Pathophysiology of Haemostasis and Thrombosis最新文献

{"title":"Prothrombin complex concentrates for urgent anticoagulation reversal in patients with intracranial haemorrhage.","authors":"D Imberti,&nbsp;G Barillari,&nbsp;C Biasioli,&nbsp;M Bianchi,&nbsp;L Contino,&nbsp;R Duce,&nbsp;M D'Incà,&nbsp;L Mameli,&nbsp;L Pinna,&nbsp;W Ageno","doi":"10.1159/000252822","DOIUrl":"https://doi.org/10.1159/000252822","url":null,"abstract":"<p><strong>Background: </strong>Intracranial haemorrhage (ICH) is a serious and potentially fatal complication of oral anticoagulant therapy (OAT). Prothrombin complex concentrates (PCCs) produce a rapid and effective reversal of OAT effects, but little evidence exists on their efficacy and safety in the management of ICH in patients on OAT.</p><p><strong>Aim: </strong>To evaluate the efficacy and safety of PCCs for the rapid reversal of OAT in patients with ICH.</p><p><strong>Methods: </strong>Patients suffering from acute ICH while receiving OAT were eligible for this prospective cohort study if their international normalized ratio (INR) was > or = 2.0. Stratified 35-50 IU kg(-1) PCC doses were infused based on initial INR.</p><p><strong>Results: </strong>A total of 92 patients (50 males; mean age 74 years, range 34-92 years) were included. The median INR at presentation was 3.3 (range 2-9). At 30 min after PCC administration the median INR was 1.4 (range 0.9-3.1), declining to < or = 1.5 in 75% of patients. The benefit of PCC was maintained for a long time, since in 98% of all post-infusion time points through 96 h the median INR remained < or = 1.5 (median 1.19; range 0.9-2.3). During hospitalization neither thrombotic complications nor significant adverse events were observed and 11 patients died (11.9%). None of the deaths was judged to be related to PCC administration.</p><p><strong>Conclusions: </strong>PCC administration is an effective, rapid and safe treatment for the urgent reversal of OAT in patients with ICH. Broader use of PCC in this clinical setting appears to be appropriate.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"259-65"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252822","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral factor Xa inhibitors for venous thromboembolism prevention in major orthopedic surgery: a review.","authors":"Davide Imberti,&nbsp;Domenico Prisco","doi":"10.1159/000252816","DOIUrl":"https://doi.org/10.1159/000252816","url":null,"abstract":"<p><p>Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopedic surgery, and routine thromboprophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of VTE in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, these drugs have several limitations, and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors of factor Xa, rivaroxaban, apixaban, LY517717, YM150 and betrixaban. Specifically, the results of phase II and III studies and the designs of ongoing clinical trials in patients undergoing elective hip and knee replacement are reviewed.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"217-26"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue factor and cancer.","authors":"Chloe Milsom,&nbsp;Janusz Rak","doi":"10.1159/000175154","DOIUrl":"https://doi.org/10.1159/000175154","url":null,"abstract":"<p><p>Tissue factor (TF), the key regulator of haemostasis and angiogenesis, is also involved in the pathology of several diseases, including cardiovascular, inflammatory and neoplastic conditions. In the latter, TF is upregulated by cancer cells, as well as by certain host cells, and it is the interactions between these distinct pools of TF-expressing cells that likely influence tumour progression in several ways. Furthermore, the release of TF microparticles into the circulation is thought to contribute to the systemic coagulopathies commonly observed in cancer patients. The direct regulation of TF by oncogenic events has provided a plausible explanation for the relatively common overexpression of TF in various cancers and its involvement in tumour growth, angiogenesis, metastasis and coagulopathy. However, this constitutive influence is modified by the tumour microenvironment, cellular interactions and host factors rendering TF expression patterns complex and heterogeneous. It appears that in many biological contexts TF plays a central role in disease progression and thereby potentially constitutes an attractive therapeutic target, especially in scenarios where the risk of bleeding can be avoided by selecting appropriate medications, refined dosing or by targeting the signalling component of TF activity. The efficacy and safety of such approaches still awaits clinical verification.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 3-4","pages":"160-76"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000175154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27952325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The plasminogen activator system and cancer.","authors":"Brandon McMahon,&nbsp;Hau C Kwaan","doi":"10.1159/000175156","DOIUrl":"https://doi.org/10.1159/000175156","url":null,"abstract":"<p><p>The fibrinolytic system, more appropriately referred to as the plasminogen activator system, controls not only the intravascular fibrin deposition but also participates in a wide variety of physiologic and pathologic processes. In cancer, the components of this system are involved in tumor growth, invasion and metastasis, through their effect on angiogenesis and cell migration. These components are found in most tumors and their expression signifies not only their function but also carries a prognostic value. Their expression is in turn modulated by cytokines and growth factors, many of which are up-regulated in cancer. Though both plasminogen activators, tPA and uPA, are expressed in tumor cells, uPA with its receptor (uPAR) is mostly involved in cellular functions, while tPA with its receptor annexin II on endothelial surface regulates intravascular fibrin deposition. Among the inhibitors of fibrinolysis, PAI-1 is a major player in the pathogenesis of many vascular diseases as well as in cancer. Therapeutic intervention, either using plasminogen activators or use of experimental inhibitor agents against PAI-1, has shown encouraging results in experimental tumors but not verified clinically. Information provided in this brief review is aimed to promote greater interest in the role of the plasminogen activator system in cancer.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 3-4","pages":"184-94"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000175156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27952824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombophilia and transient risk factors for venous thromboembolism in women with distal deep vein thrombosis.","authors":"S Cozza,&nbsp;G Mercier,&nbsp;J F Schved,&nbsp;C Biron-Andréani","doi":"10.1159/000252826","DOIUrl":"https://doi.org/10.1159/000252826","url":null,"abstract":"We retrospectively investigated consecutive women aged 12–49 years diagnosed with VTE and referred to our Thrombosis Center to be investigated for thrombophilia screening in the last 3 years. DVT was objectively confirmed by bilateral B-mode compression ultrasound and PE by ventilation/perfusion lung scan, computed tomography or angiography. Patients underwent objective investigation for PE only if they had pulmonary symptoms, whereas patients with symptomatic PE underwent objective investigation for DVT. DVT of the calf vein was considered distal, thrombosis involving the remaining vein segments was considered proximal. The transient risk factors considered were: surgery, trauma, leg cast, oral contraceptives, hormonal replacement therapy, pregnancy and puerperium. We previously described the methods used for thrombophilia screening [9] . All subjects gave their informed consent to participate in the study in accordance with the Local Ethics Committee Recommendations. We analyzed the presence of consensual thrombophilia and transient risk factors in 47 women with distal DVT complicated (n = 6) by PE or not (n = 41), 47 with proximal DVT complicated (n = 5) by symptomatic PE or not (n = 42), and 21 women with isolated PE. Women with isolated PE were younger at the time of the first event (mean age 24.5 years) than those with Dear Sir, Although deep vein thrombosis (DVT) and its major complication, pulmonary embolism (PE), are usually considered a single disease entity, venous thromboembolism (VTE) has a wide spectrum of clinical manifestations. A variety of risk factors may play different roles in determining the various locations of thrombi [1] . For example, the factor II 20210A (FII20210A) polymorphism has been reported to be more than twice as common in patients with cerebral venous sinus thrombosis than in patients with DVT [2] . Several studies have provided evidence for a reduced incidence of PE in relation to DVT in patients with the factor V Leiden (FVL) mutation [3–5] . Recently, 3 studies accessing the rate of thrombophilia and the location of lower-extremity DVT reported discordant results [6–8] . Patients with a deficiency in antithrombin (AT), protein C (PC) or protein S (PS), or a high level of factor VIII (FVIII) were excluded from these studies. In the present study, we investigated whether thrombophilic defects including AT, PC, PS deficiency or a high FVIII level play a different role in patients presenting with isolated PE, distal or proximal DVT. We also analyzed the association between the presence of transient risk factors at the time of VTE and the location of VTE.","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"282-4"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of platelet and fibrin ultrastructure in identifying disease patterns.","authors":"E Pretorius","doi":"10.1159/000252821","DOIUrl":"https://doi.org/10.1159/000252821","url":null,"abstract":"<p><p>Platelets and fibrin play an important role in the coagulation process where they are involved in the maintenance of haemostasis. Many diseases like cancer, thrombotic disease, bleeding disorders, asthma and even conditions like HIV/AIDS are associated with ultrastructural changes in platelets and fibrin, and because of this altered morphology in many diseases, the question now arises whether ultrastructural and morphological analyses of platelets and fibrin networks have a place in contemporary medical research. The present work aims to demonstrate the usefulness of ultrastructural analyses in the broadening of knowledge of disease patterns and suggests that information gained by studying ultrastructure may enhance treatment regimes. We propose an altered haemostasis with changed coagulation factors resulting in a thrombotic event is present in the human body long before the actual event. Thus, by studying the coagulum and platelet profile, preventative actions can be taken. It is therefore concluded that morphology and ultrastructure do indeed have a place in medical research based on the fact that the knowledge obtained through these studies helps in the broadening of knowledge of disease patterns.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"251-8"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252821","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood coagulation and cancer: thrombosis and survival, clinical relevance and impact. An introduction.","authors":"J H M J Vestjens,&nbsp;S Sassen,&nbsp;M H Prins","doi":"10.1159/000175149","DOIUrl":"https://doi.org/10.1159/000175149","url":null,"abstract":"<p><p>There is a strong association between deep venous thrombosis and cancer. In this review, we will discuss the increased incidence of cancer following an idiopathic venous thrombotic event (VTE) and the increased incidence of VTE and its recurrence in cancer patients. Furthermore, we will review the adverse impact VTE has on cancer patients' morbidity and mortality. Finally, the potential influence of anticoagulation on survival of cancer patients is discussed. Although the data are encouraging, anticoagulation is still of limited value for routine clinical practice in anticancer treatment.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 3-4","pages":"113-21"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000175149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27952320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nattokinase-promoted tissue plasminogen activator release from human cells.","authors":"Chieko Yatagai,&nbsp;Masugi Maruyama,&nbsp;Tomoko Kawahara,&nbsp;Hiroyuki Sumi","doi":"10.1159/000252817","DOIUrl":"https://doi.org/10.1159/000252817","url":null,"abstract":"<p><p>When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"227-32"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of the postulated mechanisms linking cancer and thrombosis.","authors":"Hugo ten Cate,&nbsp;Anna Falanga","doi":"10.1159/000175150","DOIUrl":"https://doi.org/10.1159/000175150","url":null,"abstract":"<p><p>Blood coagulation appears to play an important role in the occurrence of cancer and its effects may be twofold. First, in patients with cancer, blood coagulation is activated in the direction of a prothrombotic state. Second, a procoagulant environment may promote cancer in different ways. In this chapter we discuss some of the mechanisms that may be involved in this interplay between coagulation and cancer. Blood coagulation proteins interact with cells in the vasculature to maintain hemostasis. However, many proteins that are involved in coagulation and anticoagulation, as well as fibrinolysis, are also found in extravascular tissues. In different organs, these proteins may be involved in cell-signaling mechanisms, through interaction with cell receptors like protease-activated receptors (PARs). Such interactions may drive inflammation, angiogenesis and cell proliferation. The potential procarcinogenic actions of proteases like thrombin may be counteracted by the anticoagulant and anti-inflammatory actions of the protein C-thrombomodulin mechanism. In the blood of cancer patients, the balance is usually shifted towards a procoagulant direction. The resulting excess thrombin- and fibrin-forming activity promotes venous thrombosis and may in the extravascular compartment stimulate cancer progression. The activation of platelets and their interaction with leukocytes may propagate this process. In addition to the therapeutic modulation of the prothrombotic environment, the induction of specific anticoagulant proteins including thrombomodulin may have effects on tumor growth or dissemination, but the nature of these effects still remains hard to predict. The interplay between cancer and blood coagulation merits further experimental and clinical research.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 3-4","pages":"122-30"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000175150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27952321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rice variety (HYJA-Ri4) enhances arterial thrombus formation in an animal model of thrombosis.","authors":"Aki Naemura,&nbsp;Yoshinobu Ijiri,&nbsp;Mitsuhiro Kodama,&nbsp;Yoshinori Honda,&nbsp;Junichiro Yamamoto","doi":"10.1159/000252819","DOIUrl":"https://doi.org/10.1159/000252819","url":null,"abstract":"<p><p>Epidemiological evidence exists for a causative role of inappropriate diets in the development and clinical outcome of thrombotic diseases. Our previous studies have shown that some fruits and vegetables have antithrombotic activity. As rice is a principal ingredient of everyday food in Japan, the aim of the present study was to determine rice varieties with antithrombotic effect. Western-style high-fat diet containing flour prepared from whole-grain rice of different varieties was fed to atherosclerosis-prone (apolipoprotein E- and low density lipoprotein receptor-deficient) mice for 3 months. A laser-induced carotid-artery thrombosis model was used. None of the five tested rice varieties showed an antithrombotic effect. The effect of HYJA-Ri1, HYJA-Ri2, HYJA-Ri3 and HYJA-Ri5 rice on experimental thrombus formation did not differ significantly from the controls. However, HYJA-Ri4 rice significantly enhanced the thrombotic reaction (p = 0.0078), thus having a prothrombotic effect. Our findings suggest that HYJA-Ri4 rice should not be included in an antithrombotic diet.</p>","PeriodicalId":19817,"journal":{"name":"Pathophysiology of Haemostasis and Thrombosis","volume":"36 5","pages":"241-4"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000252819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28582575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}