bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Weights of Factor VIII (AHF) and Factor IX (PTC) by Electron Irradiation
Authors: Aronson David L , Preiss John W , Mosesson Michael W 
Published: July 2018

SummaryThe molecular weights of AHF (factor VIII) and of PTC (factor IX) have been estimated by their sensitivity to inactivation by 7 kilovolt electrons. The molecular weight of AHF was found to be 180 000 by this method and that of PTC was found to be 110 000.
A Comparison of Plasma and Serum Factor VII Activity and the Formation of Tissue Thromboplastin
Authors: Fantl P , Osborn E. C 
Published: July 2018

Summary1. A mixture of human serum or plasma and bovine plasma free of factors VII and X gave, with human brain extract, identical clotting times.2. An assay of factor VII in materials low in prothrombin using human plasma euglobulin was devised.3. Factor VII isolated from human plasma or serum gave similar activity with human brain extract.4. From a preparation containing factors VII and X which was added to human brain extract in the average 31% factor VII and 25% factor X was recovered. This was not dependent on the activity of factors VII and X in the original preparation. This indicates that factors VII and X are in equilibrium with tissue thromboplastin.5. Factors VII and X are not species specific but a higher concentration of these factors is required for prothrombin conversion in a heterologous reaction mixture.6. Factor VII activity is identical in silicone-coated or uncoated glass surfaces.
Determination of Fibrinogen and Fibrinogenolytic Activity
Authors: Nilsson Inga Marie , Olow Bertil 
Published: July 2018

SummaryA method for determining plasma fibrinogen and fibrinogenolytic activity, with epsilonaminocaproic acid (ε-ACA) as an inhibitor of fibrinolysis, in patients with high fibrinolytic activity, is described in detail.The fibrinogen was determined by a modification of Morrison’s syneresis method in parallel in 1. citrated plasma that was incubated for 2 hours at 37° C, after which further digestion was prevented by addition of ε-ACA and is referred to as fibrinogen A, and 2. in citrated plasma prepared from blood collected in tubes containing ε-ACA to prevent activation of plasminogen and is referred to as fibrinogen B.
The difference between fibrinogen B and fibrinogen A gives the amount of lysed fibrinogen in 2 hours at 37° C. Fibrinogen B gives the fibrinogen concentration at the moment of sampling.The method is recommended to be used for evaluation of the true plasma fibrinogen level and the degree of fibrinogenolytic activity. This is particularly important during thrombolytic therapy.
The Measurement of Fibrinolytic Activity with I131-labelled Clots. II. Application
Authors: Wit C. Dudokde , den Ottolander G. J. H , Krijnen H. W 
Published: July 2018

Summary1. The application has been described of a method, using I131-labelled clots as a substrate for the measurement of plasmin, urokinase and streptokinase.2. With this method the inhibition of these fibrinolytic agents by plasma has been studied.3. A striking difference in the fibrinolytic and fibrinogenolytic effect of urokinase and streptokinase was found. Urokinase appeared to be an effective fibrinolytic agent in the presence of plasma and gave rise to little fibrinogenolysis, while streptokinase appeared much less effective in this respect in the presence of plasma, but gave marked fibrinogenolysis.
Factor V Leiden, C>T MTHFR Polymorphism and Genetic Susceptibility to Preeclampsia
Authors: Grandone Elvira , Margaglione Maurizio , Colaizzo Donatella , Cappucci Giuseppe , Paladini Dario , Martinelli Pasquale , Montanaro Sergio , Pavone G , Minno Giovanni Di 
Published: July 2018

SummaryWe performed a case-controlled study to investigate whether the FV Leiden mutation and the C>T677 polymorphism of the 5,10 methylene tetrahydrofolate reductase (MTHFR) are associated with the occurrence of preeclampsia in 96 otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden carriers were 10 (10.5%) in cases and 3 (2.3%) in controls (OR: 4.9, 95% Cl: 1.3-18.3). MTHFR TT homozygotes were 28 (29.8%) in cases and 24 (18.6%) in the control group (OR: 1.8,95% Cl 1.0-3.5). No difference in any of the polymorphisms was found between proteinuric (n = 45) and non-proteinur-ic (n = 51) patients. Moreover, MTHFR polymorphism does not affect the association between FV Leiden and preeclampsia. In conclusion, FV Leiden mutation and MTHFR TT genotype are associated with the occurrence of preeclampsia, suggesting that, during pregnancy, women carrying these gene variants are prone to develop such a complication.
The Origin of P-selectin as a Circulating Plasma Protein
Authors: Fijnheer R , Frijns C J M , Korteweg J , Rommes H , Peters J H , Sixma J J , Nieuwenhuis H K 
Published: July 2018

