Lee , Francis Charles 
Published: March 2018

SummaryWe have recently reported that fibrinogen and fibrin bind to fibroblast growth factor-2 (FGF-2) and potentiate its ability to stimulate proliferation of endothelial cells. In the present report, we have investigated the potential of fibrinogen and fibrin to protect FGF-2 from proteolytic degradation. FGF-2 was incubated with trypsin or chymotrypsin in the presence or absence of fibrinogen or fibrin and proteolysis of FGF-2 was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. In the absence of fibrinogen there was progressive tryptic degradation of FGF-2, but in the presence of fibrinogen, FGF-2 was completely protected from trypsin with no evidence of degradation. The degree of protection was maximum at a molar ratio of FGF-2 to fibrinogen 1:2. Fibrinogen afforded similar protection from degradation by chymotrypsin. Polymerized fibrin provided partial protection of FGF-2 from tryptic degradation, with intact FGF-2 present for up to 360 min. Fibrin provided nearly complete protection from chymotrypsin. These observations indicate that binding of FGF-2 to fibrinogen or fibrin provides protection from proteolytic degradation, and this may modulate its cell proliferative activity.
Influence of SIN-1 on Platelet Ca2+ Handling in Patients with Suspected Coronary Artery Disease: Ex Vivo and In Vitro Studies
Authors: Le Feuvre Claude , Brunet Annie , Do Pham Thuc , Metzger Jean-Philippe , Vacheron André , Devynck Marie-Aude , Le Quan Sang Kim-Hanh 
Published: March 2018

SummaryThe 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin.
In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2− scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect.This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2− release, independently of H2O2 formation.
Systemic Endothelial Cell Markers in Primary Antiphospholipid Syndrome
Authors: Williams Frances M. , Parmar Kiran , Hughes Graham R. , Hunt Beverley 
Published: March 2018

SummaryThe pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.
Duration of Oral Anticoagulant Treatment in Patients with Venous Thromboembolism and a Deficiency of Antithrombin, Protein C or Protein S - A Decision Analysis
Authors: van den Belt Angelique , Hutten Barbara , Bossuyt Patrick , Prins Martin 
Published: March 2018

SummaryPatients with a first venous thromboembolic event and a deficiency of the coagulation inhibitors antithrombin, protein C or protein S have an increased risk of recurrent venous thromboembolism compared to patients without such a deficiency. A decision analysis was performed to assess the effect of continuing treatment with vitamin K antagonists on mortality by a reduction in fatal recurrent pulmonary embolism and an induction of fatal haemorrhages associated with their use. The treatment decision involves continuation or discontinuation of vitamin K antagonists in patients with a first spontaneous or secondary venous thromboembolism and an antithrombin, protein C or S deficiency. Although the efficiency of oral anticoagulation is high in all age groups early after the first thromboembolic event, it decreases over time. Our analysis indicates that the optimal treatment duration will vary, depending on the type of the initial event (spontaneous or secondary; deep venous thrombosis or pulmonary embolism), age, and time passed since the initial thromboembolic episode. Moreover, life-long duration of the prophylaxis seems not warranted in all patients.
Pentoxifylline Prevents Upregulation of Monocyte Tissue Factor in Renal Transplant Recipients Undergoing Post-graft Complications
Authors: Susen Sophie , Hazzan Marc , Labalette Myriam , Zawadzki Christophe , Dessaint Jean , Lelièvre Gaston , Noël Christian , Jude Brigitte 
Published: March 2018

SummaryPentoxifylline (PTX) has been demonstrated to improve graft survival in renal transplant recipients undergoing post graft complications. As activated monocytes are possible initiators of vascular damage through tissue factor (TF) expression, we evaluated the monocyte TF expression and endothelium activation markers in 140 consecutive patients receiving cadaveric kidney grafts, randomized in a double-blind study comparing PTX versus placebo. Monocyte TF expression and plasma von Willebrand factor, tissue plasminogen activator, thrombomodulin and tumor necrosis factor-α (TNF-α) levels were determined before transplantation and each month after. Additional samplings were realized in case of acute rejection. TF and TNF-α expression were significantly modified after graft. In patients with complications, PTX prevented the increase of TF expression at month one, and after rejection episodes. Endothelium activation markers were significantly modified after graft and in patients with complications but PTX had no significant effect on their plasma levels. These results suggest that the protective effect of PTX on graft survival could be related to the prevention of monocyte TF upregulation associated with complications.
Genetic Modulation of Oral Anticoagulation with Warfarin
Authors: Colaizzo Donatella , D’Andrea Giovanna , Brancaccio Vincenzo , Ciampa Antonio , Grandone Elvira , Di Minno Giovanni , Margaglione Maurizio 
Published: March 2018

