bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism
Authors: Dupe R J , English P D , Smith R A G , Green J 
Published: July 2018

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.
High and Low Affinity Heparin Compared with Unfractionated Heparin as Antithrombotic Drugs
Authors: Merton R E , Thomas D P , Havercroft S J , Barrowcliffe T W , Lindahl U 
Published: July 2018

SummaryA preparation of heparin was separated by affinity chromatography into two fractions: one of high (HAH) and the other of low (LAH) affinity to antithrombin III. These two fractions were compared with unfractionated heparin (UFH) by in vitro assay and their ability to impair experimental stasis thrombosis was also examined. Although the in vitro activity of HAH was double that of UFH, HAH was less effective than UFH as an antithrombotic drug; LAH was virtually inactive, both in vitro and in vivo. A mixture of 30 μg/kg of HAH and 50 μg/kg of LAH was as effective in preventing thrombosis as 80 μg/kg of UFH, and was more effective than 40 μg/kg of HAH alone, demonstrating that LAH potentiates the action of HAH in vivo.
Histidine-Rich Glycoprotein Modulates the Anticoagulant Activity of Heparin in Human Plasma
Authors: Lijnen H R , Van Hoef B , Collen D 
Published: July 2018

SummaryAddition of 0.05 IU of heparin per ml normal plasma prolongs its thrombin time from 20 to 27s, but that of plasma specifically depleted in histidine-rich glycoprotein (by immunoadsorption) from 20 to 180s. Reconstitution of the depleted plasma with normal plasma or with purified histidine-rich glycoprotein normalizes its thrombin time.In 54 plasma samples from hospitalized patients a significant negative correlation was found between the anticoagulant activity of heparin measured by thrombin inhibition and the plasma level of histidine-rich glycoprotein (r = 0.69). It is concluded that the level of histidine-rich glycoprotein modulates the anticoagulant activity of heparin in human plasma to an extent which appears to be pharmacologically and possibly clinically relevant.
Effects of Acetylsalicylic Acid on Human Platelet Function In Vivo at Salicylate Steady State
Authors: Simrock R , Missalla A , Schwidtal P , Lischke V , Breddin H K 
Published: July 2018

SummaryThe results of clinical trials concerning the use of acetylsalicylic acid (ASA) as antithrombotic drug are contradictory. Inhibition by ASA of platelet prostaglandin synthesis and aggregation is prevented by its metabolite salicylic acid (SA) in animals and in human platelets in vitro. It was suggested that ASA might produce its own inhibitor, thereby diminishing its efficiency in thromboembolic disease.In four healthy male subjects there was no difference in inhibition of collagen-induced platelet aggregation after the administration of 500 mg ASA alone or at salicylate steady state (3 g SA daily). But the inhibition of tissue-extract-induced platelet shape change was diminished and shortened by pretreatment with SA. We conclude that SA does not inhibit the effects of ASA on human platelet aggregation in vivo in therapeutic dose ranges. The clinical importance of the SA/ASA-interaction on tissue-extract-induced platelet shape change remains to be clarified.
A Study of a Caucasian Family with Variant von Willebrand’s Disease in Association with Vascular Telangiectasia and Haemoglobinopathy
Authors: Hanna W , McCarroll D , Lin D , Chua W , McDonald T P , Chen J , Congdon C , Lange R D 
Published: July 2018

SummaryA family was identified which carries multi-haematological disorders including Type IIA von Willebrand’s disease, vascular telangiectasia, and a haemoglobinopathy (haemoglobin S trait). In the affected individuals, the von Willebrand’s disease varies in its expression from an asymptomatic form to a severe form especially in those patients with telangiectasia. Some patients have vascular telangiectasia in the mucous membranes of the mouth and lips. In two patients endoscopy disclosed telangiectasia in the mucous membranes of the gastrointestinal tract. All of the patients who had telangiectasia also had von Willebrand’s disease. An incidental finding was the presence of an abnormal haemoglobin (haemoglobin S) in some family members. The pattern of inheritance of the haemoglobinopathy was unrelated to the inheritance pattern of von Willebrand’s disease. The presence of haemoglobin S did not interfere with the aggregation of platelets in response to ristocetin.
Platelet Survival in Streptozotocin-Induced Diabetic Rats
Authors: Winocour P D , Laimins M , Colwell J A 
Published: July 2018

