bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemostatic Responses to Mental Stress during the Menstrual Cycle
Authors: Jern Christina , Manhem Karin , Eriksson Elsa , Tengborn Lilian , Risberg Bo , Jern Sverker 
Published: July 2018

SummaryTo study the effect of sex hormones on the hemostatic responses to stress, blood samples were collected before, during, and after 20 min of mental stress from 9 healthy, non-smoking female volunteers, examined in the follicular and luteal phase. Mental stress caused significant increases in heart rate, blood pressure, and plasma catecholamines. In addition, analysis of variance indicated significant changes of leukocyte count, hematocrit, fibrinogen, von Willebrand factor antigen, t-PA activity and antigen in response to the stress test. However, in contrast to a male group previously investigated, there were no significant changes in factor VII coagulant activity in either menstrual phase. Overall the responses were more pronounced in the luteal as compared to the follicular phase. The findings support the concept that both gender and physiological variations in female sex hormones may modulate hemostatic responses to psychosocial stress.
Comparison of Real-Time B-Mode Ultrasonog raphy and Bilateral Ascending Phlebography for Detection of Postoperative Deep Vein Thrombosis Following Elective Hip Surgery
Authors: Borris Lars C , Christiansen Hanne M , Lassen Michael R , Olsen Agnete D , Schøtt Peder ,   (The Venous Thrombosis Group)
Published: July 2018

SummaryA prospective study compared real-time B-mode ultrasound examination with bilateral ascending phlebography in the diagnosis of postoperative deep vein thrombosis in 60 patients undergoing elective total hip replacement. The overall sensitivity and specificity of the ultrasound method were 54 and 91%, respectively, and the positive and negative predictive values were 83 and 69%, respectively. The rather low overall sensitivity of the ultrasound method in this study was due to difficulty in detecting thrombi smaller than 1 cm wherever they were located in the deep veins, and in diagnosing thrombi in the calf, regardless of their size. We conclude that real-time B-mode ultrasonography is a technique that can easily be used routinely for detection of postoperative DVT in hip surgery, but its sensitivity for proximal thrombosis (63%) is too low for it to be used alone.
Binding of Tissue Plasminogen Activator to Cultured Human Fibroblasts
Authors: Reilly Thomas M , Whitfield Mark D , Taylon David S , Timmermans Pieter B M W M 
Published: July 2018

SummaryThe binding of 125I-labeled, one-chain tissue plasminogen activator (t-PA) by WI-38 cultured human lung fibroblasts was investigated. Binding of t-PA to WI-38 monolayers was specific, saturable and temperature dependent. One and two-chain t-PAs were comparable in their ability to compete with 125I-labeled, one- chain t-PA for binding to fibroblasts, while no inhibition of binding was observed with a 500-fold molar excess of urokinase. Studies with various compounds suggest that neither the catalytic site, the fibrin binding site, nor the carbohydrate moieties on t-PA are involved in its binding to WI-38 cells. At higher temperatures, the amount of cell-bound 125I-t-PA that was removed by either incubation in binding buffer containing an excess of unlabeled t-PA, or by brief treatment with acidic buffer, was small (approximately 20%) suggesting that much of the t-PA is internalized. Electrophoretic analysis of extracts prepared from cells that had been incubated with 125I-t-PA revealed the presence of a major band of 70,000 Mr, which corresponds to intact t-PA. Our results suggest that WI-38 fibroblasts are capable of binding and internalizing t-PA, and that these processes involve a receptor site specific for t-PA.
Separation of Plasminogen Activators from Human Plasma and a Comparison with Activators from Human Uterine Tissue and Urine
Authors: Kok Preben 
Published: July 2018

SummaryNormal human plasma contains acid-stable as well as labile plasminogen activators. The activity of activators in plasma euglobulins was inhibited by EACA in an uniform pattern, similar to that obtained with the major activators in human uterine tissue or with the purified porcine tissue activator, but different from the patterns obtained with plasmin or with urokinase.Gel filtration at high ionic strength separated activators corresponding to particle sizes of 60,000 dalton and about 10,000 dalton, corresponding to two activators similarly obtained from human tissue. The 60,000 dalton activator was precipitated in the euglobulin fraction. Its concentration increased in plasma after exercise. The 10,000 dalton activator was found mainly in the supernatant. Gel filtration in 0.15 M solutions yielded activators in fractions of molecular sizes of 100-140,000 dalton and 200,000 dalton or larger.The activity of normal and exercise euglobulins was inhibited by antiserum to a plasminogen activator prepared from porcine tissue, but it was not inhibited by antiserum to urokinase. Plasminogen activators in human plasma euglobulins resembled immunochemi- cally the activators in human uterine tissue.
Protein C Deficiency in Insulin-Dependent Diabetes: A Hyperglycemia-Related Phenomenon
Authors: Ceriello Antonio , Quatraro Antonio , Russo Patrizia Dello , Marchi Egidio , Barbanti Miriam , Milani Maria Rita , Giugliano Dario 
Published: July 2018

