bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Local Anaesthetics and Antiarrhythmic Agents on the Responses of Rabbit Platelets to ADP and Thrombin
Authors: Anderson Esther R , Foulks J G , Godin D V 
Published: July 2018

SummaryLocal anaesthetics and antiarrhythmic agents produced changes in responses of rabbit platelets to ADP and thrombin that varied with the agent and its concentration. In high concentrations all local anaesthetics decreased aggregation rates. At lower concentrations several local anaesthetics increased aggregation rates. Depending on the agonist and local anaesthetic, increases were produced at all or only at low or high agonist concentrations. Local anaesthetics failed to influence shape change except at concentrations much greater than those which inhibited aggregation. Inhibition of aggregation by procaine was potentiated by small organic anions suggesting effects at different sites on the platelet membrane. The inhibitory effect of local anaesthetics was decreased by increasing Ca. Kinetic analysis indicated different mechanisms for this Ca effect, i. e., predominantly competitive for procaine or lidocaine and predominantly non-competitive for tetracaine or ethyl lidocaine. Local anaesthetics may affect aggregation by modifying the participation of Ca in this process.
Purification and Properties of an Abnormal Blood Coagulation Factor IX (Factor IXBm)/Kinetics of Its Inhibition of Factor X Activation by Factor VII and Bovine Tissue Factor
Authors: Østerud B , Kasper C K , Lavine K K , Prodanos C , Rapaport S I 
Published: July 2018

SummaryAn abnormal blood coagulation factor IX has been isolated from the blood of a hemophilia B patient with a variant of the disease (hemophilia Bm) characterized by a normal concentration of factor IX antigen, negligible factor IX coagulant activity, and a prolonged prothrombin time with bovine tissue factor. The isolated protein (factor IXBm) had the same apparent molecular weight as normal factor IX (55,000) and the same mobility on two dimensional immunoelectrophoresis as normal factor IX. Factor IXBm underwent limited proteolysis induced by activated factor XI, in the presence of Ca2+ ions, or induced by the reaction product of tissue factor, factor VII and Ca2+ ions. A timecourse study showed that activated factor XI cleaved factor IXBm and factor IX at similar rates. However, in contrast to normal factor IX, the limited protelysis of factor IXBm did not generate procoagulant activity.In kinetic experiments purified factor IXBm behaved like a competitive inhibitor (Ki of 0.017 μM) of the activation of factor X by bovine tissue factor and factor VII. Normal factor IX was also found to inhibit the reaction but required a four-fold higher concentration to achieve the same inhibitory effects as factor IXBm.
Recent Investigations of the First Bleeder Family in Åland (Finland) Described by von Willebrand
Authors: Nyman D , Eriksson A W , Blombäck M , Frants R R , Wahlberg P 
Published: July 2018

SummaryThe still living members of the original bleeder family on the Åland Islands described by von Willebrand in 1926 have been reinvestigated by using modem laboratory techniques for the measurement of the Factor VIII complex and with regard to platelet aggregation. The low level of F VIII: C activity demonstrated in 1957 could be confirmed in some of the family members, who however all had only mild bleeding symptoms. More consistently, in 6 out of 10, a low F VIIIR: Ag was found; all of those also had a low F VIII: RCoF. In none of the members were excessively low values for any of the parameters found. However, the spectrum of the whole F VIII complex indicates that the original family described by von Willebrand belongs to von Willebrand’s disease, type I.
Evidence of a Hypercoagulable State in Patients with Acute Lymphoblastic Leukemia Treated with Low Dose of E.coli L-Asparaginase: A GIMEMA Study
Authors: Leone Giuseppe , Gugliotta Luigi , Mazzucconi Maria Gabriella , De Stefano Valerio , Belmonte Monica Mattioli , Dragoni Francesco , Specchia Giorgina , Centra Antonietta , Gamba Gabriella , Camera Andrea , Mandelli Franco 
Published: July 2018

SummaryBlood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10–14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.
Platelet Coagulant Activities and Retinal Vein Thrombosis
Authors: Walsh Peter N. , Goldberg Richard E. , Tax Richard L. , Magargal Larry E. 
Published: July 2018

