bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological Evidence for Prothrombin in Human Platelets
Authors: Alexander R J 
Published: July 2018

SummaryAn attempt was made to isolate from plasma the platelet surface substrate for thrombin, glycoprotein V (GPV), because a GPV antigen was reported to be present in plasma (3). Plasma fractionation based on procedures for purification of GPV from platelets revealed a thrombin-sensitive protein with appropriate electrophoretic mobility. The protein was purified; an antiserum against it i) reacted with detergent-solubilized platelet proteins or secreted proteins in a double diffusion assay, ii) adsorbed a protein from the supernatant solution of activated platelets, and iii) inhibited thrombin-induced platelet activation, but the antiserum did not adsorb labeled GPV. The purified protein was immunochemically related to prothrombin rather than to GPV. Other antibodies against prothrombin were also able to adsorb a protein from platelets. It is concluded that 1) plasma does not contain appreciable amounts of GPV, and 2) platelets contain prothrombin or an immunochemically similar protein.
The Anticoagulant Effect of Heparinoid Org 10172 During Haemodialysis: An Objective Assessment
Authors: Ireland Helen , Lane D A , Flynn Angela , Anastassiades E , Curtis J R 
Published: July 2018

SummaryThe heparinoid of natural origin Org 10172 has anti-factor Xa activity but minimal anti-thrombin activity, and little effect upon broad spectrum assays such as the KCCT in vitro. Its anticoagulant effects have been compared to those of commercial heparin in 7 patients undergoing haemodialysis for chronic renal failure. Commercial heparin was administered in a dose (5,000 iu bolus + 1,500 iu/hour continuous iv infusion) previously shown to inhibit fibrin formation during haemodialysis. This produced mean anti-factor Xa levels in plasma between 0.7-1.0 iu/ml and largely suppressed fibrin formation for 5 h dialysis measured as mean FPA levels in plasma. Administration of Org 10172 as a bolus of 1,350 anti-factor Xa u or 2,000-2,400 anti-factor Xa u produced plasma anti-factor Xa levels of less than 0.5 u/ml and allowed fibrin clot and FPA generation during dialysis. Org 10172 administered as a bolus dose of 4,000-4,800 anti-factor Xa u produced mean anti-factor Xa levels of greater than 0.5 u/ml, allowed dialysis of 6 patients for 5 h and appreciably suppressed FPA generation during dialysis, with little effect on the KCCT.It is concluded that the anti-factor Xa activity of Org 10172 may reflect its ability to inhibit fibrin during dialysis and that single bolus injection of Org 10172 may be a useful alternative method of achieving anticoagulation.
Identification of t-PA as the Major Active Plasminogen Activator in Human Milk
Authors: Marshall J M , Rees M C P , Cederholm-Williams S A 
Published: July 2018

SummaryHuman colostrum and milk contain high levels of plasminogen activator when compared with blood. These levels are inversely related to the duration of lactation and the activity appears to be due to tissue type plasminogen activator present in multiple (65-190 Kd) molecular weight forms.
Effects of a Thromboxane Synthetase Inhibitor and a cAMP Phosphodiesterase Inhibitor, Singly and in Combination, on Platelet Behaviour
Authors: Sills T , Heptinstall S 
Published: July 2018

SummaryThe effects of dazoxiben, a thromboxane synthetase inhibitor, and AH-P 719, a cAMP phosphodiesterase inhibitor, on arachidonic acid (AA)-induced platelet behaviour were determined. The levels of cAMP present in platelet-rich plasma (PRP) after stimulating the platelets with AA in the absence and presence of the agents were also measured.AH-P 719, as well as dazoxiben, was more effective as an inhibitor of AA-induced platelet behaviour in PRP from some individuals than in PRP from others, and the effectiveness with which it inhibited platelet behaviour paralleled that of dazoxiben. A combination of both agents was more effective than either agent alone.Both AH-P 719 and dazoxiben increased the level of cAMP in AA-stimulated platelets but again they were more effective in PRP from some individuals than others. A combination of AH-P 719 and dazoxiben always resulted in higher levels of cAMP than either agent alone.These results imply that cAMP is involved in determining the effects of thromboxane synthetase inhibitors on platelet behaviour, and indicate that the anti-thrombotic potential of a combination of a thromboxane synthetase inhibitor and a cAMP phosphodiesterase inhibitor may be greater than that of the individual agents.
Fibrinolytic Activity and Protein C in Preeclampsia
Authors: Aznar J , Gilabert J , Estellés A , España F 
Published: July 2018

