bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARISON OF A BOLUS AND A INFUSION DOSE REGIMEN OF RECOMBINANT TISSUE TYPE PLASMINOGEN ACTIVATOR (rt-PA) ON THE RATE OF THROMBOLYSIS IN THE RABBIT JUGULAR VEIN MODEL (RJVM)
Authors: Refino C J , Hultgren B , Hollenbach S , Hotchkiss A 
Published: August 2018

The success of intravenous infusion of rt-PA in the treatment of myocardial infarction, along with new applications in deep vein thrombosis and pulmonary embolism has stimulated interest in optimizing dosage regimens. Dosage strategies should be tested in a relevant animal model before clinical use. In the RJVM, net lysis is calculated frcm the difference in 1-125 fibrinogen present in a rabbit jugular vein thrombus, pre and post thrombolytic therapy, therefore changes in the rate of lysis would not be detected. To continuously monitor rates of lysis in the RJVM, a flat surface garrma detector probe was secured over the jugular vein thrombus of the anesthetized rabbit, and Gamma counts were accumulated for one minute, at 10 minute intervals. Rates of lysis and net lysis were calculated frcm these data. Net lysis was also determined by the traditional method in order to validate the new technique. Using this experimental design we compared the efficacy of a bolus (0.4 mg/kg over 1 min) to an infusion (0.4 mg/kg over 2 hours, 10% given as an initial bolus). A control group received an infusion of rt-PA excipient. The bolus group was terminated at 60 minutes, since there was no detectable lysis in any of these animals after 30 mins. There was an excellent correlation between the net lysis calculated either by the probe or the traditinal procedure (Y = 1.0 × −2.8, r = 0.88). The lysis rates were:From these data we conclude that in the RJVM a bolus of rt-PA offers no clear advantage in efficacy over a comparable dose given as a 2 hr infusion. This observation appears to hold true even during the first 30 minutes of treatment where any advantage the bolus might have would most likely be evident
COAGULATION CHANGES UNDER THREE DIFFERENT DOSAGE REGIMENS OF SINGLE-CHAIN UROKINASE TYPE PLASMINOGEN ACTIVATOR
Authors: Zimmermann R , Horn A , Bode C , Harenberg J , Schuler G , Schwarz F , Tillmanns H , Kübler W 
Published: August 2018

Therapy with streptokinase and urokinase induce effective thrombolysis but may be complicated by hemorrhagic side effects. In order to minimize these complications single-chain urokinase-type plasminogen activator (scu-PA) was given in patients with acute transmural myocardial infarction at three different dosage regimens consecutively in combination with heparin. In a first group four patients received 15 mg, thirteen 48 mg (group II) and five 72 mg (group III) of scu-PA intravenously. In 22 cases detailed clotting analyses could be performed. Results: The coagulation analysis demonstrated a reduction of the fibrinogen concentration by 11 % in group I, 17 % in group II and 44 % in group III. Plasminogen decreased by 9 % in the first, 43 % in the second and 61 % in the third group. The level of∝2-anti-plasmin showed a reduction of 12 % in group I, 48 % in group II and 80 % in group III. Fibrin degradation products increased in all groups. The euglobulin clot lysis time was moderately shortened in group I but significantly in the groups II and III. Reptilase and thrombin coagulase time were prolonged moderately. Thrombin clotting time and aPTT could be attained at therapeutic range by additional application of heparin. Antithrombin III showed no alteration. Thrombolysis could be achieved in none of the patients in group I but with good results in group II and III.Our data suggest that intravenous application of scu-PA at a dosage of 48 mg is able to induce effective thrombolysis with only slight destruction of fibrinogen. At higher dosages a further increased rate of thrombolysis may be possible but also a higher rate of fibrinogenolysis may be considered.
MULTICENTRIC SPANISH STUDY OF BIOLOGICAL CAUSES OF DEEP VEIN THROMBOSIS
Authors: Felez J , Rodriguez-Pinto R , Oliver A , Velasco F , de Diego I , Steegmann L J , Martin S 
Published: August 2018

