bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboxane A2 and Prostacyclin Generation in the Microvasculature of Patients with Atherosclerosis – Effect of Low-Dose Aspirin
Authors: Kyrle P A , Minar E , Brenner B , Eichler H G , Heistinger M , Marosi L , Lechner K 
Published: July 2018

SummaryGeneration of thromboxane A2 (TxA2) and prostacyclin (PGI2) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time was investigated in 7 patients with atherosclerosis (angiographically verified obstructions of the femoral arteries) and in 7 normal control subjects apparently free of atherosclerotic lesions. Similar amounts of TxA2 (measured as thromboxane B2, TxB2) were generated at the site of plug formation in the patients with peripheral vascular disease (PVD) and in the control subjects. Significantly lower levels of PGI2 (measured as 6-keto-prostaglandin F1α, 6-keto- PGF1α) were found in blood from an injury of the microvasculature in the patients compared with the controls. These data do not suggest a major role of the platelet prostaglandin metabolism in the development of atherosclerosis. However, decreased synthesis of PGI2 by endothelial cells might contribute to the development and/or progression of atherosclerotic lesions. In the patients with PVD, low-dose aspirin (50 mg/day for 7 days) resulted in a >90% inhibition of the TxB2 production at the site of plug formation. Following low-dose aspirin 6-keto-PcF1α levels were below 20 pg/ml (limit of sensitivity of our radioimmunoassay procedure) in the majority of the samples.We therefore conclude that in patients with PVD a decreased synthesis of PGI2 by endothelial cells might contribute to the progression of atherosclerosis. Furthermore, low-dose aspirin treatment results in a similar inhibition of the platelet prostaglandin generation as recently observed in healthy subjects.
Pharmacokinetics and Haemostatic Status During Consecutive Infusions of Recom binant Tissue-Type Plasminogen Activator in Patients with Acute Myocardial Infarction
Authors: Seifried E , Tanswell P , Ellbrück D , Haerer W , Schmidt A 
Published: July 2018

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.
Indirect Activation of Blood Coagulation in Colon Cancer
Authors: Wojtukiewicz Marek Z , Zacharski Leo R , Memoli Vincent A , Kisiel Walter , Kudryk Bohdan J , Rousseau Sandra M , Stump David C 
Published: July 2018

SummarySystemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the “a” subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of Bβ chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin- generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.
Effect of Retraction on the Lysis of Human Clots with Fibrin Specific and Non-Fibrin Specific Plasminogen Activators
Authors: Sabovic M , Lijnen H R , Keber D , Collen D 
Published: July 2018

SummaryThe effect of the serum content of human clots on their sensitivity to lysis with plasminogen activators was studied in a system composed of 125I-fibrin labeled clots immersed in buffer or in citrated plasma. The effect was studied with plasma clots before or after mechanical compression and with whole blood clots before or after retraction, using either the fibrin specific plasminogen activators recombinant tissue-type plasminogen activator (rt-PA) or recombinant single chain urokinase-type plasminogen activator (rscu-PA), and the non-fibrin specific activators recombinant two chain urokinase-type plasminogen activator (rtcu-PA), or streptokinase (SK).In a buffer milieu, all plasminogen activators had a similar fibrinolytic potency towards serum-rich clots (non-compressed plasma clots or non-retracted blood clots): 50% clot lysis in 4 h required 50 to 85 ng plasminogen activator per ml. Serum-poor clots (compressed plasma clots or retracted blood clots) were resistant to lysis in a buffer milieu but became sensitive to lysis following preincubation in plasma for 48 h. These findings indicate that plasma proteins entrapped in clots contribute significantly to their sensitivity to lysis and suggest that the amount of bound or entrapped plasminogen may be a limiting factor. In a plasma milieu, all plasminogen activators lysed serum- rich plasma or blood clots, albeit at higher concentrations (3 to 40 times higher than in the buffer milieu) and with different efficiencies: 50% clot lysis in 4 h required approximately 600 ng/ ml of rtcu-PA but 1,500 to 2,000 ng/ml of rscu-PA. These findings suggest that components of plasma are responsible for increased resistance of clots towards lysis and that the effect is variable for different plasminogen activators. Serum-poor plasma or blood clots were very resistant to lysis with non-fibrin specific agents, but became more sensitive after preincubation in plasma. However, serum-poor plasma or blood clots were sensitive to lysis with fibrin specific plasminogen activators, suggesting that during clot lysis with fibrin specific agents, plasminogen recruited from surrounding plasma may contribute significantly to clot lysis. The concentration of plasminogen activator required to obtain 50% clot lysis in a plasma milieu of compressed plasma clots or retracted blood clots was 390 and 1,600 ng/ml respectively for rt-PA and 1,100 and 3,200 ng/ml respectively for rscu-PA. These data suggest that in a plasma milieu retracted blood clots are more sensitive to lysis with fibrin specific plasminogen activators than with non-fibrin specific agents.
Time Dependence of Aequorin-lndicated Calcium Levels in Stimulated and Unstimulated Platelets: Evidence for Multiple Aequorin Environments in Platelets
Authors: Lages Bruce , Weiss Harvey J 
Published: July 2018

