bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effects of Estrogens on Antithrombin III.
Authors: Nagasawa H. , Hotta Y. , Takara N. , Fujimaki M. , Fukutake K.
Published: June 2019

After the addition of purified estrogen preparation to the plasma, the anticoagulant activity of antithrombin III measured by Bigg’s method decreases in proportion to the amount of estrogen added. And the biological activity of antithrombin III in the plasma mixed with estrogen decreases proportionally in single immunodiffusion assay with anti-antithrombin III serum. The same findings mentioned above are also observed in the experiences with estron, equilin, equilenin and estradiol.

Furthermore, the rocket formation of antithrombin III fraction prepared by Abild-gaard’s method in crossimmunoelectrophresis also disappeares by the addition of estrogen into the reaction mixture, and the electric mobility of antithrombin III fraction with estrogen increases the migration to the anode in polyacrylamide gel electrophoresis.
Isolation and Characterization of Human Platelet β-Thromboglobulin
Authors: Pepper D. S. , Moore S. , Cash J. D.
Published: June 2019

The thrombin released products from washed human platelets were separated by filtration on 4% agarose in 0.15 M NaCl. The high molecular weight PF4 complex was dissociated and re-chromatographed in 0.75 M NaCl. The low molecular weight fraction, including β thromboglobulin and a low MW anti-heparin was freed of plasminogen anti-activator by dissociation and chromatography in pH 3.5 pyridine acetic acid. The anti-activator was irreversibly denatured and albumin was removed in the void volume of the column. A more suitable purification procedure for recovery of all activities was affinity chromatography on heparin-agarose. The anti-activator was excluded and could be obtained free of plasma proteins by Sephadex G-200 chromatography. The βTG eluted at 0.3 M NaCl and the low MW anti-heparin at 1.5 M NaCl. The pure βTG (MW 36,000) was injected into rabbits and the resulting antiserum used to produce a radioimmunoassay for the release reaction in vivo.
Haemostatic Changes Following Snake Bite by Echis Carinatus; Trial of Heparin
Authors: Prentice C. R. M. , Warrell O.A. , Forbes C. D. , Edgar W.
Published: June 2019

A study was made of 21 patients following snake-bite by Echis carinatus. All patients had non-clotting blood and several had a haemorrhagic disorder. The platelet count was not reduced during the initial period of defibrination. Coagulation tests showed initial absence of clottable fibrinogen, marked reduction of factor VIII to 23%, factor V to 9%, factor XIII to titre 1 in 8, and moderate reduction of factor II to 44%. Antithrombin III and plasminogen activator showed no significant change. Serum FDP levels were elevated initially ; Polyacrylamide gel electrophoresis of FDP showed that fragment D rather than D-dimer, was present, indicating that FDP were derived from non-cross linked fibrin. Fourteen of the patients were assigned to treatment with specific antiserum plus heparin or antiserum alone. Both groups showed rapid recovery of the haemostatic defect within 12 hours indicating efficacy of the antiserum; there was no significant increase in recovery rate in the heparin treated group. We conclude that heparin confers no advantages when specific antiserum is available. The presence of noncross linked FDP indicates early fibrinolysis of fibrin or soluble fibrin complexes before cross linking can occur.
Fibrinolysis and Microthrombosis in Unselected Autopsies
Authors: Lindeman J. , Haverkate F.
Published: June 2019

Blood samples taken from the right heart were analysed for euglobulin finbrinolytic activity and plasminogen. Tissue fibrinolytic activity of normally appearing parts of nine different organs from each case was investigated with the Todd slide technique. The same tissues were also studied for the presence of microthrombi.

The main results and conclusions are:

1. High blood activity was found in 17 of 60; no blood activity in 20 of 60.

2. High blood activity was associated with the mode (sudden death) rather than with the cause of death or basis illness.

3. In cases with blood activity, enzymatically determined plasminogen was zero, whereas antiplasminogen-related antigen was high, suggesting postmortem breakdown of plasminogen and no clearing.

4. High blood activity was related with average or high tissue activity.

5. In cases with high activity, almost no fibrin microthrombi were present outside local pathologic processes.

6. Autopsies with low or no tissue activity generally showed no blood activity.

7. In cases with low or no tissue activity, more fibrin microthrombi were found and gram negative endotoxic shock was frequently the cause of death.

