bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Ciprofibrate on Platelet Aggregation and Fibrinolysis in Patients with Hypercholesterolaemia
Authors: Simpson Iain A , Lorimer A Ross , Walker Isobel D , Davidson John F 
Published: July 2018

SummaryThe fibrinolytic and platelet effects of Ciprofibrate, a new lipid lowering drug, were studied in 7 patients with hypercholesterolaemia over a 12 week period. A significant reduction in plasma fibrinogen was noted and a lesser increase in fibrinolytic activity. However, no change in platelet aggregation was noted. As expected Ciprofibrate produced a significant hypolipidaemic effect in these patients.We have described effects of Ciprofibrate which may have potential benefits in this high risk patient group.
Reactivity of Small Molecular Forms of Human Factor VIII/von Willebrand Factor with Botrocetin and Anti-Factor VIII-Coated Latex Particles
Authors: Furlan M , Perret B A , Beck E A 
Published: July 2018

SummaryTwo recently developed tests for measurement of factor VIII/von Willebrand factor (FVIII/vWF), i.e. platetelet agglutination by botrocetin and a kinetic latex antigen assay, were compared with ristocetin cofactor and electroimmunoassay, in respect with FVIII/vWF size-distribution. FVIII/vWF was measured in six cases of atypical von Willebrand’s disease (type II), in gel-filtered fractions of normal cryoprecipitate and in the course of depolymerization of purified normal FVIII/vWF by disulfide reduction. Small molecular forms of FVIII/vWF from normal and variant type II plasma, and those derived by disulfide reduction of high-molecular weight FVIII/vWF, showed remarkably decreased reactivity in ristocetin-, botrocetin- and latex-assay. We conclude that for botrocetin-induced platelet agglutination, as well as for agglutination of antibody-coated latex particles, multiple interactions with repeating subunits of FVIII/vWF are required. As a practical consequence, the combined measurement of FVIII/vWF by the latex test and electroimmunoassay provides a simple tool for discriminating between the classical von Willebrand’s disease and its variants.
Purification and Characterization of Tissue-Type Plasminogen Activator in Maxillary Mucosa with Chronic Inflammation
Authors: Hamaguchi Yukiyoshi , Ohi Masuichi , Sakakura Yasuo , Miyoshi Yasuro 
Published: July 2018

SummaryTissue-type plasminogen activator (TPA) was purified from maxillary mucosa with chronic inflammation and compared with urokinase. Purification procedure consisted of the extraction from delipidated mucosa with 0.3M potassium acetate buffer (pH 4.2), 66% saturation of ammonium sulfate, zinc chelate-Sepharose, concanavalin A-Sepharose and Sephadex G-100 gel filtration chromatographies.The molecular weight of the TPA was approximately 58,000 ± 3,000. Its activity was enhanced in the presence of fibrin and was quenched by placental urokinase inhibitor, but not quenched by anti-urokinase antibody. The TPA made no precipitin line against anti-urokinase antibody, while urokinase did.All these findings indicate that the TPA in maxillary mucosa with chronic inflammation is immunologically dissimilar to urokinase and in its affinity for fibrin.
Questions and Answers on Prothrombin Time Standardisation in Oral Anticoagulant Control
Authors: Loeliger E A , Poller L , Samama M , Thomson J M , Van den Besselaar A M H P , Vermylen J , Verstraete M 
Published: July 2018

SummaryOne of the reasons why oral anticoagulants fell into disrepute is the absence of internationally accepted standardised procedures for controlling the level of anticoagulatiori. This deplorable situation resulted in over- and under-coagulation and uncertainty in the therapeutic range. International conformity can now be obtained by using an International Normalised Ratio (INR) which is derived from the individual result obtained in a given plasma sample and the International Sensitivity Index (ISI) of the tissue thromboplastin reagent used. Any thromboplastin reagent can be calibrated against an international primary or secondary W.H.O. reference preparation, so as to obtain its International Sensitivity Index. The new system of reporting the level of anticoagulation was designed and can only safely be applied in patients taking oral anticoagulants.
Further Studies on the Hypercoagulable State of Patients with Cushing’s Syndrome
Authors: Patrassi G M , Zanon R Dal Bo , Boscaro M , Martinelli S , Girolami A 
Published: July 2018

SummaryFactors XII, XI, IX and VIII, plasminogen and alpha2-antiplasmin levels were found to be increased in a group of patients affected by Cushing’s syndrome. High activity of these coagulation factors could be due to their increased release and synthesis mediated by cortisol. A significant correlation between the main arterial pressure and either factor VIII antigen, ristocetin cofactor or factor XII activity was found. Moreover a similar correlation between factor XII activity and either factor VIII antigen or ristocetin cofactor was seen. In conclusion, the presence of a hypercoagulable state in Cushing’s syndrome seems confirmed. Synergic release of factor XII and factor VIII from endothelium could be due to high blood vessel tone secondary to hypercorticism. Finally, decreased fibrinolytic activity was suspected according to plasminogen and alpha2-antiplasmin increase.
Similar Mechanism of Various Lupus Anticoagulants
Authors: Exner Thomas 
Published: July 2018

SummaryPotent lupus inhibitors from various patients were mixed with platelet free normal plasma and were compared in activated partial thromboplastin time (APTT), dilute prothrombin time (dil. PT), kaolin clotting time (KCT), contact product clotting time (CPCT), and Russell viper venom clotting time (RWCT) tests. In the last three tests platelets and platelet lipid substitutes were avoided to enhance the sensitivities of these tests for the lupus anticoagulant. Correlations between the KCT and the other tests were mostly good, indicating that different lupus inhibitors functioned by a similar mechanism. There was no significant trend between particular clinical symptoms and individual coagulation test combinations. The KCT was found to be the most sensitive test for the lupus inhibitor, followed by the CPCT, RWCT, dil. PT and APTT tests. Activated platelets tended to correct the APTT lupus inhibitor defect in all except the strongest inhibitor cases.
Reliability and Clinical Impact of the Normalization of the Prothrombin Times in Oral Anticoagulant Control
Authors: Loeliger E A , Besselaar A M H P van den , Lewis S M 
Published: July 2018

SummaryIn 1983, the World Health Organization (WHO) published recommendations for normalization, in oral anticoagulant control, of the prothrombin time (PT). The common denominator is the International Sensitivity Index (ISI) of a thromboplastin, obtained by means of thromboplastin calibration. The common scale is that of the International Normalized Ratio (INR). The INR is the PT ratio Patient PT/normal PT which would have been found normal PT with the WHO primary international reference preparation (IRP) 67/40. The reliability of the INR depends on the extent of calibration precision, patient-specific influences, as well as interlaboratory variation in the PT determination. Under well-controlled conditions the overall coefficient of variation (CV) of the INR is 11-13.5%, if thromboplastins of ISI ≃ 1 are used. For so-called low-sensitivity thromboplastins (ISI ≃ 2-2.5), the overall variation is larger due to a large between-laboratory variation of the measured PT-ratiosThe user of thromboplastin will be provided with a chart or graph enabling him to convert the conventional terms used for expressing PTs into INRs. For quality assurance, and to prepare his own calibration chart if necessary, he should check normalization by means of control plasmas to which INRs have been assigned.There is sufficient clinical evidence to express optimal therapeutic ranges in terms of INR. Manufacturers should revise and adapt their inserts where necessary in order to conform to these requirements.
Dynamics of Platelet Tubulin in Response to Changes in Free Sulfhydryl Groups
Authors: Steiner M 
Published: July 2018

SummaryPools of polymerized and total tubulin were measured in human platelets as a function of free sulfhydryl groups both in acid-soluble and acid-precipitable cell fractions. Changes in free thiols were produced either by storage of platelets at room temperature or by addition of the potent oxidizing agent diazene dicarboxylic acid (diamide) and were correlated with shifts in the dynamic equilibrium between assembled and disassembled microtubules and platelet aggregation. Diamide at concentrations of 0.5 to 5 mM depleted acid soluble SH groups and reduced protein thiols while causing a progressive decrease in polymerized tubulin. Similar changes, although not as severe, were initiated by storage of platelets at room temperature. Platelet aggregation especially that induced by collagen showed a positive correlation with the pool of polymerized tubulin. Our results indicate that the state of oxidation of sulfhydryl groups especially in the acid- precipitable fraction plays an important role in determining the position of equilibrium between polymerized and depolymerized tubulin.
A Role for Pericellular Proteoglycan in the Binding of Thrombin or Antithrombin III by the Blood Vessel Endothelium? – The Effects of Proteoglycan-Degrading Enzymes and Glycosaminoglycan-Binding Proteins on 125I-Thrombin Binding by the Rabbit Thoracic Aorta In Vitro
Authors: Hatton Mark W C , Moar Sue L 
Published: July 2018

