bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Admission Plasma Fibrinogen Levels Useful in the Characterization of Risk Groups after Myocardial Infarction Treated with Fibrinolysis?
Authors: Pollak Hans , Fischer Michael , Fritsch Stephan , Enenkel Wolfgang 
Published: July 2018

SummaryThe aim of our study was to prove or disprove the independent prognostic importance of fibrinogen after myocardial infarction. Plasma fibrinogen levels were determined on admission in 135 patients with an acute myocardial infarction and symptoms up to 4 h (mean: 1.8 h) immediately before starting fibrinolytic treatment with 1.5 mio U. streptokinase i.v. All patients were free from other diseases which are known to cause elevated fibrinogen levels. Coronary angiography was carried out in 87%. During a mean follow-up period of 26.2 months 31 coronary events could be observed in 26 patients: 18 reinfarctions, 6 cases of sudden death, and 7 coronary artery bypass graft surgeries because of new symptoms. While plasma fibrinogen levels were higher in smokers than in non-smokers (3.30 vs 2.94 g/l p = 0.011) and correlated with the number of involved coronary arteries (p = 0.08), values were similar in patients with and without coronary events during follow-up (3.07 vs 3.16 g/l, p = 0.70). This applied as well to univariate analysis as to multivariate Cox's regression model. We conclude that plasma fibrinogen levels determined very early in patients with acute myocardial infarction do correlate with other important prognostic variables, but have no independent prognostic importance.
Characterization of Genetic Defects of Hemophilia B of Chinese Origin
Authors: Lin Shu-Wha , Shen Ming-Ching 
Published: July 2018

SummaryTo define the precise genetic defects of hemophilia B of Chinese origin, we have used the polymerase chain reaction (PCR) combined with direct sequencing to analyze the amplified DNA fragments containing the entire coding regions and their flanking introns of the factor IX gene from 6 affected individuals. Among these patients, two are siblings with normal factor IX antigen level (CRM+) yet reduced factor IX clotting activity (28%). Analysis of their factor IX genes revealed a G to A transition at nucleotide residue 10394, which causes substitution of an arginine for a glycine at amino acid residue 48. This is a novel mutation which resides in the first EGF-like domain of factor IX. Studies of two other hemophilia B patients with CRMr phenotypes (factor IX antigen level <35%, and clotting activity <1%), demonstrated a distinct mutation in each individual's factor IX gene. In one case, a guanine to adenine (residue 6365) transition results in replacement of arginine by glutamine at the –4 codon of the propeptide of factor IX. In the other, thymine at 6442 was mutated to cytosine which causes an arginine for cysteine substitution at residue 23. We have also characterized 2 discrete CRM- patients. Both exhibited an identical mutation at nucleotide residue 6460 which generates a translation termination codon (CGA to TGA) at the 29th amino acid. The mutation created a new NlaIII restriction enzyme site which could be used to identify this variant.
Comparative Fibrinolytic Properties of Staphylokinase and Streptokinase in Animal Models of Venous Thrombosis
Authors: Lijnen H R , Stassen J M , Vanlinthout I , Fukao H , Okada K , Matsuo O , Collen D 
Published: July 2018

SummaryThe thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function and the maximal percent clot lysis (c), the maximal rate of lysis (z = ¼ac · e
b
) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 ± 1,100% lysis per mg/kg streptokinase administered versus 1,100 ± 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 ± 440 versus 1,200 ± 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits, as revealed by a higher z-value (950 ± 350% lysis per mg/kg staphylokinase administered versus 330 ± 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 ± 0.010 mg/kg staphylokinase versus 0.091 ± 0.008 mg/kg for streptokinase). The plasma clearance following bolus injection of staphylokinase or streptokinase in hamsters or rabbits was comparably rapid (1.1 to 1.4 ml/min in hamsters and 14 to 15 ml/min in rabbits) as a result of a short initial half-life (1.8 to 1.9 min in hamsters and 1.7 to 2.0 min in rabbits). These results in two quantitative rodent models of thrombolysis suggest that staphylokinase is a potent thrombolytic agent with an in vivo thrombolytic potency that is comparable to that of streptokinase. Further investigation of the thrombolytic potential of staphylokinase seems to be warranted.
Ascorbic Acid Increases the Thrombogenicity of Cellular Matrices
Authors: Hindriks Georg A , Sixma Jan J , de Groot Philip G 
Published: July 2018