SummaryP-selectin is a 140 kD protein found in the α-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and EDl-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p <0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the sP-selectin concentration was 110 ± 39 ng/ml (n = 10), compared to 122 ± 38 ng/ml in healthy controls (n = 26). However, their mean platelet count was lower (58 X 109/1 versus 241 X 109/1 in the control group). Accordingly, the levels of sP-selectin expressed per platelet increased to significantly higher levels (2.0 ± 1.2 versus 0.6 ± 0.2 fg/platelet in the control group-; p <0.0001). This suggests increased platelet turnover in patients with ITP. High levels of sP-selectin were found in patients with sepsis (398 ± 203 ng/ml; n = 15) and with thrombotic thrombocytopenic purpura (TTP; 436 ± 162 ng/ml; n = 12). Compared with patients with ITP, the concentration of sP-selectin per platelet was higher in patients with sepsis (4.8 ± 4.3 fg/platelet; p <0.005) or TTP (17.1 ± 9.5 fg/platelet; p <0.001). Endothelial cells are very likely to be the source in these patients and the presence of endothelial cell activation was confirmed by increased levels of circulating E-selectin and ED 1 -fibronectin.This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.
von Willebrand Factor and Factor VIII: C in Acute Cerebrovascular Disease
Authors: Catto Andrew J , Carter Angela M , Barrett Jennifer H , Bamford John , Rice Penny J , Grant Peter J 
Published: July 2018

Summary
Background. Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VIII :C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined.
Methods and results. We studied 208 cases of stroke whose pathological type was defined by cranial computed tomography. Cerebral infarcts were grouped according to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The results in patients were compared with 184 healthy reference subjects. In patients, vWF and FVIII: C levels were determined initially and after three months. Patients were followed prospectively for six months or until death.Levels of vWF and FVIII :C were elevated initially (1.86 IU/ml and 2.20 U/ml respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the initial sample, vWF was associated with age (p = 0.01). FVIII: C was related to age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008).Initial vWF levels were higher in subjects with large vessel disease (TACI/PACI) group compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs. 1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII :C levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001).Analysis of six-month case fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12,2.66) for an increase of 1 U/ml], even after allowing for stroke type.
Conclusion. The relationship of vWF with stroke mortality has not previously been described. Although we have not demonstrated a causal role for vWF in the pathogenesis of CVD, elevated circulating levels of vWF may be associated with increased risk of death following stroke. A prospective study would be required to establish whether vWF is predictive for the development of CVD.
On the Relationship between Changes in the Deep Veins Evaluated by Duplex Sonography and the Postthrombotic Syndrome 12 Years after Deep Vein Thrombosis
Authors: Franzeck U K , Schalch I , Bollinger A 
Published: July 2018

SummaryIn a prospective study we performed color duplex ultrasonography to evaluate patency and valvular function of previous thrombosed veins 12 years after the acute thrombosis.Normal clinical findings were found in 64% of the patients, mild postthrombotic skin changes in 28%, and marked trophic changes in 5%; only 1 venous ulcer occurred.In 39 patients, 114 initially thrombosed vein segments were evaluated. Thirty-seven of 72 proximal segments were completely recanalized (23 with valvular incompetence) and 21 segments exhibited partial recanalization (19 with valvular incompetence). Superficial femoral vein segments were completely occluded in 19%, however, excellent collateralization was provided via the deep femoral vein. Thromboses of the posterior tibial vein demonstrated a high rate of recanalization with development of valvular incompetence in 52%.Whereas obstruction and valvular incompetence as single factors led to a postthrombotic leg in 8.5% and 33%, respectively, the most frequent cause for the development of the postthrombotic syndrome was the combination of reflux plus obstruction in the deep veins (50%).Compression therapy with elastic compression stockings is recommended for at least 5 years after the acute thrombosis.
Multicenter Retrospective Study on the Utilization of FEIBA in France in Patients with Factor VIII and Factor IX Inhibitors
Authors: Negrier C , Goudemand J , Sultan Y , Bertrand M , Rothschild C , Lauroua P ,   the members of the French FEIBA study group
Published: July 2018

SummaryFactor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers.The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.
The Anticoagulant and Hemorrhagic Effects of DHG, a New Depolymerized Holothurian Glycosaminoglycan, on Experimental Hemodialysis in Dogs
Authors: Minamiguchi Kazuhisa G , Kitazato Keiko T , Sasaki Eiji , Nagase Hideki , Kitazato Kenji 
Published: July 2018