SummaryRabbit thoracic aorta segments were treated with either proteoglycan-degrading enzymes or with glycosaminoglycan- binding proteins to examine the nature of the endothelial and subendothelial binding sites of 125I-thrombin. Treatment (5-30 min) with enzymes (heparitinase, chondroitinases AC or ABC) caused a decrease in 125I-thrombin binding by the endothelium (30-70%) and by the subendothelial (intima-media) layer (20-50%); a low- specificity protease destroyed endothelial binding almost entirely and reduced binding to the subendothelium by approximately 60% over a similar period. Of the glycosaminoglycan-binding proteins, pretreatment of the aorta wall with protamine caused a 30% decrease in thrombin binding to the endothelium whereas lipoprotein lipase (present during 125I-thrombin uptake) decreased binding by up to 40%. Pretreatment with antithrombin III did not significantly affect binding of either 125I-thrombin or 125I-FPR-inactivated thrombin. In contrast to thrombin, 125I- antithrombin III was not readily uptaken by the aorta segments. These observations indicate that, whereas the minimal binding by 125I-antithrombin III probably does not involve endothelial proteoglycan, a strong case can be made for endothelial and subendothelial proteoglycan binding sites for thrombin..
Prevention of Postoperative Thromboembolism in Sweden – The Development of Practice During Five Years
Authors: Bergqvist David 
Published: July 2018

SummaryAll climes in Sweden (223) dealing with general, urologie, orthopaedic, and gynaecologic surgery were sent a questionnaire concerning their policy about prophylaxis against postoperative thromboembolism in 1982. The praxis was also compared with that obtained in a similar survey in 1977. 96% replied. 91% used some sort of specific prophylaxis which is significantly more than in 1977. Also a significantly larger number of patients were operated on with prophylaxis than in 1977 (25 vs 19%). The dominating methods were dextran 70 and low-dose heparin. Compared with 1977 peroral anticoagulation, low-dose heparin and mechanical methods had decreased significantly, low-dose heparin in combination with dihydroergotamine increased significantly and dextran showed an unchanged use.
A Functional Plasminogen Assay Utilizing the Potentiating Effect of Fibrinogen to Correct for the Overestimation of Plasminogen in Pathological Plasma Samples
Authors: Gram Jørgen , Jespersen Jørgen 
Published: July 2018

SummaryAn overestimation of the plasminogen concentration occurs in patients with elevated levels of fibrin degradation products (fdp) and/or fibrinogen, when using assays based on the activation of plasminogen by streptokinase (Sk) followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be overcome by addition of fibrinogen in excess to the plasminogen assay thereby obtaining maximum stimulation of the Sk-plasminogen complex. The late degradation products of fibrinogen and fibrin, Dcate and Ddimer, respectively, had no potentiating effect on the Sk-plasminogen complex. The modified assay was designed as a manual method or for a centrifugal analyzer. The excellent reproducibility is illustrated by the coefficient of variation (CV) within series being 1.3% (n = 24) and from day to day being 1.9% (n = 20).
Platelet Regeneration Time After Aspirin Ingestion and Platelet Survival Time After Labelling with 51Chromium or 111Indium Oxine – A Comparative Study
Authors: Boneu A , Sié P , Bugat R , Caranobe C , Eber M , Cazenave J P , Boneu B 
Published: July 2018

