bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the Platelet Function by the Effect of Plasmin on Human Factor VIII
Authors: Castillo R. , Maragall S. , Martín E. , Argelagués E. , Qrdinas A. 
Published: May 2019

Plasmin-treated human purified factor VIII prepared from normal and afibrinogenemia plasmas inhibits the ADP-induced aggregation and the collagen-induced 14C serotonin release of normal and von Willebrand human platelet rich plasmas (PRP). These results reconfirm the fact that the inhibition of the human platelet function by the effect of plasmin on the plasmatic protein is mainly linked to the digested factor VIII but not to the fibrinogen,fact that we had previously proved when ADP-induced aggregation of normal washed platelets was inhibited by plasmin-treated normal human serum,but not by plasmin-treated von Willebrand plasma. The factor VIII breakdown products were revealed by crossed immunoelectrophoresis,sepharose 4B chromatography and SDS Polyacrylamide electrophoresis.The defective ADP-induced aggregation that we have observed in PRP from patients between the 8th and the 24th hour of thrombolithic treatment,is only due to the proteolithic effect of plasmin on the plasmatic factor VIII and not to a direct action of the plasmin on the platelet membrane,since washed platelets from these patients aggregate normally by ADP with normal platelet poor plasma(PPP),and the collagen-induced 14C serotonin release is also correct.
Amino Acid Sequence Studies on the γ-Chain of Human Fibrinogen
Authors: Bouma H. , Cottrell B. A. , Friezner S. J. , Takagi T. , Doolittle R. F. 
Published: May 2019

The γ-chain of human fibrinogen contains 400±10 residues, eight of which are methionines. As such, we have isolated and characterized nine cyanogen bromide peptides. The alignment of these fragments was attained by the isolation of key overlap peptides derived from the tryptic digestion of citraconylated γ-chains and succinylated and aminoethylated γ-chains. In the latter case we synthesized a radioactive aminoethylating agent which was especially useful in isolating all the cysteine-containing peptides. The amino acid sequence of most of these fragments has been accomplished by a variety of procedures. In general, our results are in harmony with those recently reported by Henschen et al. (Hoppe-Seyler’s Z. Physiol. Chem., 357, 605, 1976), although some differences exist.The most interesting structural features revealed by the sequence data include significant homologies with the α- and β-chains, especially with regard to the arrangement of certain key cysteine residues. Thus, the sequence at residues γ 135–139 is Cys-Gln-Glu-Pro-Cys, in striking parallel with the sequence at residues γ 19–23, which is Cys-Pro-Thr-Thr-Cys. The occurrence of similar pentapeptide skeins in the α- and β-chains, in each case separated by about the same number of residues, has both structural and evolutionary connotations.
Activation Studies on a Human Prothrombin Variant: Prothrombin Barcelona
Authors: Benarous R. , Rabiet M.J. , Labie D. , Josso F. 
Published: May 2019

Prothrombin Barcelona tested in the plasma from homozygous patients is characterized by a functional defect (5% activity by a one-stage assay) contrasting with a normal prothrombin concentration found by immunochemical assay.This low biological activity is the expression of a very slow rate of conversion of prothrombin into thrombin. It may be postulated that the abnormal kinetics of conversion of this variant might involve an inhibition of one of the proteolytic cleavages responsible for the activation process. To test this hypothesis, purified normal and abnormal prothrombins were submitted to proteolysis with factor Xa and thrombin, either with or without protease inhibitors. Prothrombin cleavage was checked at various times by SDS gel electrophoresis.In the presence of factor Xa, conversion of normal prothrombin into intermediate II started within 30 min and was almost complete within two hours. In the same conditions, conversion into intermediate II of prothrombin Barcelona was only initiated after two hours. Conversely upon treatment of both prothrombins with thrombin, a slight delay in the formation of intermediate I was observed with prothrombin Barcelona, this formation being nevertheless complete after one hr.In conclusion, the abnormal activation of prothrombin Barcelona seems mainly due to a decreased and delayed formation of intermediate II.
Venous Doppler Velocity Examination in Pulmonary Thromboembolism
Authors: Griggs T.R. , Bustad L.B. , Ely C.A. 
Published: May 2019

The Doppler ultrasonic velocity detector, which is sensitive for deep vein thrombosis in 90% of cases demonstrated by venography in our institution, might be useful in the evaluation and management of patients with pulmonary thromboembolism (PE). This study describes the association of results of Doppler velocity examinations with the presence or absence of PE as documented by pulmonary angiography in 51 patients. Results are shown in the table. Doppler studies were performed within 48 hr of angiography.Five patients with positive angiograms had initial or recurrent PE while on anticoagulants. Four of the 5 had positive Doppler studies and the fifth had an incomplete test because of a cast. One patient developed Doppler positivity 2 days before reembolization.One conclusion is clear: Negative venous Doppler examinations must not be used to rule out PE. The study also raises 2 questions:1) Does negative Doppler examination at the time of PE represent complete embolization of thrombus and low risk of immediate recurrence? 2) Is positive Doppler study at the time of PE an indication for early venous plication?
Isopycnicyty and Relations Between Platelet Volume, Density and Age
Authors: Boneu B. , Caranobe C. , Vigoni F. , Blasco A. , Bierme R. 
Published: May 2019

The conflicting results, published in literature, concerning the correlation and significance of platelet volume, density and age are possibly due to the different experimental procedures utilized : medium, densities or centrifugation. We present here the results obtained in man with two methods of centrifugation (I : 800g/60mn ; II : 7000g/20mn) and three different linear isoosmolar gradients (a : Ludox-PVP ; b : Albumin ; c : Metrizamide).With the methods I a, b, c we obtain only one gaussian platelet population. There is an evident relationship between apparent platelet densities and their volumes : the denser the platelets the larger they are. The platelets of each fraction present a log normal volume distribution. The platelet survival studies (51 Cr) demonstrate that platelet volume and age are independent. With the methods II a, b, c we also obtain only one gaussian platelet population but no significant variation of volume between dense and light platelets (except for Ludox-PVP). The mathematical analysis of platelet kinetics (75 Se - 51 Cr) indicates : (1) that young platelets (age < 48h) present the same heterogeneity as the whole platelet population, but the mean density is lower ; (2) the potential survival of platelets of various densities is identical ; (3) the young platelets increase slightly their density during the first four days of their survival. Thus there is continuously some sort of exchange between platelet populations, (peripheral maturation phenomenon).In conclusion ours are conflicting results too. We demonstrate in fact that the second method achieves an isopycnic separation but not the first one.
Typical Changes of Platelet Volume During and After Extracorporeal Circulation
Authors: Wenzel E. , Saavedra E. , Volkmar I. , Monadjemi H. , Pöhler E. , Stapenhorst K. , Harbauer G. , Isringhaus H. 
Published: May 2019

In 32 patients undergoing open-heart-surgery with extracorporeal circulation (ECC), platelet volume distribution curves (PVD) during and immediately and 24 and 48 hours after cardiopulmonary bypass were examined by an electronic particle size analyzer based on the Coulter-Counter-System. The PVD changes, i.e., the reduction of the mean platelet volume (MPV) and the platelet fall correlates significantly with the bypass time (r = 0.78). Two hours after the end of ECC, these changes remained completely irreversible or only partially reversible in patients with perfusion times longer than 60 minutes. In most of the patients with shorter perfusion times, we observed a normalisation of PVD curves and return of platelets to counts approaching normal levels.Some plasma coagulation parameters (i.e., concentration of clottable fibrinogen, FDP) were estimated in parallel and were found to be in good correlation with the platelet defects.In patients with marked changes of MPV up to 48 hours after the end of surgery, a pathologic volume distribution curve of thrombocytes was observed, but platelet counts returned in most of them to normal values. This indicates that the determination of PVD, as a simple reliable diagnostic parameter, gives more essential information about platelet damage than does the platelet count alone.
New Chromogenic Peptide Substrate for Factor Xa
Authors: Aurell L. , Simonsson R. , Arielly S. , Karlsson G. , Friberger P. , Claeson G. 
Published: May 2019

The chromogenic substrate Bz-Ile-Glu-Gly-Arg-pNA is based on the primary structure preceding the bonds split by factor Xa in bovine prothrombin. Substitution of amino acids in this natural sequence by closely related amino acids has only given inferior substrates. Thus, the natural sequence seems very important. However, we have found that the free γ-carboxyl group of Glu is not indispensable. Substrates with the above structure but having been derivatized on the γ-carboxyl group of Glu, in the form of simple esters or amides, show improved properties. Especially Km of the new substrates compare favourably with our first substrate. Some of the amides also show increased Vmax.These improved properties have made it possible to increase sensitivity, shorten incubation times and lower substrate consumption in several methods where this type of substrate is utilized.
Human Prothrombin/Phospholipids Interaction. Competitive Effect of an Anticoagulant Venom Phospholipase A2
Authors: Boffa G.A. , Benarous R. , Boffa M.C. 
Published: May 2019

