bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coagulation and Fibrinolytic Activity in Behçet's Disease
Authors: Hampton K K , Chamberlain M A , Menon D K , Davies J A 
Published: July 2018

SummaryCoagulation and fibrinolytic activities were studied in 18 subjects with Behçet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behçet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/1, p <0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p <0.002; plasminogen activator activity (106/ECLT2) 219 (94-329) vs 137 (78-197) units, p <0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p <0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p <0.002. Protein C antigen was significantly lower: 97 (70-183) vs 126 (96-220)%, p <0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and Bβ15-42, plasminogen, α-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behçet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behçet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behçet's disease was detected.
Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity
Authors: Sane David C , Moser Tammy L , Greenberg Charles S 
Published: July 2018

SummaryVitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN.Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.
Loss of Thrombin-Induced Ca2+ Mobilization in a Subpopulation of Platelets during Storage
Authors: Fijnheer Rob , Homburg Christa H E , Hooibrink Berend , Boomgaard Martine N , de Korte Dirk , Roos Dirk 
Published: July 2018

SummaryThrombin-induced changes in cytosolic free Ca2+ ([Ca2+]i) were studied in human platelets that had been stored for up to 6 days. Changes in [Ca2+]i were measured with Indo-1-loaded platelets and quantitated with two different methods: (i) measurement of the changes in total fluorescence; (ii) measurement of the [Ca2+]i changes in individual platelets in a flow cytometer, allowing the detection of non-responding platelets. The maximal concentration of [Ca2+]i after stimulation with 0.5 U of thrombin/ml decreased from 544 ± 58 nM (mean ± SEM, n = 6) on day 0, to 276 ± 9 nM on day 3 and to 203 ± 23 nM on day 6. The percentage of platelets responding to 0.5 U of thrombin/ml declined from 90 ± 2% on day 0 to 72 ± 4% on day 3, and to 47 ± 8% on day 6. Nevertheless, also the responding platelets showed a decreased rise in [Ca2+]i.The study shows that during platelet storage a decrease in the rise in [Ca2+]i upon thrombin stimulation occurs. This decrease is partly due to the formation of a subpopulation of platelets that is completely unresponsive and partly due to a decreased responsiveness in the remainder of the platelets; it is not due to a gradual decline in [Ca2+]i rise in all platelets. This phenomenon provides new insight in the functional defect of stored platelets.
Plasminogen Activators t-PA, u-PA and Its Inhibitor (PAI) in Normal Males and Females
Authors: Koh Stephen C L , Yuen R , Viegas O A C , Chua S E , Ng B L , Sen D K , Ratnam S S 
Published: July 2018

SummaryWe determined the plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity and their antigen levels including urokinase plasminogen activator (u-PA) in 33 male and 27 female normal subjects. Males had mean t-PA activity of 0.50 iu/ml which was significantly lower (p <0.01) than the females 0.64 iu/ml. Males had higher (p <0.001) mean PAI activity (15.5 AU/ml) as compared to females 10.3 AU/ml. The respective mean levels of t-PA and PAI antigen were significantly higher (p <0.01) in males (8.1 ng/ml and 17.6 ng/ml) than in females (6.2 ng/ml and 12.1 ng/ml). The mean u-PA level in males was 1.54 ng/ml which was significantly higher (p <0.01) than in females with 1.02 ng/ml. In post-venous occlusion studies, females had a greater mean response of 8.6 fold in t-PA activity as compared to males with a mean of 4.5 fold increase. The mean t-PA antigen response in males was 2.0 fold increase as compared to 2.6 fold increase in the females. No significant responses were seen in both sexes in either PAI activity or antigen levels when compared with the resting state. In zymography studies, free t-PA, its inhibitor complexes and u-PA were demonstrated in the euglobulin fractions of stored plasma. This study demonstrates that significant differences in t-PA, u-PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions.
The Measurement of Haemostatic Factors in 16 European Laboratories: Quality Assessment for the Multicentre ECAT Angina Pectoris Study
Authors: Thompson S G , Duckert F , Haverkate F , Thomson J M 
Published: July 2018

SummaryAs part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first Qa exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre’s performance in comparison to that of others was adopted, which preserved the confidentiality of each centre’s results. The factor VIII clotting activity assay (VIII: C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest betweenduplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWFR:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.
High Risk of Acquired Immune Deficiency Syndrome (AIDS) and of AIDS Related Complex (ARC) in Hemophiliacs Seropositive for more than 5 Years
Authors: Stain C , Pabinger-Fasching I , Guggenberger K , Köller U , Stain M , Hartl H , Heinz F , Mayerhofer S , Kyrle P A , Lechner K , Korninger C 
Published: July 2018