SummaryVarious parameters of the fibrinolytic system and antigenic and functional protein C and its inhibitor were studied during normal pregnancy and in patients with preeclampsia.The fast acting tissue-type plasminogen activator inhibitor level was found to increase progressively during normal pregnancy. This increase was more evident in cases of severe preeclampsia (p<0.05). No variations were observed in protein C levels in normal pregnancies but a reduction in protein C level was noted in patients with severe preeclampsia (p<0.01). In preeclampsia, the protein C inhibitor level was higher than in normal pregnancy; it was also higher in normal pregnancy when compared to the control group.
Increase in Plasma Concentrationof Plasminogen Activator Inhibitor, Fibrinogen, von Willebrand Factor, Factor VIII: Cand in Erythrocyte Sedimentation Rate with Age
Authors: Aillaud M F , Pignol F , Alessi M C , Harle J R , Escande M , Mongin M , Juhan-Vague I 
Published: July 2018

SummaryElderly patients have previously been shown to have an increased plasma concentration of tissue plasminogen activator (t-PA) antigen (t-PAAg). Since the concentration of t-PA Ag dependson both free t-PA and t-PA complexed with inhibitors, mainly plasminogen activator inhibitor (PA inhibitor), we have investigated the relationship between the plasma concentration of PA inhibitor and age in 20 elderly and 20 young individuals. Elderly individuals showed a slight increase in PA inhibitor, in parallel with increase on others, acute-phase proteins, fibrinogen, von Willebrand factor, factor VIII :C, and the erythrocyte sedimentation rate. The increase i PA inhibitor as well as other acute-phase proteins in the elderly may be significant in relation to the increased incidence of thrombotic disease.
A Low Molecular Weight Heparin Alters the Fetal Coagulation System in the Pregnant Sheep
Authors: Andrew M , Ofosu F , Fernandez F , Jefferies A , Hirsh J , Mitchell L , Buchanan M R 
Published: July 2018

SummaryStandard heparin and a LMWH, CY222 do not cross the placenta nor alter fetal coagulation when injected into the pregnant ewe. We found that another LMWH, Pharmuka-10169 (PK-10169) alters fetal coagulation without crossing the placenta in the pregnant sheep. To characterize this anticoagulant we measured the in vitro and in vivo effects of 125I-PK-10169 in maternal and fetal plasmas following administration of PK-10169 to the mother or fetus. The fetal anticoagulant activity was not neutralizable by protamine sulphate and was attributable to the inhibition of thrombin but not factor Xa. In vitro, the fetal anticoagulant activity had properties similar to dermatan sulphate : both catalyzed the inhibition of thrombin but not factor Xa by sheep plasma; and neither was neutralizable by protamine sulphate. These effects were due to the enhanced neutralization of thrombin by heparin cofactor II. We conclude that PK-10169 does not cross the placenta, but does induce the release of an endogenous dermatan sulphate-like substance which alters fetal coagulation.
Platelet Behaviour in Non-Insulin-Dependent Diabetes -Influence of Vascular Complications, Treatment and Metabolic Control
Authors: Peacock I , Hawkins M , Heptinstall S 
Published: July 2018

SummaryPlatelet-rich plasma was prepared from 47 patients with noninsulin-dependent diabetes treated with glibenclamide and metformin, and 21 controls. The release of radio-labelled 5-hydroxy-tryptamine in response to aggregating agents (adenosine diphosphate, adrenaline and sodium arachidonate), and the effects on release of a selective thromboxane inhibitor (UK-34787) were investigated. Subsequently, 20 of the diabetic subjects were chosen at random for treatment with insulin; the remainder continued to take tablets. Platelet studies were then repeated, in all patients, after 4 and 6 months.The results showed an association between platelet behaviour and the presence of vascular complications, and were consistent with previous observations of reduced platelet reactivity in patients taking sulphonylureas. There was no correlation of platelet reactivity with blood glucose, glycosylated haemoglobin or lipid levels.
Differences in Coagulation and Haemostatic Parameters in Normal Women of Childbearing Age from Different Ethnic Groups and Geographical Locations
Authors: Bocaz J A , Barja P , Bonnar J , Daly L , Carrol A , Coutinho E , Goncalves M , Tsakok M , Koh S , Thomson J M , Poller L , Heady A , Holck S , Pinol A 
Published: July 2018