The high anticoagulant activity of the phospholipase A2 isolated from a Viperidae venom was explained by the formation of a complex with phospholipid at its protein binding site (1). The anticoagulant effect was reversible with specific antiphospholipase A2 immunoglobulins.The interaction between 125 I prothrombin and phospholipid in the presence of calcium was impaired by the phospholipase. A competitive effect between prothrombin and the phospholipase was demonstrated. It did not appear sufficient to explain the anticoagulant property of the enzyme. This effect was abolished after photo-oxidation of the phospholipase. In the presence of another Viperidae phospholipase A2, devoid of anticoagulant activity, no competitive effect was observed.The presence of several sites responsible for anticoagulant, catalytic and recognition properties have been looked for by various partial chemical denaturation processes.
Turnover Studies of Des-A Fibrin and Fibrinogen in Healthy Human Beings
Authors: Müller-Berghaus G. , Mahn I. 
Published: May 2019

Soluble fibrin was injected into man. Two methods were used to prepare soluble des-A fibrin. Purified human 1-125-fibrinogen was transformed into soluble des-A fibrin (des-A FM):(1) by thrombin in the presence of 2.0 M urea (method according to Hogg and Blombäck, 1975), (2) by ancrod. Eight male volunteers were injected either with thrombin-induced soluble I-125-fibrin (FM-T) or ancrod-induced soluble I-125-fibrin (FM-A). The control consisted of I-131-fibrinogen injected simultaneously with soluble I-125-fibrin.The mean distribution volume of des-A FM-T was 48.9 ml/kg and that of des-A FM-A 50.3 ml/kg which is similar to that of the injected fibrinogen (43.0 ml/kg) indicating a homogenous distribution of the injected FM in the circulating blood. The injected des-A FM disappeared faster from the circulating blood than des-AB fibrin monomer. Six hours after injection 99.5% of the injected FM-A and 95% of the injected FM-T were removed from the circulating blood. The FM were cata-bolized since free I-125 were quantitatively recovered from the urine. The elimination curve of des-A FM-A as well as des-A FM-T does not represent a mono-phasic exponential decay.The experiments demonstrate that des-A fibrin can be traced in man and is cleared from the circulating blood at a high elimination rate.(Supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg)
A Study of the Asphctic Newborn Related to Hypercoagulability by Determination of Soluble Fibrin Monomer Complex (SFMC) and Plasmin Inhibitor
Authors: Susuki S. , Graeff H. , Hafter R. 
Published: May 2019

Gordblood samples from 80 healthy newborns and 19 asphyctic newborns were examined. SFMG and fibrinogen were precipitated from plasma with β-alanine.Agarose gel filtration of redissolved precipitate resulted in separation of SFMC and fibrinogen. Other parameters such as TEG, Prothrombin time (PT), Partial thromboplastin time (PTT), and Plasmin-inhibitors (α2-macrogloblin, α1-antitrypsin, antithrombin III)were also determined. (Results)(1) The percent amount of SFMC of total fibrinogen content in asphyctic newborn increased 4.73 ± 1.55%, while the remaining normal infants showed only 3.17 ± 0.55% (P < 0.05)(2) In neither PT nor PTT can a significant difference be seen, although asphyctic newborn showed the tendency of hypercoagulability in TEG.(3) α1-antitrypsin (92.8 ± 21.5)and antithrombin III(8.4 ± 2.3) levels were much lower in the group with asphyxia.These results indicate that a low level of Plasmin-inhibitors act synergestically with a high activator value.The low antithrombin III level in particular could be one of the reason for the development Hypercoagulability and DIC in asphyctic newborn infants.
In vivo effects of human granulocyte neutral proteases on blood coagulation in green monkeys (cercopithecus aetiops)
Authors: Egbring R. , Gramse M. , Heimburger N. , Havemann K. 
Published: May 2019

Two neutral proteases (elastase-1ike = ELP, and chymotrypsin-like = CLP) derived from human PMN in highly purified form inactivate in vitro humanisolated coagulation factors (Thromb. Res. 6, 315, 1975). These effects can be observed also in human plasma, despite its high antiprotease capacity. (Blood February 1977).ELP and CLP (both free of endotoxin) were infused into green monkeys either separate or in combination to investigate a possible role of these proteolytic enzymes also in vivo. Activity of coagulation factors I - XIII and antiprotease potential has been followed for a 24 hour period in short intervals.A loss of activity of coagulation factor II, V, VIII, IX, X and XIII could be demonstrated. Fibrinogen concentration decreased and fibrinogen split products could be detected. In two-dimensional immunelectrophoresis α1-antitrypsin-ELP and α2-macroglobulin-ELP-complexes were demonstrable for about 6 hours after protease infusion. Bleeding complication occurred after injection of both enzymes.The results indicate a direct proteolysis of coagulation factors by PMN neutral proteases in vivo.We suggest that similar conditions are present in patients with acute leukemia or septicemia.
Primary Structure of Human Platelet Factor 4.
Authors: Morgan F.J. , Begg G.S. , Chesterman C.N. 
Published: May 2019

The amino acid sequence of human platelet factor 4 (PF4) has been studied. PF4 is a platelet specific protein with antiheparin activity, released from platelets as a proteoglycan complex, whose measurement may provide an important index of platelet activation both in vivo and in vitro. These studies were undertaken to characterize fully the PF4 molecule. PF4 is a stable tetramer, composed of identical subunits, each with a molecular weight based on the sequence studies of approx. 7,770. Each PF4 subunit contains 69 amino acids, including 4 half-cystine (# 10, 12, 36, 37), one tyrosine (# 59), 3 arginine and 8 lysine, but no methionine, phenylalanine or tryptophan residues. The basic residues are predominantly in the C-terminal region. The tryptic peptides were aligned after studies which included tryptic digestion of citraconylated RCM-PF4, and automated Edman degradation of RCM-PF4 and citraconylated tryptic peptides. No glycopeptides were detected. This structural information should enable clear distinction to be made between PF4 and other platelet proteins such as β thromboglobulin. The provisional amino acid sequence of each subunit is:Glu-Ala-Glu-Glu-Asp-Gly-Asp-Leu-Gln-Cys-Leu-Cys-Val-Lys-Thr-Thr-Ser-Gln-Val-Arg-Pro-Arg-His-Ile-Thr-Ser-Leu-Glu-Val-Ile-Lys-Ala-Gly-Pro-His-Cys-Cys-Pro-Thr-Ala-Gln-Ile-Leu-Ala-Thr-Leu-Lys-Asn-Gly-Arg-Lys-Ile-Pro-Leu-Asp-Leu-Gln-Ala-Tyr-Leu-Lys-Ile-Lys(Lys, Lys, Ser, Glx, Leu, Leu)
Fibrinogen/Fibrin Interaction with Platelets
Authors: Michaeli D. , Orloff K. 
Published: May 2019

There is considerable evidence that fibrinogen is involved in ADP-induced platelet aggregation. On the basis of fluorescent probe experiments, it was concluded that fibrinogen increases the exposure of hydrophobic regions on the platelet membrane. A proposal was made that fibrinogen enhancement of ADP-induced aggregation is mediated via a thrombin-fibrinogen interaction leading to the formation of fibrin bridges between platelets. Evidence militating against this mechanism will be reviewed.Platelets are capable of interacting with nascent fibrin, which in turn induces the aggregation and release reactions. Platelets can similarly react with fully polymerized fibrin. Fragment D inhibited these interactions, probably due to its binding to fibrin, and thereby blocking sites on fibrin that are involved in its interaction with platelets.
A Prospective Trial of Sulfinpyrazone After Peripheral Vascular Surgery
Authors: Blakely J.A. , Pogoriler G. 
Published: May 2019

169 patients were randomly allocated to Sulfinpyrazone or placebo after peripheral vascular surgical procedures. Randomization was stratified for surgeon and type of operation (endarterectomy, vein graft, or prosthesis) and aorto-iliac or femoral popliteal site. Treatment was begun with Sulfinpyrazone 200 mgs. t.i.d. or equivalent placebo. Platelet tests were performed at intervals and patients with active collagen aggregation were given increments to 1200 mgs. daily or equilivent placebo. Patients were followed for up to 3 years. Claudication distances, peripheral pulses, readmissions, and returns to surgeon were documented at intervals. Three endpoints were assessed without knowledge of treatment category; occlusion at operated site, occlusion in same leg, and all peripheral vascular events, as well as other episodes of vascular disease. 137 patients had femoral popliteal and 27 had aortoiliac surgery. There was no evidence of benefit in either group with respect to any of the endpoints. There was 1 death in the treated group and 2 deaths in the control group. Suspect drug toxicity was similar in treatment and control groups (22 vs. 19) although more patients were withdrawn from the treatment group as a result (11 vs. 50, mostly because of rash, dyspepsia, and nausea.This study suggests that Sulfinpyrazone does not prolong patency after peripheral vascular surgery.
Abnormal Platelet Ultrastructure in Fulminant Hepatic Failure
Authors: Bullock G. , Weston M.J. , Rubin M.H. , Roberts J. , Langley P.G. , White Y. , Williams R. 
Published: May 2019

Platelets obtained from eight patients with varying degrees of liver damage have been studied with respect to their ultrastructure. These platelets were isolated from platelet-rich plasma which had been utilised in the pharmacological studies described by Dr. Weston (previous abstract) and were compared with control platelets isolated from five normal subjects. The latter were chosen for normal bleeding times and response of their platelets to aggregation with ADP and collagen.Marked differences were seen between control platelets and those from the test group in that there was an alteration in the microtubular content and disposition. In addition, these changes were partially reversed during the recovery period suggesting that production of new normal platelets was taking place. This is one of the few conditions where platelet structure has been correlated with a clinical disorder.
Furosemide, Fibrinolytic Activity and Urokinase Excretion
Authors: Chohan I.S. , Singh I. , Vermylen J. , Verstraete M. 
Published: May 2019

Plasma fibrinolytic activity, as measured by the fibrin-plate method, is enhanced after an intravenous injection of 40 mg furosemide. The effect is evident within 30 minutes of the injection and attains a peak after 6 hours. If a second injection of furosemide is given at this stage, the increased fibrinolytic activity persists, and a slightly higher peak than the first is obtained again 6 hours after this injection. After the furosemide injection, there is an initial decrease of urokinase excretion which returns to normal after 3 to 6 hours.The decrease of urokinase excretion is attributed to a dilution effect during increased diuresis and the rise in fibrinolytic activity by furosemide is attributed to its vasodilatory activity and cyclic-AMP phosphodiesterase inhibitory capacity. It also appears related to the Hageman factor dependent pathway of fibrinolysis. In the treatment of high altitude pulmonary oedema, furosemide restores factor XII and fibrinolytic activity, which are both depressed in this disease (I. Singh and I.S. Chohan, Int. J. Biometeor. 18, 33, 1974).
Furosemide and Platelet Functions
Authors: Chohan I.S. , Singh I. , Vermvlen J. , Verstraete M. 
Published: May 2019

Furosemide inhibits primary platelet aggregation by adenosine-5'-diphosphate and prolongs the latent period before Thrombofax- or collagen-induced platelet aggregation, both in vitro and ex vivo. Furosemide also inhibits the release of platelet factor 4 and 14C-serotonin. The inhibitory concentrations of furosemide in vitro range between 0.5 and 2.5 mM. The ex vivo effects were obtained after an intravenous injection of 40 mg furosemide.The furosemide concentrations required for ex vivo inhibition are hundred fold lower than those required for in vitro effect. This suggests in vivo metabolic effects of this drug, such as, calcium ions shifts, or action of other metabolic products of furosemide. In support of this concept platelet aggregation was found more disturbed six hours than 10 minutes after injection of the drug.
Studies on Spontaneous Platelet Aggregation (PAT III) in Patients with Vascular Disease
Authors: Krzywanek H.J. , Breddin K. 
Published: May 2019

Aggregation tests were performed in 345 patients with peripheral occlusive arterial disease (PAD), 274 patients with coronary heart disease (CHD), and 502 diabetics (D). 263 healthy volunteers (N) served as controls. As in previous studies an age dependent increase of strongly enhanced spontaneous platelet aggregation in obviously healthy subjects can be demonstrated, reaching 28% in the 50-59 years’age group. In the various patient groups the incidence of enhanced aggregation is much higher throughout all age groups than in the control s.The overall incidence of missing spontaneous platelet aggregation vs. strongly enhanced aggregation is summarized below. The difference between normals and the various patient groups is significant (X2-test, α<0.0001).A prospective investigation has been started to establish whether enhanced spontaneous platelet aggregation is a risk factor and an early indicator of progressive atherosclerosis.