8. Hyalin microthrombi or globular clots were commonly found in autopsies with low and high activity.
Evidence of Placental Microangiopathy in Pre-Eclamptic States
Authors: Chervet D. , Beguin F. , Vassiliakos P. , Cox J. , Bouvier C. A.
Published: June 2019

It has been suggested that a consumption coagulopathy does occur in pre-eclampsia and this has been related to intravascular clotting at the glomerular level and in the decidual spiroid arteries of the mother, but surprisingly little studies of the placental vessels have been reported. From biological data before and after delivery, and conventional, electronic and immunofluorescent studies of the placenta at birth, we present evidence for a consumption coagulopathy, renal involvement and diminution of placental secretion before delivery, and demonstrate the anatomopathologrcal substrate for microangiopathy at the placental level. The predominant feature is intense thickening of both trophoblastic and vascular basement membrane in the villosities, intravascular clotting with platelets and fibrin thrombi, and striking modifications of vascular endothelium. While numerous trophoblastic syncytial cells have been found in circulating maternal blood, little or no circulating endothelium has been found so far, probably because they do not cross the thickened trophoblastic basement membrane. It is interesting to consider the described lesions in comparison with those observed in graft-rejection.
Essential Fatty Acid Deficiency, a New Model for Basis Research in Thrombogenesis
Authors: Hornstra G. , Haddeman E.
Published: June 2019

Platelet membranes are of primary importance in platelet thrombotic phenomena, whereas in the regulation of platelet function prostaglandins are thought to play a major role. Since esential fatty acids (EFA’s) are of great physiological importance, both as membrane components and as precursors of prostaglandins, EFA-deficiency may present an interesting model for basic research into thrombotic mechanisms.

In rats EFA-deficiency caused impaired formation of arterial thrombi but aggregation of blood platelets in response to ADP, both in vivo and in vitro is normal. In contrast, platelet aggregation induced by collagen and Thrombofax® is definitely depressed, as is the release of newly absorbed 5-HT. Thrombin-induced release is enhanced. Platelet factor 3 content and -availability is significantly reduced. Platelet morphology, platelet count and recalcification plasma clotting times are normal.

It is concluded that decreased arterial thrombosis tendency in EFA-deficiency is caused by decreased thrombotic properties of the blood platelets. Disturbed platelet membrane integrity and — prostaglandin production will be discussed as possible mechanisms of action.
The Effect of Reserpine on Aggregation of Avian Thrombocytes
Authors: Belamarich F. A.
Published: June 2019

Avian nucleated thrombocytes are aggregated by acid-soluble collagen, and serotonin (5-hydroxytryptamine) is released from the thrombocytes during the process of aggregation. The action of collagen is inhibited by aspirin and methysergide, a serotonin antagonist. Exogenous serotonin can also induce aggregation. These observations suggest that serotonin, which has been shown to be stored in avian thrombocytes, acts similar to released ADP in mammalian platelets.

Measurement of serotonin content in the blood of Peking ducks (Anas platyrhynchos) which had been given reserpine (3 mg/kg, blood withdrawn 20 hours after injection) showed that the serotonin content of whole blood and thrombocyte-rich-plasma fell to approximately 90 percent of the control level. Analysis of aggregation of thrombocytes from control and reserpinized ducks showed that reserpinization markedly decreased aggregation induced by collagen, while it enhanced aggregation induced by serotonin. These results are consistent with the concept of released serotonin playing a role in thrombocyte aggregation.

(Supported by a grant from National Heart and Lung Institute HE 10002.)
Oral Anticoagulant Therapy and its Control: An International Survey
Authors: Lam-Po-Tang P. R. L. C.
Published: June 2019

This is a survey made for the International Study Group for Anticoagulant Control. A questionnaire was sent to 37 countries and there were 31 replies. The information obtained indicated that the most widely used test in oral anticoagulant therapy is the one stage prothrombin estimation. There was a great diversity in the method of reporting prothrombin time results ; percentage activity of normal on the basis of saline dilution curve was marginally the most popular. Only 3 countries had any national or regional systems for anticoagulant control.

Recommendations for the therapeutic range of dosage varied widely. The upper limit in one country may be the lower limit in another. The variation of therapeutic range was was still considerable in different countries even when a standard thromboplastin was used.