SummaryPlatelet survival in diabetes mellitus may be decreased or normal, and it is not clear whether altered platelet survival is due to a platelet or to a non-platelet defect. Therefore, platelet survival studies were performed at intervals up to 28 days in streptozotocin-induced diabetic and normal rats, using washed platelets from diabetic or normal animals.When compared to platelets from control rats, there was a significant decrease in platelet survival when platelets from 7 and 14 day diabetic rats were injected into normal controls or into diabetic rats.After 28 days of diabetes, platelet survival in diabetic rats was significantly lengthened, whether the platelets came from control or diabetic rats.
Conclusions. (1) Shortened platelet survival in the diabetic rat is caused initially by a platelet defect. Later, non-platelet factors become dominant. (2) These findings may help explain reported discrepancies in results of platelet survival in diabetes mellitus.
Metabolism of Sodium Pentosan Polysulphate in Man – Catabolism of Iodinated Derivatives
Authors: MacGregor I R , Dawes J , Paton L , Pepper D S , Prowse C V , Smith M 
Published: July 2018

SummaryAn iodinated derivative of the heparin analogue SP54 has been prepared and used in conjunction with unlabelled SP54 to study the catabolism and organ distribution of this potential antithrombotic agent in healthy human volunteers. As observed previously with 125I-heparin, we found that the 125I-SP54 was rapidly cleared from the circulation, returning later in a desulphated form. Organ distribution studies with 123I-SP54 suggested that the liver and spleen were major sites of desulphation. Gel filtration and Polybrene binding showed the presence of sulphated macromolecular SP54 and desulphated macromolecular and depolymerised SP54 in post-injection urines. No depolymerised material was present in plasma suggesting depolymerisation occurs in the kidney.
Effect of Plasma Dilution on Adsorption of Fibrinogen to Solid Surfaces
Authors: Brash J L , ten Hove P 
Published: July 2018

SummaryThe adsorption of various plasma proteins to three solid surfaces has been studied as a function of plasma concentration. Albumin adsorption on glass showed no dependence on plasma concentration and increased to a plateau value on both polyethylene and siliconized glass. Immunoglobulin G (IgG) adsorption showed no dependence on plasma concentration on any surface. Fibrinogen adsorption increased with plasma concentration and then decreased, the maximum occurring at about 1% normal plasma concentration and varying somewhat with the surface. On glass the kinetics of fibrinogen adsorption was dependent on plasma concentration: at concentrations less than the adsorption maximum, the kinetics was conventional, with adsorption increasing onto a plateau; at concentrations greater than the adsorption maximum, kinetics curves also showed maxima the position of which shifted to longer times as plasma concentration decreased. These data are interpreted in terms of competitive adsorption between fibrinogen and other, as yet unidentified species in plasma. The data reported are in general agreement with the model of Vroman (12) for plasma-surface interactions which holds that initially adsorbed fibrinogen is later replaced by high molecular weight kininogen (HMWK), the rate of replacement depending on the relative activity of the surface in promoting coagulation.
Abnormal Platelet Serotonin Uptake and Binding Sites in Myeloproliferative Disorders
Authors: Caranobe C , Sié P , Fernandez F , Pris J , Moatti S , Boneu B 
Published: July 2018

SummaryA simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.
Blood Changes and Enhanced Thromboxane and 6-Keto Prostaglandin F1α Production in Experimental Acute Plasmodium Bergei Infection in Hamsters
Authors: Essien E M , Arnout J , Deckmyn H , Vermylen J , Verstraete M 
Published: July 2018

SummaryGolden hamsters inoculated intraperitoneally with Plasmodium bergei infected mouse blood regularly developed P. bergei parasitaemia. This was associated with progressive thrombocytopenia and leucocytosis as the degree of parasitaemia increased with time. When infected whole blood was stimulated with collagen, significantly enhanced thromboxane B2 (TXB2) production per platelet was seen. 6-keto prostaglandin (PG) F1α formation in the same system increased from the sixth infection day onwards and correlated with the relative leukocytosis. The production of 6-keto PGF1α by aorta rings was significantly higher during the 4-7th days postinoculation. The increase in thromboxane production however was much more important than that of 6-keto PGF1α and it therefore is concluded that P. bergei parasitaemia in hamsters tilts the haemostatic balance towards the platelet hyperaggregability that has also been described in P. falciparum infection in man.
Inhibition by Heparin of Platelet Accumulation In Vivo
Authors: Barrett P A , Butler K D , Morley J , Page C P , Paul W , White A M 
Published: July 2018