SummaryTo determine whether platelets play a role in the pathogenesis of retinal vein occlusion (RVO), platelets and coagulation were evaluated in 28 patients with RVO. Platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation were 2–4 fold increased in 9 patients with acute primary RVO but not in patients with acute secondary (10 patients) or chronic (9 patients) RVO. Platelet factor 3 activity, platelet aggregation, serotonin release by platelets and plasma coagulation were normal in all patients. Platelets may provide a trigger mechanism for venous thrombosis in the eye when local conditions permit.
The Activation of Plasma Factor XIII with the Snake Venom Enzymes Ancrod and Batroxobin Marajoensis
Authors: Walter M , Nyman D , Krajnc V , Duckert F 
Published: July 2018

SummaryThe snake venom enzymes Ancrod and Batroxobin marajoensis are able to activate human plasma factor XIII as shown by the formation of the γ-dimers. The concentration of γ-dimers increases with the concentration of the activating enzymes. Factor XIII activated by Ancrod or Batroxobin marajoensis is, however, unable to catalyse the incorporation of the amine dansylcadaverine into casein. The partially activated factor XIII is therefore not demonstrable by means of the artificial test system. This factor XIII loses little activity and remains activable by thrombin.
Spontaneous Atrial Thrombosis in Aged Syrian Hamsters
Authors: McMartin Donald N. 
Published: July 2018

SummaryMany of the aging Syrian hamsters maintained in our Division spontaneously develop atrial thrombosis accompanied by a consumption coagulopathy. The 50% mortality level is reached earlier by females (16 months) than by males (24 months). The incidence of thrombosis increases with age, beginning at 13.5 months in females and at 21.5 months in males, and the overall incidence (73%) is nearly the same for both sexes. Bilateral ventricular hypertrophy was found in thrombosed hearts. The hearts of most aged hamsters, whether thrombosed or not, had myxoid valvular thickenings and myocardial degeneration. Myodystrophic changes included hypertrophied nuclei, cytoplasmic vacuolation, fiber atrophy, and finally replacement fibrosis. Thrombosis probably resulted from local blood stasis secondary to cardiac failure. These hamsters may be an especially useful model for comparative study of the effects of aging and myocardial degeneration on spontaneous thrombosis.
Intravascular Coagulation in Liver Transplantation – Is It Present or Not?
Authors: Bakker C M , Metselaar H J , Gomes M J , Porte R J , Groenland Th N , Schalm S W , Terpstra O T , Stibbe J 
Published: July 2018

SummaryIt is still not clear whether disseminated intravascular coagulation (DIC) contributes to the hemostatic disturbances in orthotopic liver transplantation (OLT). Theoretically the lack of hepatic clearance of procoagulant factors during the anhepatic period and the release of thromboplastic material from the graft might trigger DIC. During heterotopic liver transplantation (HLT) the host liver is left in situ and procoagulant factors may still be cleared; DIC, if present, may not occur until after reperfusion. The aim of the present study was to gain more insight into the underlying mechanism of the coagulation changes during liver transplantation by comparison of OLT and HLT. Thrombin-antithrombin-III complexes (TAT), and indicator of thrombin generation, fibrin degradation products (FbDP) and routine clotting times were assayed in 12 OLTs, 18 HLTs and in a control group of 10 partial hepatic resections (PHR).TAT increased dramatically after reperfusion to 136 μg/l in OLT and to 94 μg/l in HLT (p n.s.). In contrast, FbDP levels increased only in OLT, to a maximum of 13.8 μg/ml. Routine clotting times changed mildly and similarly in both OLT and HLT.Conclusions: Graft reperfusion triggers excessive thrombin formation, but there are no other signs of subsequent DIC. Any thrombin formed is probably rapidly inhibited by antithrombin-III. The rise in FbDP during OLT is the result of increased fibrinolysis, which occurred only in OLT and not in HLT.
Pentasaccharide and Orgaran® Arrest, whereas Heparin Delays Thrombus Formation in a Rat Arteriovenous Shunt
Authors: Vogel Gerard M T , van Amsterdam Ronald G M , Kop Wim J , Meuleman Dirk G 
Published: July 2018