305 unselected patients under long-term oral anticoagulation treatment for having presented one o more ep^L sodes of deep vein thrombosis and/or pulmonary embolism, have been studied for the following anomalies: Dysfibrinogenemia, Lupus anticoagulant, Antithrombin-III deficiency, Protein C, Protein S, Heparin Cofactor II, and anomalies in the fibrinolytic components t-PA PAI and Plasminogen. Protein C antigen and activity as well as free Protein S antigen levels have been related to those found in a control group at different intensities of oral anticoagulantAs shown in the table this study, performed on unselected patients from the clinical point of view, has not only confirmed the presence of a previously known congenital defect in 16 patients (5%) but also has per miteed the identification of a previously unkown de- -feet in 45 patients (15%)Since the identification of a congenital abnormality permits to prevention of new thrombotic episodes and the identification of the afected members, these re- -suits support the convenience of performing such syste matic biological studies in patients suffering from thrombosis
PROFILE DIAGNOSIS OF HEMOSTATIC DISORDERS BY SIMULTANEOUS ASSAY OF HEMOSTATIC MOLECULAR MARKERS
Authors: Teruya J , Shimizu N , Matsuda J , Kazama M , Abe T 
Published: August 2018

Simultaneous measurements of molecular markers of platelet, coagulation, fibrinolysis, and vascular system give us precise-and comprehensive information about hemostatic profile of various diseases. We adopted 6-thromboglobulin(B-TG) and platelet factor 4(PF4) for platelet function, fibrinopeptide A(FPA) and soluble fibrin monomer complex(SFMC) for coagulation, fibrinopeptide BB15-42(BB) and fibrin degradation product(FDP), for fibrinolysis, and tissue plasminogen activator(TPA) antigen for vascular system.(l).The results of normal values were as follow(n=20); 6-TG 40.6ng/ml, PF4 9.9ng/ml, FPA 3-lng/ml, BB 8.2ng/ml, and TPA 4.4ng/ml. (2).The mean values of 6-TG and PF4 were 72.1ng/ml and 30.9ng/ml, respectively in all patients with SLE(n=53)-FPA and BB were 7-lng/ml and 32.2ng/ml, respectively. All the markers mentioned above were significantly increased compared with normal. It means that hemostatic profile of SLE was hyperfunction of platelet, coagulation, and fibriolysis systems. (3)-In patients with ischemic heart diseases(IHD) including angina pectoris and acute myocardial infarction(n=17) B-TG and PF4 increased to 60.1ng/ml and 21.7ng/ml, respectively. But FPA did not change significantly. And BB increased to 4l.8ng/ml. It means that occurrence of IHD is closely related to hyperfunction of platelets rather than coagulation. (4). Patients with occlusive cerebrovascular accident(CVA) were divided into two groups; cases with high FPA and those with normal FPA. The average value of FPA of the former group was 10.2ng/ml and they had higher levels of BB of 23.1ng/ml than normal. TPA was measured before and after venous occlusion (VO) of lOOmmHg for 7 minutes. TPA increased 2 or 3 folds after VO test in normal subjects, but in 5 of 17 cases of CVA it did not change before and after VO test.It was postulated that the profile diagnosis of hemostatic disorders is possible by simultaneous measurement of molecular markers, because this method informs us what aspect of hemostatic function is hyperactive. It will also provide us the appropriate indication of treatment for various types of thrombotic disease.
IS BETATHROMBOGLOBULIN (BTG) OF PROGNOSTIC VALUE IN PATIENTS WITH TRANSIENT CEREBRAL ISCHEMIA (TIA) ?
Authors: Strano A , Davi G , Catalano I , Francavilla G , Notarbartolo A 
Published: August 2018