SummaryIn vivo platelet aggregation has been studied using a novel, minimally invasive technique. No aggregatory effects of heparin were observed on normal circulating platelets nor was there enhancement of aggregation of platelets during activation by fhtravenous injection of ADP, collagen, PAF acether or thrombin. On the contrary, high doses of heparin were found to inhibit platelet accumulation induced by ADP, collagen or PAF-acether. Inhibition of these responses necessitated doses of heparin in excess of those required for anti-coagulant effects. The present experiments do not establish a mechanism for such inhibition. Extension to other species, including man, is needed before attributing clinical relevance to the present observations.
Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency
Authors: Morgan Kangathevy , Schiffman Sandra , Feinstein Donald 
Published: July 2018

SummaryTwo patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients’ plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients’ plasmas adsorbed to Protein A- Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – II. Turnover of Natural and Recombinant Urokinase in Rabbits and Squirrel Monkeys
Authors: Collen D , De Cock F , Lijnen H R 
Published: July 2018

SummaryThe turnover of recombinant pro-urokinase (Rec-pro-UK), recombinant urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) was studied in rabbits and in squirrel monkeys (Samiri sciureus). Following intravenous injection, urokinase activity disappeared rapidly from the blood. The initial disappearance rate could be described by a single exponential term with a t½ of 3 to 6 min for each molecular form of urokinase in both species. Urokinase related antigen, measured with a radioimmunoassay in the plasma of the squirrel monkeys disappeared with a t½ of 3.5 min for Rec-pro-UK, 6.0 min for Rec-UK and 8.0 min for Nat-UK.The clearance and organ distribution of Rec-pro-UK, Rec-UK and Nat-UK was studied with the use of 125I-labeled preparations. In each case the radioactivity initially disappeared rapidly from the plasma, also with a t½ of a few min, but then the disappearance rate slowed down. Labeled Rec-UK in which the active site histidine was irreversibly blocked by alkylation, disappeared equally rapidly from the plasma. Measurement of the organ distribution of 125I at different time intervals revealed that all three types of urokinase were rapidly accumulated in the liver, which was followed by release of degradation products in the blood. Experimental hepatectomy prolonged the t½ of each type of urokinase very markedly (t½ >30 min).These findings indicate that urokinase is rapidly removed from the blood by clearance and degradation in the liver. Recognition by the liver does not require a functional active site and is not mediated via carbohydrate side chains. Inactivation by plasma protease inhibitors does not represent a significant pathway of urokinase inhibition in vivo.
Preoperative AT-III Values and Clinical Postoperative Thrombosis: A Comparison of Three Antithrombin-III Assays
Authors: Lynch Dona M , Leff Linda K , Howe Stephen E 
Published: July 2018

SummaryThree antithrombin-III assays (Sigma functional plasma, von Kaulla functional serum, and Calbiochem-Behring radial immunodiffusion) are compared using preoperative serum and plasma from 48 patients admitted for cardiovascular or other major vascular surgery. Medical records were reviewed for evidence of thrombotic complications. Eight patients (17%) in this selected population had clinical evidence of postoperative thrombotic complications. The sensitivity and specificity for each AT-III assay were calculated, and the positive and negative predictive values in this population were determined. Sigma’s plasma AT-III had the highest positive predictive value (67%) and negative predictive value (100%). The functional serum and RID assays had significantly lower positive predictive values (23% and 38% respectively) and negative predictive values of 86%. Using the Two Sample t-Test to evaluate differences in AT- III values between the two patient groups, i.e., those who experienced thrombotic complications and those who did not, only the functional plasma AT-III method was statistically significant at a 95% confidence interval.
Platelet Survival and Function in Animals with Prosthetic Mitral Valve: The Effect of Nafazatrom
Authors: Al-Mondhiry H , Pierce W S , Richenbacher W 
Published: July 2018

