bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relation of Plasma Coagulation Factor VII and Fibrinogen to Carotid Artery Intima-Media Thickness
Authors: Sosef M N , Bosch J G , van Oostayen J , Visser T , Reiber J H C , Rosendaal F R 
Published: July 2018

SummaryPlasma clotting factor VII and plasma fibrinogen have been claimed as independent risk factors for occlusive cardiovascular disease. The aim of this study was to investigate whether these coagulation parameters affect early atherosclerosis, additional to their possible effect on arterial thrombosis.We used high-resolution quantitative ultrasonography to measure carotid intima-media thickness in 121 healthy volunteers, aged 18 to 56 years. It has previously been demonstrated that an increased artery wall thickness is seen in advanced atherosclerosis. To validate our methodology for relatively young individuals, we assessed the association of intima-media thickness with the risk-factor status of our subjects, by including classical cardiovascular risk factors, e. g. age, sex, serum cholesterol, smoking habits and blood pressure. Thereafter, we studied the effect of factor VII and fibrinogen plasma levels on carotid intimamedia thickness, as well as that of polymorphisms of the factor VII and fibrinogen genes.All classical risk factors except smoking and family history were associated with intima-media thickness. When adjusted for by multivariate linear regression analysis, age, blood pressure and cholesterol appeared to be independent determinants of intima-media thickness. Factor VII and fibrinogen levels showed no association in multivariate analysis with intima-media thickness. We conclude that artery wall thickness measurement by ultrasound is a useful tool to investigate the role of clotting factors in early atherosclerosis. Factor VII and fibrinogen levels in young and middle-aged volunteers have no association with early artherosclerotic vessel wall changes.
Desulfated Hirugen (Hirudin 54-65) Induces Endothelium-Dependent Relaxation of Porcine Pulmonary Arteries
Authors: Glusa Erika 
Published: July 2018

SummaryDesulfated hirugen (hirudin 54-65) at concentrations from 0.1 to 2 μM was found to relax PGF2α-precontracted ring segments of porcine pulmonary arteries with intact endothelium. The relaxation was associated with a pronounced increase in cGMP in the vessels. This endothelium-dependent relaxant effect depended on the extracellular calcium ion concentration and was probably due to the release of endothelium-derived NO as indicated by its susceptibility to blockade of the NO synthesis by NG-nitro-L-arginine. In the presence of indomethacin (3 μM) the maximum hirugen effect was significantly diminished by about 25%. In contrast, neither the sulfated hirugen nor recombinant desulfato hirudin at equimolar concentrations exerted endothelium-dependent relaxation. Hence, the relaxant effect did not correspond to the anticoagulant activity. Desulfated hirugen can be assigned to the group of well-known peptides causing vasodilatation via an endothelium-dependent mechanism.
The Influence of Acenocumarole on the Fibrinogen-turnover in Normal Subjects, Venous Thrombosis and Congestive Heart Failure
Authors: Maas A. P. C. van der , Teulings F. A. G , Schopman W , Ottolander G. J. H. den 
Published: July 2018

SummaryUsing 131Iodine-tagged fibrinogen the influence of acenocumarole on the biological half-life of fibrinogen was investigated in healthy patients, patients with venous thrombosis and patients with congestive heart failure.In 16 healthy patients the mean t½ was 3.8 days. In two of them after administration of acenocumarole the t½ was lengthened. This supports the opinion of a continuous deposition of fibrin on the vascular endothelium in the hemostatic balance.In 13 patients with venous thrombosis the mean t½ was 2.45 days, lengthening to the normal range after acenocumarole therapy. The time interval between the start of acenocumarole therapy and the moment of normalization of the t½ was approximately 4 days. The prothrombin time-index at this moment was 2.3 (thrombotest 5%), which argues in favour of a vigorous anticoagulant therapy.In our 10 patients with congestive heart failure probably venous thrombosis occurred in 40%. Prophylactic anticoagulant therapy as in surgical patients therefore has to be considered.
The Kinin System of Human Plasma
Authors: Özge-Anwar Ayşe H. , Movat H. Z , Scott J. G 
Published: July 2018