SummaryWe have studied the influence of ascorbate on extracellular matrix formation in cultured human endothelial cells, smooth muscle cells and fibroblasts and measured the influence of the changed composition of their isolated extracellular matrices on their affinity for platelets. When endothelial cells were grown for a week in the presence of ascorbate, no influence on proline incorporation in their extracellular matrix was found. In accordance, no influence on platelet adhesion or aggregate formation on these matrices was detected. When smooth muscle cells were cultured in the presence of ascorbate, a strong increase in the amount of collagen types I and III in the extracellular matrix was found. When these matrices were perfused with whole blood, a significant enhanced increase in aggregate formation was observed. No influence was seen on the total coverage of the matrix with platelets. When fibroblasts were grown in the presence of ascorbate, no significant increase in proline incorporation in their matrix was measured. However, an increased adhesion of platelets was seen to the matrices at lower shear rates. We conclude that ascorbate feeding has a significant effect on endogenous deposited matrices of smooth muscle cells and fibroblasts, and that the changed composition had profound effects on platelet interaction with these matrices.
α2-Antiplasmin, Plasminogen Activator Inhibitor (PAI) and Dilute Blood Clot Lysis Time in Selected Disease States
Authors: Cucuianu Mircea , Knauer Oliver , Roman Stefan 
Published: July 2018

SummaryThis paper is an attempt to assess the relevance of the inhibitors of fibrinolysis for clot lysis in selected disease states and to discuss the mechanisms leading to acquired abnormal levels of such inhibitors. When compared to 20 control subjects the 30 hypertriglyceridemic patients (14 with type IIb and 16 with type IV) displayed significantly (p <0.001) increased plasma plasminogen activator inhibitor (PAI) activity (221 ± 88% and 290 ± 104% respectively; mean ± SD), moderately (p <0.01) increased α2 antiplasmin (α2AP) level (112 ± 11% and 115 ± 16%) and accordingly an obviously prolonged dilute blood clot lysis time (DBCLT). Neither PAI activity and α2AP level nor DBCLT were significantly different from controls in the 10 patients with hyperlipoproteinemia type IIa. The 18 patients with severe hepatic cirrhosis had low α2AP level (59 ± 19.7%) and accelerated clot lysis, while mean PAI activity (160 ± 87%) was slightly (p <0.05) increased. In the 17 nephrotic patients α2AP was increased (115 ±12%) while PAI activity was similar to controls and DBCLT rather shorter. Two liver secretion enzymes, namely serum Cholinesterase and plasma protein C, were found to be decreased in cirrhotic patients, similar to control values in hyperlipoproteinemia type Ha and obviously increased in nephrotic patients as well as in hypertriglyceridemic subjects. The relevance of PAI and α2AP for clot lysis was considered in relation to data in the literature concerning the behaviour of t-PA and factor XIII. Enhanced hepatic synthesis of protease inhibitors and factor XIII as a possible cause of delayed clot lysis in hypertriglyceridemia was envisaged.
Thrombosis: A Study of Coagulation Parameters and Mechanisms during Allograft Rejection
Authors: Mandel Stanley R , Shermer Richard , Clark Richard , Staab Edward V , Webster William P 
Published: July 2018

SummaryThrombosis of the microvasculature has been recognized as the end product of organ rejection, but the exact biological pathway through which this occurs has not been clarified. Normal, factor VII deficient and heterozygous hemophilic (factor VIII) dogs were grouped to study the intrinsic and extrinsic clotting and platelet mechanisms during unmodified renal allograft rejection. The observed alterations of the hemostatic mechanisms are related to the changes observed in the microvasculature. Six groups of donor-recipient animals were studied: Group I - autografts (control); Group II - normal to normal allografts with bilateral nephrectomy; Group III - heterozygotes for factor VIII deficiency; Group IV - normal to normal allografts with unilateral nephrectomy; Group V - normal to factor VII deficiency without nephrectomy; and Group VI - normal to normal allografts with unilateral nephrectomy and dipyridamole. Each engrafted animal was followed pre- and posttransplantation for change in the blood clotting factors, fibrin split products, platelets, white blood cells, renal function and microvasculature. The animals with factor VII deficiency rejected in a similar fashion as the control animals. The group with impaired factor VIII synthesis and platelet function had longer survival times. These data suggest that the intrinsic clotting pathway and platelets are the primary mechanism through which thrombosis occurs secondary to immune injury.
Separation of Fibrinogen Degradation Products (FDP) by Means of Adsorption to Insolubilized Fibrinmonomer (FM-ag)
Authors: Heene D L , Matthias F R , Wegrzynowicz Z , Hocke G 
Published: July 2018

SummaryThe phenomenon of complex formation between fibrinmonomer and fibrinogen degradation products was investigated by means of adsorption of FDP to insolubilized thrombin- modified fibrinogen (FM-ag). Since it could be demonstrated that there are different adsorption characteristics for early FDP and late FDP, the possibility of separation of FDP by means of affinity chromatography on FM-ag columns was evaluated using plasmic digests of 3H-Ac-labelled fibrinogen. The identification of FDP was performed by disc-electrophoresis. The results indicate that the adsorption of early FDP is comparable to the behaviour of fibrinogen, whereas late FDP show essential difference in the affinity towards FM-ag, evident by the result that fragment E adsorbs only to a minimal extent. Fragments D and E derived from fibrinogen as well as from non-crosslinked fibrin, revealed identical adsorption characteristics. Under specified conditions the procedure is suitable as a preparative method for the separation of fragments D and E.
Cancer Procoagulant in Acute Non Lymphoid Leukemia: Relationship of Enzyme Detection to Disease Activity
Authors: Donati M B , Falanga A , Consonni R , Alessio M G , Bassan R , Buelli M , Borin L , Catani L G , Pogliani E , Gugliotta L , Masera G , Barbui T 
Published: July 2018

SummaryBlast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (cp). Thii factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. Tb assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinaie inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-cP polyclonal antibody. Data obtained in gL newlydiagnosed ANLL patients (subtypes M1 to M5, EAB classification) confirmed the presence of cp in M1- to M4 groups (mean + sE Fvll-independent activity: M1 = 2.1 ± 0.7 unit/mg; M2 = 5.7 ± 1.7 unit/mg; M3 = 31.5 ± 8 unit/mg M4 = 1.6 ± 1.2 unit/mg; CP was absent in the M5 type. In eight patients analy zedin a subsequent phase of partial remission, specific activity had dropped from 26.9 ± 7.8 to 10.5 ± 4.0 unit/mg. Activiiy was virtually absent (0−0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII indbpendent activity rose to 24.2 ± 8.2 unit/mg.These results suggest that CP activity may be closely associated with the presence of myeloid malignant cells in the bone marrow, a finding of potential relevance not only to the coagulation disorders of acute leukemia, but also to the early deteition of blast cells in ANLL.
Coagulation, Fibrinolytic and Platelet Function in Patients on Long-Term Therapy with Aspirin 300 mg or 1200 mg Daily Compared with Placebo
Authors: Hampton K K , Cerletti C , Loizou L A , Bucchi F , Donati M B , Davies J A , de Gaetanox G , Prentice C R M 
Published: July 2018

SummaryAspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2- dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1α excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was norrnal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.
Characterization of Domain Deletion and/or Duplication Mutants of a Recombinant Chimera of Tissue-Type Plasminogen Activator and Urokinase-Type Plasminogen Activator (rt-PA/u-PAI)
Authors: Nelles L , Lijnen H R , Van Nuffelen A , Demarsin E , Collen D 
Published: July 2018