SummaryThe mode of action of glycosaminoglycans (GAGs) towards thrombus formation in a rat arteriovenous shunt was studied by simultaneous examination of thrombus weight, platelet consumption and thrombin generation during 45 min of blood circulation. A comparison was made between the effects of heparin, the heparinoid Org 10172 (Orgaran®), and the chemically synthesized methoxy derivative of the antithrombin III binding pentasaccharide fragment of heparin (Org 31540).All three compounds inhibited thrombus growth by 30% at a dose of 80 anti-Xa U/kg i. v. when assessed after 15 min of circulation through the shunt. In addition, a systemic decrease of 27% of platelet numbers in the placebo group was inhibited by heparin and Orgaran® with 63% and by pentasaccharide with 48%. At a later stage, after 45 min of circulation, at comparable plasma anti-Xa levels, thrombi which had formed in the presence of Orgaran® or pentasaccharide, but not in the presence of heparin, became less or non thrombogenic. This non-thrombogenicity was reflected by i) an inhibition of the local deposition of [51Cr]platelets of 75% with Orgaran® and of 57% with pentasaccharide, and ii) an inhibition of ex-vivo thrombus-induced thrombin generation in pooled rat plasma of 67% with Orgaran® and of 52% with pentasaccharide (inhibition compared to placebo).Although the mechanism of inducing non-thrombogenicity of a (developing) thrombus by Orgaran® and pentasaccharide requires further investigation, the suppression of the local thrombin generation potency, measured by thrombus-induced thrombin generation in pooled plasma, is much more correlated with thrombus growth than systemic anticoagulant activity. This suppression is likely to be due to the anti-Xa activity, as reflected by the efficacy of the pure Xa inhibiting pentasaccharide. Limitation of thrombus growth adds to the prophylactic perspective of Orgaran® and pentasaccharide in preventing thrombosis.
Heparinised Clotting Factor Concentrates in Patients with Christmas Disease and Liver Disease
Authors: Preston F. E , Malia R. G , Lilleyman J. S , Blackburn E. K 
Published: July 2018

SummaryEvidence has been sought of activation of the coagulation system in two groups of patients following the infusion of two heparinised clotting factor concentrates. No changes were detected in 13 patients with mild hepatic dysfunction. In six studies on patients with Christmas disease induced abnormalities occurred in only one. Activation of the coagulation mechanism did not occur in another individual who had received the same batch of material.
The Rapid Fibrin Plate – a Method for Plasminogen Activator Assay
Authors: Marsh N. A , Gaffney P. J 
Published: July 2018

SummaryMost of the technical problems associated with the fibrin plate method have been overcome in recent years with the exception of the long incubation period. This study was carried out to investigate plasminogen-enrichment as a means of shortening this period.Fibrin plates made up to contain 2.0 casein units of added plasminogen each, were opaque, firm, did not lyse spontaneously and yielded biometrically-valid parallel-line assays for streptokinase and urokinase after a 3 hour incubation period. Urokinase assays were more accurate than those for streptokinase probably because of the latter’s shallow dose-response curve. Plasminogen-enrichtment appears therefore to be a convenient way of producing a “rapid” fibrin plate requiring incubation for 3 hours compared with the usual 16 to 20 hours.
Platelet Aggregate Ratios – Standardization of Technique and Test Results in Patients with Myocardial Ischemia and Patients with Cerebrovascular Disease
Authors: Prazich Julie A. , Rapaport Samuel I. , Samples John R. , Engler Robert 
Published: July 2018

SummaryThe technique for measuring platelet aggregate ratios described by Wu and Hoak (1974) was evaluated in normal subjects. The following had no influence upon the test result: age, sex, fasting versu the postprandial state, and the degree of stasis prior to drawing the sample. Variance within subjects was small compared to variance between subjects (0.0009 versus 0.0053, p < 0.01). Platelet aggregate ratios were then measured in 36 patients with coronary artery disease hospitalized with acute chest pain. Their mean platelet aggregate ratio of 0.86 was identical to the mean ratio for 47 normal subjects. Greater variability was found within patients (between samples) than within the normal subjects. This observation raises doubts about the significance of a single measurement of platelet aggregate ratio in such acutely ill patients. Mean platelet aggregate ratios measured daily did not differ over a 7-day period between 11 patients who developed a myocardial infarction and 10 patients who did not. A normal mean platelet ratio was also found on a single measurement from 30 patients with a history of completed stroke (0.87) and from 11 patients with a history of transient ischemic attacks (0.92).
Defective Platelet Adhesion and Aggregation on Subendothelium Exposed in Vivo or in Vitro to Flowing Blood of Fawn-Hooded Rats with Storage Pool Disease
Authors: Tschopp Th. B , Baumgartner H. R 
Published: July 2018

SummaryCitrated rat blood was exposed to either subendothelium or the fibrillar collagen of enzymatically modified subendothelium of rabbit aorta in a perfusion system under laminar blood flow conditions at a wall shear rate of 830 s−1. The resulting platelet surface interaction was estimated by a morphometric method.With blood of fawn-hooded (FH) rats, which suffer from hereditary platelet “storage pool disease”, platelet spreading was slower on both exposed surfaces and resulted in a lower rate of surface coverage with platelets on subendothelium if compared with controls.The rate of adhesion of FH-platelets to the fibrillar collagen, however, was slightly higher as compared to controls despite reduced platelet spreading. This was probably due to the absence of platelet thrombus formation observed with FH-rat blood, whereas massive platelet thrombus formation took place in the controls. It is suggested that platelets of controls which arrive near the surface are preferentially incorporated into the rapidly forming platelet thrombi rather than reaching the surface, and hence do not increase surface-coverage with adhering platelets.The defective platelet adhesion and aggregation in the FH-rat was also apparent after desendothelialization of the aorta in vivo, although to a lesser extent, probably due to the extremely low thrombogenicity of rat aorta subendothelium.
Exterior and Interior Events in Early Stage of Thrombin-induced Platelet Aggregation
Authors: Hashimoto Shuichi , Shibata Sachiko , Kobayashi Bonro 
Published: July 2018

SummaryTreatment of washed rabbit platelets with 1 u/ml of thrombin at 37° C resulted in a disappearance from platelets of a protein with 250,000 dalton molecular weight which was shown to be originated from plasma membrane. Parallel loss of adenyl cyclase was noted, and both reactions were complete within 30 sec. From the patterns of disc electrophoretograms, the importance of quick suppression of thrombin action in demonstrating the primary event was stressed.Thrombin induced an apparent activation of membrane bound phosphodiesterase. This reaction was also complete within 30 sec. The cellular component which contained the enzyme activity was distinct from plasma membrane. Soluble phosphodiesterase was not influenced by thrombin at all.These reactions required intact platelet cells to react with thrombin, and no reaction was detected when subcellular preparations were treated with thrombin.Possibility of collaboration of changes in externally located synthetic enzyme with those in internally located degrading enzyme in the early phase of thrombin action on platelets was suggested.
Effect of Calcium ion on the interaction between Thrombin and Heparin. Thermal Denaturation
Authors: Machovich Raymund , Arányi Péter 
Published: July 2018

SummaryHeat inactivation of thrombin at 54° C followed first order kinetics with a rate constant of 1.0 min−1 approximately. Addition of heparin resulted in protection against thermal denaturation and, at the same time, rendered denaturation kinetics more complex. Analysis of the biphasic curve of heat inactivation in the presence of heparin revealed that the rate constants of the second phase changed systematically with heparin concentrations. Namely, at 4.5 × 10−6M, 9 × 10−6M, 1.8 × 10−5M and 3.6 × 10−5M heparin concentrations, the rate constants were 0.27 min−1, 0.17 min−1, 0.11 min−1 and 0.06 min−1, respectively.Sulfate as well as phosphate ions displayed also enzyme protection against heat inactivation, however, the same effect was obtained already at a heparin concentration, lower by three orders of magnitude.The kinetics of enzyme denaturation was not affected by calcium ions, whereas in the presence of heparin the inactivation rate of thrombin changed, i. e. calcium ions abolished the biphasic character of time course of thermal denaturation.Thus, the data suggest that calcium ions contribute to the effect of heparin on thrombin.
Studies of Heparin Affinity to Antithrombin III and Other Proteins in Vitro and in Vivo
Authors: Takeda Y , Kobayashi N 
Published: July 2018