AbstractAequorin-induced calcium signals were examined in human unstimulated platelets and platelets stimulated with various agonists as a function of time. The total aequorin response in unstimulated platelets, obtained by Triton x-100 lysis in the presence of 1 mM Ca, decreased in a distinctly non-linear manner over 20-60 min. This decrease was slightly, but significantly, greater in platelets maintained in the continuous presence of 1 mM Ca than in platelets maintained without external Ca, and could not be accounted for completely by leakage of aequorin from the cells. Basal Ca levels in unstimulated platelets also decreased in a non-linear manner, with a similar sensitivity to the contmuous presence or absence of external Ca. These observed changes in aequorin response thus appear to be at least partially due to an mtracellular discharge of aequorin, and are therefore consistent with the view that aequorin in platelets is heterogeneously d1stnbuted among localized environments differing in Ca concentration. The aequorin signals observed initially in platelets stimulated by ADP or epinephrine were lost completely over a penod of 30-60 min in almost all cases studied, while initial rates of aggregation were either unchanged (epinephrine) or only partially decreased (ADP) over this same time period. In contrast, thrombin- and A23187-induced aequorin signals were virtualy unchanged over periods up to 90 min. Minimal changes with time also occurred in the aequorin signals induced by phorbol ester or by collagen in the presence of indomethacin. These differences in time dependence suggest that the signals generated by ADP and epinephrine may derive from different sources of aequorin than those associated with the signals induced by other agonists. Thus, differences in indicator localization may indeed contnbute to the observation of aequorin, but not quin 2/fura-2, signals following epinephrine stimulation as previously suggested, but this may not be the sole explanation for the discrepancies between these two Ca indicators seen with other agonists.
Platelet Mobilization Induced by PAF and Its Role in the Thrombocytosis Triggered by Adrenaline in Rats
Authors: Castro-Faria-Neto Hugo C , Bozza Patricia T , Martins Marco A , Dias Paulo M F L , Silva Patricia M R , Cordeiro Renato S B 
Published: July 2018

SummaryThe injection of PAP (6 μg/kg, i. v.) induced, in rats, haemoconcentration accompanied by an increase in the platelet number, as attested by the counts of platelets in blood samples diluted in formalin-free EDTA solution. This increase was significant at 15 min, peaked from 1 to 4 h and returned to basal levels 24 h after the lipid administration. The release of platelets induced by PAP was inhibited dose-dependently by specific PAP receptor antagonists such as WEB 2086 (0.5-2 mg/kg), BN 52021 and 48740 RP (5-25 mg/kg). Furthermore, platelet mobilization was clearly impaired in splenectomized animals stimulated by PAP, whereas thrombocytopenia and haemoconcentration by the same stimulus were intact. It was also noted that a second injection of PAP, 24 h after the initial stimulation with the lipid, failed to induce an increase in platelet counts, indicating autodesensitization. Desensitization to PAP or pretreatment with PAP antagonists clearly prevented the increase in the platelet counts after stimulation by adrenaline (15 μg/kg). These findings suggest that, in rats, PAP can induce release of platelets by a spleen-dependent mechanism and that this lipid may be relevant to the thrombocytosis triggered by adrenaline.
A Randomised Trial of Subcutaneous Low Molecular Weight Heparin (CY 216) Compared with lntravenous Unfractionated Heparin in the Treatment of Deep Vein Thrombosis
Authors: Ninet J , Bachet Ph , Prandoni P , Ruol A , Vigo M , Barret A , Mericq O , Boneu B , Janvier G , Duroux P , Girard Ph , Laprevote-Heully M C , Sourou P , Robert D , Chagny M , Nenci G , Agnelli G , d’Addato M , Palumbo H , Bensaid J , Gouffault J , Leborgne P , Hellocco A Le , Ducreux J C , Tempelhoff G , Sala-Planell E , Rosendo-Carrera A , Torres-Gomez A , Blettery B , Bachmann F , Gaux J C , Muntlak H , Caulin Ch , Bergmann J F ,   A Collaborative European Multicentre Study
Published: July 2018