TIA and stroke have for a long time been recognized as being associated with various abnormalities in platelet function.Plasma levels of BTG, a marker of platelet release reaction, have been found raised in TIA patients. However plasma measurements can be influenced by venipuncture or handling of the samples Therefore we measured urinary BTG levels and compared plasma and urinary levels of this protein in 18 patients with TIA and 18 controls of equivalent age (41-68 years) and sex.Plasma BTG levels were not different between TIA subjects (24.1 ± 8.6 ng/ml) and controls (20.2 ± 6.4 ng/ml). Urinary BTG levels were significantly different between TIA patients (0.72 ± 0.24 ng/ml) and controls (0.28 ± 0.09 ng/ml) and platelets from TIA patients were more sensitive to ADP than those from controls.After 6 months of ticlopidine administration urinary BTG levels in TIA patients fell to within normal ranges, plasma BTG values remained in the normal range and the the AC50 for ADP was significantly increased.We conclude that only urinary BTG levels may have diagnostic usefulness to evaluate a slight but continous platelet activation of circulating platelets, for istance, by ulcerated plaques in cranial arteries. The interpretation of elevated plasma BTG levels is hampered by the influence of the blood sampling technique which may give rise to false high levels due to platelet release during or after blood sampling. Urinary BTG levels provide a means for following the effects of therapy.In 4 patients,in whom ischemic attacks occured during the course of treatment, urinary and plasma BTG were not higher than in subjects in whom no further events occured. Therefore our data suggest that measurements of urinary and plasma BTG values have no prognostic value in TIA patients.
SOLCO-TRANS AUTOTRANSFUSION AND PLATELET FUNCTION DURING AORTIC SURGERY
Authors: Blbby S R , Crow M J , Puri S R , Penny A F , Rajah S M , Kester R C 
Published: August 2018

The potential for HIV transmission from bank blood has renewed interest in methods of operative autotransfusion. Widespread acceptance of such techniques will depend on the safety and function of the salvaged blood. In 11 patients undergoing elective aortic reconstruction, we have studied changes in platelet function during the use of Solco-trans* - a simple, disposable, non-mechanical autotransfusion device. All patients received 1 mg/kg heparin prior to aortic cross-clamping, after which 440 mis blood was salvaged into the Solco-trans device, which contained 60 mis ACD-A. Platelet count, aggregation to collagen and ADP, thrombin-stimulated total ATP, APTT and plasma heparin levels were measured:- 1) pre-operatively, 2) post-heparinisation, 3) in the operative pool, and 4) in the Solco-trans reservoir, whilst citrate, ionised calcium, plasma Hb and pH were recorded only in the Solco-trans device.CONCLUSION: There is a significant decrease in platelet numbers, aggregation and ATP content (p<0.05, Wilcoxon signed rank test)in the acidotic, hypocalcaemicand highly hoemolysed environment of the Solco-trans reservoir. In large volume autotransfusion, additional fresh platelet concentrates will be required.*Cabot Ltd
RELATIONSHIPS BETWEEN HAEMOSTATIC ENDOTHELIAL FUNCTIONS AND GLOMERULAR FILTRATION RATE IN SHORT-TERM TYPE I DIABETES MELLITUS
Authors: Montani N , Solerte S B , Gamba G , Fioravanti M , Ferrari E 
Published: August 2018

It is known that the increase of glomerular filtration rate (GFR) represents an early sign of diabetic nephropathy. The changes of endothelial functions observed in diabetes might play a role in this respect. As F VIII vWF and fibronectin are synthetized by endothelial cells, we evaluated these components in 33 diabetic patients with short-term Type I (insulin dependent) diabetes mellitus, without retinopathy and macro-vascular complications. 15 pts. (mean age 29 ± 7 yrs; mean diabetes duration 2.9 ± 0.9 yrs) presented high GFR (154 ± 19 ml/min per 1.73 m2 ; albuminuria 7.2 ± 3.2 μg/min) and 18 pts. (mean age 30 ± 6 yrs; mean diabetes duration 3.0 ± 1 yrs) normal GFR (105 ± 11 ml/min per 1.73 m2 ; albuminuria 5 ± 2.8 μg/min).The following results were obtained:In conclusion the significant increase of FVIIIR:Ag and fibronectin levels in short-time type I diabetic patients with high GFR suggests an early endothelial cell function damage also related to the Door metabolic control.
ACCELERATED IN VITRO HAEMOSTASIS AND DECREASED SPONATEOUS THROMBOLYSIS IN DIABETICS
Authors: Rademaker M , Thomas D J , Kirby J D , Kovaos I B 
Published: August 2018