SummaryA comparative study of coagulation and fibrinolytic laboratory parameters was undertaken in four countries (Salvador, Brazil; Singapore; Santiago, Chile and Dublin, Ireland) among apparently healthy women of reproductive age. A continuous external quality control scheme of the laboratory measurements was employed to permit comparison among centres. Significant and consistent differences were found between the four centres. In Dublin, the prothrombin time and activated partial thromboplastin time (APTT) were accelerated, and the specific factor assays showed more activity, whereas the antiprotease levels were higher than in the other centres. In Salvador, a contrasting tendency was found with longer prothrombin times and APTT and lower Factor VII and antiprotease levels. The results from the other two centres were approximately midway between these two extremes. The study has revealed important differences in the coagulation and haemostatic tests between women from widely diverse geographical areas. It is not certain whether these are due to ethnic, nutritional or economic factors but they may be related to the apparent varying incidence of thrombosis in these ethnic groups.
Low Molecular Weight Heparin (KABI2165) as Thromboprophylaxis in Elective Visceral Surgery
Authors: Koller Matthias , Schoch Ursula , Buchmann Peter , Largiadèr Felix , von Felten Arthur , Frick Paul G 
Published: July 2018

SummaryIn two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 x 7′500 anti-factor Xa IU LMW heparin daily with 2 x 5′000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p <0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 x 2′500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups.2′500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.
Interleukin 1 Stimulates Endothelial Cell Tissue Factor Production and Expression by a Prostaglandin-Independent Mechanism
Authors: Schorer Anna E , Kaplan Manuel E , Rao Gundu H R , Moldow Charles F 
Published: July 2018

SummaryActivation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.
The Interaction of the Factor Vlll/von Willebrand Factor Complex with Hematin
Authors: Green David , Furby Fiona H , Berndt Michael C 
Published: July 2018

SummaryIntravenous infusion of hematin, used in the treatment of acute porphyria, induces a decline in the plasma factor VIH/von Willebrand factor complex (VIII/vWF) and thrombocytopenia. We investigated this problem by studying the interaction between hematin, purified VIII/vWF, and platelets in vitro. Hematin was labeled with either 59Fe or 3H and characterized by gel chromatography. Hematin self-aggregated, forming a complex with an average molecular weight of approximately 10,000 daltons. When incubated with VIII/vWF for 30 min at 37° C and applied to Sepharose CL-4B, the hematin eluted with the VIII/vWF in the void volume. Hematin inhibited the dissociation of factor VIII antigen (VIII :Ag) from the von Willebrand antigen (vWF:Ag) in 0.25 M CaCl2, and reversed the aggregation of VIII:Ag induced by 0.1 M 6-aminocaproic acid. Both hematin and the hematin-VIII/vWF complex bound to washed normal platelets and to platelets from a patient with Bemard-Soulier syndrome. Thromb-asthenic platelets were not aggregatable by hematin, and bound significantly less hematin-VIII/vWF than normal platelets suggesting that hematin-induced platelet activation was required for binding. Likewise, binding was inhibited by PGE1 which also prevented aggregation. We conclude that hematin forms complexes with VIII/vWF, alters the functional activity and dissociation of this compound, and participates in the binding of VIII/vWF to platelets.
Comparative Study of Size, Total Protein, Fibrinogen and 5-HT Content of Human and Canine Platelet Density Subpopulations
Authors: Mezzano Diego , Aranda Eduardo , Foradori Arnaldo 
Published: July 2018

