bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation
Authors: Vries Aiko P. J. de , Veeger Nic J. G. M , Son Willem J. van , Bakker Stephan J. L , Meer Jan van der , Lijfering Willem M 
Published: December 2007

SummaryRenal transplant recipients are at an increased risk of venous thrombosis, which has been regarded as a postoperative complication, although it may persist afterwards. As numerous case reports have shown that active cytomegalovirus (CMV) infection can be found at time of onset of venous thrombosis, and is frequently found in renal transplant recipients, we hypothesized that one might be the result of the other. To calculate the risk of (recurrent) venous thrombosis in renal transplant recipients, and to see whether CMV infection influenced this risk, we retrospectively analysed 606 living consecutive renal transplant recipients. CMV status at time of transplantation and at time of enrolment was determined. Absolute risks of first venous thrombosis and recurrence were compared with CMV status, and were corrected for surgery related venous thrombosis, age, and anticoagulant treatment. Annual incidence of venous thrombosis was 0.88% (95% CI, 0.65–1.15) in all recipients and 0.59% (95% CI,0.41–0.83) corrected for surgery related venous thrombosis. CMV positive and seroconverted recipients tended to have an increased risk of venous thrombosis compared to CMV negative recipients; corrected relative risks were 2.0 (95% CI, 0.9–5.2) and 1.7 (95% CI, 0.6–4.7), respectively. The cumulative 10-year recurrence rate of venous thrombosis in CMV seronegative, seroconverted, and seropositive recipients was 10%,51% and 59%, respectively. We conclude that CMV infection tended to be associated with an increased risk of (recurrent) venous thrombosis. Prospective studies are warranted to establish this observation, which suggests that CMV infection influences the high risk of (recurrent) venous thrombosis in renal transplant recipients.
Thrombophilias and adverse pregnancy outcome – A confounded problem!
Authors: Janssen Nard G , Kalk Jakoba J , Hague William M , Dekker Gustaaf A , Kist Willem J , de Vries Johanna I. P. 
Published: December 2007

SummaryIt was the objective of this study to analyse the influence of confounders, such as ethnicity, severity of illness and method of testing, in articles concerning the still moot relationship of thrombophilias to adverse pregnancy outcome (APO). Relevant casecontrol studies were identified using Medline and EMBASE databases between 1966 and 2006. Search terms were recurrent fetal loss, intrauterine fetal death, preeclampsia, HELLP-syndrome, eclampsia, fetal growth restriction, abruptio placentae, combined with maternal thrombophilias. Data was extracted from the articles per subgroup ofAPO regardless of confounder. These subgroups were tested if they fulfilled the heterogeneity testing criterion (I2 > 35%) to weigh the influence of the confounder. Confounders were selected and examined with Mantel- Haenszel method. Increased thrombophilia prevalence was confirmed in most adverse pregnancy outcomes. Ethnicity, genetic testing only and severity of illness were confounders in the various forms of APO. Stronger relationships between factor V Leiden and severity of disease were found in 2nd and 3rd trimester than 1st trimester recurrent fetal loss, in preeclampsia with: blood pressure ≥160/110 mmHg than ≥140/90 mmHg; proteinuria ≥5 grams per day than < 5 grams; onset before than after 28 weeks, in fetal growth restriction <3rd percentile than <5th, than <10th, and in earlier occurrence of abruptio placentae than 3rd trimester. In conclusion, reports on the prevalence of maternal thrombophilias and APO are influenced by various confounders, which are not always appropriately analysed. The differences we have identified reflect the differential impact of these confounders. These data emphasise the importance of more uniform research.
Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: Experience in the standard clinical setting
Authors: Santagostino Elena , Faradji Albert , Iorio Alfonso , Meer Jan van der , Ingerslev Jørgen , Lambert Thierry , Maas-Enriquez Monika , Gorina Eduard , Musso Roberto ,   for the KOGENATE® Bayer European PMS Study Group
Published: December 2007

SummaryThe safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; KOGENATE® FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1–19 exposure days (EDs). Patients accumulated a mean (± SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical pro- cedures, and the response to infusion was “excellent” or “good” in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0–19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.
Effects of primary and secondary prophylaxis on the clinical expression of joint damage in children with severe haemophilia A
Authors: Kurnik Karin , Friedrichs Frauke , Halimeh Susan , Krümpel Anne , Bidlingmaier Christoph , Schobess Rosemarie , Nowak-Göttl Ulrike 
Published: December 2007