SummaryIn 30 insulin-dependent diabetic patients protein C (PC) antigen and PC activity were significantly lower than those of matched control healthy subjects. An inverse correlation between fasting plasma glucose and both PC concentration and activity was present in diabetics, while a direct correlation between PC concentration and PC activity was observed. Induced hyperglycemia in diabetic and normal subjects was able to decrease both PC antigen levels and PC activity, and heparin reversed in part this effect.In diabetic patients euglycemia obtained by insulin infusion restored to normal the depressed PC levels. Heparin did not alter both the basal PC concentration and activity in healthy controls.These data stress the major role of hyperglycemia in determining PC decrease in diabetics, and suggest that PC reduction is probably associated to hyperglycemia-enhanced thrombin formation.
Increased Monocyte Procoagulant Activity Independent of the Lupus Anticoagulant in Patients with Systemic Lupus Erythematosus
Authors: de Prost D , Ollivier V , Ternisien C , Chollet-Martin S 
Published: July 2018

SummaryMonocytes can play a role in the activation of coagulation via increased procoagulant activity (PCA). We investigated the level of monocyte PCA in 19 patients with systemic lupus erythematosus (SLE), given the high rate of thrombotic events in this condition. Nine of these subjects also presented the lupus anticoagulant (LA). The PCA generated by patient monocytes was significantly higher than control values and was identified as tissue factor-like. Moreover, the number of monocytes with membrane-associated D dimer, a parameter whieh we have shown to be correlated with the PCA expressed in vitro by endotoxin-activated monocytes, was also significantly increased. Serum from both groups of patients (i.e. SLE and SLE + LA) stimulated the generation of PCA by control monocytes. By contrast, purified IgG from both patient groups had the same effect as control IgG on PCA generation by control monocytes. The nature of the stimulating agent in the serum was not identified. In conclusion, increased monocyte PCA may account for the increased incidence of thrombosis in SLE patients, although other, superimposed, factors would appear to exist in SLE + LA patients, given the higher incidence of thrombosis in this subgroup.
Subcutaneous vs Intravenous Heparin in the Treatment of Deep Venous Thrombosis – A Randomized Clinical Trial
Authors: Pini M , Pattacini C , Quintavalla R , Poli T , Megha A , Tagliaferri A , Manotti C , Dettori A G 
Published: July 2018

Summary271 patients with acute symptomatic deep venous thrombosis of lower limbs, confirmed by strain-gauge plethysmography and/ or venography, were randomly assigned to receive intermittent subcutaneous heparin calcium or heparin sodium by continuous intravenous infusion for 6–10 days. Heparin dosage was adjusted to maintain activated partial thromboplastin time values (Throm-bofax reagent) at 1.3–1.9 times the basal ones. Strain-gauge plethysmography was repeated at the end of heparin treatment, and evaluation of therapy was performed by comparing the indexes of venous hemodynamics and by assessing the incidence of pulmonary embolism and of bleeding complications.In the intravenous group, Maximal Venous Outflow (MVO) increased from 20.8 ± 12.8 to 28.4 ± 17.5 ml/min per 100 ml of tissue and Venous Capacitance (VC) from 1.39 ± 0.92 to 1.94 ± 1.0 ml/100 ml of tissue (mean ± SD). In the subcutaneous group, MVO increased from 21.0 ± 12.7 to 27.5 ± 18.1 and VC from 1.60 ± 0.86 to 2.06 ± 1.0. The median improvement of MVO and VC were 22% and 36% respectively in the IV group and 20% and 24% in the SC group. Clinical pulmonary embolism occurred in 2 patients in the intravenous group (1 fatal) and in 4 in the subcutaneous group (1 fatal). 9 major bleeding complications occurred in the intravenous group (1 fatal) and 5 in the subcutaneous group (1 fatal). The differences were not significant at the statistical analysis.The results suggest that subcutaneous intermittent heparin has a comparable efficacy to continuous intravenous heparin in the treatment of deep venous thrombosis.To the same conclusion points an overview of the seven randomized trials which compared these treatment modalities.
Identification of Different Forms of Human C4b-Binding Protein Lacking β-Chain and Protein S Binding Ability
Authors: Hessing Martin , Kanters Deon , Hackeng Tilman M , Bouma Bonno N 
Published: July 2018

SummaryHuman C4b-binding protein (C4BP) is a multimeric regulatory component of the complement system that circulates in plasma either as a free protein or in a noncovalent complex with the vitamin K-dependent protein S. The major form of C4BP is composed of seven identical α-chains (70 kDa) and one β-chain (45 kDa). C4BP was purified from human plasma after barium citrate adsorption using anti-C4BP monoclonal antibody affinity chromatography. C4BP-high and low Mr forms were both obtained from the barium citrate precipitate and the supernatant. C4BP-high and low forms from the barium citrate precipitate were separated by sodium dodecylsulfate polyacrylamide slab gel electrophoresis and extracted with Triton X-100. Both forms contained the β-chain as was demonstrated on sodium dodecylsulfate polyacrylamide slab gel electrophoresis under reduced conditions after silverstaining and with Western-blotting using monoclonal antibodies specific for the β-chain. The C4BP-high and low forms demonstrated similar protein S binding affinity (KA: 3.18 × 108 and 3.21 × 108 M-1, respectively) in a C4BP-protein S binding assay and a protein S ligand blot using a peroxidase-conjugated monoclonal anti-protein S antibody. The barium citrate supernatant contained two forms of C4BP-high and one form of C4BP-low. One form of C4BP-high did contain the β-chain and was capable of protein S binding (KA: 4.35 × 108 M-1). The two other forms of C4BP lacked the β-chain and were unable to bind protein S.
A Collaborative Study to Establish the Second International Standard for Streptokinase
Authors: Heath A B , Gaffney P J 
Published: July 2018

SummaryAn International Standard for Streptokinase - Streptodomase (62/7) has been used to calibrate high purity clinical batches of SK since 1965. An international collaborative study, involving six laboratories, was undertaken to replace this standard with a high purity standard for SK. Two candidate preparations (88/826 and 88/824) were compared by a clot lysis assay with the current standard (62/7). Potencies of 671 i.u. and 461 i.u. were established for preparations A (88/826) and B (88/824), respectively.Either preparation appeared suitable to serve as a standard for SK. However, each ampoule of preparation A (88/826) contains a more appropriate amount of SK activity for potency testing, and is therefore preferred. Accelerated degradation tests indicate that preparation A (88/826) is very stable.The high purity streptokinase preparation, coded 88/826, has been established by the World Health Organisation as the 2nd International Standard for Streptokinase, with an assigned potency of 700 i.u. per ampoule.
Heparin Effect on Bone Density
Authors: Ginsberg J S , Kowalchuk G , Hirsh J , Brill-Edwards P , Burrows R , Coates G , Webber C 
Published: July 2018

SummaryIn order to provide estimates of the risks of symptomatic osteoporosis and reduced bone density in premenopausal women treated with long-term (greater than 1 month) heparin therapy, we evaluated a cohort of 61 consecutive premenopausal women previously treated with long-term heparin (cases) and a group of controls matched for age, parity and duration between the last pregnancy and evaluation. All patients underwent dual photon absorptiometry of the lumbar spine and single photon absorptiometry of the wrist and most cases underwent plain lateral radiography of the thoracolumbar spine in order to exclude silent fractures. Although none of the cases suffered symptomatic fractures (0 of 61, 95% confidence intervals 0.0 to 5.9%), there was a significantly greater proportion of cases than controls with bone density below our pre-defined levels. The long-term implications of our findings are uncertain but because it is possible that the reduction in bone density predisposes women to fractures, this potential risk should be considered when treating women with long-term heparin.
Ristocetin and Botrocetin Involve Two Distinct Domains of von Willebrand Factor for Binding to Platelet Membrane Glycoprotein lb
Authors: Girma J P , Takahashi Y , Yoshioka A , Diaz J , Meyer D 
Published: July 2018

SummaryWe have evidence that ristocetin and botrocetin mediate binding of von Willebrand Factor (vWF) to platelet glycoprotein lb (GPIb) through two distinct domains on the vWF molecule. This was established by using monoclonal antibodies (MAbs) to vWF and synthetic peptides derived from the sequence of vWF. MAb 322 and MAb NMC/vW 4 both recognize native vWF as well as fragments containing the GPIb-binding domain of vWF, obtained with the following enzymes: trypsin (116 kDa), V-8 pro tease (Spill, 320 kDa) and V-8 protease plus subtilisin (33-28 kDa). Nevertheless, the lack of reciprocal displacement between the two MAbs in experiments of competitive inhibition for binding to vWF demonstrate that their respective epitopes are separate. Both MAbs inhibit 125I-vWF binding to platelet membrane GPIb and vWF-dependent platelet agglutination induced by ristocetin. However, only MAb NMC/vW4 inhibits these functions in the presence of botrocetin and when ristocetin-induced platelet agglutination is inhibited by MAb 322, botrocetin is still able to restore the agglutination. The involvement of two distinct domains of vWF for binding to GPIb in the presence of ristocetin or botrocetin was confirmed in experiments of binding of 125I-vWF to platelets using as competitor synthetic peptides corresponding to the GPIb binding domain of vWF (Cys 474 to Pro 488 and Ser 692 to Pro 708). At a final concentration of 2.5 mM both peptides inhibit more than 90% of the binding of vWF to ristocetin-treated platelets but are unable to modify this binding in the presence of botrocetin. In conclusion our data suggest that botrocetin and ristocetin involve distinct sites on vWF for binding to GPIb.
The Anticoagulant Mechanism of Action of Recombinant Hirudin (CGP 39393) in Plasma
Authors: Lindhout Theo , Blezer Ron , Coenraad Hemker H 
Published: July 2018

