bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interaction of Immobilized Thrombin with Human Antithrombin III
Authors: Marciniak E , Gora-Maslak G 
Published: July 2018

SummaryInteraction of human antithrombin III (AT III) with human α-thrombin coupled to Sepharose 4B was investigated. Despite markedly reduced esterolytic, amidolytic and especially coagulant activity, more than 90% of immobilized thrombin formed stable complexes with purified AT III. Presence of high affinity heparin did not facilitate the inhibition to the degree seen in reactions conducted with soluble thrombin. Instead, heparin induced proteolysis of up to 66% of the inhibitor that remained in solution. This led to the isolation of a homogeneous protein fragment which migrated in SDS-gel electrophoresis as a band of 50,000 Mr, cross-reacted with antibodies to human AT III but showed no biologic activity nor sufficient affinity for heparin. Out of the three major inhibitors capable of binding soluble thrombin in human plasma, only AT III reacted with immobilized thrombin. However, Sepharose-coupled thrombin mixed with plasma in the presence of heparin produced outstanding quantities of residual immunoreactive AT III devoid of inhibitory activity. These data suggest that presence of high affinity heparin in the environment of thrombin attached to a solid support may dramatically decrease the efficiency of enzyme inhibition.
Dysfunctional Plasminogen in Full Term Newborn - Study of Active Site of Plasmin
Authors: Benavent A , Estellés A , Aznar J , Martinez-Sales V , Gilabert J , Fornas E 
Published: July 2018

SummaryThe functional activity and active site of plasmin	in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen descried in a previous paper.The functional activity of newborn plasminogen measured on chromogenic substrate was approximately 18% that of adult plasminogen when streptokinase was used as an activator and 12% when urokinase was used.Proteolysis of newborn plasminogen by urokinase yielding a two-chain plasmin form occurred normally, but the incorporation of diisopropylphosphorofluoridate into the light chain of newborn plasmin was approximately 23% of that observed in the light chain of adult plasmin.These observations suggest that the abnormality of full-term newborn plasminogen is located in the active site of the molecule.
Stanozolol-Induced Changes in Fibrinolysis and Coagulation in Healthy Adults
Authors: Kluft C , Preston F E , Malia R G , Bertina R M , Wijngaards G , Greaves M , Verheijen J H , Dooijewaard G 
Published: July 2018

SummaryThe effects of orally-administered stanozolol, 5 mg b. d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and anti thrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects.The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, “free” plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.
The Importance of Corticoids Added to Continued Treatment with Factor VIII Concentrates in the Suppression of Inhibitors in Haemophilia A
Authors: Aznar J A , Jorquera J I , Peiró A , Garcia I 
Published: July 2018

SummaryA protocol is presented to suppress inhibitors in haemophilia A using continued treatment with f. VIII (50 U/kg b.w./day) and fluprednisolone (0.5 mg/kg b.w., for 21 days) until reaching correct in vivo recovery after therapeutic administration.5 high responder patients were treated whose inhibitors were detected at least 2 years before beginning the treatment. The inhibitors were eradicated in 4 patients using continued treatment for between 4 and 24 months. Patient 1 was treated exclusively with factor and the others also with corticoids when the level was 0 B.U. (or 20 B.U., patient 4). The patients began tri-weekly prophylactic treatment and rehabilitation exercises after recovery test normalization. After progressive reduction of the prophylactic treatment they started on demand treatment. After more than 5 months of this treatment no anamnestic response has been detected in any patient, in spite of several factor VIII administrations.
Evidence that von Willebrand Factor is Not Required for the Clotting of Plasma in the Presence of Platelets and Kaolin (Hardisty-Hutton Test)
Authors: McPherson Jean , Soberano Mercedes E , Macdonald Cheryl , Zucker Marjorie B 
Published: July 2018

SummaryAntihemophilic factor (AHF) essentially free of von Willebrand factor (vWF) was used to determine whether vWF affected the coagulant activity of AHF in a kaolin-activated system using platelet-rich plasma. The AHF was prepared by sequential chromatography on solid-phase polyelectrolyte (PE E-5), and on Sepharose CL-4B in the presence of a high concentration of CaCl2. Residual traces of vWF antigen were removed by affinity chromatography with immobilized anti-vWF IgG. The essentially vWF-free AHF corrected the clotting defect of plasma from three patients with severe von Willebrand’s disease (vWD) as measured by the kaolin-activated clotting time in the presence of normal or vWD platelets (Hardisty-Hutton test). Addition of hemophilic plasma as a source of vWF did not cause additional improvement, nor did a potent antibody to vWF raised in rabbits inhibit the ability of AHF to shorten the clotting time of vWD plasma. Thus we found no evidence that vWF is necessary for AHF to function in the coagulation of recalcified kaolin-activated vWF-deficient platelet-rich plasma.
A Double-Blind Trial of Ticlopidine in Sickle Cell Disease
Authors: Semple M J , Al-Hasani S F , Kioy P , Savidge G F 
Published: July 2018