SummaryPatients with severe haemophilia A (HA) can either be treated by regular FVIII infusions twice or three times per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of haemophilic arthropathy, there is still a lot of controversy surrounding recommendations on age and dose at start of prophylactic regimens. The present database study was performed to investigate the role of primary versus secondary prophylaxis in HA children. The outcome variable was imaging-proven haemophilic joint damage. Forty-two children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 pa- tients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was not significantly different between the two patient groups (p=0.944),and no statistically significant differences were found in patients with target joints (p=0.3), nor in children in whom synovitis had occurred (p=0.77). No conclusion can be drawn from the data presented herein whether primary prophylaxis or an early start of secondary prophylaxis is superior with respect to joint outcome in children with severe HA.
Increased thrombin generation and fibrinogen level after therapeutic plasma transfusion: Relation to bleeding
Authors: Meijden Paola E. J. van der , Oerle René van , Curvers Joyce , Pampus Elisabeth C. M. van , Schols Saskia E. M , Heemskerk Johan W. M 
Published: December 2007

SummaryIn a clinical setting, fresh frozen plasma (FFP) is transfused to diluted patients with complicated surgery or trauma, as guided by prolonged conventional coagulation times or low fibrinogen levels. However, the limited sensitivity of these coagulation tests may restrict their use in measuring the effect of transfusion and hence predicting the risk of perioperative bleeding. We used the more sensitive, calibrated automated thrombogram (CAT) method to evaluate the result of therapeutic FFP transfusion to 51 patients with dilutional coagulopathy. Thrombin generation was measured in pre- and post-transfusion plasma samples in the presence of either platelets or phospholipids. For all patients, the transfusion led to higher plasma coagulation factor levels, a shortened activated partial thromboplastin time, and a significant increase in thrombin generation (peak height and endogenous thrombin potential). Interestingly, thrombin generation parameters and fibrinogen levels were higher in posttransfusion plasmas from patients who stopped bleeding (n=32) than for patients with ongoing bleeding (n=19). Plasmas from 15 of the 19 patients with ongoing bleeding were markedly low in either thrombin generation or fibrinogen level. We conclude that the thrombin generation method detects improved haemostatic activity after plasma transfusion. Furthermore, the data suggest that thrombin generation and fibrinogen are independent determinants of the risk of perioperative bleeding in this patient group.
Efficacy and safety of enoxaparin in unselected patients with ST-segment elevation myocardial infarction
Authors: Gitt Anselm , Jünger Claus , Bauer Timm , Heer Tobias , Koeth Oliver , Wienbergen Harm , Zahn Ralf , Senges Jochen , Zeymer Uwe 
Published: December 2007

SummaryIn randomized clinical trials the low-molecular-weight heparin enoxaparin has been shown to reduce ischemic complications in patients with acute ST elevation myocardial infarction (STEMI) treated with fibrinolysis. Little is known about the use and efficacy of enoxaparin in unselected patients with STEMI in clinical practice. In a retrospective analysis of the prospective ACOS registry we compared the outcomes of patients with STEMI treated with enoxaparin or unfractionated heparin. A total of 6,299 patients with STEMI < 12 hours were included in this analysis, 609 (10%) were treated with enoxaparin and 5,690 (90%) with unfractionated heparin. In the multivariable propensity score analysis enoxaparin was associated with a reduction in the combined endpoint of death and non-fatal reinfarction in the entire group (odds ratio 0.59; 95% CI 0.43–0.80) and the subgroups of patients treated without early reperfusion (odds ratio 0.65, 95% CI 0.43–0.97), fibrinolysis (odds ratio 0.64; 95% CI 0.33–1.26) and primary percutaneous coronary intervention (odds ratio 0.33;95% CI 0.15–0.72).There was no significant increase in severe bleeding complications with enoxaparin (6.5% versus 5.5%, p=0.4). In clinical practice in unselected patients with STEMI treated with or without early reperfusion therapy early treatment with enoxaparin compared to unfractionated heparin is associated with a significant reduction of the combined endpoint of inhospital death and reinfarction without a significant increase in severe bleeding complications.
Alcohol consumption is associated with a decreased risk of venous thrombosis
Authors: Rosendaal Frits R , Doggen Carine J. M , Pomp Elisabeth R 
Published: December 2007

