bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of Functional and Inactivated α2-Macroglobulin in Sepsis
Authors: Abbink J J , Nuijens J H , Eerenberg A J M , Huijbregts C C M , Strack van Schijndel R J M , Thijs L G , Hack C E 
Published: July 2018

SummaryAlpha2-macroglobulin (α2M) in vitro inhibits numerous proteinases that are generated during inflarnmatory reactions and therefore, probably plays an important role in diseases such as sepsis. To monitor the state of α2M in sepsis, we developed novel assays for functional and inactive α2M. Functional α2M in palsama trypsin. Inactive α2M (iα2M) was assessed with a monoclonal antibody, mcAb M1, that specifically reacts with a neodeterminant exposed on iα2M. This mcAb in combination with chromogenic substrates was used to detect α2M-proteinase complexes.Functional α2M was reduced in plasma from 48 patients with clinical sepsis compared to healthy controls (p <0.0001). Levels of functional α2M on admission and the lowest levels encountered in 23 patients with shock were lower than in 25 normotensive patienis (p = 0.023 and p = 0.009, respectively). Increased levels of iα2M (>30 nM) at least on one occasion were found in only 4 of the 48 patients, being not different in hypotensive compared With normotensive patients, and not in patients who died compared with those who survived. Levels of functional α2M correlated significantly with levels of factor XII and prekallikrein suggesting that decreases in α2M at least in part were due to contact activation. Indeed, in two patients with increased iα2M, complexes between α2M and kallikrein were demonstrated in addition to plasmin- and thrombin-α2M complexes.
Ticlopidine and Clopidogrel (SR 25990C) Selectively Neutralize ADP Inhibition of PGE1-Activated Platelet Adenylate Cyclase in Rats and Rabbits
Authors: Defreyn G , Gachet C , Savi P , Driot F , Cazenave J P , Maffrand J P 
Published: July 2018

SummaryTiclopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGEj-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGEr stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGEX-induced cAMP elevation but this effect seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGEr activated platelet adenylate cyclase in rats and rabbits.
Subcutaneous Heparin Therapy during Pregnancy: a Need for Concern at the Time of Delivery
Authors: Anderson David R , Ginsberg Jeffrey S , Burrows Robert , Brill-Edwards Pat 
Published: July 2018

SummarySubcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic complications it has been our practice to have women eithei discontinue their heparin injections with the onset of labour or to terminate heparin injections 12 h prior to elective induction. To determine the safety of our anticoagulant protocol at delivery we reviewed consecutive patients treated with subcutaneous heparin therapy during pregnarcl, at our centre. Over a 23 month period we found that six of 11 women receiving subcutaneous heparin during pregnancy delivered while their aPTT was prolonged. In addition, three women received intravenous protamine sulphate prior to delivery and in one patient major bleeding occurred during an emergency cesarean section. Those women who had elevated aPTTs at the time of delivery all gave birth within 28 h of their last injection of heparin. In order to avoid a prolonged aPTT at delivery, we have now adopted a more conservative approach to the management of subcutaneous heparin use at term. Subcutaneous heparin is discontinued 24 h prior to commencing an elective induction of labour.
The British System for Anticoagulant Control
Authors: Poller L 
Published: July 2018

SummaryThe British system for anticoagulant control based on the use of a national reagent with a national system of reporting supported by national quality control using lyophilized plasma preparations appears to offer a model which many countries abroad seem interested in adopting to solve their own national problems. Good progress has already been made in this direction in some Commonwealth countries and in South Africa. At a symposium at the 3rd Mediterranean Congress on Thromboembolism in 1973 invited participants from all over the world agreed to set up an International Study Group to provide an international organisation for anticoagulant control, and an encouraging start has been made.
The Effect of Fatty-acid Autoxidation Products on Blood Coagulation
Authors: Barrowcliffe T. W , Guttteridge J. M. C , Dormandy T. L 
Published: July 2018

