bluuebunny/crossref_metadata_2025_split huggingface dataset:
4-Hydroxycoumarin Oral Anticoagulants : Pharmacokinetics-Response Relationship
Authors: Thijssen H H W , Hamulyák K , Willigers H 
Published: June 2018

SummaryThe blood coagulating factors II and VII and prothrombin times (Thrombotest) were followed during a dosage interval (= 24 h) in patients on acenocoumarol (n = 6) and on phenprocoumon (n = 6) therapy. The patients were on stable anti-coagulation (%TT: 7-13%) for at least 6 months. The study was performed to investigate the concentration-response relationship of the 4-hydroxycoumarin-type oral anticoagulants. The three parameters were stable during the 24-h interval for patients on phenprocoumon therapy. Patients on acenoumarol showed fluctuations in their factor VII levels; peak activities were observed at about 2 h, trough activities at about 16 h after acenocoumarol intake. Factor II and Thrombotest activities were stable. Plasma levels of phenprocoumon were stable during daytime whereas acenocoumarol levels declined exponentially (t½ about 12 h). The results indicate the oral anticoagulants to exhibit a concentration-response relationship common to drug-receptor interactions. The results also suggest that for stable and long-lasting anticoagulant therapy oral anticoagulants with half-lives beyond the dosage interval (t½>24 h) should be preferred.
Morphometric Analysis of Density Subpopulations of Normal Human Platelets
Authors: Chamberlain K G , Froebel M , Macpherson J , Penington D G 
Published: June 2018

SummaryPlatelets from seven normal subjects were fractionated on continuous Percoll density gradients and low density (LD), intermediate, and high density (HD) platelets were prepared for transmission electron microscopy followed by computerised morphometric analysis. Normal ultrastructural appearance and discoid shape were preserved by incubation of the platelets in nutrient medium at 37 °C immediately before fixation. HD platelet sections had a larger mean cross-sectional area but a lower ratio of the major to the minor axis compared to LD platelet sections. HD platelets contained more alpha granules, dense granules and mitochondria per square micron of section area than LD platelets. The percentage of section area occupied by open canalicular system was greater in the LD platelets while the percentage area occupied by glycogen fields was over ten-fold higher in the HD platelets. The mean cross-sectional areas of individual alpha granules and dense granules increased with density while the opposite trend was found for mitochondria. It is suggested that these ultrastructural differences mainly arise during thrombopoiesis and may indicate some functional specialization among platelets.
Effect of Lupus Anticoagulant on Antithrombogenic Properties of Endothelial Cells - Inhibition of Thrombomodulin-Dependent Protein C Activation
Authors: Cariou Roger , Tobelem Gérard , Bellucci Sylvia , Soria Jeannette , Soria Claudine , Maclouf Jacques , Caen Jacques 
Published: June 2018

SummaryWe have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient’s IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient’s IgG.The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient’s IgG or Fab’ fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient’s IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.
Aging and Diabetes Increase the Aggregating Potency of Rat Skin Collagen Towards Normal Platelets
Authors: Grigorova-Borsos A M , Bara L , Aberer E , Grochulski A , André J , Mozère G , Peyroux J , Sternberg M 
Published: June 2018

SummaryAcid-soluble collagen samples were prepared from individual skins of 24 month old rats (n = 8), 2 month old young controls (n = 8) and from 6 month old streptozotocin-diabetic rats (n = 5) and their age-matched controls (n = 10). Less collagen was obtained by acid extraction and salt precipitations from skins of diabetic and aged rats than from those of their respective controls. The collagen preparations from diabetic and aged rats showed an increased ratio of beta/alpha components. The rate of “in vitro” fibrillogenesis was less for collagen from diabetic rats than from controls. It was not modified for collagens from aged rats. The aggregating potency towards normal human platelets was markedly increased for collagens from aged and diabetic rats: reduced latency time (p <0.01) and increased velocity (p <0.01) were observed for collagens from aged rats when compared with young rats (16.5 μg/ml). Increased velocity (p <0.01) was also observed for collagens from diabetic rats (8.25, 11 and 16.5 μg/ ml), without modification of latency time.
A Prospective Study of HIV-Infected Haemophilic Boys and the Prognostic Significance of Immune and Haematological Abnormalities
Authors: Williams M D , Al-Rubei K , Hill F G H 
Published: June 2018