SummaryModerate alcohol consumption is associated with lower levels of several coagulation factors. It is an established protective factor for cardiovascular disease; however, the effect on venous thrombosis is unknown. In a large population-based case-control study, we evaluated the association between alcohol consumption and the risk of venous thrombosis. The MEGA study included consecutive patients with a first venous thrombosis between March 1999 and September 2004 from six anticoagulation clinics in the Netherlands. Partners of patients were asked to participate, and additional controls were recruited using a random digit dialling method. All participants completed a standardized questionnaire, and blood samples were collected. A total of 4,423 patients and 5,235 controls were included in the analyses. Alcohol consumption was associated with a reduced risk of venous thrombosis, with 2–4 glasses per day resulting in the largest beneficial effect (odds ratio [OR] 0.67, 95% confidence interval [CI95] 0.58–0.77) compared to abstainers. The effect was more pronounced in women (OR 0.66, CI95 0.53–0.84) than men (OR 0.82, CI95 0.63–1.07) and also more striking for pulmonary embolism (OR 0.56, CI95 0.46–0.70) than for deep venous thrombosis of the leg (OR 0.74, CI95 0.63–0.88). Compared to abstainers, fibrinogen levels were decreased in individuals who consumed alcohol (maximum decrease: 0.30 g/l). FactorVII and vonWillebrand levels were mildly decreased in these individuals but not consistently over the categories of alcohol consumption. In conclusion, alcohol consumption is associated with a reduced risk of venous thrombosis, which may be in part mediated by decreased fibrinogen levels. Thromb
Persistent hyperfibrinogenemia in acute ischemic stroke / transient ischemic attack (TIA)
Authors: Assayag Einor Ben , Bova Irena , Shopin Ludmila , Cohen Michael , Berliner Shlomo , Shapira Itzhak , Shenhar-Tsarfaty Shani , Bornstein Natan M 
Published: December 2007

SummaryIncreased fibrinogen concentration is a well known phenomenon following acute ischemic stroke. However, the natural course of this hyperfibrinogenemia is uncertain. We aimed to clarify whether it is of a transient or more persistent nature in patients who harbor an underlying morbid biology of atherothrombo-inflammation. Venous blood for fibrinogen measurements was obtained from the control group participants and from stroke patients within 24 hours of admission, as well as 12 months following the acute event. In order to perform a time course analysis, we divided our cohort into tiles of time from symptoms' onset and compared the fibrinogen concentrations usingANOVA. Elevated fibrinogen concentrations were found in stroke patients on admission compared with matched controls (p<0.001).Analysis of variance in the different tertiles of time from symptoms' onset identified that fibrinogen concentrations were already relatively high during the initial phase of the event and did not differ significantly between the tiles (p=0.268). Moreover, when we calculated the absolute differences between the patients' fibrinogen concentrations and that of the matched controls there was clearly a minor increment during the time course from symptoms' onset in the stroke patients group. In conclusion, persistent hyperfibrinogenemia is present in patients with acute ischemic cerebral events and it might be present during the earlier stages of the disease as presently shown. Prompt and longterm, rather than short term, interventions to reduce the concentrations of this protein might therefore be of relevance.
Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor
Authors: Yano Koichiro , Tsubota Ken-ichi , Ishikawa Takuji , Wada Shigeo , Yamaguchi Takami , Mori Daisuke 
Published: December 2007

SummaryWe propose a method to analyze platelet adhesion and aggregation computationally, taking into account the distinct properties of two plasma proteins, vonWillebrand factor (vWF) and fibrinogen (Fbg). In this method, the hydrodynamic interactions between platelet particles under simple shear flow were simulated using Stokesian dynamics based on the additivity of velocities. The binding force between particles mediated by vWF and Fbg was modeled using the Voigt model. Two Voigt models with different properties were introduced to consider the distinct behaviors of vWF and Fbg. Our results qualitatively agreed with the general observation of a previous in-vitro experiment, thus demonstrating that the significant development of thrombus formation in height requires not only vWF, but also Fbg. This agreement of simulation and experimental results qualitatively validates our model and suggests that consideration of the distinct roles of vWF and Fbg is essential to investigate the physiological and pathophysiological mechanisms of thrombus formation using a computational approach.
Factor XIa and tissue factor activity in patients with coronary artery disease
Authors: Undas Anetta , Gissel Matthew T , Szuldrzynski Konstanty , Zmudka Krzysztof , Mann Kenneth G , Butenas Saulius 
Published: December 2007