SummaryThe size, total protein, fibrinogen and 5-HT content were evaluated in density subpopulations of human and canine platelets fractionated in linear arabinogalactan gradients. The methodology was assessed to ascertain that platelet separation was by density and to discard artifactual changes and platelet release during the procedure. EDTA or PGEi increased the size of human PRP-platelets, but not of dog platelets. In humans, high density (HD) platelets were 1.26 times larger and contained 1.88 times more fibrinogen, 2.23 times more 5-HT and 1.37 times more protein than low density (LD) platelets; in dogs, these density cohorts did not differ in protein content, but LD platelets were 1.29 times larger and had 1.33 times more fibrinogen and 5-HT than HD platelets. These findings suggest that cell density is mostly dependent on the protein content per unit volume of platelets (and not on dense bodies). The differences in fibrinogen and 5-HT content between HD and LD cohorts in humans and dogs may be related to platelet age. The difference in volume between HD and LD platelets in dogs is of uncertain interpretation.
Verapamil Inhibits Platelet Aggregation by a Calcium-Independent Mechanism
Authors: Bonadonna Giovanni , Lechi Clara , Corradini Paola , Sinigaglia Daniela , De Togni Piero , Miroslawa Grzeskowiak 
Published: July 2018

SummaryWe studied the inhibitory effects of the calcium channel blocker verapamil both on platelet aggregation and intracellular calcium [Ca2+]i in platelets loaded with a fluorescent indicator (quin 2).The inhibitory effects of verapamil on the platelet aggregation response to both thrombin and ionomycin were seen to be clearly dissociated from the verapamil-induced inhibition of the [Ca2+]i increase produced by these agonists. Verapamil-induced inhibition of platelet aggregation was also obtained when using the “calcium-independent” agonist phorbol-myristate acetate (PMA). It may be deduced that a calcium-independent mechanism plays a role in verapamil-induced inhibition of platelet aggregation. We postulate that this mechanism may operate via a protein-kinase C pathway.
Intrathoracic Platelet Accumulation in the Guinea-Pig Induced by Intravenous Administration of Arachidonic Acid - Effect of Cyclooxygenase and Thromboxane Synthetase Inhibitors
Authors: Barrett P A , Butler K D , Shand R A , Wallis R B 
Published: July 2018

SummaryIntravenous administration of arachidonic acid to guinea-pigs caused a dose-related, rapid accumulation of 51Cr-labelled platelets in the thorax. Inhibitors of cyclooxygenase inhibited the platelet accumulation, induced by arachidonic acid (30 mg/kg), at doses which did not alter the thoracic blood volume (as measured by 131I-labelled human albumin). Thromboxane synthetase inhibitors had different effects on platelet accumulation depending on the dose. CGS 12970 (3 mg/kg) and N(1-carboxyheptyl) imidazole (100 mg/kg) reduced platelet accumulation. High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes. This increase in thoracic blood volume was abolished if the guinea-pigs were also pretreated with diclofenac (1 mg/kg) in addition to the thromboxane synthetase inhibitor. Increases in thoracic blood volume were also obtained following infusions of PGI2 but not PGD2 or PGE2.
Different Effects of Aspirin, Dipyridamole and UD-CG 115 on Platelet Activation in a Model of Vascular Injury: Studies with Extracellular Matrix Covered with Endothelial Cells
Authors: Eldor A , Vlodavsky I , Fuks Z , Muller T H , Eisert W G 
Published: July 2018

SummaryCultured endothelial cells produce an extracellular matrix (ECM) which activates platelets, similarly to deendothelialized vascular segments. Platelet-rich plasma (PRP) was incubated with endothelial cells cultures seeded in various densities on ECM. The interaction of the platelets with this artifical intima was evaluated by phase microscopy and by thromboxane A2 (TXA2) and prostacyclin (PGI2) measurement. Large platelet aggregates were formed on exposed ECM. Platelets aggregation but not adhesion on the ECM was markedly inhibited by the presence of endothelial cells. Pretreatment of the endothelial cells with 0.1 mM aspirin reduced their PGI2 synthesis and was associated with platelet aggregation on the ECM. 10 μM dipyridamole markedly inhibited platelet activation by ECM when the drug was added to citrated whole blood before PRP preparation. UD-CG 115 which elevates cyclic AMP in cardiac muscle, inhibited platelet aggregation and TXA2 production induced by ECM, in the presence as well as in the absence of endothelial cells, without any effect on endothelial PGI2 production.
Characterization of an Abnormal Antithrombin (Milano 2) with Defective Thrombin Binding
Authors: Tripodi A , Krachmalnicoff A , Mannucci P M 
Published: July 2018