SummaryHuman plasma was adsorbed to celite. The celite eluates were chromatographed on QAE-Sephadex A-50, followed by gel filtration, isoelectric focusing and preparative polyacrylamide electrophoresis.By anion-exchange chromatography, factor XI a, kallikrein and y-globulin were isolated from the excluded protein peak. Factor XIa (MW ∼170,000) corrected the deficiency in plasmas deficient in factors XII or XI, but had no effect on the kininsystem. Its isoelectric point was about 8.0-8.5. Kallikrein had a molecular weight of ∼ 90,000 and a pi of 7.8-8.0 The two substances could be isolated also by polyacrylamide electrophoresis.Highly anionic fractions contained a fragment of factor XII a (prekallikrein activator), which activated prekallikrein and retained some of the clot-promoting property of the intact factor XIIa molecule. Its molecular weight was about 37,000, the pi about 4.4 and it migrated as a prealbumin by disc electrophoresis.It is concluded that, by massive contact exposure, most of factor XII a converts to the highly anionic, low-molecular-weight prekallikrein activator. Since the prekallikrein activator is a fragment of factor XII a, we recommend that it be referred to as “XII f”.
The Effect of Several Tissue Thromboplastins on the Activation of the Abnormal Factor X (Factor X Friuli)
Authors: Girolami A , Lazzarin M , Molaro G 
Published: July 2018

SummaryThe effect of several tissue thromboplastins on the abnormal factor X (factor X Friuli) has been investigated.The prothrombin time varied between 33.6 and 69 sec. The prothrombin time percentile values (saline dilution curve and Quick’s formula for citrated plasma) varied between 6.6 and 22% and between 10.9 and 32.8%, respectively. The prothrombin time patient/normal ratio varied between 2.24 and 4.43.The factor X level varied between 3.5 and 20% of normal.Significant correlations were found to exist between the percentile factor X level and the prothrombin time in seconds, the percentile prothrombin time values and the prothrombin time patient/normal ratio. Thromboplastins of human origin yielded the lowest factor X values namely 5% thereby appearing to be practically “inert” with regard to the abnormal factor X. Thromboplastins obtained from rabbit lung on the contrary yielded the highest values, namely 15.3%. Thromboplastins obtained from simian or rabbit brain gave values intermediate between these two extremes.
Urokinase Levels in Urine after Nicotinic Acid Injection
Authors: Holemans R , McConnell D , Johnston J.G 
Published: July 2018

Summary1. Blood fibrinolytic activity and urokinase excretion were studied in a group of young healthy male subjects before and after intravenous injection of nicotinic acid. Although each of the subjects had a marked increase in blood fibrinolytic activity after injection of nicotinic acid, there was no significant change in urokinase excretion.2. These data do not support the theory that urokinase is filtered blood activator of plasminogen. It is suggested that release of urokinase into urine is primarily dependent on the time of contact between urine and walls of collecting ducts and other parts of the urine conducting system.
The Monoiodoacetate (MIA) Tolerance Test, a New Quantitative Method for the Fibrin Stabilizing Factor (Factor XIII) Assay
Authors: Sigg P 
Published: July 2018

SummaryA new quantitative test for the fibrin stabilizing factor (FSF, factor XIII) determination is described. The test is based on the principle of the reversible inhibition of the FSF action by monoiodoacetate (MIA).The definition of the MIA tolerance is given. The normal range is about 45. The MIA tolerance is studied under various conditions. No FSF free material is necessary for its performance.
Blood Factor XI after Fat-Rich Meals
Authors: Egeberg O 
Published: July 2018

SummaryControlled meals were given to normal persons and to certain patients, and blood coagulation was investigated before and after the meal, especially with an assay sensitive for activated antihemophilic C factor (AHC5 = activated f. XI).After bread and rich amounts of margarine (produced mainly from hydrogenated marine oils), the AHC’ assay in fresh plasma registered a significant acceleration about 5 hours after the meal. No significant changes were measured in the levels of AHA (f. VIII), AHB (f. IX) and proconvertin (f. VII). A weaker tendency to acceleration in AHC5 assay seemed also to occur after intake of vegetable margarine (produced from hydrogenated vegetable oils). Bread with low or high amounts of cow butter gave no acceleration.The active principle in the postprandial plasmas could not be demonstrated after a few days of storage at — 20° C.The hypothesis that the acceleration effect is due to an activation of blood AHC was supported by the observation that no corresponding effect was measured after margarine meals to patients with AHC deficiency.Patients with von Willebrand’s disease showed the same activation as normals.The activation seemed to be prevented by intake of linseed oil prior to the margarine meal.The results are discussed.
Use of a Lyophilized Reference Plasma to Compare Coagulation Test Procedures
Authors: Kahan J , Nohén I 
Published: July 2018