SummaryChimeric molecules comprising the A-chain of tissue-type plasminogen activator (t-PA) and the catalytic domain of urokinase-type plasminogen activator (u-PA) have intact enzymatic characteristics of u-PA, but only partial fibrin-binding properties of t-PA (Nelles et al., J Biol Chem 1987; 262: 10855–62). The following domain deletion and/or duplication mutants of such a t-PA/u-PA chimera were constructed, purified and charactertzed: rt-PA-ΔFE∇/u-PA, with deletion of the finger-like (F) and epidermal growth factor-like (E) domains, rt-PA-ΔK1∇K2/u-PA, with kringle 1 (K1) replaced by a second copy of kringle 2 (K2), and rt-PA-ΔFEK1∇K2/u-PA, with F and E domain deletions in rt-PAΔK1∇K2/u-PA.The specific activities on fibrin plates of the single-chain (sc) chimeras ranged between 68,000 IU/mg for rt-PA-ΔK1∇K2/scu-PA and 200,000 IU/mg for rt-PA-ΔFEK1∇K2/scu-PA, as compared to L20,000 IU/mg for rscu-PA. The specific activities of their plasmin-generated two-chain (tc) derivatives ranged between 120,000 IU/mg for rt-PA-ΔK1∇K2/tcu-PA and 240,000 IU/mg for rt-PA-ΔFEK1∇K2/tcu-PA, as compared to 100,000 IU/mg for rtcu-PA. All two-chain chimeras activated plasminogen following Michaelis-Menten kinetics, with catalytic efficiencies between 0.072 μM−1s−1 for rt-PA-ΔK1∇K2/tcu-pA and 0.081 pM−1 s−1 for rt-PA-ΔFEK1∇K2/tcu-PA, as compared to 0.088 μM−1 s−1 for rtcu-PA. CNBr-digested fibrinogen enhanced the initial rate of plasminogen activation by a factor 2.2 to 6.2, as compared to 4.9 for rtcu-PA. The fibrin-affinity of the chimeras decreased in the order rt-PA > rt-PA-ΔK1∇K2/u-PA > u-PA and that for lysine in the order rt-PA-ΔFEK1∇K2/u-PA > > t-PA/u-PA ⩽ st-PA > rt-PA-ΔFE/u-PA > u-PA. All single-chain plasminogen activators caused a time and concentration-dependent clot lysis in an in vitro plasma clot lysis system, with equi-effective doses (causin g 50% clot lysis in 2 h) ranging between 0.53 and 0.90 μg/ml, as compared to 1 .7 μg/ml for rscu-PA, and were associated with comparable residual fibrinogen levels of approximately 80%.Thus, substitution of K1 by a second copy of K2 in the chimeric protein t-PA/u-PA enhances the affinity for both fibrin and lysine significantly and improves the fibrinolytic potency in an in vitro clot lysis system marginally.
Lack of Platelet Response to Collagen Associated with an Autoantibody against Glycoprotein Ia: A Novel Cause of Acquired Qualitative Platelet Dysfunction
Authors: Deckmyn Hans , Chew Shern L , Vermylen Jos 
Published: July 2018

SummaryPlatelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient’s platelet membrane glycoproteins (GP) were seen.Tleatment of the patient with immunosuppressive agents temporarily improved both the bleeding tendency and the collagen responsiveness of the platelets. An IgG was found to be present in the plasma, directed against a protein comigrating with GPIa, and coadsorbing with GPIa to insoluble collagen fibers in a Mg+2-dependent manner. Furtherrnore, GPIa was recognized by the patient’s antibody when affinity-purified GPIa-IIa was used as antigen. Finally, the GPIa-IIa complex was immunoprecipitated from a platelet lysate by patient’s plasma.In addition, purified platelet specific IgG’s from the patient inhibited aggregation of normal platelets induced by collagen or by wheat germ agglutinin. We conclude that the lack of response to collagen of the patient’s platelets may well be due to the presence of an autoantibody against GPIa.
1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia
Authors: Casonato Alessandra , Teresa Sartori M , de Marco Luigi , Girolami Antonio 
Published: July 2018

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.
Does Increased Platelet Aggregation Have a Prognostic Value in the Deterioration of Background Diabetic Retinopathy?
Authors: Plu G , Lecrubier C , Scarabin P Y , Baudoin C , Samama M ,   on behalf of the Damad Study Group
Published: July 2018

SummaryMany case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy.