bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-Dimer Test and Diagnosis of Deep Vein Thrombosis: A Comparative Study of 7 Assays
Authors: Elias A , Aptel I , Huc B , Chale J J , Nguyen F , Cambus J P , Boccalon H , Boneu B 
Published: July 2018

SummaryThe current D-Dimer ELISA methods provide high sensitivity and negative predictive value for the diagnosis of deep vein thrombosis but these methods are not suitable for emergency or for individual determination. We have evaluated the performance of 3 newly available fast D-Dimer assays (Vidas D-Di, BioMerieux; Instant IA D-Di, Stago; Nycocard D-Dimer, Nycomed) in comparison with 3 classic ELISA methods (Stago, Organon, Behring) and a Latex agglutination technique (Stago). One-hundred-and-seventy-one patients suspected of presenting a first episode of deep vein thrombosis were investigated. A deep vein thrombosis was detected in 75 patients (43.8%) by ultrasonic duplex scanning of the lower limbs; in 11 of them the thrombi were distal and very limited in size (<2 cm). We compared the performance of the tests by calculating their sensitivity, specificity, positive and negative predictive value for different cut-off levels and by calculating the area under ROC curves. The concordance of the different methods was evaluated by calculating the kappa coefficient. The performances of the 3 classic ELISA and of the Vidas D-Di were comparable and kappa coefficients indicated a good concordance between the results provided by these assays. Their sensitivity slightly declined for detection of the very small thrombi. Instant IA D-Di had a non-significantly lower sensitivity and negative predictive value than the 4 previous assays; however its performance was excellent for out-patients. As expected, the Latex assay had too low a sensitivity and negative predictive value to be recommended. In our hands, Nycocard D-Dimer also exhibited low sensitivity and negative predictive value, which were significantly improved when the plasma samples were tested by the manufacturer. Thus significant progress has been made, allowing clinical studies to be planned to compare the safety and cost-effectiveness of D-Dimer strategy to those of the conventional methods for the diagnosis of venous thrombosis.
Glanzmann’S Thrombasthenia: Pregnancy And Parturition
Authors: Sundqvist S B , Nilsson I M , Svanberg L , Cronberg S 
Published: July 2018

A 35-y-old patient with severe Glanzmann's thrombasthenia became pregnant. Only four such cases are so far known. Two of them were treated successfully with platelet concentrates. Our patient, who had received multiple transfusions, had antibodies against tissue antigens. These were of IgG type. PIPA-test (Kekomäki, R. Medical Biology 54:112, 1977) verified the presence of platelet antibodies. The second wave of aggregation induced by ADP in normal platelet-rich plasma was inhibited by her IgG fraction. Transfusion of HLA matched platelets did not result in any survival of the transfused platelets in her circulation, as revealed by the absolutely absence of aggregability even after the transfusion. Thus no specific treatment was available.During the 24-32 weeks there were signs of activation of the coagulation and the fibrinolytic systems in the form of a decreasing number of platelets and the presence of FDP and fibrin monomers. VIII:C and VIIIR:Ag were remarkably low throughout the pregnancy and the fibrinogen content did not reach the upper limit of the reference area. The oestriol content in plasma and the biparietal diameter as measurements of the condition of the foetus, remained normal during this period, but there was an unexplainable decrease of the plasma oestriol content during the last month of pregnancy.When signs of activation of the coagulation system had disappeared, tranexamic acid was given as prophylaxis (Astedt and Nilsson, Br Med J 1:756, 1978). Apart from transient haematuria in the 24th week of gestation, no complications were seen during the rest of the pregnancy.In the 42nd gestational week the patient delivered a boy, spontaneously per vaginam. No abnormal bleeding occurred either during or after the delivery. Intense and prolonged drug induced contraction of the uterus might have helped to decrease the bleeding. No transfusion of platelets or blood was given.
Contact Activation By Ellagic Acid - The Concept Of Soluble Activator Disputed
Authors: Exner T , Rickard K A 
Published: July 2018

Ellagic acid (EA) has often been described as a “soluble” activator of the contact mechanism in contrast to kaolin, silica or glass which are insoluble. We have found that EA is not effective as a contact activator when in true solution but is active only when present as a particulate solid or dispersion.A pH titration of EA was carried out and it was found that EA dissolved readily in alkaline solutions. When adjusted to neutral pH these formed supersaturated solutions which slowly precipitated forming fine microcrystalline dispersions. At high EA concentrations there was concurrent development of turbidity and contact activity. At lower EA levels no turbidity was visible, yet contact activity increased on standing, presumably as EA particle size increased. Contact activity was reduced in all ellagic acid preparations by centrifugation after standing.Substancesof low molecular weight in true solution do not sediment under these conditions and do not show turbidity. These are properties of particles or aggregates. These observations support the old theory that only particulate materials providing a liquid/negatively charged solid interface of substantial size function as true activators.It is probably important to distinguish between activation of the contact mechanism by substances which may be in true solution such as various organic sulphates and those which are dispersions of solids, functioning possibly by a different mechanism.
Endotoxins And Procqagulant Activities Of Ascitic Fluid
Authors: Murr H , Schüssler P , Rindfleisch G E , Eisenburg J , Hiller E 
Published: July 2018

Procoagulant activities in ascitic fluid of patients with cirrhosis of the liver have been reported repeatedly. It has been suggested that they cause DIC after reinfusicn of ascitic fluid, however, the nature of these factors is unknown. Since endotoxins have been found in ascitic fluid and it is known that they can greatly augment the procoagulant activities of monocytes and macrophages, we assayed for the presence of endotoxin and compared the procoagulant activities in each of 15 specimens of ascitic fluid caused either by cirrhosis of the liver or by metastasizing tumors.Endotoxins were assayed by the limulus test. Procoagulant activities were determined by thrcmbelastography, thrombin generation test, the presence of soluble fibrin monomer complexes ( SFMC ) and the ability to activate prothrombin complex and factor X.Endotoxins were detected in 12 of 15 specimens of ascitic fluid caused by cirrhosis of the liver. In 11 of the endotoxin positive and in 2 of the 3 endotoxin negative samples procoagulant activity was present ( i.e. shortened reaction time, increased thrombin generation, activation of prothrombin complex ). In contrast, in only one out of the 15 samples of tumerous ascitic fluid the limulus test was positive. Nevertheless, in 9 of these 15 specimens procoagulant activity was present. In all specimens increased amounts of SFMC were found.The precise mechanism for the activation of the coagulation system following ascitic fluid reinfusion remains to be established. In addition to stimulation of macrophages by endotoxin other factors like tissue thromboplastin release from tumor cells or injured tissues may account for the procoagulant activity of ascitic fluid.
Prostanoids And Endotoxaemia In The Mini-Pig
Authors: Westwick J , Krishnamurthi S , Scully M , Newman Y , Webb P , Kakkar V V 
Published: July 2018

Infusion (iv) of endotoxin (E coli 0111 B4) at a cone, of 1, 10, 100 or lOOOng/kg/min into mini-pigs with sampling every 20 mins produced a dose related fall in WBC, platelets, blood pressure (BP) and early large increases in plasma thromboxane (Tx) B2 with only minor changes in plasma 6-oxo-PGF1α conc. In 5 pigs endotoxin infusion at 100 ng/kg/min for 40 min produced elevated plasma levels of TxB2 from pre-infusion value of 40±5 to 750±50pg/ml, while WBC, platelets and BP expressed as % of pre-infusion value were 40±8, 81±6 and 105±5% respectively. At the end of the endotoxin infusion (100 min) plasma TxB2 had decreased to 120±10pg/ml; WBC, platelets and BP were 22±4, 62±4, 63±5% of pre-infusion value. In 5 other pigs receiving saline only, no significant changes in any of the above parameters were observed.Thus there is an excess of thromboxane production compared to PGI2 in endotoxaemia. We attempted to determine the contribution of this prostanoid imbalance to endotoxaemia, by treating groups of 5 to 9 mini-pigs with either PGI2 (125 ng/kg/min, continuously), or a potent and selective Tx synthesis inhibitor, UK, 37, 248 (7.5mg/kg as a bolus 10 min before) or lignocaine (20mg/kg as bolus 10 mins before followed by an infusion of 2mg/min) prior to endotoxin infusion. Both PGI2 and lignocaine maintained the BP at pre-endotoxin values, but did not have a significant effect on the leucopenia and thrombocytopaenia or on the elevation of plasma TxB2 While the Tx synthesis inhibitor produced a significant (p<0.05) but not a maximum inhibition of the drop in BP, a marked inhibition of plasma TxB2 formation, but with no effect on the leucopenia or thrombocytopaenia induced by the endotoxin infusion.Although Tx formation is a sensitive indicator of endotoxaemia and precedes the development of hypotension, it is not contributory to the thrombocytopaenia or the leucopenia. How ever both PGI2 and the Tx synthesis inhibitor by correcting the prostanoid balance appear to be therapeutically useful in endotoxaemia.
Prevention Of Shwartzman’S Phenomenon In Factor XIII Deficiency
Authors: Young Lee Soo , Keun Chang Sung , Chung Soo II 
Published: July 2018

Cross-linked clots formed in vitro are reported to be more resistant to fibrinolysis but the relevance of these observations to the situation in vivo is uncertain. The possible role of Factor XIII in the formation of diffuse intravascular fibrin deposition was examined in experimentally induced Factor XIII deficient rabbits. Factor XIII deficiency was induced by intravenous infusion of IgG isolated from goat anti-rabbit platelet Factor XIII. Control received normal goat IgG. The Shwartzman reaction was produced by two injections of bacterial endotoxin given 24 hours apart.The most striking histological differences were observed after 48 hours. A large number of glomerular loops were enlarged and engorged with red blood cells and platelet- fibrin thrombi; extensive bilateral cortical necrosis was observed in 8 out of 10 endotoxin injected control rabbits but none in the Factor XIII deficient group.Fibrinogen levels in control rabbits were increased 3-4 fold (1.1g/100 ml), at 24 hours and slightly decreased at 48 hours after endotoxin injection, whereas in Factor XIII deficient animals, the rate of increase was slower but reached similar levels at 48 hours. Fibrinolytic activity in vivo, studied by the degradation of infused 125I-fibrinogen, was significantly increased in both endotoxin injected groups, irrespective of Factor XIII levels.These results strongly suggest that cross-linked thrombi are more resistant to fibrinolysis in vivo as well as in vitro.
Diagnosis Of Venous Thrombosis: The Case For Phlebography
Authors: Salzman E W 
Published: July 2018

Radiographic phlebography is the most accurate test for diagnosis of deep vein thrombosis (DVT) in the lower extremities. Its sensitivity is approached only by 125I- fibrinogen scanning in the calves, and it is far superior proximally. Its specificity is exceeded only by autopsy. Other attractive features of phlebography are its safety and objectivity, the fact that it requires no special equipment, the permanent record it provides, and its ability to distinguish fresh thrombi from old. On the other hand, phlebography is invasive and uncomfortable, requires physician’s skills and is expensive. Venous thrombosis may be induced by phlebography, most often in the superficial veins of the foot or ankle; the frequency of this complication is reduced by dilution of the contrast agent or the use of new non ionic media. Phlebography provides an immediate answer, unlike labelled fibrinogen scanning. It can be employed as an outpatient procedure in patients in whom DVT is suspected and can thus avoid unnecessary hospitalization.The use of phlebography is essential to monitor thrombolytic therapy of DVT, in which complete dissolution of thrombi is necessary to maintain venous valvular function. It is also essential in patients with suspected recurrence or extension of DVT when noninvasive tests were previously positive. It is the preferred diagnostic procedure when anticoagulant therapy is hazardous or in other clinical settings in which the uncertainties associated with noninvasive methods might complicate management.
Haemodialysis Without Heparin, A Possible Benefit From The Use Of Ticlopidine (TCP) In End Stage Renal Disease Haemodialysis (HD) Patients
Authors: Mion C , Chong G , Nguyen Q V 
Published: July 2018

In order to test the efficacy of TCP as an anti- thrombogenic agent during HD, we attempted to suppress heparin in 10 stable end stage renal disease patients, treated for 4 months or more, and taking a 500 mg daily dose of TCP and no other anticoagulant therapy. The dialysis schedule was: 3 weekly 3-5 hours HD; single use Cordis HFAK IV dialyser, 1.3 m2 surface area; heparin dosage: 25-66 units per kg body weight per hour given 50% intravenously as a loading dose and 50% as a continuous infusion during dialysis. Two protocols were followed. In protocol I, the maintenance dose was progressively reduced (10% of the initial dose every 3 HD) down to complete suppression; thereafter, the loading dose was progressively reduced and eventually suppressed. Reduction in dialyser fiber bundle volume (ΔFBV) was measured on each dialyser. When FBV was >15%, heparin dosage was maintained at the lowest level obtained. In 3/5 patients, total suppression of heparin was obtained and 25 dialyses without heparin were realised (6, 10 and 9 dialyses in each patient); dialyser efficiency was maintained despite formation of heparin deposit on the outlet blood chamber of the dialyser. In 3 other patients, total heparin dose was reduced by 75%.In protocol II, progressive reduction of heparin dosage was done simultaneously on loading and maintenance doses; AFBV was also measured in each dialysis and heparin was maintained at a level compatible with ΔFBV <10%. In 5 patients, a 70-80% decrease in heparin dosage was obtained without reduction in dialyser performance.In conclusion, TCP made possible HD without heparin and allowed a striking reduction in heparin dosage without loss of dialyser performance.
The Effect On Serum-Thromboxan B2 Production, Platelet Aggregation, Serotonin Release, PF-4 And 6-Keto-PGF1αOf A Novel Specific Thromboxan A2 Synthetase-Inhibitor In Patients With Hyperactive Platelets
Authors: Knudsen J B , Juhl A , Gormsen J 
Published: July 2018

A novel, specific Thromboxan A2-synthetase inhibitor 4-1-2- (1 H-imidazol-l-yl)ethoxy-benzoic acid hydrochloride was given to nine patients with hyperactive platelets (defined by an aggregation threshold 0.05 ug/ml epinepherine) and nine controls. The effects on serum Thromboxan B2, platelet aggregation, serotonin release, PF-4, and 6-keto-PGF1 were evaluated in sequential blood samples from h to 24 h after single dose of loo mg. The serum-thromboxan production measured by RIA was reduced 96% ± 4.3 sd 1/2 h to 2 h after dosing. Platelet+aggregation was reduced 89 ± lo.2% with epinephrine, 92 ± 11.4% with collagen and 56 ± 14.3% with ADP. Serotonin release induced by ADP was reduced 65 ± 9.8%, while PF-4 showed no consistant changes. When crushed rat aorta or microsome preparations from human umbilical cord arteries were incubated with PRP from patients before and after dosing, and aggregation induced by 16 uM ADP, a 6 fold increase in 6-keto PGF1α production measured by RIA was observed. The Ivy-bleeding time was prolonged by 65±14sd %.Conclusion: Specific inhibition of the platelet thromboxane synthetase in patients induces a highly effective inhibition of thromboxane production, and inhibition of platelet aggregability and serotonin release and an increase in Endoperoxide availability which by rat and human endothelial cell prostacycline synthetase can be utilized for increase prostacyclin production.
Radioimmunoassay Of Bβ 15-42 Peptide From Human Fibrinogen
Authors: Kudryk B , Robinson D , Netré C , Hessel B , Blombäck M , Blombäck B 
Published: July 2018

Early plasmin attack of fibrinogen or fibrin results in the removal of C00H- and NH2-terminal portions of the Aα and 3β chains, respectively. This paper describes a radioimmunoassay (RIA) for measurement, in clinical blood samples, of peptides containing the Bβ 15-42 sequence. Bβ 15-42 was prepared from the NH2-terminal CNBr fragment of human fibrinogen (N-DSK) by sequential proteolysis with Batroxobin and thrombin. Antiserum was obtained by immunizing rabbits with Bβ 15-42 peptide and BSA. The peptide was labeled with 125I by the chloramine-T method. A double antibody RIA was subsequently made.Radiolabeled Bβ 15-42 (tracer) was bound by antiserum and binding was inhibited by excess cold peptide. Free tracer can be separated from bound by second antibody or by charcoal. Fibrinogen and N-DSK completely cross-react. However, the slope of the inhibition curve is different to that of free Bβ 15-42. Plasma, with Trasylol and heparin,must be treated with ethanol in order to precipitate fibrinogen prior to its use for RIA. The level of peptides with Bp 1542 sequence in treated plasma from normal men and women (20-43 year old) showed a mean value of 1.71±0.59 pmol/ml. Some patient plasma (e.g. uremics) showed 10-20 times higher values.The immunoreactive material isolated by gel filtration from normal and patient plasma, as well as from streptokinase-plasmin digests of either plasma or purified fibrinogen, all,in gel chromatography, displayed the same molecular weight range.This RIA is a rapid, specific and sensitive method to measure earliest stage of plasmin proteolysis and will be useful in clinical studies on all disease states associated with fibrino(geno)lysis.
Studies Of The Heterogeneity Of Purified Antithrombin III
Authors: Barrowcliffe T W , Eggleton C A , Mahmoud M 
Published: July 2018