SummaryWe studied the inhibitory action of recombinant desulphatohirudin (CGP 39393) on thrombin generation in whole plasma. Human plasma was activated either with thromboplastin or factor IXa. Hirudin delayed thrombin generation, but it was unable to prevent the explosive appearance of thrombin. The
dose-dependent prolongation of the lag phase of the intrinsic and extrinsic thrombin generation curve was not the result of titration of thrombin activity by hirudin but the result of a delayed formation of the prothrombin converting complex (prothrombinase). In case of extrinsic activation, hirudin did not affect factor Xa generation, but prolonged the lag phase of the factor Va generation curve, causing its appearance when factor Xa generation was already in the decay phase. Because of its inhibitory action on the thrombin-mediated activation of factor VIII, hirudin prolonged the lag phase of the factor X converting complex that consists of factor IXa and factor VIIIa. Our observations with hirudin are in keeping with the notion that inhibition
of the thrombin-mediated amplification reactions in blood coagulation is a very efficient way to delay or inhibit completely thrombin generation. However, although hirudin neutralizes stoichiometric amounts of thrombin, the interaction between in situ generated thrombin and hirudin appears not to be fast enough to prevent trace amounts of thrombin to activate factors VIII and V. Consequently, an explosive thrombin generation is observed even when free hirudin is present.
Chlorobutanol, a Preservative of Desmopressin, Inhibits Human Platelet Aggregation and Release In Vitro
Authors: Chen Shih-Luen , Yang Wu-Chang , Huang Tung-Po , Wann Shiang , Teng Che-ming 
Published: July 2018

SummaryTherapeutic preparations of desmopressin for parenteral use
contain the preservative chlorobutanol (5 mg/ml). We show here
that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited
by chlorobutanol. Chlorobutanol had no effect on elastase- treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecitic toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.
Hypersensitivity to Thromboxane A2 in Cholesterol-Rich Human Platelets
Authors: Tomizuka Takuya , Yamamoto Kyohei , Hirai Aizan , Tamura Yasushi , Yoshida Sho 
Published: July 2018

SummaryThe effect of changes in platelet membrane cholesterol content on thromboxane A2 (TXA2)-induced platelet activation was studied. Concentrations of 9,ll-epithio-ll,12-methano-TXA2 (STA2), a stable analogue of TXA2 which can cause half-maximal aggregation and release of [14C]serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA2-induced increase in cytosolic calcium concentration and [32P]phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site (Bmax) for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant (Kd) for SQ29548 did not differ between cholesterol-rich and cholesterol-normal platelets. The present study suggested that sensitivity to TXA2 was increased by the incorporation of cholesterol into platelet membrane and that the cause of hypersensitivity to TXA2 in cholesterol-rich platelets may be partly explained by an increase in binding capacity for TXA2.
Relationships of Plasma Viscosity, Coagulation and Fibrinolysis to Coronary Risk Factors and Angina
Authors: Lowe G D O , Wood D A , Douglas J T , Riemersma R A , Macintyre C C A , Takase T , Tuddenham E G D , Forbes C D , Elton R A , Oliver M F 
Published: July 2018

SummaryPlasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and Bβ15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide Bβ15-42). Increased viscosity and fibrinogen in smokers were partly reversed in exsmokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.
Assessment of Therapeutic Quality Control in a Long-Term Anticoagulant Trial in Post-Myocardial Infarction Patients
Authors: Azar Aida J , Deckers Jaap W , Rosendaal Frits R , van Bergen Paul F M M , van der Meer Felix J M , Jonker Jan J C , Briëf Ernest 
Published: July 2018

SummaryVarious methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ration (INR). We compared the following approaches: (1) total INR’s or the most recent measurement; (2) percent time within therapeutic range, with INR changing directly or halfway between visits; and (3) total observation time assuming INR changing linearly. The study population comprised 1700 post myocardial infarction patients. Treatment comprised 3725 patient-years. There were 61,471 INR assessments with target therapeutic level of 2.8–4.8. Acenocoumarol as well as phenprocoumon were employed. Therapeutic achievement in the first months of treatment was low: less than 60% of INR’s were in range. Treatment stabilized after 6 months. Patients on acenocoumarol were within range 70% of the time compared to 80% for phenprocoumon. Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels. Our findings call for an urgent improvement of standard of anticoagulant control in the first months following commencement of treatment.