SummaryBaseline studies of 111indium oxine labelled platelet life-span, platelet α-granule release products, β-thromboglobulin (βTG) and platelet factor 4 (PF4), and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease, who were subsequently randomised in a prospective double-blind trial of ticlopidine (250 mg. b. d.) or placebo for one month and the investigations repeated. Control studies indicated that 5 of the 9 patients had shortened platelet survivals: mean βTG (50.8 ng/ ml) and PF4 (19.5 ng/ml), factor VIII: C (283.4 i. u./dl) and factor VIIIR: AG (168.7 u/dl) levels were raised. Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels, though it was associated with reduced values of βTG and PF4. One patient taking ticlopidine developed an infarctive sickle crisis. Although ticlopidine blocked platelet activation, this alone did not improve platelet survival or prevent sickle crisis: in view of evidence of platelet activation in sickle cell disease, however, a longer trial of prophylactic antiplatelet drugs might be warranted.
Effect of Vitamin E on Platelet Aggregation in Diabetes Mellitus
Authors: Watanabe J , Umeda F , Wakasugi H , Ibayashi H 
Published: July 2018

SummaryVitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E in platelets was significantly reduced in diabetics compared with age matched controls. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane production and aggregation which relate to the development of vascular complications.
Correction of Clotting Factor “Deficiencies” in Plasma from Patients with Lupus-Like Anticoagulants
Authors: Clyne Lionel P , Honig Christine L , Dainiak Nicholas 
Published: July 2018

SummaryIdentification of spurious coagulation factor deficiencies that are known to occur in association with lupus-like anticoagulants (LLACs) requires the use of cumbersome laboratory procedures. To determine whether single-stage assays employing the APTT system may be used to identify such artifacts, we measured multiple clotting factor levels by several techniques in plasma of six patients with typical LLACs. While normal activities of factors VIII, IX, XI and XII were measured in only 4/24 APTT assays (17%) employing human plasma substrate, normal factor activities were present in all 24 APTT assays employing bovine, canine or rabbit plasma substrate. Normal factor II, V and X activities were recorded in all but one case in assays that utilized a modified Stypven time, while normal factor VIII levels were determined in 5/6 plasmas when the thromboplastin generation test was employed. These results indicate that the use of heterologous plasma substrates in the APTT system may provide a simple method to identify such coagulation factor “deficiencies”.
Intra-Platelet Platelet Factor 4 (IP.PF4) and the Heparin-Mobilisable Pool of PF4 in Health and Atherosclerosis
Authors: O’Brien J R , Etherington M D , Pashley M 
Published: July 2018

SummarySome patients with clinical evidence of atherosclerosis and others with diabetes were compared with appropriate controls. The intraplatelet level of platelet factor 4 (PF4) was significantly decreased in the arteriopaths and was lower in the diabetics when compared with controls. Patients with transient ischaemic attacks and stroke have even lower values.Intravenous heparin liberates large amounts of PF4 from an unknown reservoir, perhaps the endothelium, into the plasma. Arteriopaths liberated significantly more PF4 than the controls and the diabetics most. If a second heparin injection is given 24 hr after the first, the resultant plasma PF4 level was on average half that achieved after the first injection and again the patients had higher levels than the controls. Thus the reservoir originally “emptied” of PF4 by the heparin had been partially refilled in 24 hr and the reservoir in the atherosclerotic patients then contained more than the controls. Patients with atherosclerosis and especially diabetics differ from controls in the PF4 content of their platelets and in their response to heparin and in the rate of refill of the “heparin-mobilisable pool of PF4”.
Modulation of Rapid Plasminogen Activator Inhibitor in Plasma by Stanozolol
Authors: Verheijen J H , Rijken D C , Chang G T G , Preston F E , Kluft C 
Published: July 2018

SummaryFibrinolytic activity in plasma euglobulin fractions can be increased by oral administration of stanozolol. This increase is not caused by increased synthesis or release of tissue-type plasminogen activator. A decreased level of fast acting t-PA inhibition is very probably the cause of the higher activity. These results suggest that this inhibition has a regulatory role on fibrinolysis in vivo.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – I. Fibrinolytic and Fibrinogenolytic Properties in Human Plasma In Vitro of Urokinases Obtained from Human Urine or by Recombinant DNA Technology
Authors: Zamarron C , Lijnen H R , Van Hoef B , Collen D 
Published: July 2018