SummaryPolyunsaturated fatty acids were allowed to autoxidise in air over 4 days. The water soluble oxidation products were extracted at daily intervals and tested for their effect on blood coagulation. After 1 day there was slight acceleration of the recalcification and RVV times, but from 2–4 days the extracts became increasingly inhibitory. The P.T. and P.T.T. were also inhibited. In the thrombin generation test the extracts delayed the appearance of thrombin, but the peak thrombin level was increased and its rate of decay was reduced. When added to phospholipid the extracts altered their coagulant activity. The presence of autoxidation products could account for some of the variable results obtained with different preparations of phospholipids.
Plasmin Inhibition of Thrombin-induced Platelet Aggregation
Authors: Miller Jonathan L , Katz Alfred J , Feinstein Maurice B 
Published: July 2018

SummaryThe effects of plasmin treatment upon washed human platelets were studied in an attempt to elucidate the mechanisms underlying thrombin-induced platelet aggregation. At calcium concentrations of 10–20 μM, plasmin (0.2 CTA U/ml) inhibited thrombin-induced aggregation almost completely, but did not diminish the thrombin-induced release of adenine nucleotides, 5-hydroxytryptamine, or calcium. Increasing the calcium concentration partially antagonized plasmin’s inhibition of aggregation.Studies utilizing calcium chelators and the Kunitz soybean trypsin inhibitor (SBTI) as a plasmin inhibitor indicated that in order to achieve maximal block of aggregation, plasmin must act upon a substrate made fully available only after an initial thrombin-platelet interaction has taken place. Moreover, the time course of this inhibition parallels the time course of the thrombin-induced release reaction.Plasmin inhibition of aggregation could not be mimicked by exposing the platelets to proteolytic digests of fibrinogen at concentrations as high as 17% total platelet protein. Nor could inhibitory activity be recovered from supernatants of plasmin -treated platelets, upon centrifugation and treatment with SBTI.With the use of a “cold initiation” technique, the release by thrombin of 46.7 ± 6-7 (mean ± SEM) μg of fibrinogen immunological equivalents per mg platelet protein could be demonstrated. Platelets in which thrombin-induced aggregation was abolished by plasmin treatment (and the plasmin subsequently inactivated by SBTI) aggregated normally upon addition of as little as 10 μg human plasma fibrinogen per mg platelet protein.It is concluded that plasmin inhibition of aggregation most likely results from its attack upon a protein that is released or becomes fully available subsequent to interaction of thrombin with a platelet receptor mediating release. The results of this study are consistent with a cofactor role for fibrinogen in the aggregation of human platelets by thrombin.
Characterization of the Fawn-Hooded Rat as a Model for Hemostatic Studies
Authors: Raymond Sharon L , Jean Dodds W 
Published: July 2018

SummaryA large colony of fawn-hooded (FH) rats, comprising five original families and six generations of their progeny, was developed for genetic and comparative studies of their bleeding tendency. The characteristics of the bleeding diathesis in these rats are similar to those originally reported in related rats by Tschopp and Zucker. FH rats have normal clot retraction, ADP-induced platelet aggregation and platelet ADP ; variable aggregation with collagen; minimal aggregation with adrenaline and cobra venom factor; and reduced platelet ATP, ATP/ADP ratio, serotonin content and 14C-serotonin release. In comparison to age- and sex-matched Wistar rats, FH rats have significantly prolonged partial thromboplastin time, shortened Russell’s viper venom time and increased factor X and XI levels. Other coagulation screening tests and specific assays for fibrinogen, plasminogen and factors VII, VIII and IX were normal. Some age- and sex-related differences in coagulation and other parameters were observed within each rat strain. Plasma proteins, glycoproteins and cerulo-plasmin (copper oxidase activity) showed no abnormalities, nor did initial studies of immunoglobulins and complement. However, FH rats have significantly lower glucose and higher cholesterol levels than comparable Wistar rats.
Changes in Human Amniotic Fluid Fibrinolytic Inhibitor Levels during Pregnancy
Authors: Aznar J , Hernandez A , Parrilla J.J , Estelles A , Gilabert J 
Published: July 2018

SummaryThe amniotic fluid (AF) when incubated with the patient’s own plasma diminishes the lytic activity of the plasma. It is suggested that this inhibition is due to the presence of fibrinolytic inhibitors in the AF. The inhibitors rate increases as pregnancy advances. Evaluating these inhibitors in a group of 65 women before and after the 38th week of pregnancy, a higher rate of fibrinolytic inhibitors is found after the 38th week. The said differences are statistically significant. For the moment it does not seem that the increasing of the inhibitors in the last part of pregnancy might be used as a fetal maturity test.
In Vitro and in Vivo Functions of Thrombin-Treated Platelets
Authors: Reimers Hans-Joachim , Kinlough-Rathbone Raelene L. , Cazenave Jean-Pierre , Senyi Andrew F. , Hirsh Jack , Packham Marian A. , Mustard J. Fraser 
Published: July 2018

SummaryThrombin-induced platelet aggregation has been generally believed to be irreversible. However, thrombin-induced aggregation of washed platelets is reversible if fibrin formation is prevented or the fibrin which binds the platelets together is removed from the platelet aggregates. After treatment with high concentrations of thrombin (0.5 units/ml) single platelets can be recovered that have lost practically all of their releasable serotonin and adenine nucleotides. These platelets are able to aggregate upon addition of low concentrations of ADP in the presence of fibrinogen. They aggregate in response to the ionophore A23, 187 in the absence of added fibrinogen, whereas sodium arachidonate-induced aggregation requires added fibrinogen. Thrombin-treated platelets change their shape in response to collagen in the absence of fibrinogen, and will aggregate upon the addition of collagen providing fibrinogen is present. This response to collagen can be blocked with aspirin but not with a mixture of creatine phosphate/creatine phosphokinase. Upon a second exposure to thrombin, thrombin-pretreated platelets do not change their shape and do not undergo aggregation. Thrombin-pretreated platelets will not retract a thrombin-induced fibrin clot unless ADP, sodium arachidonate, the ionophore A23, 187 or collagen are added together with thrombin.The ability of thrombin-treated platelets to adhere to the exposed subendothelial surface of the rabbit aorta is reduced, compared with untreated control platelets. The thrombin-treated platelets shorten the bleeding time of thrombocytopenic rabbits. However, they are not as effective in shortening the bleeding time as normal control platelets. When injected into rabbits with a normal platelet count, the thrombin-treated platelets that circulate after infusion survive for the same length of time as untreated control platelets. These findings indicate that thrombin-induced platelet aggregation with extensive release of granule constituents is not irreversible and that thrombin treatment does not cause irreversible damage of all platelets that would lead to their immediate elimination from the circulation. Furthermore, these platelets can still be haemostatically effective. It is conceivable that platelets that have lost their amine storage granule contents during a release reaction in vivo, such as may occur in certain cases of intravascular coagulation and repeated episodes of thrombosis, may be found in the circulation of man.
Platelet Aggregation by Thimerosal
Authors: Leone G , Boni P , Vincenti A 
Published: July 2018

SummaryThimerosal, a sulphydryl inhibitor, induces aggregation of normal platelet rich plasma over a wide range of concentrations. Low doses induce a monophasic response preceded by a lag phase, high doses produce an immediate biphasic response.Thimerosal induces platelet aggregation through its binding by sulphydryl groups.Thimerosal induced aggregation is not mediated by ADP, it is not influenced by fibrinogen, von Willebrand factor, calcium, and magnesium ions of the medium.Thimerosal induced platelet aggregation is normal in patients affected by thrombocyto-pathia (defect of ADP release) but not in patients affected by Glanzmann’s thrombasthenia. Mercaptopropionglycine, a substance which tends to preserve SH groups, inhibits platelet aggregation induced by thimerosal, thrombin, collagen, and ADP.A mechanism is proposed for thimerosal induced aggregation and the role of SH groups also in ADP, thrombin and collagen induced aggregation is indicated.
Biological Properties of Dialysable Peptides Derived from Plasmin Digestion of Bovine Fibrinogen Preparations
Authors: Buczko W , Gaetano G. de , Franco R , Donati M. B 
Published: July 2018

SummaryDialysable peptides (M. W. less than 12,000) were obtained by plasmin digests of purified bovine fibrinogen. The biological effects of these peptides were studied in rats in three different test systems: ADP-induced platelet aggregation, isolated atria contractility and vascular permeability.The effects induced by the peptides were: inhibition of ADP-induced platelet aggregation, increase in the frequency of isolated atria contractions and local increase in vascular permeability. All these activities were concentration dependent. Six micrograms of the peptides were still effective in increasing vascular permeability; in the in vitro systems the smallest effective dose ranged between 165 and 650 μg/ml.Following elution through a Sephadex G-25 gel with bidistilled water, four fractions were obtained. The second fraction (M.W. about 5,000) was the most active, followed by the first and then the third one; the fourth fraction was inactive.These data suggest that local accumulation of peptides in vivo may be of clinical relevancy.
Haemophilia in Australia
Authors: Rickard Kevin A. 
Published: July 2018

SummaryThe major problems currently facing haemophilia management in Australia relate to (1) a need for better co-ordination of our entire national effort for haemophilia therapy and (2) a need to improve the efficiency of our preparation of factor VII concentrates. If we could simply double or treble our factor VIII yields from the same volume of donor plasma many of our urgent treatment problems could be solved.
Deep Vein Thrombosis in Obstetric Patients: Diagnosis and Risk Factors
Authors: Boer Karin de , Büller Harry R , ten Cate Jan W , Levi Marcel 
Published: July 2018

SummaryThis study was performed to assess the prevalence of deep vein thrombosis (DVT) in consecutive obstetric patients with clinical symptoms of DVT, using impedance plethysmography (IPG) as the diagnostic method and to establish the safety of withholding anticoagulant therapy in patients with a repeatedly normal IPG. In addition, in patients with DVT the prevalence of coagulation and fibrinolytic disorders, which may explain the occurrence of venous thrombosis was investigated.Of the 77 obstetric patients with symptoms of DVT 32 (42%) had an abnormal IPG. The remaining 45 patients had a repeatedly normal IPG and showed no venous thromboembolism during a 6 months follow-up period. Twenty percent (six patients) of the patients with an abnormal IPG had a coagulation or fibrinolytic abnormality. These observations suggest that serial IPG can be used effectively in the management of obstetric patients with clinically suspected DVT and that hemostatic abnormalities are frequently found in those patients with DVT
Comparison of the In Vivo Anticoagulant Properties of Standard Heparin and the Highly Selective Factor Xa Inhibitors Antistasin and Tick Anticoagulant Peptide (TAP) in a Rabbit Model of Venous Thrombosis
Authors: Vlasuk George P , Ramjit Denise , Fujita Tsuneo , Dunwiddie Christopher T , Nutt Elka M , Smith Donna E , Shebuski Ronald J 
Published: July 2018

SummaryAn in vivo thromboplastin (TP)-induced venous stasis thrombosis model in rabbits was used to compare the efficacy of standard heparin with the selective factor Xa inhibitors, recombinant tick anticoagulant peptide (rTAP) and recombinant antistasin (rATS), in prophylactic prevention of thrombus formation. Heparin significantly reduced TP-induced clot formation at doses of 55 and 100 U kg−1 h−1 yielding clot weights of 9 ± 4 and 6 ± 2%, respectively. Clot formation was significantly decreased by i.v. infusions of rTAP at doses of 21, 37 and 64 Μg kg−1 min−1 resulting in normalized clot weights of 13 ± 3, 8 ± 2 and 2 ± 1%, respectively. rATS was approximately 10-fold more potent than rTAP, reducing normalized clot weights to 16 ± 5, 2 ± 1 and 1 ± 0.8% at rATS doses of 1.25, 2.5 and 5.0 Μg kg−1 min−1, respectively. These data suggest that factor Xa-mediated inhibition of coagulation with rTAP and rATS is as effective as conventional anticogulant treatment with heparin in preventing venous thrombosis.
The Characterisation of Thrombus Development in an Improved Model of Arterio-Venous Shunt Thrombosis in the Rat and the Effects of Recombinant Desulphatohirudin (CGP 39393), Heparin, and lloprost
Authors: Peters R F , Lees C M , Mitchell K A , Tweed M F , Talbot M D , Wallis R B 
Published: July 2018

SummaryAn existing arterio-venous shunt thrombosis model in the rat has been modified to increase its usefulness for the testing of antithrombotic agents and characterised using morphological and radiometric techniques. The thrombus formed on the cotton thread held in the shunt was found to be composed of platelet aggregates surrounded by red thrombus. After 30 min of blood flow there was a 15-fold increase in the platelet content of the thrombus and a 4-fold increase in the fibrin(ogen) content compared with an equivalent weight of whole blood.Use of the anticoagulants recombinant desulphatohirudin (CGP 39393, 4 mg/kg, s.c.) and unfractionated heparin (800 IU/ kg, s.c.) showed that approx. 90% inhibition of thrombus weight and approx. 80% inhibition of fibrin(ogen) content could be achieved without significant effect on the platelet content. Conversely, using the platelet inhibitor lloprost (1 Μg kg−1 min−1), a reduction in thrombus weight of 50% was associated with 75% inhibition of platelet content and only 20% inhibition of fibrinogen). These observations suggest that the growth of this type of thrombus is largely the result of continued fibrin formation rather than continued platelet recruitment and activation.
Influence of Tryptophan Modification upon Digestion of Antithrombin III by Elastase
Authors: Scully M F , Shah N , Ellis V , Kakkar V V 
Published: July 2018

SummaryChemical modification of tryptophan residues in antithrombin III by dimethyl (2-hydroxy-5-nitrobenzyl) sulfonium bromide (HNBSB) generates products with similar levels of modification (equivalent to 0.9 mole 2-hydroxy-5-nitrobenzyl [HNB] incorporated/mole of antithrombin III) but with high or low affinity for heparin-Sepharose. Upon digestion with pancreatic or neutrophil elastase the low affinity forms generate a product of molecular weight form (55 kDa) not seen in digests of native antithrombin III or modified forms with high affinity for heparin. When measured as loss of activity the obserued rate of digestion of the latter in the absence of heparin was more rapid than that of native antithrombin III. The differences in digestion are considered to be related to conformation at differences between the various forms.
Antithrombotic and Anticoagulant Activity of Depolymerized Fragment of the Glycosaminoglycan Extracted from Stichopus japonicus Selenka
Authors: Suzuki Norihiko , Kitazato Kenji , Takamatsu Junki , Saito Hidehiko 
Published: July 2018

SummaryThe antithrombotic and anticoagulant activities of depolymerized fragment (DHG-l) of glycosaminoglycan extracted from Stichopw japonicus Selenka (FGAG) were compared with those of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). DHG-1 at more than 0.3 mg/kg i. v. significantly prevented death of mice treated with thrombin (800 U/kg i.u.). Under the same conditions, FGAG, UFH and LMWH significantly prevented death of mice at more than 0.3, 0.3 and 0.6 mg/kg i.v., respectively. In normal plasma, the concentration required to double the activated partial thromboplastin time (doubling APTT) of DHG-I, FGAG, LMWH and UFH were 12.0, 2.4, 5.8, and 1.2 μg/ml, respectively. In antithrombin III (AT Ill)-depleted plasma, doubling APTT of DHG-1, FGAG, and UFH were 11.3, 2.1, and 18.5 μg/ml, respectively. Prothrombin activation in contact-activated plasma was inhibited completely for 60 s at doubling APTT by all glycosaminoglycans used in this study. DHG-I, however, showed much less antithrombin activity than UFH as tested by thrombin clotting time in plasma and chromogenic assay in the presence of AT III. Moreover, DHG-1 showed much less inhibitory activity on factor Xa, factor IXa, and glass surface-induced factor IXa generation than UFHThese results suggested that DHG-1 is one of the promising antithrombotic agents with quite different anticoagulant property from UFH or LMWH.
Antithrombotic Activity of a Novel C-Terminal Hirudin Analog in Experimental Animals
Authors: Broersma R J , Kutcher L W , Heminger E F , Krstenansky J L , Marshall F N 
Published: July 2018

SummaryA synthetic hirudinsgs55-65 C-terminal fragment analog was evaluated for anticoagulant activity and in models of experimental thrombosis in mice and rats. Intravenous injection caused doserelated inhibition of thrombin and anticoagulation in rat blood samples, protection from thromboembolism in mice and inhibition of stasis-induced venous thrombosis in rats. Antithrombotic effectiveness corresponded with anticoagulant activity. Anephric animals exhibited longer duration of activity than normal animals suggesting the kidney as a major route of elimination.