Deficiency of antithrombin III (At III), whether hereditary or acquired, is now recognised as a major predisposing factor for the development of venous thromboembolism. Purified At III concentrates are undergoing clinical trials in various conditions associated with At III deficiency; such concentrates may be given in addition to heparin and their potency is usually assessed by heparin co-factor assays. In an international collaborative study, a reference preparation of purified At III had a lower concentration by heparin co-factor than by immunological assays and this was shown to be due to the presence of non-heparin-binding antigens. In the present study we have examined purified At III from several manufacturers by heparin co-factor (amidolytic), progressive antithrombin (clotting) and immunological assays, and their heparin-binding abilities have been studied by crossed immunoelectrophoresis and heparin-agarose affinity chromatography.There was good agreement between progressive antithrombin and immunological assays, but in some concentrates the heparin co-factor assays gave lower activity. The proportions of non-heparin-binding material varied considerably, from less than 5% to as much as 50% of the total At III antigen in some concentrates. The non-binding material isolated from a heparin column had little heparin co-factor activity, but was able to neutralise thrombin and Factor Xa. Gel filtration and polyacrylamide gel electrophoresis showed no major distinction between heparin-binding and non-binding antigens, indicating the absence of At III-protease complexes.These studies show that some At III concentrates contain substantial amounts of partially denatured molecules, in which the heparin-binding ability of the At III has been impaired but its thrombin and Xa neutralising activity left relatively intact.
Kinetics, Redistribution And Fate Of Indium-111-Labelled-Platelets In Patients With Aortic Aneurysms
Authors: Heyns A duP , Lötter M G , Badenhorst P N , de Kock F , Pieters H , Herbst C , Nel C J C 
Published: July 2018

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.
Interruption Of Malignancy-Associated Platelet Consumption With A Combination Of RA233 And Sulfinpyrazone
Authors: Slichter S J , Weiden P L , O’Donnell M R , Storb R 
Published: July 2018

Fifty-five dogs with spontaneous tumors of varied histology were evaluated by platelet counts and 51Cr labeled autologous platelet survivals to determine if platelet hemostasis was altered. None of the dogs received cancer-directed therapy during the course of these studies. In 12 dogs with local tumors, platelet counts were 303,000/ul - 28,000 (normal 391,000/ul - 34,000, P > O.05), and platelet survival was 4.9 days - 0.2 (normal 5.6 days - 0.2, p < 0.05). In contrast, 23 dogs with metastatic tumor had platelet counts of 268,000/ul ± 26,000 (p < 0.005) and platelet survivals of 3.4 days ± 0.3 (p < 0.001). When the platelet survival was less than 4 days, the platelet count was also depressed with a correlation coefficient of 0.60.After baseline studies, 17 additional dogs with metastatic disease were treated with drugs (RA233 and sulfinpyrazone) that interfere with two different enzyme systems. Although there was some improvement in platelet survived in 6 of 9 dogs treated with RA233 or sulfinpyrazone alone (2.4 days ± 0.3 baseline vs. 3.5 days ± 0.4 treated, p < 0.05), platelet counts were not elevated (241,000/ul ± 54,000 baseline vs. 201,000/ul ± 46,000 treated). However, when the two drugs were given in combination to 8 other dogs, all had increased platelet survivals (2.7 days ± 0.4 baseline vs. 4.4 days ± 0.6 treated, p < 0.02), and this was associated with improved platelet counts in 6 of 8 (259,000/ul ± 46,000 baseline vs. 367,000/ul ± 47,000 treated, p < 0.05). Five had completely normal platelet survivalsThis study indicates that metastatic tumors, regardless of histology, are associated with significant platelet consumption resulting in depressed platelet counts. This consumption can be modified and platelet counts increased by treatment with a combination of two platelet active drugs that may act synergistically. We plan to determine whether similar treatment programs would maintain platelet counts and/or improve the survival of transfused platelets in human subjects with malignant disorders.