SummaryFifty-seven haemophilic boys have been studied prospectively determining T lymphocyte subsets and haematological parameters over a period of 26 months. Clinical follow up of these patients has continued for a further 41 months. At the beginning of the study 21 boys were HIV antibody seropositive and seroconversion was documented in a further 9 during the study period, giving a 52.6% incidence of HIV seropositivity. It has been possible to define a group of patients with persistently falling T4 values and these have shown clinical evidence of HIV infection. Although persistent generalized lymphadenopathy has been observed in 30% of HIV antibody positive boys and some boys have had unexplained fevers, only one boy has progressed to have the acquired immune deficiency syndrome (AIDS) some 5 years and 3 months from HIV seroconversion. This boy had a persistently falling T4 value. The importance of these findings is discussed. To date the abnormalities found in these haemophilic boys irrespective of their age are similar to those already reported in adult haemophiliacs.
Platelet Inhibition in the Management of Thrombosis
Authors: Didisheim Paul , Kazmier Francis J. , Fuster Valentin 
Published: June 2018

SummaryThe role of platelets in the initation of arterial thrombosis is clear. In venous thrombosis as well, platelets may in some circumstances play a significant role.For these reasons, and because of the complications and limitations of anticoagulant therapy, antithrombotic trials have been launched with several agents which inhibit platelet function.Regarding postoperative deep vein thrombosis, neither aspirin nor dipyridamole alone appears effective, although the combination offers promise. Results with the dextrans are conflicting. In recurrent idiopathic deep vein thrombosis, sulfinpyrazone may be beneficial.On the arterial side, transient cerebral ischemic attacks may be favorably affected by either aspirin or sulfinpyrazone. Prevention of thromboembolism associated with prosthetic heart valves appears possible with combination warfarin-dipyridamole therapy, and the beneficial effect of sulfinpyrazone on shortened platelet survival in this group suggests that this agent may also be effective. Sulfinpyrazone may also be beneficial in preventing thrombosis in arteriovenous canulas.The issue which has attracted the greatest attention and about which no clear answer exists at present is whether antiplatelet agents can modify the course of acute myocardial infarction. Several trials with aspirin are currently underway, and it would be premature to recommend its use in this condition until the results of these trials are available, probably in 1975.
Self-Damping Mechanism in Blood Coagulation
Authors: Nemerson Y , Silverberg S.A , Jesty J 
Published: June 2018

SummaryTwo reactions of the extrinsic pathway of coagulation, the activations of Factor X and prothrombin, have been studied in purified systems and shown to be self-damping. Factor X was activated by the tissue factor - Factor VII complex, and prothrombin by two systems: the coagulant protein of Taipan venom, and the physiological complex of activated Factor X, Factor V, lipid, and calcium ions. In each case the yield of enzyme, activated Factor X or thrombin, is a function of the concentration of activator. These and other observations are considered as a basis for a control mechanism in coagulation.
Fibrinolytic Activity at High Altitude and Sodium Acetate Buffer
Authors: Chohan I. S , Singh I , Balakrihsnan K 
Published: June 2018

SummaryAt high altitude there is a tendency for fibrinolytic activity to be enhanced depending, perhaps, on the duration of exposure and this seems to be a protective mechanism against the development of high altitude pulmonary oedema which is associated with diminished fibrinolytic activity. The fibrinolytic response at high altitude seems to be fluctuated during the process of acclimatisation though being maintained at a plateau higher than that in the plains. It apparently results from hypoxic stress but more likely reflects the physiological response to the hypercoagulable state at high altitude. As clot lysis times in high altitude pulmonary oedema are unusually prolonged an attempt at shortening their observation in the test system is desirable. Sodium acetate, 0.12 M solution with pH 7.4 as a diluent in the low temperature technique of dilute clot lysis time is potentially effective to accelerate the lysis time by approximately 33 % compared to phosphate buffer solution of similar pH and molarity. Also the end point of disintegration of clot is more abrupt and sharply defined. Sodium acetate buffer can advantageously replace phosphate buffer as a diluent in this technique.
Regional Quality Control of Coagulation Assay Procedures (Normotest, Simplastin-A and Thrombotest)
Authors: Kahan Johan 
Published: June 2018

SummaryThe report is based on the first 8 months’ operation of an extended regional quality control program involving 20 hospital laboratories in the Stockholm area. The test material was a commercially available lyophilized human reference plasma containing uniformly reduced levels of factors II, VII and X, and optimal concentrations of fibrinogen and factor V. Each participant received 2 batches of the test material with different activity at each 4-week period. Participants were requested to analyze the specimens, independently and in duplicates, along with ordinary patient samples three times weekly during each period. The levels of the factors in the batches were changed in each period. The total number of reported results was 3113. The statistical analysis of values included the calculation of means and variances within and between different thromboplastins (Normotest, Simplastin-A, Thrombotest), different techniques (venous and capillary blood, automatic and manual end-point determination), and laboratories classified according to the category and number of personnel and of performed coagulation tests. Systematic differences between thromboplastins, techniques and laboratories, even using the same type of thromboplastin, contributed a significantly greater amount than within-laboratory random variation to the total variation of determinations. The obtained results indicate the urgency of the quality control of coagulation activity tests.
Hemostatic Defect due to Acquired Circulating Inhibitors against Lipid Procoagulant and Factor VIII
Authors: Pechet Liberto , Snyder L Michael , Chesney Carolyn , Colman Robert W. 
Published: June 2018

SummaryAn 85 year old woman was studied because of severe bleeding. Acquired inhibitors to factor VIII and to phospholipid procoagulants were demonstrated. Platelet factor 3 (Pf3) assay was prolonged with both kaolin and Russell’s Viper Venom (StypvenE). It was normal with patient’s washed platelets and normal plasma, but abnormal when normal platelets were incubated with patient’s plasma. The inibitor also blocked the coagulant action of Bell and Alton thromboplastin, inosithin, phosphatidyl ethanolamine and phosphatidyl choline, but not that of tissue thromboplastin or cardiolipin. All other platelet functions were normal. The inhibitors were purified by A1 (OH3) absorption, heating at 56°, precipitation by 50% ammonium sulfate, followed by dialysis and DEAE-cellulose chromatography. A partial separation of the two inhibitors was achieved.Cyclophosphamide treatment resulted in cessation of bleeding and disappearance of the inhibitors. This seems to be the first instance of an acquired circulating inhibitor specifically directed against phospholipid procoagulants in a patient who also had an inhibitor to Factor VIII.
Abnormal Antithrombin III (Antithrombin III ‘Budapest’) as a Cause of a Familial Thrombophilia
Authors: Sas G , Blaskó G , Bánhegyi D , Jákó J , Pálos L. Á 
Published: June 2018

SummaryA family with a high incidence of spontaneous thromboembolism has been investigated and those members affected were found to have significantly depressed levels of plasma and serum heparin cofactor activity; i.e., antithrombin III and anti-Xa activity. Further studies revealed that despite a marked diminution of antithrombin III activity in these patients measurement of antithrombin III by immunological techniques showed the levels to be normal. It is concluded that this anomaly represents a defect in the synthesis of the antithrombin III molecule. The abnormality appeared to be inherited but the mode of inheritance could not be determined with the available data.
Thrombin Interaction with Human Platelets Potentiation of Thrombin-induced Aggregation and Release by Inactivated Thrombin
Authors: Phillips David R. 
Published: June 2018

SummaryThe possibility that thrombin acts on platelets by a mechanism other than proteolysis was investigated. The proteolytic site of thrombin was modified with phenylmethylsulfonyl fluoride (PMSF). This modified enzyme did not induce platelet aggregation or the platelet release reaction. Platelets were then incubated with the inactivated enzyme (PMS-thrombin) and later with active thrombin. In this sequence of incubation, PMS-thrombin enhanced not only platelet aggregation induced by active thrombin but also the thrombin-induced release reaction. Preincubation with PMS-thrombin was essential for this enhancement as the inhibited enzyme did not affect aggregation if added after active thrombin. The effect of PMS-thrombin was limited to thrombin-induced reactions of the platelet. The inhibited enzyme had no effect on aggregation induced by adenosine diphosphate or collagen, or on thrombininduced coagulation of fibrinogen. These results suggest (1) that both proteolytic and binding sites for thrombin are present on the human platelet plasma membrane ; and (2) that interaction of thrombin with the binding site potentiates the activity of the proteolytic site.
Concentration Effects of Platelets, Fibrinogen and Thrombin on Platelet Aggregation and Fibrin Clotting
Authors: Chao Francis C. , Tullis James L. , Kenney Dianne M. , Conneely Gail S. , Doyle John R. 
Published: June 2018

SummaryThe effects of varying concentrations of platelets, fibrinogen and thrombin on platelet aggregation and on fibrin clotting were investigated. The results indicated that a threshold thrombin to platelet concentration ratio may be required to cause platelet activation. Above the threshold ratio, platelets exhibited properties which enhanced thrombin action in causing aggregation and fibrin clotting. At T/P ratios below the threshold level, the presence of platelets reduced thrombin activity, in other words, platelets exerted an antithrombin action. Fibrinogen at low concentrations (0.02-1.5 mg/ml) enhanced platelet aggregation induced by thrombin; whereas, at high concentrations of fibrinogen (2.0-4.0 mg/ml), aggregation was markedly inhibited. Continuous mixing of samples of platelets and fibrinogen at physiological concentrations with thrombin at low concentrations ( ˂ 2.0 U/ml) resulted in platelet aggregation. On the other hand, fibrin clots formed in samples without mixing or with high thrombin concentrations (≥ 5.0 U/ml). These results suggested that the quantitative relationships between platelets, fibrinogen and thrombin, and the presence or absence of cell contact may be important factors in determining the overall hemostasis.
Fibrinogen-Fibrin-Related Antigen Pattern in Human Blood
Authors: Jacobsen Carl D. , Hoak John C. , WU Kenneth K. , Fry Glenna L. 
Published: June 2018

SummaryIn serum from patients with DIC at least 3 different FR-antigenic components could be found. It was difficult to demonstrate these components in the corresponding plasma samples. It is possible that a portion of these antigens formed as a result of in vitro clotting despite the presence of proteolytic inhibitors. These results suggest that the interpretation of “increased split products in serum” may be more complex than current concepts indicate.
The Use of the Fibrinogen Turnover and the Isotope Scanning of the Legs for the Diagnosis of Venous Thrombosis in Non Surgical Patients
Authors: den Ottolander G. J. H , van der Maas A. P. C , Schopman W 
Published: June 2018

SummaryIn 2 groups of non surgical patients with venous thrombosis (V. T.) the fibrinogen turnover rate was determined in addition to scanning of the legs.In the first group of 13 patients with clinical signs of V. T. the Tx/2 of 131I-fibrinogen was shorter than in a normal group. In the second group of 10 patients with V. T., diagnosed only by local scanning of the legs using 125I-fibrinogen, the T72 was also shortened.Because of the longer half life time of the 125I-label, observations can be carried out during a period of 20 days, so that 125I-fibrinogen is preferable to 131I-fibrinogen. Of 33 elderly patients treated for congestive heart failure a positive leg scan was observed in 15. Treatment with intravenously injected heparin immediately interferes with further accumulation of radioactivity and corrects the shortened TVa to normal values, in contrast to treatment with oral anticoagulants.
Substrate Composition and the Effect of ε-Aminocaproic Acid on Tissue Plasminogen Activator and Urokinase-induced Fibrinolysis
Authors: Thorsen Sixtus , Astrup Tage 
Published: June 2018

SummaryThe influence of variations in substrate composition on the biphasic pattern of inhibition by e-aminocaproic acid (EACA) of urokinase-induced fibrinolysis, first observed on bovine plasminogen-rich fibrin, was studied using a fibrin clot lysis time assay. Different species of fibrinogen and plasminogen or plasmin were used. Preparations of different degrees of purification were compared at varying concentrations. The behavior of urokinase was compared with that of a porcine tissue plasminogen activator. Variations in the conditions of the assay greatly influenced the results. The concentration of fibrinogen had a particularly marked influence. At increased fibrinogen concentrations the biphasic response of urokinase was enhanced and a weak biphasic effect was also produced by the tissue activator which usually yields a uniformly increasing inhibition curve. The phase of fibrinolysis enhancement produced by urokinase with genuine plasminogen substrates occurs at substrate concentrations and EACA levels present in patients treated with EACA. The observed variations may explain discordant findings reported by various investigators.
Storage of Human Blood Platelets
Authors: Hardeman M. R , Heynens Carina J L. 
Published: June 2018

SummaryStorage experiments were performed at 4°, 25° and 37° C with platelet-rich plasma under sterile conditions. In some experiments also the effect of storing platelets at 4° C in whole blood was investigated.Before, during and after three days of storage, the platelets were tested at 37° C for their serotonin uptake and response to hypotonic shock. In addition some glycolytic intermediates were determined.A fair correlation was noticed between the serotonin uptake and hypotonic shock experiments. Both parameters were best maintained at 25° C. Also platelet counting, performed after the storage period, indicated 25° C as the best storage temperature. Determination of glycolytic intermediates did not justify any conclusion regarding the optimal storage temperature. Of the various anticoagulants studied, ACD and heparin gave the best results as to the serotonin uptake and hypotonic shock response, either with fresh or stored platelets. The use of EDTA resulted in the lowest activity, especially after storage.The results of these storage experiments in vitro, correspond well with those in vivo reported in the literature.
The Inhibition of Platelet Aggregation by an Aorta Intima Extract
Authors: Heyns A. du P , van den Berg D. J , Potgieter G. M , Retief F. P 
Published: June 2018

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.
Preferential Disappearance of Aerobically Generated ATP from Platelets during Thrombin-induced Aggregation
Authors: Matsui Satoko , Watanabe Yasuko , Kobayashi Bonro 
Published: June 2018

SummaryThrombin-induced nucleotide disappearance from rabbit platelets labelled with 32P under oxidative and glycolytic conditions was observed. After adding thrombin to a platelet suspension previously incubated with 32P in the presence of succinate or of glucose + KCN, radioactive ATP formed under the oxidative condition disappeared rapidly from cells and medium, while that formed under the glycolytic condition remained within aggregates. Since no significant difference was observed between the amounts of ATP generated during thrombin-induced aggregation in both systems, the preservation of radioactive ATP in aggregates under glycolytic conditions cannot be attributed to an increase in ATP generation through glycolysis during aggregation. Rather, it is conceivable that consumption of newly synthesized ATP is markedly stimulated under oxidative conditions. Sonic disruption of labelled platelets followed by subcellular fractionation revealed that ATP generated in both the oxidative and glycolytic systems was found in the soluble fraction of the cells. The possible presence of sub compartments in “the rapidly labelled pool” of ATP in the soluble fraction is discussed.