SummaryA group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 patients have developed the lymphadenopathy syndroffie, 9 patients AIDS and 11 patients ARC (CDC IV C 2). 6/9 cases of AIDS and 10/11 cases of ARC have occurred only after 1985. Patients, who subsequently became symptomatic, had significantly higher IgG levels in 1983, otherwise no predictive laboratory tests were identified. Patients with T4 counts above 500/μl became symptomatic later, but after 5 years the indicence of AIDS was comparable in patients with original T4 counts of more than or below 500/μl.
Platelet Distribution in Rabbits Following lnfusion of Liposomes
Authors: Doerschuk Claire M , Gie Robert P , Bally Marcel B , Cullis Pieter R , Reinish Lawrence W 
Published: July 2018

SummaryThis investigation determined the organ distribution of liposomes containing egg phosphatidylcholine and cholesterol with egg phosphatidylglycerol (PG liposomes) or without (PC liposomes) and the effect of each liposome on platelet distribution in rabbits. Eight minutes after51 chromium-labelled platelets were given intravenously, either saline (n = 7), iodinated PG liposomes (n = 5) or iodinated PC liposomes (n = 5) were infused. T\ro minutes later the organ distribution of 51Cr-platelets and 125I-liposomes were compared. The PG liposomes produced a 41λ5% reduction in circulating platelet counts while PC liposomes did not. The PG liposomes decreased circulating 51Cr-platelets by a factor of 2 and increased platelet recoveries in the liver and lungs. The increased platelet recovery in the liver was associated with a greater PG liposome recovery. When animals receiving PG liposomes were studied over 60 minutes, both the labelled and unlabelled platelet counts returned to control values by 30 minutes and the 51Cr-platelet distribution between organs was similar to control values. These data indicate that platelets and PG liposomes initially sequester together and that this plateletliposome interaction is specific for PG liposomes. However, the platelet sequestration is transient and by 60 minutes the platelets were released and circulating.
The Effect of Vascular Cell Seeding on Platelet Deposition in an In Vitro Capillary Perfusion Model
Authors: Dekker A , Poot A , Beugeling T , Bantjes A , van Aken W G 
Published: July 2018

SummaryIn view of the reported beneficial effects of cell seeding on the performance of synthetic vascular grafts, we determined the deposition of 111Indium-labelled human platelets in polyethylene capillary tubes covered with human endothelial cells (HEC) or smooth muscle cells (SMC) using an in vitro perfusion model. Platelet deposition decreased with increasing vascular cell coverage and was virtually absent when the number of adherent vascular cells of both types exceeded 50,0001cm2. Platelet deposition increased with increasing she ar rate (300-900 s-1) only when surface coverage was less than 50,000 vascular cells/cm2.Deposition of Ca2+-ionophore A 23187-activated platelets in capillary tubes completely covered with SMC was significantly higher compared to capillaries covered with a similar number of HEC.When HEC-lined capillaries were treated with aspirin, only the deposition of activated platelets increased slightly, but significantly. This platelet reactivity was more evident when the endothelial lining was not confluent.These results demonstrate that, although seeding of HEC and SMC may both prevent the deposition of non-activated platelets to surfaces, non-aspirin-treated confluent HEC linings offer the best protection against deposition of activated platelets.
Detection of Lupus-Like Anticoagulants by an Enzyme-Linked Immunosorbent Assay Using a Partial Thromboplastin as Antigen; A Comparative Study
Authors: Arnout J , Huybrechts E , Vanrusselt M , Falcon C , Vermylen J 
Published: July 2018

SummaryClotting assays allow qualitative rather than quantitative detection of the lupus anticoagulant. We have therefore studied the usefulness of an ELISA using a commercial partial thromboplastin, Thrombofax, oS antigen; the results obtained on 146 selected patient plasmas were compared to the results of coagulation tests (kaolin clotting time, tissue thromboplastin inhibition test, activated partial thromboplastin time) and of ELISAs using cardiolipin or phosphatidylserine as antigen. While satisfactory agreement was found within the group of coagulation tests or that of ELISAs, only a moderate agreement was obtained between clotting tests and ELISAs, the best being with the partial thromboplastin ELISA using low plasma dilutions. The study further indicates that ELISA techniques cannot entirely replace coagulation tests for the detection of a lupus anticoagulant, even when a partial thromboplastin is used as antigen. On the other hand, coagulation tests are less sensitive than ELISAs for the detection of antiphospholipid antibodies.
Physical Exercise Enhances Plasma Levels of Extrinsic Pathway Inhibitor (EPI)
Authors: Hansen John-Bjarne , Olsen Jan-Ole , Østerud Bjarne 
Published: July 2018

SummaryThe risk of cardiovascular complications is reported to be several times higher in severe exercise than in daily activity. EPI-mediated inhibition of factor VTIa/thromboplastin enzymatic activity is believed to be an important modulator of blood coagulation during hemostasis. The plasma concentration of EPI, corrected for changes in plasma volume, was determined in healthy male subjects prior to, immediately after and at various time intervals after strenuous exercise of different duration. A slight, but significant decrease in EPI (7.5 ± 2.8%, p <0.03) was found after a short term run (1.7 km), whereas no significant change was seen after a middle term run (4.8 km). In contrast, we observed a marked increase in EPI after a long term run (20.3 ± 6.9%, p <0.03) and in a second group of athletes participating in the Norwegian championship of 30 km cross country skiing (39.9 ± 10.3%, p <0.02). A peak value was reached 2 h after the run, and after that the curve started to approach baseline values. The rise in EPI might reflect a significant release of EPI from the endothelium that is greater than eventually any consumption. Another explanation for this enhancement in EPI might be that the increase in lipoprotein lipase activity after physical exercise causes a rise in the availability of EPI since EPI is known to be associated with lipoproteins in the circulation.It is hypothesized that mobilization of EPI during extensive physical exercise may suppress activation of the clotting system.
Bleeding Times in Rats Treated with Heparin, Heparin Fragments of High and Low Anticoagulant Activity and chemically Modified Heparin Fragments of Low Anticoagulant Activity
Authors: Palm Maud , Mattsson Christer , Svahn Carl Magnus , Weber Michael 
Published: July 2018

SummaryA template bleeding time study in the rat was undertaken to see if it is possible to correlate bleeding times with the molecular weight, anticoagulant activity or chemical composition of heparin or heparin-derived compounds. Heparin from porcine intestinal rnucosa (PM-heparin) and from bovine lung (BL-heparin) as well as heparin fragments from these sources were compared. Heparin fragments of low anticoagulant activity were prepared by affinity chromatography on immobilized antithrombin as well as by chemical modification. A heparin fragment of high affinity for antithrombin (HA-fragment) caused a marked and dose-dependent increase in bleeding time while the corresponding heparin fragment with low affinity for antithrombin (LA-frugment) had a marginal and non-dose dependent effect on the bleeding time. Similar results were also obtained with PM-heparin with high and low affinity for antithrombin. A high anti-FXa activity was not always correlated with a marked bleeding tendency. Provided that a fragment was devoid of activated partial thromboplastin time (APTT) activity, it was not possible to provoke a bleeding time of 20 min or longer, although the compound was administered at a dose of 1,088 U/kg (anti-FXa activity). On the other hand, & Nacetylated chemically oversulphated heparin fragment, with a very low anti-FXa activity (1 U/mg) and with an APTT activity of 34UlmtB, caused a bleeding time of 20 min or longer in 70% of the animals after injection of the same number of Aprr units, 1,088 U/kg. These data indicate that the APTT activity is a better and more sensitive indicator of the bleeding than is the anti-FXa activity.
Primary and Secondary Lysosomes in Megakaryocytes and Platelets from Cattle with the Chediak-Higashi Syndrome
Authors: Ménard Michèle , Meyers Kenneth M , Prieur David J 
Published: July 2018

SummaryThe ultrastructure of lysosomes from megakaryocytes (MK) and platelets of cattle with the Chediak-Higashi syndrome (CHS) was characterized using acid phosphatase histochemistry with beta-glycerophosphate as substrate and cerium as a capturing agent. Acid phosphatase was localized in the trans aspect of the Golgi complex and/or granules in MK at all stages of maturation. Morphometric analysis of the diameter of each lysosome was performed on MK from CHS cattle and compared to MK from normal cattle. Lysosomes in CHS MK were neither enlarged nor different with respect to classification as secondary lysosomes, which composed 35% of the lysosomes in CHS MK. Lysosomes were demonstrated in 22% of the CHS platelet sections and appeared similar to those from normal cattle, 56% of them being classified as secondary lysosomes. Why lysosomes are not enlarged in bovine CHS MK and platelets, whereas they are enlarged in most other cell types, remains unknown.
The Binding of Phosphatidylglycerol Liposomes to Rat Platelets Is Mediated by Complement
Authors: Loughrey H C , Bally M B , Reinish L W , Cullis P R 
Published: July 2018

SummaryPrevious work has shown that intravenous administration of phosphatidylglycercol (PG) containing liposomes to rats results in a rapid transient decline in platelet count (1). Here the interactions of PG liposomes with rat platelets in vitro have been examined with the aim of charactenzing factors associated with the decline. It is shown that PG liposomes induce formation of rat (but not human) platelet-liposome microaggregates in vitro. The PG liposome dependent thrombocytopenia observed in vivo can therefore be attributed to sequestration of PG liposome-platelet aggregates. Further, the aggregation of platelets with PG liposomes, which can be moni ored as a reduction in platelet count using a coulter counter, is shown to be mediated by a serum complement fgctor, likely C3b. This is indicated by a requirement of plasma for the in vitro reduction in platelet count induced by PG liposomes, and the inhibition of this effect by heat treatment of plasma, by incubation of plasma with purified cobra venom factor, or by removal of C3 from plasma.
Hereditary Protein S Deficiency in Young Adults with Arterial Occlusive Disease
Authors: Allaart C F , Aronson D C , Ruys Th , Rosendaal F R , van Bockel J H , Bertina R M , Briët E 
Published: July 2018