SummaryProperties of human, canine, and porcine heparin and S-35-heparin were first studied. Their electrophoretic mobility through 10 g % polyacrylamide gels, specific activity and their filtration patterns through Sephadex G-200 columns were closely similar. Then, S-35-heparin (0.5 mg) and cold heparin (27 mg) were simultaneously injected intravenously into 5 dogs and their plasma behavior was compared. The plasma half-lives of S-35-heparin averaged 1.18 ± 0. 13 (SD) hr and was identical with that of cold heparin, but the half-lives were much shorter and averaged 0.46 ± 0.08 (SD) hr in 5 dogs when S-35-heparin alone was injected. Studies were next made of heparin affinity to proteins including canine antithrombin III (AT) by the use of Sephadex G-200 chromatography, polyacrylamide gel electrophoresis, and S-35-heparin as a tracer. It was found that S-35-heparin-binding to alpha1, beta, and gammaglobulins and fibrinogen was readily separable upon addition of 5 mg cold heparin, but that the binding to AT was inseparable by addition of cold heparin or by electrophoresis. However, in canine plasma, both S-35-heparin and cold heparin were mostly bound to proteins other than AT, suggesting that this might be the case in vivo. To further substantiate this, studies were made of the comparative behavior of I-125-labeled AT (I-125-AT) and S-35-heparin in dogs with the idea that the plasma half-lives of both should be equal if they were irreversibly bound to each other. The plasma half-lives of I-125-AT averaged 2.10 ± 0.05 (SD) days in 5 male dogs and 1.99 ± 0.04 (SD) days in 5 female dogs, and were much different from the half-life values of S-35-heparin as given above. These results indicate that heparin in vitro is more tightly bound to AT than to other proteins, that heparin in vivo is not irreversibly bound to AT and suggest that it is mostly bound to proteins other than AT in vivo.
Heparin Elimination in Patients with Liver Cirrhosis
Authors: Teien Arne N. 
Published: July 2018

SummaryHeparin (100 U/kg body-weight) was injected intravenously, and heparin concentration in plasma determined by polybrene titration. Mean heparin half-life was 117.8 min in a group of patients with liver cirrhosis and normal renal function (n = 6) as compared to 74.0 min in the normal group (n = 6). The difference between the two groups is statistically significant (p ≈ 0. 02). Heparin half-life was correlated to galactose half-life in the patients (r = 0.83, p = 0. 05). The findings suggest that heparin is metabolized in the liver. There was a significant fall in antithrombin III activities in the normals, but not in the patients. A possible explanation may be that the normal liver removes heparin bound to antithrombin III, and that this function is impaired in liver cirrhosis.
Thrombo-Embolism in Patients with Abnormally Short Activated Partial Thromboplastin Time
Authors: McKenna Rajalaxmi , Bachmann Fedor , Miro-Quesada Miguel 
Published: July 2018

SummaryPatients with a shortened activated partial thromboplastin time (APTT) of less than 29 sec (≥2.5 SD below the mean) were followed for the development of peripheral deep vein thrombosis by clinical findings. Perfusion lung scans were performed in patients with clinical symptoms suggesting pulmonary embolism. 23 of 100 patients in this prospective study developed thrombo-embolism (TE). This represents a tenfold increase over the overall incidence of 2.2% in medical and surgical patients during the study period. Shortened APTT’s were encountered most commonly in patients with disseminated malignancy and in surgical patients. Post-op er ative patients with an APTT of ≤ 28 sec were at high risk for the subsequent development of TE (43 %). There was a correlation between frequency of shortened APTT, degree of shortening of the APTT and incidence of TE. Patients with APTT’s of ≤ 28 sec on at least three occasions or ≤ 25 sec on at least one occasion had a 53% incidence of TE. Prophylactic low dose heparin therapy is therefore recommended for all patients who show a persistent mild shortening of the APTT or a severe shortening of the APTT on at least one occasion during periods of high risk, e.g. during immobolization or after surgery.
Spurious Prolongation of the Activated Partial Thromboplastin Time
Authors: Okpara Robert A. , Carabello Joann , James Day H 
Published: July 2018

SummaryThe clinical and laboratory data of 8 patients (4 males and 4 females) with circulating anticoagulant were presented. Based on prolonged APTT, failure to correct the APTT with 50 % normal plasma and abnormal tissue thromboplastin inhibition test, the inhibitor was identified as “middle stage” – or the “lupus anticoagulant”. Thrombokinetics showed the maximal rate of change in optical density (VmaxΔOD) of plasma, resulting from clot formation to be significantly less in the plasma of patients with the inhibitor than in normal plasma. This was not completely corrected by mixing the patients’ plasma with 50% normal plasma.