The survey provided valuable data indicating the need for urgent measures to provide a uniform basis for clinical dosage of anticoagulant drugs, and its laboratory control. Given these wide variations, it would be impossible to compare the efficacy of oral anticoagulant therapy from country to country or to conduct meaningful multicentre trials.
Antithrombin Activity of Intact Human Platelets
Authors: Watanabe K. , Chao F. C. , Tullis J. L.
Published: June 2019

Antithrombin activity was identified in intact washed human platelets. Red cells and white cells had no antithrombin activity. There was no significant loss of platelet antithrombin activity after ten washings or after treatment with antibodies to antithrombin III or α2-macroglobulin. Platelets from an afibrinogenemic patient showed almost the same antithrombin activity as normal platelets. Platelet antithrombin reacted with thrombin in less than 3 seconds. This rapid reaction was different from that of antithrombin. Ill or fibrinogen. The clotting activity of ancrod was inhibited by fibrinogen but not platelets. Unlike plasma antithrombin III or fibrinogen, brief exposure to 60° C reduced platelet antithrombin activity. These results suggest that platelets possess a specific antithrombin with characteristics different from other known antithrombins.
Adverse Effect of Heparin on Thrombin Inactivation
Authors: Marciniak E.
Published: June 2019

In the presence of heparin thrombin, although fast inactivated, impairs the inhibitory capacity of antithrombin III, in result of which the final amount of neutralized enzyme markedly decreases. This adverse effect of heparin was found during the reaction of purified thrombin with both purified human antithrombin III and native plasma hepariniz purified thrombin with both purified human antithrombin III and native plasma heparinized in vitro or in vivo. In the absence of heparin, at concentration equal to that in normal plasma antithrombin III binds 450 Iowa units of thrombin; in the presence of heparin (at 1 unit concentration) this binding is reduced to 145 thrombin units. A fast depletion of inhibitory capacity is also evident after a stepwise addition of thrombin in small installments into a medium containing antithrombin III and heparin. Portions of enzyme initially added disappear with great velocity; subsequent additions, however, accumulate building up a high thrombin level not seen in the absence of heparin. The escalation of thrombin is reversely proportional to the reacting antithrombin III level, thus especially noticeable in antithrombin III deficient plasma. Residual thrombin left in the presence of heparin disappears at a fast rate upon a new addition of antithrombin III. No decrease in anticoagulant properties of heparin is observed during these interactions. Binding of factor Xa to antithrombin III which reacted with thrombin and heparin is also decreased or abolished.

These results indicate that in the presence of heparin thrombin not only exposes rapidly a binding site on the inhibitor, but also causes a further change leading to the deletion of antithrombin III binding properties. This may explain adverse, thrombotic effect of heparin sporadically seen in vivo, and suggests that heparin should be applied with caution in patients with antithrombin III deficiency.
The Significance of the Chronic Anticoagulant Treatment in Recurrent Thromboembolic Caused by Hereditary Antithrombin III Deficiency
Authors: Nagy I. , Losonczy H.
Published: June 2019

It has been known since the publication of Egeberg (1965, 1970) and Marciniak (1974) that herditary antithrombin III deficiency could be the cause of recurrent venous thromboembolism.

The authors observed in 5 cases of severe repeated venous thrombosis in young patients an antithrombin III decrease, which proved to be a hereditary abnormality. In the case of a 15 years old girl the late introduced anticoagulant treatment could not save the life of the patient, she died after repeated deep vein thrombosis. In the other cases the long-lasting anticoagulant treatment resulted in a perfect clinical improve, while the behaviour of antithrombin III was different; in some cases its quantity (determined by radial -immunodiffusion) and functional activity (examined by modified method of Gerendás and Rák) remained decreased, while in the other cases its functional activity increased during the anticoagulant treatment as it was found by Marciniak, too.

It is most likely, that there are two types of hereditary antithrombin III decrease; in one of them the quantitative and functional decrease goes parallel, in the other there is mainly a functional decrease, which improves during the chronic anticoagulant treatment. The authors demonstrated the significance of the prolonged anticoagulant treatment in the patients with hereditary antithrombin III decrease.
Characteristics of Platelet Protransglutaminase (Factor XIII)-Binding Activity in Human Plasma
Authors: Bannerjee D. , Mosesson M. W.
Published: June 2019

Human plasma Factor XIII (F. XIII) complex is composed of two types of noncovalently linked polypeptide chains termed a and b; only the a chain possesses catalytic potential. Platelet Factor XIII is comprised solely of a chains which are identical to those found in plasma. In this study platelets were utilized as a source of unbound a chains to characterize F. XIII (a chain)-binding activity in plasma and its subfractions. Upon exclusion chromatography of unheated plasma or of an unheated ammonium sulfate (20% sat.) subfraction, F. XIII activity emerged in a peak corresponding to a mol. wt. of < 500,000 (region 1). If these samples had first been heated at 60° to precipitate fibrinogen, F. XIII was eluted in a peak corresponding to a mol wt. of about 300,000 (region 2). Chromatography of the platelet zymogen alone resulted in a F. XIII peak corresponding in position to that of monomeric a chain (mol. wt. 80,000, region 3).

Exclusion chromatography of the unheated ammonium sulfate fraction yielded, in addition to the F. XIII peak in region 1, a protein peak (peak II) in region 2 which contained no F. XIII. When peak II was mixed with platelet F. XIII, and again subjected to exclusion chromatography, the platelet F. XIII peak shifted from its expected position in region 3 and emerged instead in region 2 ; this behavior demonstrated F. XIII (a chain)-binding activity within peak II. The same chromatographic shift was observed in mixtures of platelet F. XIII and normal plasma or that from a patient with congenital F. XIII (a chain) deficiency. Immunochemical analyses of chromatographic fractions indicated that a chain-binding was due to complexing of a chains with freely circulating b chains. Since a chains and b chains have different biosynthetic sites we conclude that b chains serve as an extracellular F. XIII (a chain)-binding protein.

Supported by NHLI grant HL-11409.
Interactions of Factor XIII Subunits as Studied by Affinity Chromatography
Authors: McDonagh Jan , McDonagh Richard P.
Published: June 2019

A new method for studying the interactions of plasma factor XIII subunits, as well as purifying both plasma and platelet factor XIII, has been developed using an organomer-curial linked to agarose. Native plasma factor XIII a subunit binds to the ligand accompanied by b subunit, which can be dissociated from the ligated a subunit by treatment with thrombin and calcium. With various combinations of thrombin, calcium, and alteration of ionic strength it has been shown that: (a) both unactivated a subunit and thrombin activated a’ subunit bind to the ligand; (b) “excess” b subunit present in highly purified preparations of plasma factor XIII dissociates and can be eluted at low ionic strength in the absence of calcium or thrombin; (c) in our preparations of highly purified plasma factor XIII approximately 40% of b subunit is in “excess”; (d) the remaining b subunit can be eluted with thrombin and calcium; (e) both a and a’ subunits can be eluted with dithiothreitol ; (f ) when plasma factor XIII zymogen is applied to the column approximately equal amounts of a and b subunits co-elute with dithiothreitol. These observations offer further evidence for the roles of thrombin and calcium in the activation of plasma factor XIII and provide a new tool for studying the structure-function relationships of factor XIII.

Supported by Grants HL 14228 and HL 06350 from the National Institutes of Health, U.S.A.
Action of Factor XIII on Transamidation Bounds between the Collagen Molecule Constituents
Authors: Soria J. , Soria G. , Boulard G.
Published: June 2019

By polyacrylamide gel electrophoresis in the presence of SDS we observed that collagen polymerized in the presence of factor XIII a, is dissociated by urea into sub-units with a higher molecular weight than that polymerized in the absence of factor XIII.

In the other hand, by phase contrast microscopy we have found that the structure of collagen is quite different when the polymerization process takes place in the presence or in the absence of activated factor XIII.

This modification of collagen polymerization in the presence of factor XIII a possibly acts in wound healing.
Comparison of in Vivo and in Vitro Effects of Platelet Function Suppressing Drugs
Authors: Buchanan M. , Hirsh J.
Published: June 2019

Comparison of in vivo and in vitro platelet function tests to assess the antithrombotic efficacy of drugs which suppress platelet function have been contradictory. For example, aspirin (ASA) has a potent effect in vitro but little effect when tested on platelet survival in prosthetic heart valve replacements whereas dipyridamole (DIP) has little or no effect in vitro but a marked effect on platelet survival. We have compared in parallel the in vivo and in vitro effects of a number of drugs which suppress platelet function in an animal model. Rabbits were infused with homologous 51Cr-labelled platelets and then given either ASA (10-200 mg/kg), DIP (1-20 mg/kg) or sulfinpyrazone (SUF) (30-200 mg/kg) intravenously. One hour later PRP from each rabbit was tested by ADP and collagen-induced aggregation. Then each rabbit was infused with an identical final concentration of collagen and the subsequent recovery of 51Cr platelet radioactivity was monitored. In untreated rabbits collagen infusion produced 30% reduction of 51Cr platelets which returned to within 85% of a procollagen level by 5 min. ASA (⪖ 10 mg/kg) inhibited in vitro collagen-induced aggregation while a dose of 100 mg/kg of ASA was necessary to achieve the same inhibitory effect in vivo. On the other hand, DIP (1-20 mg/kg) had no inhibitory effect on in vitro platelet aggregation whereas it inhibited aggregation in vivo. The results of SUF were similar in vitro and in vivo. These results suggest that the effectiveness of drugs on platelet function may be affected by centrifugation, addition of anticoagulant or removal of red cells. This may explain the discrepancies reported between the in vivo and in vitro effectiveness of such drugs.
Blood Platelets and Decompression Accidents in the Rat. Therapeutic Trials
Authors: Broussolle B. , Stoltz J. F. , Verry M. , Hyacinthe R.
Published: June 2019

The pathogenesis of decompression accidents involves particularly disseminated vascular microthrombi composed of platelets clumps, lipids and red blood cells grouped around air microbubbles. In rat, the role of platelets, after rapid decompression (1 bar/20 sec. after being kept at 8 ATA for one hour), is investigated by means of filtration pressure measurements and PRP platelet counts. With decompression accidents, a rise in filtration pressure is observed but there is, above all, a 51% decrease in platelet counts due to disseminated platelet aggregates formed. After slow decompression, there is also a moderate depression (15%) of platelet levels, these not rising until the third day. In order to inhibit platelet aggregation, we used injectable anti-aggregating agents: Aspirin (20 mg/kg) Diamicron (50 mg/kg), S 2574 (100 mg/kg) before and after decompression and for the following three days. The best results were had with S 2574 which prevented fall in platelet levels. Parallely, mortality is reduced if the injection is given before rapid decompression.

These results confirm the importance of platelets in decompression accidents. These therapeutic trials allow to consider the use of these products in human therapy.
Platelet Survival, Fibrinolytic Activity, Antithrombin III (AT III) Level and Fibrinogen Survival in Venous Thromboembolism (VTE)
Authors: Gallus A. S. , Walker I. R. , Hirsh J. , Halasah G. , Evans G.
Published: June 2019

Reduced platelet survival has been found in patients who have reccurrent VTE despite anticoagulant treatment, impaired fibrinolytic activity has been found in patients with recurrent VTE, and a reduced AT III level occurs in some families with VTE. This has led to the use of drugs which correct these abnormalities in patients with VTE. However, the incidence of these, and other, abnormalities of hemostasis in unselected patients with VTE is not known. We have measured 51 Cr-platelet survival, euglobulin lysis time (ELT) before and after venous tourniquet occlusion, antiplasmin activity, AT III level, and 125 I-fibrinogen survival in 57 patients documented by venography (49 patients) or lung scan (8 patients). All studies were done off treatment and at least 3 months after the most recent episode of VTE. The mean platelet half-time in patients was similar to the in 42 controls, but 7 patients with VTE (12%) had a reduced platelet half-time. The ELT was significantly longer (p < 0.005), before and after tourniquet occlusion, than in 89 controls. Thus, 40% of patients and only 10% of controls had a ELT longer than 240 minutes after tourniquet occlusion. AT III levels were normal, as was fibrinogen survival. An elevated antiplasmin level was found in one patient in this study and in two others studied while still under treatment with anticoagulants-all 3 had thromboembolic pulmonary hypertension. Abnormalities occurred with equal frequency in patients with idiopathic or secondary, and single episodes or recurrent VTE. These findings suggest that impaired fibrinolytic activity occurrs frequently in VTE, but that reduced platelet survival is uncommon. High antiplasmin levels may predispose to thromboembolic pulmonary hypertension.
Morphologic Platelet Changes in Vitro and their Effect on Platelet Aggregation Tests
Authors: Breddin K. , Ziemen M. , Bauer A.
Published: June 2019

Regular changes of the aggregation curves can be demonstrated in PRP during the first hour after blood sampling, using the photometric aggregation test (PAT III) or ADP-collagen- and epinephrine induced aggregation. In PAT III and collagen induced aggregation the time lag between the onset of rotation or addition of collagen and the start of aggregation is continously diminishing. In ADP induced aggregation the extent of desaggregation is reduced during the same period. During the first hour after blood sampling platelet morphology as established by interference phase contrast microscopy, electron microscopy or stereo scan microscopy changes drastically. Platelets form pseudopodes and swell. 30 min after blood sampling 75% of the platelets are shape changed at room temperature. At 37° C these changes are slowed, at 10° C or 4° C markedly enhanced. The enhancement or retardation of these morphologic platelet changes are closely paralleled by the differing aggregation patterns in the various tests. Some drugs like Propranolol, SH 869 or Bencyclan inhibit aggregation in vitro and in vivo and influence platelet morphology.
Light and Electron Microscopic Observations on Human blood Platelets under the Influence of Different Extracellular Cation Concentrations, with Special Reference to Microfilaments and Microtubules
Authors: Inczédy-Marcsek M. , Lindner E. , Dierichs R.
Published: June 2019

Adhesion, aggregation and spreading of platelets on an artificial surface was investigated under the influence of rising concentrations of extracellular sodium citrate and EDTA. Due to different complex stability for Ca+2 and Mg+2 decreasing ionic strength of intracellular Mg+2 and Ca+2 was achieved. Ultrastructure of platelets is demonstrated in relation to their function and compared with platelet structure under variing concentrations of extracellular Mg+2 and K+. Morphological changes are correlated with the results of coagulation tests.
Critical Analysis of Platelet Factor 4 (Antiheparin Activity) Assays
Authors: Hurlet A. , Beys G. De , Moriau M. , Monsieur A. , Schulzen E. , Masure R.
Published: June 2019

Antiheparin activity is usually achieved by a heparin-thrombin time assay. Platelet free substrate plasma is adsorbed or not, calcium chloride used or not. Those technical conditions are analysed.

Results are expressed by the amount of heparin units neutralized in the assay. With non adsorbed plasma substrate, calcium chloride generates thrombin, increasing antiheparin like activity. Lower antiheparin like activity is also observed with BaSO4 plasma substrate and with thrombin free of factor Xa. The amount of heparin units neutralized varies from 2.9 to 1.2 according to the system used.

Tested without calcium, with Xa free thrombin and BaSO4 adsorbed substrate plasma, there exists a good relationship between the amount of heparin neutralized and various dilutions of serum, platelet rich plasma and platelet extract.

An assay based on anti-Xa effect of heparin, set up according to the heparin assay of Yin, is compared to the method described above.
Fibrinogen Degradation in Normal and Fibrinolytic Plasma
Authors: Scully M. F. , Kakkar V. V.
Published: June 2019

It has recently been shown that an α2-macroglobulin-plasmin complex isolated from normal plasma is capable of substantially degrading purified fibrinogen in solution in a manner similar to free plasmin (Harpel, P. C. and Mosesson, M. W., J. Clin. Invest., 52, 2175, 1973).

To detect the presence of such fibrinogenolytic activity in normal plasma, 125I-fibrinogen was added to plasma which was then incubated at 37° C for 72 hours. No apparent degradation of the chains of clottable fibrinogen occurred under these conditions. There was, however, a 16% loss in clottability over this period, as measured by radioactivity. 5 units of urokinase/ml of plasma produced an 18% loss in clottability but no degradation of clottable fibrinogen chains occurred. The addition of 50 and 500 units of urokinase/ml of plasma produced, respectively, a 20% and 65% loss of clottability and a 25% and 80% degradation of α chains.

If heterogeneity of fibrinogen in normal plasma is due to degradation of native fibrinogen by α2-macroglobulin-plasmin complex then our observations suggest that further degradation of fibrinogen only occurs in the presence of high levels of plasminogen activator.