SummaryWe studied the use of depolymerized holothurian glycosaminoglycan (DHG) as an anticoagulant in experimental beagle-dog hemodialysis using a hollow-fiber dialyzer compared to that using unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and nafamostat mesilate (FUT). Effectiveness was based on 5 h hemodialysis and no marked clot deposition in the extracorporeal circuit. At effective doses, UFH and LMWH significantly prolonged template bleeding time, in sharp contrast to FUT and DHG, which scarcely prolonged bleeding time during hemodialysis. DHG prolonged activated partial thromboplastin time (APTT) about 6 times that of normal plasma and prolonged thrombin clotting time (TCT) markedly; FUT showed marked APTT prolongation but hardly prolonged TCT in the hemodialysis circuit at the effective dose. The anticoagulant profile of DHG thus differs completely from that of FUT. These results suggest that DHG may be useful as anticoagulant for hemodialysis with low hemorrhagic risk.
A 6-month Venographic Follow-up in 164 Patients with Acute Deep Vein Thrombosis
Authors: Holmström Margareta , Lindmarker Per , Granqvist Staffan , Johnsson Hans , Lockner Dieter 
Published: July 2018

SummaryA total of 164 patients were recruited from a randomized trial comparing a low molecular weight heparin, dalteparin, given subcutaneously once daily with a continuous intravenous infusion of unfractionated heparin in the initial treatment of acute deep vein thrombosis. The primary objective of this follow-up study was to investigate whether there were any differences between the two treatment groups with respect to Marder score changes 6 months after the initial diagnosis using repeated venography. The secondary objectives were to analyse whether certain haemostatic and acute phase parameters or patient characteristics influenced the venographic outcome. Results: Complete lysis of the thrombus was observed in 38.4% of the patients and a partial lysis in another 54.3% assessed by venography 6 months after the acute event. Extension of the thrombus was seen in 7.3% of the patients. There were no significant differences in the change in mean Marder score before treatment and at the 6 month follow-up between the two treatment groups, irrespective of thrombus localisation. In a regression model, male gender, low levels of orosomucoid and increased levels of d-di- mer in plasma on day 5 were independently associated (p <0.05) with an enhanced absolute resolution of the thrombus at 6 months. No differences in symptoms and signs in the thrombotic leg at follow-up, comparing the treatment given, or thrombus extension at diagnosis and 6 months later, were demonstrated. Conclusion: Dalteparin given once daily subcutaneously was as effective as continuous intravenous infusion of unfractionated heparin in the initial treatment of deep vein thrombosis assessed by Marder score evaluation 6 months after the acute event.
Homocysteine Metabolism in Endothelial Cells of a Patient Homozygous for Cystathionine β-synthase (CS) Deficiency
Authors: Molen E F van der , Hiipakka M J , van Lith-Zanders H , Boers G H J , Heuvel L P W J van den , Monnens L A H , Blom H J 
Published: July 2018

SummaryHomocystinuria due to cystathionine β-synthase (CS) deficiency is the most common inborn error of methionine metabolism. Patients with CS-deficiency have an extremely high risk of vascular disease. The underlying mechanism is still unsolved. Dysfunction of endothelial cells could be the trigger in the formation of atherosclerosis and thrombosis. Therefore, differences in cell function were studied between normal and CS-deficient human umbilical endothelial cells (HUVECs). Total homocysteine (tHcy) concentrations in culture media as a measure of homocysteine export increased in all cell lines, including the cell line with CS-deficiency, with constant amounts of approximately 2.5 μM every 24 h. von Willebrand factor (vWF), tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in culture media were used as markers of endothelial function and increased also with progression of culture time. The effects of additions of folate, vitamin B6 and methionine to the culture medium were studied. The homocysteine export and the markers of endothelial function did not differ between the control and the CS-deficient HUVECs under various test conditions. These data show that CS-deficient endothelial cells have normal homocysteine export and normal endothelial cell function. In CS-deficient patients the very high blood levels of homocysteine, probably due to deficient CS function in liver and kidney, seems to be the hazardous factor to endothelial cells, thus promoting atherosclerosis and thrombosis in CS-deficient patients.
Different Requirement of Intracellular Calcium and Protein Kinase C for Arachidonic Acid Release and Serotonin Secretion in Cathepsin G-activated Platelets
Authors: Rotondo Serenella , Evangelista Virgilio , Manarini Stefano , Gaetano Giovanni de , Cerletti Chiara 
Published: July 2018

SummaryPrevious studies have shown that platelet stimulation with cathepsin G rapidly results in cytoplasmic calcium ([Ca2+]j) increase and activation of protein kinase C (PKC). To elucidate the relationship between these two biochemical events and their relative contribution to the regulation of platelet response to cathepsin G, arachidonic acid (AA) release and serotonin (5HT) secretion were studied. Platelets made Ca2+- depleted and -permeable by treatment with A23187 were compared to intact platelets to better dissociate calcium changes from other receptor- stimulated events. AA release elicited by cathepsin G in intact platelets was prevented by the Ca2+ chelator BAPTA; in Ca2+-depleted, -permeable platelets AA was released in direct response to added Ca2+ and was not increased by simultaneous stimulation with cathepsin G. In intact platelets, PKC inhibition by Ro 31-8220 or PKC induction with PMA either enhanced or reduced, respectively, cathepsin G-induced AA release. Both BAPTA and Ro 31-8220 prevented 5HT secretion from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin G was able to evoke 5HT secretion and p47 phosphorylation independently of [Ca2+]j increase, both effects being hampered by Ro 31-8220. Ca2+ and PKC therefore regulate PLA2 activity and 5HT secretion in cathepsin G-stimulated platelets in a different manner: the former is mainly triggered by [Ca2+]j increase, while PKC represents the major factor in determining dense granule secretion.
Perturbation of Platelet Adhesion to Endothelial Cells by Plasminogen Activation In Vitro
Authors: Chen Hsiun-ing , Wu Yueh-I , Hsieh Yu-Lun , Shi Guey-Yueh , Jiang Meei-Jyh , Chang Wen-Chang , Chuang Woei-Jer , Kan Wai-Ming , Tang Ming-Jer , Jen Chauying J 
Published: July 2018

SummaryTo investigate whether the endothelium-platelet interactions may be altered by plasminogen activation, cultured human umbilical vein endothelial cells (ECs) were treated with tissue-type plasminogen activator (t-PA) in the presence of plasminogen, and platelet adhesion to ECs was subsequently measured by using a tapered flow chamber. Our results demonstrated that platelets adhered more readily to t-PA treated EC monolayer than to the control monolayer at all shear stress levels tested. This phenomenon was treatment time-dependent and dose-dependent, and it could be blocked by adding plasmin inhibitors, such as e-amino caproic acid and aprotinin. Adherent platelets on t-PA treated EC monolayer underwent more severe shape change than those on the control monolayer. While the extracellular matrix directly treated with t-PA attracted less platelets than the control matrix did, platelet adhesion to the matrix that was produced by t-PA-treated ECs was unaltered. These data suggest that t-PA treatment on ECs compromised antiplatelet-adhesion capability on their apical surface without altering the reactivity of their extracellular matrix towards platelets.
Coagulation Disorders Caused by Hydroxyethyl Starch
Authors: Treib Johannes , Haass Anton , Pindur Gerhard 
Published: July 2018

SummaryInitially, hydroxyethyl starch (HES) was only characterized by its in vitro molecular weight (MW). This is not sufficient because HES is degraded in vivo. One relevant parameter that predicts the rate of enzymatic breakdown is the degree of substitution, a measure of the average number of hydroxyethyl groups per glucose unit. The higher this degree of substitution, the slower the break-down. In addition, because the glucose units can be substituted at carbon 2,3 and 6, different substitution patterns are possible. They are classified by their C2/C6 hydroxyethylation ratio. A higher C2/C6 ratio results in less metabolism of the starch in vivo and results in a larger in vivo MW. This in turn affects therapy, because the larger the in vivo MW, the longer is the duration of the volume effect of HES.Of particular importance is the fact that HES with a high in vivo MW affects factor VIII/von Willebrand factor which can lead to an acquired von Willebrand syndrome. During a 10-day volume therapy with a medium-MW HES 200, a form that is difficult to metabolize, we observed an 80% drop in factor VIII/von Willebrand factor. Therapy with a medium-MW HES 200, a form that is easily degraded, and therapy with a low-MW HES 70 did not result in a relevant decline of factor VIII/von Willebrand factor.This explains why hemorrhagic complications have been observed repeatedly in the United States after therapy with HES infusions, some of them lethal. In the United States high-MW HES 480 which is difficult to degrade is most frequently used and results in a larger in vivo MW and subsequent decrease in factor VIII/von Willebrand factor levels. In Europe, medium-MW HES 200 that is easily degraded and low-MW HES 70 are preferred. In the future, HES should be characterized by the in vivo, not the in vitro MW.