SummaryIn 4 collaborative trials, involving a varying number of hospital laboratories in the Stockholm area, the coagulation activity of different test materials was estimated with the one-stage prothrombin tests routinely used in the laboratories, viz. Normotest, Simplastin-A and Thrombotest. The test materials included different batches of a lyophilized reference plasma, deep-frozen specimens of diluted and undiluted normal plasmas, and fresh and deep-frozen specimens from patients on long-term oral anticoagulant therapy.Although a close relationship was found between different methods, Simplastin-A gave consistently lower values than Normotest, the difference being proportional to the estimated activity. The discrepancy was of about the same magnitude on all the test materials, and was probably due to a divergence between the manufacturers’ procedures used to set “normal percentage activity”, as well as to a varying ratio of measured activity to plasma concentration. The extent of discrepancy may vary with the batch-to-batch variation of thromboplastin reagents.The close agreement between results obtained on different test materials suggests that the investigated reference plasma could be used to calibrate the examined thromboplastin reagents, and to compare the degree of hypocoagulability estimated by the examined PIVKA-insensitive thromboplastin reagents.The assigned coagulation activity of different batches of the reference plasma agreed closely with experimentally obtained values. The stability of supplied batches was satisfactory as judged from the reproducibility of repeated measurements. The variability of test procedures was approximately the same on different test materials.
Comparative Inhibition of Extrinsic and Intrinsic Thrombin Generation by Standard Heparin, a Low Molecular Weight Heparin and the Synthetic ATIII-Binding Pentasaccharide
Authors: Lormeau Jean-Claude , Herault Jean-Pascal 
Published: July 2018

SummaryThe inhibiting effect of standard heparin, CY216 and the ATIII-binding synthetic pentasaccharide on extrinsic and intrinsic thrombin generation were quantified by evaluating the decrease of the total amount of active thrombin appearing in plasma after triggering coagulation.Heparin as well as CY 216 produced the same quantitative inhibition of extrinsic and intrinsic TGs whereas pentasaccharide inhibited more efficiently extrinsic TG.This pattern of inhibition was further confirmed on pure extrinsic or intrinsic coagulation respectively in factor IX- and factor VII-depleted plasmas.Furthermore, selective suppression of the anti-thrombin activity of CY 216 by limited amounts of PF4 affected the intrinsic TG inhibition more markedly than the extrinsic one.It was concluded that anticoagulant activity produced mainly through thrombin scavenging leads to similar quantitative impairment of extrinsic and intrinsic coagulation, while selective ATIII-mediated factor Xa inhibition results in a more marked effect against the extrinsic system.
Acquired Coagulopathy In Eight Immunosuppressed Patients With Disseminated Aspergillosis
Authors: Hussey C V , McClellan S L , Annesley W H , Farmer S , Komorowski R 
Published: July 2018

We report a retrospective review of 8 immunosuppressed renal transplant patients with disseminated invasive aspergillosis and a profound coagulopathy; which in three of the cases resulted in uncontrollable hemorrhage. The coagulopathy is characterized by hypofibrinogenemia, modest prolongation of the PT and PTT, and modest elevation of FSP’s. In six of eight cases there was hypotension refractory to dopamine infusion. The diagnosis of DIC was excluded on the basis of FSP’s <30 μg/ml and the relatively mild prolongations of the PT and PTT. Primary fibrinolysis was excluded by normal Euglobulin lysis times. The index case displayed the most profound hemorrhagic manifestations; which did not respond to therapeutic doses of EACA or heparin. Mild correction of the thrombin time and a marked but transient clinical response did occur with intravenous protamine sulfate.Strains of Aspergillus were isolated from premortem cultures in 3 cases and postmortem cultures in the remaining 5. All isolates were found to produce proteolytic enzymes with fibrinogenolytic and fibrinolytic activities. The clinical coagulopathy, refractory hypotension and abnormal coagulation test results in the cases were quite similar to the results obtained when pharmacologic doses of Brinase (a well characterized proteolytic enzyme derived from Aspergillus oryzeae) were administered to dogs. Thus, we propose that our patients’ coagulopathies were secondary to the in vivo effects of a nonspecific protease elaborated by their invasive aspergilli.
Comparison Of 125-I Fibrinogen Kinetics And Fibrinopeptide A In Patients With Disseminated Neoplasias
Authors: Mombelli G , Roux A , Haeberli A , Straub P W 
Published: July 2018