SummaryProtein S is the vitamin K dependent cofactor of activated protein C. It has an important role in the regulation of blood coagulation and fibrinolysis. Hereditary protein S deficiency is associated with familial venous thrombophilia. Since a few patients with arterial occlusions have been reported to be protein S deficient, it is speculated that hereditary protein S deficiency may be also a risk factor for the development of arterial thrombosis. In a group of 37 consecutive patients with arterial occlusive disease presenting before the age of 45, three patients were found heterozygous for hereditary protein S deficiency. None of the patients had a protein C deficiency or an antithrombin III deficiency. Family investigations showed a clear association between the hereditary deficiency and venous thrombosis, but a relation between the deficiency and arterial thrombosis was less obvious. A review of previous literature on patients with arterial thrombosis and protein S deficiency revealed that more extensive studies are needed to demonstrate whether or not hereditary protein S deficiency is a risk factor for the development of arterial thrombosis.
Isolation and Characterization of a Coagulation Factor Xa Inhibitor from Black Fly Salivary Glands
Authors: Jacobs John W , Cupp Eddie W , Sardana Mohinder , Friedman Paul A 
Published: July 2018

SummaryWe have discovered and charact enzed a novel coagulation
factor Xa inhibitor from the salivary gland of the black fly, Simulium vittatum. Salivary glands were surgically dissected from the flies and a crude salivary gland extract was tested for inhibition of a number of coagulation assays. The gland extract inhibited both thrombin and factor Xa. Tic purify further the factor Xa inhibitor, a factor Xa affinity column was utilized. Final purification of the black fly factor Xa inhibitor was achieved by reverse-phase C8 microbore high pressure liquid chromatography. Inhibition of factor Xa was nearly stoichiometric by the purified inhibitor with no inhibitor of thrombin detected. SDSpolyacrylamide gel electrophoresis indicated the inhibitor had a molecular weight of 18,000 and sequence analysis of the inhibitor revealed a blocked amino terminus. These data indicate that the blood-sucking black fly has evolved a highly potent inhibitor of mammalian coagulation factor Xa to disrupt its host normal hemostatic clotting mechanisms.
Validation of a Procedure for Potency Assessing of a High Purity Factor VIII Concentrate -Comparison of Different Factor VIII Coagulant Assays and Effect of Prediluent
Authors: Mazurier Claudine , Parquet-Gernez Armelle , Goudemand Maurice 
Published: July 2018

SummaryThe assessment of factor VIII coagulant activity (FVTII: C) in recently available highly purified and concentrated FVTII therapeutic products calls for careful evaluation of assay methodologies. We assayed more than 130 batches of a concentrate with a specific activity of about 150 FVTII :C units/mg protein, using one-stage and two-stage clotting and chromogenic methods. There was good agreement between the potency estimates obtained with the different methods. We also compared the FVTII :C potencies obtained after predilution in buffer or FVIII-deficient plasma using either calibrated plasma or FVTII concentrate as references. With the one-stage assay we found a marked discrepancy between the potency values obtained with buffer and with FVTII-deficient plasma used as prediluents. In order to validate our “in vitro” data we performed 6 “in vivo” analyses in severe haemophilia A patients. On the basis of the overall data obtained we chose to label FVIII potency by using FVIII-deficient plasma as prediluent, reference plasma as standard and the chromogenic assay method.
Potentiation of the Antithrombotic Action of Dermatan Sulphate by Small Amounts of Heparin
Authors: Thomas D P , Gray E , Merton R E 
Published: July 2018

SummaryWe have examined the effect in impairing thrombus formation of a preparation of dermatan sulphate (DS) alone and DS plus small amounts of unfractionated heparin (UFH). In rabbits given a dose of 150 μg/kg of DS alone, there was minimal reduction in serum-induced stasis thrombosis (Wessler model), with an overall score of 92.5% (100% = no impairment of thrombus formation). When the same dose of DS containing UFH was given (two different subgroups given DS containing 0.25 and 2.5% heparin by dry weight, respectively), the overall thrombus score was reduced to 60% (P <0.003), with no significant difference between the two subgroups. To achieve a comparable result with DS alone, a dose of 1 mg/kg was required. We conclude that very small amounts of UFH significantly enhance the antithrombotic action of DS, by a mechanism that has yet to be determined.