SummaryThe fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec- UK) obtained by expression of the human urokinase cDNA in E. coli, were compared with those of natural urokinase (Nat-UK) of urinary origin and of tissue-type plasminogen activator (t-PA) in a system, composed of a radioactive human plasma clot immersed in citrated human plasma.The specific fibrinolytic effects of Nat-UK, Rec-pro-UK and Rec-UK were very similar, causing significant clot lysis at concentrations of 100 IU/ml plasma or more. t-PA caused equivalent degrees of clot lysis at 10-fold lower concentrations.Activation of the fibrinolytic system in the plasma (fib- rinogenolysis), was not observed with t-PA in concentrations which induced complete clot lysis within 5 hr (20-30 IU/ml plasma). With Nat-UK and Rec-UK, all concentrations which caused significant clot lysis (100-200 IU/ml plasma) also caused extensive activation of the plasma fibrinolytic system. With Rec- pro-UK an intermediate response was obtained. The highest amounts required for complete clot lysis in 5 hr (200 IU/ml plasma) also caused significant fibrinogenolysis. At intermediate concentrations (50-100 IU/ml), however, significant clot lysis (40-80%) was observed without systemic fibrinolytic activation.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – IV. Variability in Fibrinolytic Response of Plasma of Several Mammalian Species
Authors: Lijnen H R , De Wreede K , Demarsin E , Collen D 
Published: July 2018

SummaryThe fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec- UK) were compared with those of natural urokinase (Nat-UK) and of tissue-type plasminogen activator (t-PA) in an in vitro system consisting of 125I-labeled autologous plasma clots immersed in plasma of humans, five primate species, dogs, rabbits and pigs. With each of the four plasminogen activators, a dose-dependent clot lysis was observed, the degree of which differed, however, very markedly from one species to the other.At a concentration of 100 IU/ml of urokinase extensive plasma clot lysis was obtained in plasma of man, Macaca mulatta, Macaca fascicularis and Macaca radiata, while the plasma clots of Papio cynocephalus, Papio anubis and rabbit, dog and pig were much more resistant to lysis. No significant differences in the extent of lysis were observed between Rec-pro-UK and Rec-UK nor between Rec-UK and Nat-UK. Comparable degrees of lysis were obtained with t-PA at 3- to 5-fold lower concentrations. Lysis with Rec-UK or Nat-UK was always associated with extensive activation of the fibrinolytic system in plasma, evidenced by fibrinogen breakdown and plasminogen activation and a2-antiplasmin consumption. With t-PA, extensive clot lysis was obtained in the absence of fibrinolytic activation in the plasma. With Rec-pro-UK the response was intermediate; at high concentrations (200 IU/ ml) extensive lysis in the reactive species was associated with fibrinogen consumption, while at intermediate concentrations (50-100 IU/ml) significant clot lysis was obtained in the reactive species in the absence of marked activation of the fibrinolytic system in the plasma.
Acquired von Willebrand’s Syndrome Associated with Hydatid Disease of the Spleen – Disappearance after Splenectomy
Authors: Richard C , Sedano M C , Cuadrado M A , Recio M , Hermosa V , Zubizarreta A 
Published: July 2018

SummaryA new case of acquired von Willebrand’s syndrome (vWS) is described in a 31-year-old woman with a hydatid splenomegaly and with a history of repeated abortions at an advanced stage of pregnancy, a positive serology for syphilis and a mildly elevated titre of antinuclear antibodies, with no family history of bleeding.There is an inhibitory effect on factor VIII: C (antihaemophilic factor) as well as on factor VIIIR: Ag (related antigen) and on factor VIIIR:RCo (ristocetin cofactor), and it is precipitated by rabbit anti-IgG antiserum. This inhibitory effect was demonstrated using the patient’s plasma heated to 56° C for one hour so as to dissociate circulating immunocomplexes.All the abnormalities of haemostasis, as well as the positive serology for syphilis, disappeared after splenectomy, and the ANA titre reverted to normal.The clinical and biological peculiarities of the case are discussed, and are interpreted in the light of the findings recorded in patients showing “lupus” anticoagulant.
Role of Endogenous Proteinase Inhibitors in the Regulation of the Blood Clotting System of the Horseshoe Crab, Limulus Polyphemus
Authors: Armstrong Peter B , Levin Jack , Quigley James P 
Published: July 2018

SummaryBlood clotting in Limulus is dependent on the activity of a proteinase which converts the zymogen, coagulogen, into a form that undergoes polymerization to form the clot. The abilities of a series of recently discovered endogenous proteinase inhibitors to inhibit this enzyme and thereby serve as potential regulators of its activity were explored. The blood plasma of Limulus contains a single inhibitor that is functionally and structurally homologous to vertebrate α2 macroglobulin. During exocytosis, the blood cells (amebocytes) release a series of inhibitors, including small quantities of the α2 macroglobulin homologue; a low molecular weight, acid-and heat-stable inhibitor; and an acid-labile activity. Of the three inhibitory activities, only the cell-released, acidlabile inhibitor is capable of inhibiting the clotting enzyme.
The Fast Inhibitor of Tissue Plasminogen Activator in Plasma During Pregnancy
Authors: Wiman B , Csemiczky G , Marsk L , Robbe H 
Published: July 2018

SummaryThe novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In healthy fertile non-pregnant women, the inhibitor concentration was found to be 0.4 ± 0.7 U/ml. In pregnant women the concentration stayed at this level until week 10, but then an almost linear increase was found, reaching about 6.5 U/ml at week 40. In plasma samples from the patients with risk pregnancies many with deviating concentrations were found. Thus, in the last trimester a range of 0-24.0 U/ml was found in these patients, as compared to 4.0-6.4 U/ml in healthy pregnant women. The pathophysiological impact of this finding is at present unclear.
A Collaborative Study Designed to Establish the 4th International Standard for Heparin
Authors: Thomas D P , Curtis A D , Barrowcliffe T W 
Published: July 2018

SummaryAn international collaborative study, in which 22 laboratories participated, was carried out to establish a replacement for the International Standard for Heparin. A total of 248 assays were analyzed, including APTT, thrombin inhibition and anti-Xa assays, as well as pharmacopoeial assays. Overall, there was less than 5% difference in the mean potency estimates of the candidate preparations, by all assay methods. The freeze-dried preparation 82/502 demonstrated the closest parallelism by bioassay to the existing standard and was established by WHO as the 4th International Standard for Heparin, with an assigned unitage of 1780 i.u. per ampoule.
Masking of Fibrinolytic Response to Stimulation by an Inhibitor of Tissue-Type Plasminogen Activator in Plasma
Authors: Brommer E J P , Verheijen J H , Chang G T G , Rijken D C 
Published: July 2018

SummaryPatients with hyperlipoproteinaemia or spontaneous thromboembolism, known to be poor responders to DDAVP or to venous occlusion with regard to the rise in fibrinolytic activity of the blood, appeared to show a normal increase in t-PA-antigen after the same procedure. In their plasma a higher than normal level of free, fast-acting t-PA-inhibitor was found as measured by titration with purified t-PA. This free t-PA-inhibitor level only decreased after the test, in contrast to its complete disappearance in normal responders. The same happened in a healthy volunteer who failed to exhibit a rise in fibrinolytic activity after exhaustive exercise.We suppose that the lack of response of the fibrinolytic activity in these cases is due to a high inhibitor level and not to impaired release of t-PA into the blood.In contrast, patients with terminal renal insufficiency showed only a slight increase in t-PA-antigen after DDAVP. The level of free fast-acting inhibitor was normal in most cases and did not change appreciably during DDAVP-infusion. In these patients, a true impairment of the release of t-PA appears to exist.
Pharmacokinetics and Anticoagulant Effect of Hirudin in Man
Authors: Markwardt F , Nowak G , Stürzebecher J , Grießbach Uta , Walsmann P , Vogel G 
Published: July 2018

SummaryThe pharmacokinetics and the effects on the haemostatic system of hirudin were assessed in six healthy subjects after single intravenous or subcutaneous dose (1000 AT-U/kg). When hirudin was given intravenously first-order elimination kinetics followed the initial distribution phase. The decline in plasma hirudin concentration was most adequately expressed by a biexponential equation describing a two compartment model. A mean elimination half-life of 0.84 hr and a mean volume of distribution of 12.9 1 were calculated. After subcutaneous injection a low hirudin level (∼0.5 AT-U/ml) was maintained for a prolonged period of time.In the 24 hour-urine up to 50 per cent of the administered amount of hirudin was excreted in active form.Thrombin time, partial thromboplastin time and prothrombin time measured in plasma samples ex vivo were prolonged dependent on the hirudin plasma level. Platelet counts, fibrinogen level and the fibrinolytic system were unchanged. Bleeding time was prolonged twice at maximum.Subcutaneous or intravenous administration of pure hirudin was tolerated without side-effects.
Platelet Survival in Patients with Angiographically Diseased and Normal Coronary Arteries
Authors: Verhaeghe R , Piessens J , Suy R , Verstraete M 
Published: July 2018

SummaryPlatelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary artery disease. Therefore, platelet kinetics were studied in 69 patients with angiographically documented coronary artery disease and in 16 patients with a normal coronary angiogram. Platelet survival time was calculated from the decay of radioactivity after injection of 51Cr-labeled autologous platelets. None of the mathematical models used was able to discriminate between the two patients groups. No correlation existed between survival time and extent of the arterial disease. Patients with a high serum cholesterol did not exhibit an enhanced platelet consumption. Thus, these studies do not support the idea that platelet turnover is enhanced in patients with coronary artery disease as compared to those with normal coronary arteries.