To answer the question of whether and to what extent an elevated fibrinopeptide A (FPA) or an accelerated fibrinogen turnover reflect circulating thrombin action, the effect of heparin on FPA and on 125-I fibrinogen kinetics was studied in 15 patients with disseminated neoplasias. The plasma FPA levels were grossly elevated (4.6-20, mean 12.5 ng/ml) in 6 patients with evidence of thromboembolic disease or DIC, and moderately to grossly elevated (0.4-10.4, mean 4.8 ng/ml) in most of the other patients. The FPA fall found in 10/10 patients after heparin bolus suggested that plasma FPA were reflecting thrombin action on fibrinogen. However, in several cases the slew rate of FPA decrease was consistent with localized or extravascular, rather than with circulating thrombin action.Although continuous heparin therapy normalized the FPA levels in 5 of the 6 treated patients, the acceleration of fibrinogen turnover was as important as in untreated patients (mean values in heparin treated and untreated patients: half-life t1/2: 2.85 vs 2.23 d, catabolic rate constant j3: 0.40 vs 0.48 d-1, turnover: 67.6 vs 70.2 mg/kg/d, respectively, with normal values of t1/2: 3.78-4.57 d, j3: 0.22-0.33 d-1, turnover 16.6-26.6 mg/kg/d). The comparison between data of the FPA-RIA and fibrinogen kinetics suggests that mechanisms other than thrombin-mediated fibrin formation substantially contributed to increase the fibrinogen turnover. It is concluded that the results of the FPA-RIA and of the 125-I fibrinogen kinetics have to be interpreted with caution in the diagnosis of low-grade or compensated intravascular coagulation.
Activation And “Inactivation” Of A Plasminogen Proactivator (Preurokinase) In Human Tissue Culture Media
Authors: Wijngaards G , Bernik M B 
Published: July 2018

Besides active plasminogen activators, the synthesis of a proactivator (preurokinase) has been reported in cell and tissue cultures. It is suggested that slow activation of the proactivator in the culture medium occurs by an unknown proteolytic mechanism. Rapid activation can be obtained by incubation with plasmin or trypsin, whereas incubation with thrombin results in a preurokinase which has lost its capacity to be activated. These studies were performed with the fibrin plate method (FPM) which in itself involves further exposure of preurokinase to plasmin over a 16 to 20 hr period.In the present study the effect of incubation of some culture media with plasmin and thrombin, on the activation of proactivator, was measured using the clot lysis time method (CLTM) and an immediate assay with the synthetic substrate S-2322.The results with the CLTM showed that incubation of particular culture media with plasmin increases the activator activity immunologically related to urokinase. Incubation with thrombin was without effect, but when followed by incubation with plasmin a decreased level of activatable preurokinase was found. The decrease correlated positively with the thrombin concentration and incubation time and negatively with previous treatment of thrombin with antithrombin III. The S-2322 method showed very similar results, while comparison of the results of both CLTM and S-2322 method with those of the FPM revealed only small differences. Results indicate that preurokinase is hardly activated by plasmin in fibrinolytic assays, not even during the long incubation time of the FPM. Accordingly, it seems unlikely that there will be a positive feedback in thrombolysis as a consequence of activation of preurokinase by plasmin. (Supported, in part, by NATO Research grant RG 018.80).
On The Nature Of The Activated Prothrombin Complex
Authors: Penner J A , Cobel-Geard R , Hassouna H I 
Published: July 2018