SummaryFour members of an Italian family (two with histories of venous thromboembolism) had a qualitative defect of antithrombin III reflected by normal antigen concentrations and halfnormal antithrombin activity with or without heparin. Anti-factor Xa activities were consistently borderline low (about 70% of normal). For the propositus’ plasma and serum the patterns of antithrombin III in crossed-immunoelectrophoresis with or without heparin were indistinguishable from those of normal plasma or serum. A normal affinity of antithrombin III for heparin was documented by heparin-sepharose chromatography. Affinity adsorption of the propositus’ plasma to human α-thrombin immobilized on sepharose beads revealed defective binding of the anti thrombin III to thrombin-sepharose. Hence the molecular defect of this variant appears to be at the active site responsible for binding and neutralizing thrombin, thus accounting for the low thrombin inhibitory activity.
The Plasmin Heavy Chain - Urokinase Conjugate: A Specific Thrombolytic Agent
Authors: Nakayama Y , Shinohara M , Tani T , Kawaguchi T , Furuta T , Izawa T , Kaise H , Miyazaki W , Nakano Y 
Published: July 2018

SummaryLow molecular weight urokinase (LMW-UK) was coupled to the heavy chain of plasmin to make it able to bind to fibrin. The purified conjugate (PHC-UK conjugate), which consisted of equimolar concentrations of each starting material had a molecular weight of 93,600, bound tightly to fibrin-monomer-Sepharose and was not washed off with 1 M NaCl, but was eluted specifically with s-amino caproic acid. The conjugate showed higher fibrinolytic activity than HMW-UK. A control conjugate prepared by coupling human serum albumin to LMW-UK (HSA-UK conjugate) showed the same fibrinolytic activity as HMW-UK. The half-lives of these two conjugates in rabbits were about 3 times that of HMW-UK. In an experimental pulmonary embolism model in rabbits, the PHC-UK conjugate showed about 10 times higher thrombolytic activity than HMW-UK, while the HSA-UK conjugate showed similar thrombolytic activity as HMW-UK, and moreover caused severe systemic fibrinogen breakdown. Thus the significant increase in thrombolytic activity after injection of PHC-UK conjugate into rabbits may be due to its newly acquired fibrin binding activity, and not to increase in its half-life. It is concluded that the PHC-UK conjugate may be useful in treatment of thrombosis.
The Negative Impact of Biological Variation in the Effect and Clearance of Warfarin on Methods for Prediction of Dose Requirements
Authors: Weiss Peretz , Halkin Hillel , Almog Shlomo 
Published: July 2018

SummaryWithin-individual variation over time in the clearance (Cl) and effect (PT%) of warfarin, was measured in 25 inpatients (group I) studied after standard single or individualized split loading doses and 1-3 times (n = 16) 8-16 weeks later during maintenance. Mean Cl (2.5 α 0.9 ml/min) was similar in both phases but significant changes occurred in 6/16 patients, exceeding those expected from within-individual variation alone (defined by its 95% tolerance limits -24% to +62%). Initial PT% (21 α 5) was unaffected by dosing schedule, total or free plasma warfarin, varying between patients by only 18-24%. Mean initial and maintenance dose-PT% ratios (8.2 mg/d: 21% and 4.1 mg/d: 40%) were similar but significant changes in sensitivity to warfarin occurred in 4/16 patients. In group I and 64 other outpatients on maintenance therapy, between-individual variability was 36-52% for Cl and 49-56% for effect. PT% correlated best (r = 0.56) with free and total plasma warfarin but poorly with dose (r = 0.29), with only 30% of PT% variance explained at best, due to high between patient variability.Warfarin dose prediction whether based on extrapolation from initial effects to the maintenance phase, or on iterative methods not allowing for between- or within-patient variation in warfarin clearance or effect which may occur independently over time, have not improved on empirical therapy. This, due to the elements of biological variability as well as the intricacy of the warfarin - prothrombin complex interaction not captured by any kinetic-dynamic model used for prediction to date.