SummaryCytochrome P450 CYP2C9 gene variants have been associated with hyperresponsiveness to small doses of warfarin and a higher bleeding complication rate. The aim of this study was to investigate whether CYP2C9 gene variants affect doses of drug prescribed to acquire the target anticoagulation intensity and the occurence of bleeding complications. In a cohort of 180 patients followed up at one specialized clinic from the start of the anticoagulation with warfarin, we have investigated whether CYP2C9 gene variants have affected doses of drug prescribed to acquire the target anticoagulation intensity and the incidence of bleeding complications.The adjusted dose required of warfarin was higher among patients with the CYP2C9*1 haplotype (5.6 mg) than those of patients carrying the CYP2C9*2 (4.7 mg; p = 0.007, Scheffé’s test) or the CYP2C9*3 haplotype (4.0 mg; p <0.001, Scheffé’s test). The occurrence of bleeding complications was more frequent among patients with the CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the CYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16–5.73). An interaction between the presence of local bleeding sources and the CYP2C9*2 and/or the CYP2C9*3 haplotype was observed (p <0.001). Patients with both local sites of potential bleeding and CYP2C9*2 and/or the CYP2C9*3 haplotype had the higher estimated risk of bleeding (OR: 12.81; 95% CI: 2.86–57.26).CYP2C9 gene variants modulate the anticoagulant effect of the dose of warfarin prescribed. The incidence of bleeding complications in CYP2C9*2 and CYP2C9*3 carriers was significantly higher than that in noncarriers and interacted with the presence of local bleeding sources.
Hepatitis C Virus Transmission through Quarantine Fresh-frozen Plasma
Authors: Legler T. J. , Nübling C. M. , Riggert J. , Unger G. , Wolf C. , Heermann K.-H. , Köhler M. , Humpe A. 
Published: March 2018

SummaryIn 1994, quarantine fresh-frozen plasma (Q-FFP) was introduced in Germany in order to reduce the risk of HIV and HCV transmission. In 1998, an acute HCV infection of a patient was reported to us. The lookback revealed that this patient had received two Q-FFP from a donor who had seroconverted for HCV in the meantime. Recipients of further plasma donations from this donor were identified. Back-up specimens of these donations were investigated in several laboratories. A total of 25 additional HCV-PCR positive plasma units had been transfused to 12 further patients. HCV infections were diagnosed in seven of these recipients, three patients had already been deceased. One of the remaining two recipients was already HCV positive prior to transfusion, in the other patient, no HCV infection was detectable. This patient had received three units of an “early” plasma donation , which was tested negative by PCR in one laboratory, but positive in the other. The subsequent, clinically infectious donation had the same discrepant PCR results. Thus, eight cases of HCV transmission were revealed and classified as “certain” with regard to causality, also due to an identical HCV genotype, i.e. 3e. Some of these infections would have been prevented by application of a different anti-HCV assay. The assay used in the respective plasmapheresis station was in-sensitive in this individual case for more than 400 days after the first PCR positive donation. This caused the release of the above mentioned infectious units. Upon re-testing the backups, three of four other anti-HCV assays revealed a positive result already 104 days after the first PCR-positive donation. The donor had increased ALAT levels (> 23 IU/L) at nine of 28 donations, two of these were higher than 2.5 times the upper normal limit, and two were higher than 68 IU/L, which is the cut-off value for male blood donors in Germany. The results of these (look-back) studies arouse several queries, i.e. differences in the diagnostic sensitivity between current anti-HCV and PCR tests, the accuracy of risk-estimates (especially when based on hemovigilance studies for Q-FFP), the value of ALAT testing, and currently practised release algorithms for Q-FFP.
Mice Deficient in Hepsin, a Serine Protease, Exhibit Normal Embryogenesis and Unchanged Hepatocyte Regeneration Ability
Authors: Yu I.-Shing , Chen Huei-Jane , Lee Ying-Shuan , Huang Pei-Hsing , Lin Shu-Rung , Tsai Tzan-Wu , Lin Shu-Wha 
Published: March 2018

SummaryHepsin, a liver-enriched novel serine protease, has been implicated in participating with normal cell growth, embryogenesis, and blood coagulation pathway. To study its function in vivo, we have disrupted the mouse hepsin gene by homologous recombination. Targeted disruption of the hepsin gene and ablation of hepsin message were demonstrated by Southern blotting, Northern blotting and RT-PCR analysis. Homozygous hepsin −/− mice were viable, fertile, and exhibited no gross abnormalities, as judged by the size, weight and blood coagulation (PT) assays. However, the serum concentration of the bone form of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase of the hepsin −/− mice was mildly elevated, in spite of no obvious pathological change of hepatocytes. To examine whether hepsin is involved in controlling cell growth in adult tissues, 70% hepatectomy was applied to the hepsin −/− mice. Liver regeneration proceeded normally in the hepsin −/− mice as judged by the liver mass restoration rate. These results suggest that loss of hepsin function causes no effect in cell growth and embryogenesis in vivo, which is in contradiction to the studies using in vitro cell culturing system. Moreover, gross mass regeneration of liver after damage proceeds normally in the absence of functional hepsin.