Prothrombin complex concentrates containing FVIII bypassing activity have been employed effectively in the management of patients with factor VIII and IX inhibitors. The active component has not been identified although the protease forms of factor IX and X, as well as VII exist in variable concentrations in these products.As a means of establishing the role of each factor in the concentrates, monospecific antibodies to prothrombin, FX and FVII were coupled to Sepharose 4B by means of cross linking reagent cyanogen bromide. These insol- ubilized antibodies were used to selectively remove all prothrombin FX or FVII from the therapeutic concentrate, Autoplex (570 u/vial) supplied by Hyland Labs, Costa Mesa, by batch adsorption. A control was prepared by reacting the concentrate with cyanogen bromide treated beads whose active sites had been blocked with ethanolamine. Successful removal of specific factors from concentrates was evaluated by immunodiffusion assays and by standard clotting assays using substrate deficient plasma. Thrombin was not found to be present in any of the products following extraction. Thrombogenicity was tested in an animal model. Concentrates reacted with cyanogen bromide beads as a control and those lacking prothrombin were found to shorten clotting time of FVIII deficient plasma and to trigger intravascular coagulation in the animals (D.I.C.). Removal of FVII produced a concentrate that was more active than the control with respect to FVIII correction and induction of D.I.C. Concentrates depleted of FX, on the other hand, lost their capacity to correct FVIII deficient plasma and to initiate D.I.C. Our findings would suggest that the content of FX and its active form FXa plays a major role in the concentrates FVIII correcting activity and most likely is responsible for its thrombogenic characteristics.
Polyvinylpyrrolidone (PVP). A New Plama Fractionation Agent
Authors: Casillas G , Simonetti C 
Published: July 2018

The techniques used currently to prepare F.VIII concentrates are chiefly based on alcoholic, cryo or PEG precipitation.Here we described the preparation of F.VIII concentrate from human and bovine plasma using a new precipitating agent (PVP). The precipitation curves of F.VIII and fibrinogen in function of the PVP concentration,pH and temperature were studied and then the optimum conditions as regard recovery,purification and fibrinogen content were adjusted.A concentrate ( 1/10 de volume of the original plasma) containing 8U F.VIII/ml (recovery 80%), 16mg/ml protein and 7mg/ml fibrinogen (recovery 20%) is obtained from human plasma in the following conditions: 4% PVP concentration, 5°C and extraction of the precipitate at 2-3°C with a 0.15M NaCl , 0.5M glycine solution.For bovine plasma the conditions are similarexcept for the precipitation,which is performed at room temperature (15-20°C).The recovery of F.VIII and fibrinogen is 90% and 10% respectively and the protein content 12mg/ml. Small variations in the pH of plasmas do not modify the results.
Hypercoagulation And The Predictability Of Thromboembolic Phenomena In Total Hip And Total Knee Surgery
Authors: Kurica K , Holmes J , Peck S , Cox B , Brantigan C , Wenzel W 
Published: July 2018

Forty patients admitted for elective total hip and total knee surgery were evaluated to determine the efficacy of the hypercoagulable profile in the predictability of high and low risk patients for the development of thromboembolic phenomena (proximal deep vein thrombosis and pulmonary embolism) after surgery. Patients were evaluated pre operatively with 99m Tc MAA venograms, ventilation perfusion lung scans, pneumatic plethysmography and a hypercoagulable profile including: thrombin generation test, plasma clot impedance test, antithrombin III. Patients with evidence of thromboembolic phenomena by 99m Tc scans or positive plethysmography were excluded. The hypercoagulable profile was repeated on the first post operative day. Both the hypercoagulable profile and the 99m Tc scans were repeated on the tenth post operative day or if the patient developed any signs or symptoms of thromboembolic phenomena. There was no prophylaxis given.Ten patients were hypercoagulable pre operatively; four developed post operative thromboembolic phenomena. Nine patients became hypercoagulable post operatively; three patients developed thromboembolic phenomena as determined by 99m Tc criteria. The remaining nineteen patients were never hypercoagulable throughout their hospital course and were discharged without evidence of thromboembolic phenomena by 99m Tc imaging criteria.The hypercoagulable screen successfully separates those patients at high and low risks for the development of post operative thromboembolic phenomena after total hip and knee surgery. These results are statistically significant to the one tail p 0.00001 level using Fisher s exact test.