SummaryA simultaneous investigation of platelet regeneration time (PRT) based upon malondialdehyde (MDA) recovery after a single oral intake of 500 mg of aspirin and of platelet survival time (PST) after labelling with 51chromium or 111Inindium oxine was performed in 25 cancerous patients. A pilot study conducted with 9 healthy volunteers demonstrated that the MDA assay was highly reproducible and specific for the platelet cycloxygenase activity. The pattern of MDA recovery after aspirin ingestion was linear in the healthy volunteers and in the patients presenting both a normal and an accelerated platelet turnover. PST were calculated using the four mathematical models recommended by the International Committee for Standardization in Hematology; the best fit was given by the multiple hit model in 22 cases and by the linear regression model in 3 cases. The mean results obtained in the patients investigated with the 51chromium were consistently shorter than those obtained in the patients investigated with the mindium oxine while the mean PRT were almost identical in the two groups. An excellent correlation between PRT and PST was observed after 111Indium oxine labelling and using the weighted mean method for PST determination. These results suggest that the 111Indium oxine technique is a better method for platelet labelling and that the results provided by the weighted mean method reflect more closely the in vivo platelet turnover than those provided by the multiple hit model.
Incorporation of Some Eicosaenoic Acids into Endothelial Cells – Effect on Platelet Inhibitory Activity and Prostacyclin Production
Authors: Sicard Béatrice , Lagarde Michel 
Published: July 2018

SummaryPrimary cultures of endothelial cells from human umbilical veins were grown until confluency. Then, dihomogammalinolenic acid (DHLA or 20:3n-6) and eicosapentaenoic acid (EPA or 20:5n-3), precursors of monoenoic and trienoic prostanoids, respectively, as well as 5,8,11-eicosatrienoic acid (20:3n-9), and isomer of DHLA, were incorporated into endothelial lipids. DHLA-rich endothelial cells had a decreased capacity of prostacyclin production. By contrast EPA- or 20:3n-9-rich endothelial cells were comparable to controls in this respect. DHLA and EPA were efficiently acylated into cell phospholipids and triglycerides at the opposite of 20:3n-9. It is suggested that both DHLA and EPA could alter the liberation of endogenous arachidonic acid for prostacyclin synthesis but this might be counterbalanced in EPA-rich endothelial cells by PGI3 production. We conclude that DHLA enrichment of endothelial cell lipids may impair the possible beneficial effect of the acid upon platelet functions whereas that of EPA would not be modified.
Isolation and Partial Characterization of Adenylate Cyclase-Enriched Membranes from Human Platelets
Authors: Shimada N , Tsubokura M , Kimura N 
Published: July 2018

SummaryIsolation of adenylate cyclase-enriched membranes from human platelets was attempted using glycerol lysis technique followed by ultracentrifugation on discontinuous sucrose gradients composed of 24, 30, 34, 37, and 41% (w/w). Adenylate cyclase activity was enriched 4-fold in sample/24% sucrose interface, 7-fold in 24%/30% sucrose interface, and 4-fold in 30%/ 34% sucrose interface fractions with the recovery of 15-20% of the total activity. The enrichment and subcellular distribution of adenylate cyclase resembled in general those of phosphodiesterase and acid phosphatase with slight differences in each other. Protein profiles from SDS-polyacrylamide gel electrophoresis showed that the heavy chain of myosin (Mr = 200,000) was enriched in sample/24% sucrose interface and lower molecular weight proteins in 34%/37% sucrose interface and pellet. The interface fractions between 24 and 34% sucrose were, therefore, collected as adenylate cyclase-enriched membranes.Adenylate cyclase associated with the membranes displayed high specific activity (0.1 and 1-2 nmol/min/mg protein in the absence and presence of stimulants, respectively), and possessed sensitivities to prostaglandins (E1, I2, and D2) as well as cholera toxin. Activation of adenylate cyclase by these compounds required added GTP, indicating that the contamination of the membrane preparations with GTP-like substance (s) was minimal, if at all present.
Determination of Soluble Fibrin in Plasma by a Rapid and Quantitative Spectrophotometric Assay
Authors: Wiman B , Rånby M 
Published: July 2018

SummaryA rapid, sensitive and quantitative spectrophotometric assay of soluble fibrin in plasma samples has been developed. The method is based on the principle that fibrin stimulates the activation of plasminogen by tissue plasminogen activator (t-PA). A sample containing fibrin is incubated with t-PA, plasminogen and a plasmin-sensitive chromogenic substrate. An increase in absorbance which is dependent on the fibrin concentration in the sample is obtained. In plasma samples an initial lag-phase, due to the presence of alpha2-antiplasmin is observed. However, the change in A405 per square minute during the later part of the reaction was found to be proportional to the fibrin content and to generate linear standard curve intercepts at the origin. The detection limit of bathroxobin-digested fibrinogen added to plasma was about 5 nmol/L. Recovery experiments at 20 and 75 nmol/L levels in plasma samples from healthy individuals were excellent. The “within-run” variation (CV) was determined as 3.7%. The formation of fibrin after addition of minute amounts of thrombin to plasma could be monitored with the method. Plasma from 8 healthy individuals was found to contain about 9.2 ± 1.9 nmol/L fibrin. Plasma samples from 46 patients with a suspected haemostatic disturbance had higher levels of soluble fibrin (53 ± 62 nmol/L). Seven of the 46 samples had concentrations above 150 nmol/L.
The Reliability of Activated Partial Thromboplastin Time Methods and the Relationship to Lipid Composition and Ultrastructure
Authors: Stevenson K J , Easton Ann C , Curry A , Thomson Jean M , Poller L 
Published: July 2018

SummaryWide variations in procoagulant properties, lipid composition and ultrastructure of five commonly used APTT methods have been demonstrated. Performance of the methods with a range of coagulation abnormalities has been ranked. Most of the reagents obtained a high score with one or more defects, but a low score with others. A consistent good ranking throughout was only observed with one reagent.The number of significant correlations between the reagents’ procoagulant activities and lipid content confirms the view that the performance of an APTT method is largely dependent upon its lipid composition. Marked differences in concentration and distribution of phospholipids, fatty acids and neutral lipids were evident. The importance of the concentration of phosphatidyl serine in regulating the procoagulant activity of an APTT method has been demonstrated. Electron microscopy provides evidence of the contrasting composition of the reagents from the more discrete uniform liposomes present in the more reliable reagents, to more ill-defined components present in those reagents which performed less well. The study highlights the need for standardisation of the APTT.
An IgM Lupus Anticoagulant that Neutralizes the Enhancing Effect of Phospholipid on Purified Endothelial Thrombomodulin Activity-A Mechanism for Thrombosis
Authors: Freyssinet J-M , Wiesel Marie-Louise , Gauchy Josiane , Boneu B , Cazenave J-P 
Published: July 2018

SummaryAn anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human a-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.
Behaviour of the Contact Phase of Blood Coagulation in the Adult Respiratory Distress Syndrome (ARDS)
Authors: Velasco F , Torres A , Guerrero A , Andres P , Guerrero R , Aljama P , Alvarez F 
Published: July 2018

SummaryIn order to assess the role of the kallikrein-kinin (K-K) system in the pathogenesis of the adult respiratory distress syndrome (ARDS) we have prospectively determined coagulation contact phase, blood gas and hemodynamic parameters in patients with ARDS at 0, 36 and 72 h from diagnosis.Compared to normal values, significantly lower mean levels of factor XII (71.4 ± 9.8%, p <0.0005), prekallikrein (PPK) (52 ± 5.7%, p <0.0005), high molecular weight kininogen (HMWK) (73 ± 2%, p <0.0005) and α2-macroglobulin (α2-M) (51 ± 7.1%, p <0.0005) were found in ARDS patients.The functional kallikrein inhibitory activity (KKI) and Cr esterase inhibitor antigenic (CIINH) were significantly higher in these patients (113.2 ± 5, p <0.005 and 124.7 ± 7.6, p <0.0005 respectively) compared with normal values during the entire study period.The KKI/CIINH ratio decreased significantly in our ARDS patients at 0, 36 and 72 h (p <0.025; p <0.05 and p <0.005 respectively).We found a significant correlation between PPK levels and oxigenation index (r = 0.69, p <0.001), PPK and the static thoracic compliance values (r = 0.64, p <0.001). There was also a significant correlation between PPK levels and Qs/Qt (r = -0.89, p <0.001). ARDS patients that survived presented a stability in the PPK values in successive tests. Nevertheless non-survivors showed a progressive decrease in PPK levels during the follow-up period.Our results suggest that the plasma kallikrein system becomes activated during ARDS and that this activation might increase the lung vessels’ permeability. In addition, PPK levels are in our opinion a useful prognostic parameter in predicting the outcome of ARDS patients.