Diabetics have an increased risk of developing coronary, cerebral, and peripheral vascular occlusions. The mechanism of the accelerated haemostatic/thrombotic system is not known and studies on 'hyperactive platelets' and the fibrinolytic system in diabetes are inconclusive. We have used the Haemostatometer to assess haemostasis and thrombolysis in diabetic patients. The Haemostatometer, a new instrument, allows quantitative measurement of haemostasis by monitoring the pattern of haemostatic plug formation (HPF) in holes punched through polyethylene tubing through which non-anticoagulated blood flows under standard conditions (1,2). The pattern and speed of blood coagulation subsequent to HPF was also measured as was the spontaneous thrombolysis time (STT) (taken as the time until expulsion of the haemostatic plug from heparinised blood). Blood was sampled from 20 diabetic patients (10 insulin (IDD) and 10 non-insulin dependant (NIDD)) as well as 20 age mathched controls. All values are for mean ± SEM. Both IDD and NIDD had shorter bleeding times (HPF) than did controls: 2.16 ± 0.44 min vs 3.08 ± 1.14 min (p=0.03) (the initial phase of HPF was even more significantly shorter: 0.53 ± 0.06 min vs 1.03 ± 0.14 min (p<0.0l). The STT in NIDD was significantly longer than in controls: 56.8 ± 3.1 min vs 36.9 ± 4.0 min (p=0.002) while in IDD, the STT was shorter at 22.0 ± 0.5 min (p=0.018 when compared vs controls 36.9 ± 4.0 min).The shortened bleeding time (HPF) in diabetics is most probably a manifestation of hyperactive platelets and could contribute to the increased risk of thrombosis seen. In NIDD the prolonged thrombolysis (STT) may be a contributing factor to the development of diabetic angiopathy, which is thought to be prevented by good diabetic control (ie insulin). This suggests that the diabetic vascular endothelium retains some capacity to generate plasminogen activator in response to insulin.(1). Gorog P and Kovacs IB. Haemostasis 16: 337-345, 1986.(2). Gorog P. Angiology 37: 99-105, 1986.
HAEMOSTATIC PARAMETERS, ENDONEURIAL OXYGEN TENSION AND SURAL NERVE HISTOLOGY IN DIABETES MELLITUS
Authors: Ford I , Newrick P G , Malik R , Preston F E , Ward J D , Greaves M 
Published: August 2018

We have examined coagulation parameters in 15 neuropathic (Group A) and 10 complication-free diabetic patients (Group B). Venesection and sample testing were performed under standard conditions. Group A underwent sural nerve biopsy and 14 also had measurements of endoneurial oxygen tension. Factor VIII related antigen was higher in Group A (l-617u/ml ± 0.67) compared to Group B (0.944u/ml ± 0.26); (mean ± SD; p<.0.05) perhaps suggesting endothelial cell damage, although this did not correlate with capillary basement membrane thickness or endothelial cell number nor with endoneurial oxygen levels. Platelets from Group A were more sensitive to arachidonate than those of Group B, showing aggregation thresholds in platelet rich plasma of 0.36 ± 0.17mM and 0.57 ± 0.9mM respectively compared with 0.65 ± 0.37mM in non-diabetic controls.Platelets from Group A subjects also produced more thromboxane B2 in response to arachidonate than Group B or normal controls (37.95 ± 27.5; 25.5 ± 13.0; 16.55 ± 15-5pmol/107 platelets). Blood fibrinolytic capacity measured by euglobulin clot lysis time, was diminished in NIDDs (post-occlusion ECLT 165.7 mins ± 116.0), compared to IDDs (55.5 ± 34.5) (p<0.05) due at least in part to excess of tissue plasminogen-activator inhibitor, although we found no significant difference in ECLT between Group A and Group B. Interaction between haemostatic and microvascular abnormalities in diabetes may contribute to the pathogenesis of diabetic neuropathy.
DIABETES MELLITUS: HYPERCOAGULABILITY AID HYPOFIBRIHOLYSIS
Authors: Alava I , Garcia Frade L J , de la Calle H , Havarro J L , Creighton L J , Gaffney P J 
Published: August 2018

A hypercoagulable state has been related to the presence of microvascular and macrovascular disease in Diabetes Mellitus. The aim of this study was to establish when this hypercoagulable state appears and the response of the fibrinolytic system.43 patients (29 males, 14 females, aged 19-73), 28 insulin-dependent (10 of them with micro and/or macrovascular disease), 15 non insulin- dependent (all of them with vascular disease) were studied.Platelet aggregation and adenine nucleotides, plasma and serum thromboxane B2 (TxB2), Factor VIII Coagulant (VIII-C), Factor VIII Related antigen (VIII-RAg), Factor VIII Ristocetin Cofactor (VIII-RCoF), Fibronectin, Tissue Plasminogen Activator (t-PA) and X-Oligomers fibrin fragments were measured.In the diabetic patients maximal aggregation was induced by a threshold concentration of adenosin diphosphate and arachidonic acid lower than in controls (p<0.01 and p<0.05). Diabetic patients also presented elevated platelet ADP and decreased platelet c-AMP. They had higher plasma TxB* levels than the control group.FVIII-C, FVIII-RAg and Fibronectin were increased (p<0.001) both in patients type I and II, with and without vasculopathy. FVIII-RCoF was highly increased in vasculopathy (p<0.001) while was non significant without it.The patients with vasculopathy presented decreased t-PA plasma levels (p<0.05). lo difference in X-Oligomers was found related to controls.These findings suggest: 1) A hypercoagulable state previously to the development of clinical vasculopathy. 2) A decreased fibrinolytic response associated to vasculopathy.
IDENTIFICATION OF A FIBRINOLYTIC DEFECT IN TWO FAMILIES WITH A TENDENCY TO THROMBOSIS
Authors: Ostermann H , Koenig S , Pollmann H , Schmitz-Huebner U 
Published: August 2018

We identified two families in whom one member each suffered from deep venous thrombosis and subsequent pulmonary emboli at the age of 15 and 17. We were able to investigate several members of both families with regard to their fibrinolytic system. Blood sampling was done before and after ten minutes of venous occlusion. Parameters measured were euglobulin clot lysis time (ECLT), tissue-type plasminogen activator (t-PA) activity, t-PA concentration and plasminogen activator inhibitor (PAI) activity, besides several other constituents of the coagulation and fibrinolytic system commonly associated with thrombophilia.In the first family six persons could be evaluated. A prolonged ECLT was found in four probands. Three of them had no measurable t-PA activity after stasis, t-PA concentration after stasis was below the normal range in two and borderline in one of them.In the second family 13 members could be invest-gated. Three adults were found to have a prolonged ECLT. Two of these had very low t-PA activity after stasis, with normal increase in t-PA antigen. Their PAI was increased above the normal range. Six children showed no measurable PAI and increased levels of t-PA activity before stasis. After stasis four children had a prolonged ECLT. Two of them had low t-PA antigen levels, while all of them showed normal t-PA activity increases.These findings suggest, that there may be hereditary defects related to activators and inhibitors of the fibrinolytic system in the investigated families. These could possibly be responsible for the occurence of venous thrombosis early in life. However, results in the second family show that not all of the prolonged ECLT values can be explained by changes of t-PA and PAI.
CLINICAL RELEVANCE OF D.DIMER AND COAGULATION INHIBITORS IN LIVER CIRRHOSIS
Authors: Aurousseau M H , Eclache V , Amiral J 
Published: August 2018

D.Dimer was measured by a latex agglutination assay and an enzyme immunoassay (E.I.A.) in 25 patients suffering from liver cirrhosis. High levels of D.Dimer (> 500 ng/ml) were found in 13/25 patients’ plasma, by the latex test as well as EIA. Fibrinogen Degradation Products (FDP), measured by the Merskey method, were present in 7/25 samples, whereas soluble fibrin monomer complexes were only detected in 2/25 patients. In both cases, D.Dimer was elevated and FDP were in the normal range. Only one patient developped a Disseminated Intravascular Coagulation (DIC). None of the others had any thromboembolic event.Anticoagulant plasma proteins, Protein C (pC), total and free Protein S (pS) and Antithrombin III (AT III), were measured, in these patients, using the Laurell method.Mean values measured were :AT III : 50 % ± 16 total pS : 69 % ± 20pC : 38 % ± 28 free pS : 63 % ± 30Using immunoassays, pS showed the lowest decrease, in comparison to the other coagulation inhibitors.These values were compared to some procoagulant activities : prothrombin, factors VII ± X and factor V.4 good correlation was observed between AT III and prothrombin (r = 0.752 p < 0.01), whereas a poorer one was obtained between pC and factors VII and X (r = 0.455 p < 0.02). There was no correlation between pC and pS, nor between pC and factor V. Despite marked decrease of coagulation inhibitors in liver cirrhosis, low incidence of thrombotic accidents was observed (1/25) probably due to a parallel decreased synthesis of procoagulant factors. However, an in vivo blood activation associated to a reactive fibrinolysis was evidenced by measurement of pathological levels of D.Dimer in 13/25 patients. In this way, D.Dimer is a more sensitive and specific marker, than total FDP, to evaluate blood activation in liver cirrhosis. D.Di Test allows a rapid estimation and gives similar results to the EIA method.
DEFIBROTIDE VS. HEPARIN IN ACUTE THROMBOFLEBITIS THERAPY
Authors: Palmieri G , Palmieri R , Ambrosi G , Ferraro R , Bucci L , Agarthi A M 
Published: August 2018

Defobrotide(D) a natural polydeoxyribonucleotide of mammalian lung origin is a new substance with no anticoagulant or hemodinamic effects?it has shown considerable profibrinolytic and antithrombotic activities. The ability of (D) to increase generation of prostaci-clmCPGI2) from vascular tissue has been demonstrated; this substance also promotes substantial release from vascular tissues of a plasminogen activator factor which plays an important role in preventing thrombotic oclusion of vascular segments.Widely accepted therapies in deep venous thrombosis and Acute Thromboflebitis (A.f.; are based on anticoagulant treatments (heparin and/or oral anticoagulant agentsWe have evaluated the efficacy of (D> in (A.T.) vs. heparin in 40 pts.(28 females 12 males;mean age=50) with an open randomized study.Group A:20 pts.have been administered CD; 200mg.four times a day l.m. for 10 days.Group B:20 pts.have been administered Sodic Heparin 30000 U.I. intravenously with successive dosage based upon APTT values.Both groups have been treated with an oral anti coagulant agentCacenocoumaro1) after the tenth day.No clinical differences between the treatments have been observed and in no pts. treated with CD; we noted significant changes m laboratory parameters evaluated: complete blood count,glycemia BUN creatinine ALT AST LDH.Clinical eficacy was excellent in both groups also supported by augmented fibrinolysis and instrumental improvement(strain-gauge plethismography;.The absolute safety of (D> therapy shows its possible alternative role when compared to heparin treatment in (A.T.> of any origin.