SummaryThromboembolism remains a serious problem in patients with prosthetic heart valves. Previous studies documented a number of platelet abnormalities in such patients and correlated the occurrence of thromboembolic complications with short platelet survival. We have studied platelet survival and platelet aggregation in eight goats fitted with prosthetic mitral valves and repeated the studies following treatment with nafazatrom, a potent antithrombotic agent. Eleven survival studies in eight animals showed a platelet survival not significantly different from control (6.52 ± 0.72 vs. 6.94 ± 0.81 days). Following seven to ten days of oral drug administration, platelet survival in the test animals was 7.34 ± 0.96 days, significantly longer than pretreatment results (p <0.01). Animals with the shortest pretreatment platelet survival achieved substantial prolongation of platelet life span following drug treatment. The drug caused no change in ex vivo platelet aggregation.
Venous Thrombosis Following Diagnostic Transvenous Catheterization by Percutaneous Catheter Insertion: An Evaluation of Desmopressin as a Thromboprophylactic Agent
Authors: Nilsen D W T , Haerem J , Westheim A , Skjennald A , Grendahl H , Godal H C 
Published: July 2018

SummaryThe preventive effect of desmopressin with respect to catheter induced thrombosis was studied in a randomized double-blind trial, consisting of 30 patients undergoing percutaneous transcubital right heart catheterization. Phlebography of the catheterized arm was performed after five days. The frequency of postcatheterization thrombosis was reduced by 33 per cent, from 86 per cent in the treatment group to 53 per cent in the control group (0.1 <p <0.2). This effect was restricted to minor thrombi, whereas major thrombosis could not be prevented.Patient materials such as that of the present study, may become useful in preliminary investigations of thromboprophylactic agents.
Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit
Authors: Prosdocimi M , Scattolo N , Zatta A , Fabris F , Stevanato F , Girolami A , Cella G 
Published: July 2018

Summary13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.
The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy
Authors: Christe M , Gattlen P , Fritschi J , Lämmle B , Berger W , Marbet G A , Duckert F 
Published: July 2018

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.
Indium-111-Labelled Human Platelets: A Method for Use in Severe Thrombocytopenia
Authors: Heyns A du P , Badenhorst P N , Wessels P , Pieters H , Kotzè H F , Lötter M G 
Published: July 2018

SummaryWe describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 × 109/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% ± 21 of platelets were harvesteo from the blood, labelled with 49% ± 24 efficiency and 15.8 × 108 labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.
The Use of Functional and Quantitative Assays to Study Glycoprotein Ib in Platelets Stored Under Various In Vitro Conditions
Authors: Taylor M Ann , Anstee D J 
Published: July 2018

SummaryThere is much evidence to suggest that platelet membrane glycoprotein Ib is involved in the haemostatic function of platelets and it has been suggested that loss of this glycoprotein may occur during in vitro storage of platelet concentrates. In this study two quantitative radioimmunoassays were developed to measure the content of glycoprotein lb in platelets stored under a range of conditions used in blood banks. One assay involved the use of iodinated Maclura pomifera lectin and the other the binding of a monoclonal antibody (AN51) specific for glycoprotein lb. The results showed that there was no significant reduction in the glycoprotein Ib content of platelets under the storage conditions used. These results suggest that any loss of haemostatic effectiveness which occurs on in vitro storage of platelet concentrates is not attributable to a selective loss of glycoprotein Ib from the platelet surface.
High Fibrinopeptide A (FPA) Levels in Acute Non-Lymphocytic Leukemia Are Reduced by Heparin Administration
Authors: Gugliotta L , Viganò Silvana , D’Angelo A , Guarini Anna , Tura S , Mannucci P M 
Published: July 2018

SummaryPlasma levels of fibrinopeptide A (FPA) in 30 untreated patients with acute non-lymphocytic leukemia (ANLL) were significantly higher than in 30 healthy controls (p <0.001). Patients without laboratory signs of disseminated intravascular coagulation (DIC) had levels of FPA higher than controls (p <0.02) but markedly lower than patients with DIC (p <0.001). Five patients with M3 leukemia had a higher mean FPA level (p <0.02) and a lower peripheral blast cell count (p <0.05) than patients with other cytological subtypes of ANLL. When patients with M3 were excluded, a significant correlation was observed between the peripheral blast cell counts and the FPA levels (r = 0.66, p <0.001). FPA levels were similar with body temperature either above or below 38° C. After intravenous bolus of heparin FPA dropped to normal levels in 14 out of 17 patients who had high baseline values. These findings indicate that intravascular thrombin formation, which probably result from the expression of procoagulant activities of blast cells, is the main cause of high FPA in the majority of patients with acute non-lymphocytic leukemia.