SummaryThe standard treatment of deep vein thrombosis is given by continuous intravenous infusion of unfractionated heparin. This entails hospitalisation, nursing care, immobility and repeated laboratory tests (e.g. activated partial thromboplastin time [APTT], platelet count). In addition approximately 10% of patients suffer major haemorrhages. The potential advantages of a low molecular weight heparin (CY 216) given subcutaneously were explored in a randomised trial with blind quantitative evaluation of venograms. The study included 166 patients and both “therapeutic efficacy” and “intention to-treat” analyses showed that subcutaneous CY 216 in fixed doses based only on body weight was more effective on the Arnesen and Marder phlebographic scores than continuous i. v. standard heparin with daily dose adjustment according to results of coagulation tests. There was no increase in the risks of pulmonary embolism, haemorrhage or clot extension.
Decreased Fibrinolysis in Reperfused Ischaemic Tissue
Authors: Cherry G. W , Ryan T. J , Ellis J. E 
Published: July 2018

SummaryThe fibrinolytic activity of skin flaps subjected to ischaemia and reperfusion was studied in five pigs. Total interference with the blood supply up to 24 hours did not in itself lead to changes in fibrinolytic activity. However, reperfusion of the skin after six hours of ischaemia caused a dramatic reduction in fibrinolytic activity measured 18 hours later.Similar studies on reperfused femoral artery and vein after six hours of ischaemia showed marked reduction in fibrinolytic activity of the vessels.It is suggested that reperfusion of tissue made ischaemic for six hours is damaging and might be a contributory factor to vascular pathology.
Vessel Wall and Thrombogenesis - Endotoxin
Authors: McKay Donald G 
Published: July 2018

SummaryThe generalized Shwartzman reaction is a definitive disease process which is the result of two minor episodes of acute inflammation of the circulating blood. The identifying feature of the reaction is thrombosis of the micro circulation, specifically of glomerular capillary thrombosis which persists long enough to cause bilateral renal cortical necrosis. The reaction is the result of an interplay between leukocytes, platelets, complement, the contact system, the extrinsic prothrombin activator system, adrenal glucocorticoids, adrenal catecholamines, alpha - adrenergic receptor sites and the fibrinolytic enzyme system. The reaction occurs only when these systems are affected within narrow quantitative limits. It is a model of the effects of bacterial endotoxin on the blood-vascular system and has important implications for acute inflammatory episodes of the circulating blood induced by other inflammatory agents such as antigen-antibody complex and particulate matter.
Studies on Thrombolysis with Streptokinase
Authors: Gottlob R , El Nashef B , Donas P , Piza F , Kolb R 
Published: July 2018

SummaryThe patterns of fibrin and the contents of plasminogen, of α1 antitrypsin and of a2-macroglobulin were studied in whole blood clots before and after retraction and in arterial and venous thrombi of various age by an indirect immunofluorescent method.By reaction with antifibrinogen a network of fibrin fibers was displayed in the first week. The fibers were condensed to form trabecula in the first months. After several months the reaction with antifibrinogen was reduced or abolished even in non organized thrombi.In clots and thrombi the plasminogen content is lost during retraction, However, a considerable increase is observed in thrombi up to several months old.The plasma plasmin inhibitors are only partially expressed during retraction. Later a considerable increase may occur.The relevance of these findings for thrombolysis is discussed.
Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention
Authors: Yamazaki Hiroh , Kobayashi Itsuro , Sano Tadahiro , Shimamoto Takio 
Published: July 2018

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.
Potentially Thrombogenic Materials in Factor IX Concentrates
Authors: Kingdon H. S , Lundblad R. L , Veltkamp J. J , Aronson D. L 
Published: July 2018

SummaryFactor IX concentrates manufactured from human plasma and intended for therapeutic infusion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombogenic materials. It was possible to rank the various materials tested according to the amount of thrombogenic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently available concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.
The Role of Vitamins in Hemostasis
Authors: Quick Armand J 
Published: July 2018

SummaryThe physiological mechanism to prevent and control abnormal bleeding is dependent on three vitamins (C, K, and Q). Two of these are unequivocally established as essential for hemostasis while the existence of the third (Q) is supported by experimental evidence and by clinical and therapeutic observations (Quick 1972; Quick 1974). The interrelationship of these three vitamins has remained moot except for clue observations. Both vitamins C and K have a key structure in their molecules which supplies a redox mechanism, ascorbic acid and 2-methyl, 1,4-naphthoquinone, respectively. Both vitamins are concerned with growth. Lack of vitamin C, which clinically is the basic defect in scurvy, does not appear to cause a defect in blood coagulation while vitamin K affects the clotting mechanism by being essential for the production of four distinct clotting factors: prothrombin, factors VII, IX and X.In this presentation an attempt is made to correlate the action of the vitamin K-dependent clotting factors grouping them in a diagram to show how two systems of thrombin formation exist, one being essentially intrinsic, the second extrinsic requiring tissue thromboplastin and factor VII. The possible interlocking of vitamin Q in this mechanism is presented.
On the Reliability of Plasminogen Measurement Employing the Proactivator-Activator Converting Method
Authors: Martin M , Auel Miss H ,   Technical Assistance
Published: July 2018

SummaryA simple plasminogen determination method is presented. It is based upon the conversion of plasminogen into activator by large and constant amounts of streptokinase. The activator contained in a standard coagulum consisting of bovine fibrin, streptokinase, and a 1:40 dilution of human plasma converts the plasminogen adsorbed on bovine fibrin into plasmin. Lysis of the test coagulum is hereby induced. The speed of such lysis is limited by the concentration of the activator incorporated in the test coagulum. The variable component of the activator being human plasminogen, the speed of lysis is directly dependent upon the concentration of human plasminogen in the standard coagulum. Using the thromboelastograph according to Hartert in recording the test clot lysis times, this method of plasminogen determination was shown to be a simple and quick procedure. The standard deviation ranged from ± 13.2 to 68 %, depending upon the plasminogen value to be measured (lower rates of error were attached to high, and higher rates of error to low, plasminogen concentrations). The biological variation of plasminogen values in a group of 26 men aged from 40 to 65 years was calculated to be ±21 %. Both plasminogen and plasmin, its activated form, were exchangeable in the test, i.e. plasminogen determinations performed by activator assay did not differentiate between plasminogen and plasmin. There was no influence by varying anti-SK titers in the plasma up to a circulating antibody content of 2 million. Furthermore, plasma antiplasmins did not affect the plasminogen measuring system. Plasminogen tested by activator assay displayed values closely related to those achieved by immunochemical methods. Plasminogen measurements were performed in patients undergoing streptokinase and urokinase infusion treatment. 5,000 u streptokinase per hour, as well as 270,000 CTA-u urokinase per hour, infused over a period of 2 days produced a fall in plasminogen down to 30-60% of normal. In contrast, 100,000 u streptokinase per hour lowered the plasminogen concentration down to values of below 1%. The foregoing data indicate that plasminogen measurement, according to the principles outlined here (activator assay), may be regarded as a valuable and rehable method for the routine control of streptokinase and urokinase therapy.
Retention of Platelet Fibrin Stabilizing Factor during the Platelet Release Reaction and Clot Retraction
Authors: Joist J Heinz , Niewiarowski Stefan 
Published: July 2018

SummaryPlatelet FSF was found to be retained by rabbit, pig or human platelets during the release reaction induced by thrombin, collagen or plasmin and during a 2 hours incubation of platelet rich fibrin clots.
Lipid Infusions in Man
Authors: Grøttum K. A , Nordøy A , Hellem A 
Published: July 2018

SummaryThe soybean lipid emulsion Intralipid was infused during two hours in 13 volunteer individuals. Biochemically, lipid infusions increased the platelet content of triglycerides, but did not cause significant platelet aggregation, and the platelet counts and survival time were unchanged. However, the lipid infusions reduced platelet and erythrocyte electrophoric mobility, reduced the availability of platelet factor 3 by ADP or kaolin and reduced platelet adhesiveness. A coating of parts of the platelet surface by lipid particles or some other changes in the platelet membrane could explain the effects on platelet electrophoretic mobility, platelet factor 3, and adhesiveness.