bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the Action Mechanism of the Antihemostatic Effect of lodopeptides
Authors: Golub A.L , Mende T.J 
Published: July 2018

SummaryA synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9 % NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl.Studies with Russell’s viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation.
Alteration of Plasma Antithrombin III Levels in Ischemic Heart Disease
Authors: Yue Robert H. , Gertler Menard M. , Starr Toby , Koutrouby Russell 
Published: July 2018

SummaryThe amount of anti thrombin III in plasma was determined quantitatively in 218 males between 45–60 years of age. The mean antithrombin III value was found to be low in the group with low risk for ischemic heart disease, intermediate in the group with high risk for ischemic heart disease and highest in the group with acute myocardial infarction. Concomitant study of kaolin-activated partial thromboplastin time revealed a sharp decrease in its mean value in the group with acute myocardial infarction. The high correlation between antithrombin III and kaolin-activated partial thromboplastin time for the entire population suggests that the development of ischemic heart disease is a gradual process and that failure of the damping mechanism results as an acute event. These findings may be useful in the determination of the coagulation state of these patients.
Fibrinogen/Fibrin Degradation Products in Serum of Patients with Idiopathic Thrombocytopenic Purpura: Elevated Levels during Severe Thrombocytopenic Phase of the Disease
Authors: Nagasawa Toshiro , Kono Ichiro , Sakurai Tetsushi , Kashiwagi Heihachiro 
Published: July 2018

SummarySera from 23 patients with idiopathic thrombocytopenic purpura (ITP), 14 patients with aplastic anemia with severe thrombocytopenia and healthy control subj ects were tested for the presence of fibrinogen/fibrin degradation products (FDP), using the tanned red cell hemagglutination inhibition immunoassay. The concentrations of circulating FDP of ITP patients (mean 12.01 μg/ml) were significantly higher than those of the patients with aplastic anemia (mean 4.01 μg/ml, p <0.05) or normal controls (mean 3.10 μg/ml, p <0.001). The patients with untreated ITP with very low platelet counts had higher levels of FDP than those of the treated group (p < 0.01). Serum FDP and a battery of other coagulation-fibrinolysis tests were serially carried out over a period of 10 weeks in two patients with ITP. The initially high FDP promptly decreased as circulating platelets increased in response to steroid in both patients, while plasma fibrinogen, euglobulin lysis time, prothrombin time and partial thromboplastin time remained essentially normal during the course of observation. The exact source of the increased serum FDP in ITP was not extablished, but a few possible mechanisms responsible for this abnormality were discussed.
On the Measurement of Spontaneous Platelet Aggregation. The Platelet Aggregation Test III.
Authors: Breddin K , Grun H , Krzywanek H. J , Schremmer W. P 
Published: July 2018

SummaryA new measuring device was developed for the study of “spontaneous” aggregating activity of thrombocytes. In the photometric platelet aggregation test (PAT III) 0.6 ml of platelet-rich plasma (PRP) are rotated in a disc-shaped cuvette at 20 rpm and 37° C. Changes in optical density of PRP which are induced by the formation of platelet aggregates are continuously registered using a chart recorder. PAT III was developed for the detection of enhanced platelet aggregation, indicating a risk of thrombosis and thromboembolic complications.In 146 healthy individuals a certain percentage showed slight primary aggregation (α1) which in some cases was followed by marked aggregation (α2) at a certain time (Tr) after the beginning of rotation. The percentage of individuals showing α2 increased with age. An increase of plasma pH in the rotating sample, which was caused by diffusion of CO2, was an important conditioning factor for aggregation. The test results depended on the platelet count in PRP. Aggregation curves were suppressed by admixture of erythrocytes and lipid turbidity. The tendency of platelets to aggregate increased within 60–90 min following blood sampling. During this period the interval to the onset of aggregation (Tr) became shorter and the maximum aggregation speed (α2) increased with time. PAT III yielded reproducible results when it was carried out more than 60 min after blood drawing.In a group of 327 diabetic patients “spontaneous” aggregation occurred more frequently in all age groups as compared with the controls.Additional equipment was available for the registration of ADP-, collagen-, or epine-phrine-induced aggregation similar to Born’s and O’Brien’s method. The device can easily be mounted on an Eppendorf photometer without further alterations.
Management of Haemophilia in Greece
Authors: Mandalaki T 
Published: July 2018

SummaryA short review is given on several aspects of the management of haemophilia in Greece. A total number of 429 patients with congenital haemorrhagic disorders has been registered. The incidence of F. VIII deficiency is 85.9% and that of F. IX 12.9%. Information concerning distribution throughout the country, age, social standard, financial position and education is given too.Haemophiliacs are systematically treated by Athens specialized Haemophilia Treatment Centres.The most widely therapeutic material still used, is fresh frozen plasma. Lyophilized cryo-precipitate and F. IX (prothrombincomplex) concentrate are also prepared but they are not for every day use. Imported concentrates are used only for very serious cases.Home therapy is attempted in limited scale and it is largely discussed.Consultation, out-patients treatment and hospitalization, if needed, are free of charge for haemophiliacs regardless of their financial position or their national insurance.
Four Heparin Preparations: Anti-Xa Potentiating Effect of Heparin after Subcutaneous Injection
Authors: Johnson E. A , Kirkwood T. B. L , Stirling Yvonne , Perez-Requejo J. L , Ingram G. I. C , Bangham D. R , Brozović Milica 
Published: July 2018

SummaryFour different heparin preparations - sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m. w. 9,000) and high molecular weight sodium heparin (mean m. w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i. u./ml) at 3-4 hours after the injection. With sodium heparin (m. w. 15,000) the highest values (0.135 i. u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0. 072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 1. u./ml at 3-4 hours after injection).These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.
Kinetic Characterization of Tissue-Type Plasminogen Activator (t-PA) and t-PA Deletion Mutants
Authors: Vries Carlie de , Veerman Harry , Nesheim Michael E , Pannekoek Hans 
Published: July 2018

SummaryThe binding of t-PA to fibrin is mediated both by its “finger” (F) and its “kringle 2” (K2) domain. In addition, these domains are involved in the stimulation of t-PA activity by fibrin. We analyzed the kinetic characteristics of Glu-plasminogen activation by t-PA and a set of t-PA deletion mutants in the absence and the presence of desA-fibrin. In the absence of desA-fibrin, the activity of t-PA (variants) is determined by the presence of the pro tease domain, irrespective of the composition of the amino-terminal heavy chain. In the presence of the cofactor desA-fibrin, the activity of t-PA (variants) is dependent on the domain composition of the heavy chain. The activity of t-PA is stimulated 2,400 fold by desA-fibrin, whereas the activity of the mutant lacking the K1 domain (del. Kl) increases 936 fold in the presence of this cofactor. Mutants lacking either the K2 domain (del. K2) or the F domain (del. F) exhibit an enhanced activity upon desA-fibrin addition of 200 and 210 fold, respectively. DesA-fibrin has no stimulatory effect on the activity of the mutant containing only the serine-protease domain (del.FE Kl K2) nor on the activity of the variant containing only the Kl domain and the serine-protease domain (del. FE K2). Furthermore, we determined the relative fibrin affinity of each t-PA variant, which is similarly dictated by the composition of the heavy chain.
Fibrinolysis and Coagulation in Patients with Infectious Disease and Sepsis
Authors: Philippé J , Offner F , Declerck P J , Leroux-Roels G , Vogelaers D , Baele G , Collen D 
Published: July 2018

SummarySepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 ± 9.4 versus 1.6 ± 1.5 ng/ml, p <0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 ± 390 ng/ml versus 120 ± 200 ng/ml, and 3.0 ± 3.6 IU/ml versus 1.0 ± 0.7 IU/ml, respectively, p <0.01). AT III was decreased in sepsis patients (58 ± 28% in sepsis versus 79 ± 26% in severe infectious disease, p <0.01) as was protein C (30 ± 18% versus 58 ± 27%, p <0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.
Platelets of Habitual Smokers Have Reduced Susceptibility to Aggregating Agent
Authors: Foo L C , Roshidah I , Aimy M B 
Published: July 2018

SummaryPlatelet aggregation to collagen, and productions of 6-ketoprostagltandin-F1-alpha and tromboxane 82 during aggregation were measured after an overnight fast, involving both food and cigarettros, in 19 clinically healthy habitual smokers (10 or more cigarettes/day) and 23 non-smokers receiving the same diet. The subjects (all males; ages == 21-30 years) were residents of a school hostel. Mean platelet aggregation was significantly lower in smokerr; than non-smokers (23.2 ohms vs 3L.5 ohmS, p < 0.005). Non-smokers had significantly higher mean concentration of 6-keto-prostaglandin-F1-alpha than smokers (109.8 pmol/1 vs 92.3 pmol/1, p < 0.05). The level of thromboxane B2 did not differ significerntly between the two groups. These observations suggest that the role of smokittg as a risk factor for ischaemic heart disease is unlikely to be related to a direct enhancement of aggregation. On the contrary, the observations seem to suggest that habitual smoking may directly reduce platelet aggregability.
Effect of TRK-100, a Stable Orally Active Prostacyclin Analogue, on Platelet Function and Plaque Size in Atherothrombotic Strokes
Authors: Isaka Yoshinari , Handa Nobuo , Imaizumi Masatoshi , Kimura Kazufumi , Kamada Takenobu 
Published: July 2018

SummaryPatients with carotid atheromatous lesions were prospectively studied with indium-111 platelet imaging, platelet aggregability and B-mode real-time ultrasound tests to determine the shortterm effects of orally active prostacyclin analogue TRK-100 (40 μg, three times daily for 4 weeks). To establish baseline values, all patients underwent indium-111 platelet imaging, platelet aggregation study and B-mode ultrasound. The results were positive for carotid plaque and platelet accumulation. Visual analysis showed repeated platelet scintigrams to be unchanged in five patients without antithrombotic therapy; repeated ultrasound studies showed no change in eight of ten plaques, while one showed progression and one regression of the plaque. In five TRK-100 treated patients, five of seven lesions with platelet accumulation at the baseline became negative, and two remained unchanged during the treatment; repeated B-mode ultrasound tests indicated eight of nine plaques remained unchanged, while one showed plaque size reduction. Quantitative analysis demonstrated that, TRK-L00 significantly reduced the ADP aggregation (1 μM) from 55.2 ± 21.3"/" to 24.0 ± 14.7% (± Sp; p <0.05) and the platelet accumulation index (25.7 ± 17.2% vs L0.4 ± 10.4%; p <0.05). However, there was no significant reduction in plaque scores during TRK-100 therapy compared with the baseline (2.70 ± 2.75 mm vs 2.51 ± 2.58 mm). The data obtained suggested that short-tenn TRK-L00 therapy has an inhibitory effect on platelet accumulation in carotid atheroma but does not cause significant changes in plaque size.
Experimental Studies on a Recombinant Hirudin, CGP 39393
Authors: Gray E , Watton J , Cesmeli S , Barrowcliffe T W , Thomas D P 
Published: July 2018

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.
Changes in Endothelial-Related Goagulation Proteins in Response to Venous Occlusion
Authors: Jennings I , Luddington R J , Harper P L 
Published: July 2018

SummaryOne hundred patients with a history of thrombophilia wer divided into two groups based on fibrinolytic response to venous occlusion. Good responders with a euglobulin clot lysis time ≤ 105 min showed significant release of tPA, PAI and vWE Of the poor responders with an ECIX > 105 min, 24% showed a subnormal increase in tPA, and a significant proportion of these also showed a reduced or absent rise in vWEWe have shown poor fibrinolytic response was related to either raised levels of PAI, poor release of both tPA and vWR or poor release of tPA or vWF alone suggesting different mechanisms of fibrinolytic impairment. Protein S levels were not significantly changed in either group following occlusion.
Stimulation of Plasmin Activity by Aspirin
Authors: Milwidsky Ariel , Finci-Yeheskel Zvendana , Mayer Michael 
Published: July 2018

SummaryThis study demonstrates an enhancing effect of aspirin on the amidolytic activity of plasmin. The stimulation of plasmin by aspirin was concentration-dependent and was attained at aspirin concentrations above 2 × 10−4 M. Aspirin produced a small, reproducible and statistically significant stimulation of the chromogenic activity of plasmin upon H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide (3-2251) or pyro-Glu-Gly-Arg-p-nitroanilide (S-2444). Kinetic analysis demonstrated a slight decrease in the affinity of plasmin for substrate 3-2251 in the presence of aspirin, reflected by a change of the Km from 3.2 × 10-4 M to 3.8 × 10-4 M, and an increase of the Vm. The reciprocal Lineweaver-Burk curve indicated an uncompetitive type of stimulation. The stimulatory effect of aspirin was abolished by the lysine analogue α-aminohexanoic acid (AHA) but not by the α-amino acid glutamic acid. The effect of AHA suggests a specific involvement of lysine binding sites (LBS) on plasmin in the interaction of the enzyme with aspirin. Tlansient acidification of plasmin abolished its response to aspirin, to AHA and to their combination. The addition of aspirin to diluted human control or pregnancy plasma in vitro stimulated the plasma-mediated cleavage of the chromogenic substrate3-2251. In contrast to its effect on plasmin, aspirin failed to change the activity of tissue-type or urokinasetype plasminogen activators. It is conceivable that in addition to the antithrombotic effect of aspirin ascribed to its interaction with the platelets, aspirin also directly stimulates plasmin activity.
Role of α2-Antiplasmin in Fibrin-Specific Clot Lysis with Single-Chain Urokinase-Type Plasminogen Activator in Human Plasma
Authors: Declerck P J , Lijnen H R , Verstreken M , Collen D 
Published: July 2018

SummaryThe role of plasma α2-antiplasmin (α2-AP) in the fibrinspecificity of clot lysis by recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and in the conversion of rscu-PA to its two-chain derivative (rtcu-PA, urokinase) was investigated in an in vitro human plasma clot lysis system. Fifty % lysis in 2 h of a 0.1 ml 125l-fibrin labeled human plasma clot immersed in 0.5 ml normal human plasma was obtained with 1.4 ± 0.15 µg/ml rscu-PA (mean ± SD, n = 8). This was associated with degradation of 23 ± 7% of fibrinogen and generation of 0.20 ± 0.09 µg/ml rtcu-PA. In α2-AP-depleted plasrna 50% clot lysis in 2 h required 2-fold less rscu-PA which was associated with 3-fold more extensive fibrinogen degradation and 2-fold more rtcu-PA generation. Fifty % lysis in? h, of a 0.1 ml α2-AP-depleted plasma clot, subriersed in 0.5 ml normal plasma, was obtained with 0.80 ± 0.05 µg/ml rscu-PA (n = 3, p <0.001 vs normal clot) and was associated with 17 ± 6% fibrinogen breakdown (p : 0.22 vs normal clot) and 0.08 ± 0.02 µg/ml rtcu-PA generation (p < 0.05 vs normal clot). In α2-AP-depleted plasma the equipotent rscu-PA concentration was 4-fold lower than in normal plasma and was associated with 3-fold more fibrinogen degradation and a similar extent of rtcu-PA generationThus, α2-AP in plasma contributes significantly to the fibrinspecificity of rscu-PA, primarily via prevention of conversion in plasma of rscu-PA to rtcu-PA. Clot associated α2-AP increases the resistance of the clot to lysis with rscu-PA, but plays an only minor role in the fibrin-specificity of clot lysis in normal plasma.
Microbubble-Induced Serotonin Secretion in Human Platelets
Authors: Malmgren R , Thorsen T , Lie R T , Holmsen H 
Published: July 2018

SummaryThe effect of nitrogen (N2) microbubbles on platelets resembles that of common platelet agonists with respect to aggregation (Thorsen T et al., Undersea Biomed Res 1986; 13:289-303). In the present study we examined the effect of microbubbles on platelet secretion of preloaded 14C-serotonin. We demonstrate that stirring of platelet-rich plasma with N2-microbubbles causes a loss of single platelets that is associated with secretion. However, secretion did not increase above baseline values until after 20 min of microbubble exposure, when platelet aggregation had reached 40%. After that time the secretion rate increased. There was no correlation between secreted serotonin and the degree of platelet aggregation. Although no 14C-serotonin secretion occurred in presence of acetylsalicylic acid (ASA), microbubble-induced platelet aggregation was only marginally reduced. Epinephrine alone caused significant platelet aggregation but no 14C-serotonin secretion and it enhanced N2-microbubble-induced platelet aggregation and secretion; ASA completely prevented secretion under these circumstances but failed to abolish the enhancement of aggregation compared with microbubbles alone. Earlier studies have shown that platelets adhere to the bubble surfaces (Thorsen T et al., Undersea Biomed Res 1987; 14:45-59). The results in the present study indicate that non-adhering platelets in the bulk phase are not activated by means of autocrine stimulation through dense granule material.
Characteristics of Thrombin-Degranulated Human Platelets: Development of a Method that Does not Use Proteolytic Enzymes for Deaggregation
Authors: Kinlough-Rathbone Raelene L , Packham Marian A , Guccione Maria A , Richardson Mary , Harfenist Elizabeth J , Mustard J Fraser 
Published: July 2018

SummaryA method has been developed for preparing suspensions of washed human platelets that have lost as much as 90% of their dense granule and alpha granule contents as a result of stimulation by thrombin (0.9 U/ml for 3 min at 37° C), and recovering the platelets without using a proteolytic erwyme. Glycyl-Lprolyl-Larginyl-L-proline (GPRP) was used to prevent polymerization of released fibrinogen and arginyl-glycyl-aspartyl-serine (RGDS) to block the interaction of released fibrinogen, vWf or fibronectin with the glycoprotein IIb/IIIa complex. The thrombin used to degranulate the platelets was neutralized with D-phenylalanyl-Lprolyl-L-arginine chlororhethyl ketone (FPRCH2CI) and prostaglandin E1 was added to return the platelets towards a disc shape. The degranulated platelets aggregated in response to ADR platelet activating factor, arachidonate and the thromboxane 42 mimetic, U46619 in the presence of added fibrinogen; the platelets changed shape but did not aggregate in response to collagen. Thrombin and the calcium ionophore, A23L87, caused aggregation without added fibrinogen. Synergism between pairs of aggregating agents at low concentrations was observed. Little TXB2 was formed when the platelets were reaggregated by thrombin. RGDS and F(ab’)2 fragments of an antibody to fibrinogen inhibited reaggregation induced by thrombin and A23187 indicating that small amounts of fibrinogen at the platelet surface may support aggregation by strong agonists. Adherence of thrombin-degranulated platelets to a collagen-coated surface was less than for controls, but spreading was more extensive. Electron-microscopic immunogold cytochemistry with anti-human fibrinogen IgG showed numerous gold particles in platelet vacuoles. Thrombin-degranulated platelets can be used to study pathways involved in platelet aggregation without the complicating effects of released granule contents including ADR and to study indirectly the factors released from platelets that contribute to the stability of platelet aggregates.