SummaryIt has been established that inflammation and enhanced procoagulant activity are associated with the pathogenesis of atherosclerotic vascular disease. We evaluated and compared the contributions of the factor (F)XIa and tissue factor (TF) activity in plasma of patients with coronary artery disease (CAD). Citrate plasma was obtained prior to therapy from 53 patients with stable angina (29 with a history of previous myocardial infarction; CAD-MI) and 30 with acute coronary syndrome (ACS) within 12 hours from pain onset. Four ACS patients treated with heparin were excluded. FXIa andTF activity were determined in clotting assays based upon the prolongation of clotting time by inhibitory monoclonal antibodies. Twenty-five of 26ACS patients (96%) and 22 of 29 CAD-MI patients (76%) had quantifiable FXIa (50 ± 33 and 42 ± 45pM, respectively).Ten of 26 (38%) ACS patients and only three of 53 (6%) stable CAD patients showedTF activity (<0.4pM). No FXIa or TF activity was observed in agematched healthy controls (n=12).For both CAD-MI andACS patients, there were correlations (p<0.05) between FXIa and interleukin-6 (R2= 0.59 and 0.39, respectively) and between FXIa and TAT (R2= 0.64 and 0.63, respectively). In conclusion, the majority of ACS and CAD-MI patients have circulating FXIa that correlates with markers of coagulation and inflammation.
Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement
Authors: Hochholzer Willibald , Frundi Devine , Stratz Christian , Valina Christian M , Bestehorn Hans-Peter , Büttner Heinz Joachim , Neumann Franz-Josef , Trenk Dietmar 
Published: December 2007

SummaryEarly studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 μM was similar irrespective of statin treatment at baseline (p=0.968). RPA at CA was 46.2 ± 16.8% in patients without statin (n=682), 45.5 ± 17.0% in patients with atorvastatin (n=255), 45.8 ± 16.3% with simvastatin (n=335), 47.3 ± 14.9% with fluvastatin (n=42) and 45.9 ± 16.2% with pravastatin (n=81; p=0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n=553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p=0.645).Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI.
Idiopathic thrombocytopenic purpura: Current concepts in pathophysiology and management
Authors: Evangelista Maria Laura , Stipa Elisa , Buccisano Francesco , Venditti Adriano , Amadori Sergio , Stasi Roberto 
Published: December 2007

SummaryIdiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count, which is the result of both increased platelet destruction and insufficient platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified. Conventional treatments for ITP aim at reducing platelet destruction, either by immunosuppression or splenectomy. Two new thrombopoietic agents, AMG 531 and eltrombopag, have been used in clinical trials to stimulate platelet production in ITP patients not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin, but still bind and activate the thrombopoietin receptor. This review will focus on the pathophysiology and treatment of ITP in adults, highlighting recent advances in both fields.
Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden
Authors: Duchemin Jèrôme , Leroyer Christophe , Delahousse Bènèdicte , Abgrall Jean François , Mottier Dominique , Couturaud Francis ,   for the Groupe d’Etude de la Thrombose de Bretagne Occidentale (G.E.T.B.O)
Published: December 2007

SummaryThe thrombin generation test appears to be a highly sensitive and specific test in the detection of thrombophilia in patients with venous thromboembolism. We aimed to determine the accuracy of the thrombin generation test to detect factorV Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden. Sixty-two first-degree relatives of 21 index cases were tested for factor V Leiden, the G20210A prothrombin gene mutation and thrombin generation. Information about oestrogen therapy and previousVTE was also collected. The normalized Thrombomodulin sensitivity ratio (n-TMsr) was defined as the ratio of endogenous thrombin potential determined in the presence and absence of thrombomodulin which was normalized against the same ratio determined in normal control plasma. The mean n-TMsr was 1.37 (± 0.33) in the 45 relatives with one or more prothrombotic state (factor V Leiden, G20210A prothrombin mutation, oestrogen therapy or hormonal therapy) and 1.02 (± 0.34) in the 17 relatives without prothrombotic state (p = 0.001). The positive predictive value was 90.3 (95%CI, 73.1 – 97.4). In relatives with an abnormal n-TMsr, the adjusted odds ratio for having a prothrombotic state was 8.3 (95%CI, 1.9 – 36.9) and the adjusted odds ratio for having the factor V Leiden was 14.3 (95%CI, 2.9 – 71.2).An abnormal thrombin generation test appears highly predictive for having factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden.