bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of Liquid Crystal Contact Thermography and Plasma Level of D-Dimer for Screening of Deep Venous Thrombosis Following General Abdominal Surgery
Authors: Bounameaux H , Khabiri E , Huber O , Schneider P-A , Didier D , Moerloose P de , Reber G 
Published: July 2018

SummaryBecause the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 pg/1, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 pg/1 for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%.Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 pg/1) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography. This sequential approach might be useful in studies of the efficacy of antithrombotic regimens for prophylaxis of DVT in patients at risk.
Release of Thromboxane A2 and β-Thromboglobulin during In-Vivo Plug Formation following Standardized Skin Incisions: Effect of a Moderate Fish Intake
Authors: Houwelingen Adriana C v , Thorngren Margareta , Hornstra Gerard , Born Gustav V R 
Published: July 2018

SummaryThis paper describes a controlled study of the effects of a fish supplement on haemostasis. This was evaluated by measuring bleeding times from skin incisions, the volume of the emerging blood, the number of platelets taking part in the formation of the haemostatic plug (platelet retention), and the release of thromboxane B2 and β-thromboglobulin in volunteers, before and after consuming a daily supplement of 100 g of fish (n = 20) or meat (n = 20) paste for 6 weeks. The fish supplement decreased the amount of thromboxane B2 released per platelet incorporated into the plug. Despite this, the skin bleeding times were hardly changed. There was also no difference in platelet retention, which was consistent with there being no difference in the release of β-thromboglobulin.These results suggest that in the effect of marine diets on haemostasis, a reduced vascular reactivity plays a more important role than decreased plug formation.
Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment
Authors: Nurmohamed Michael T , Berckmans René J , Morriën-Salomons Willy M , Berends Fenny , Hommes Daan W , Rijnierse Joep J M M , Sturk Augueste 
Published: July 2018

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.
Expression of Platelet Membrane Glycoprotein V in Human Megakaryocytes and Megakaryocytic Cell Lines: A Study Using a Novel Monoclonal Antibody against GPV
Authors: Takafuta Toshiro , Fujirmura Kingo , Kawano Hironori , Noda Masaaki , Fujimoto Tetsuro , Oda Kenji , Shimomura Takeshi , Kuramoto Atsushi 
Published: July 2018

SummaryGlycoprotein V (GPV) is a platelet membrane protein with a molecular weight of 82 kD, and one of the leucine rich glycoproteins (LRG). By reverse transcription-polymerase chain reaction (RT-PCR), GPV cDNA was amplified from mRNA of platelets and megakaryocytic cell lines. However, since there are few reports indicating whether GPV protein is expressed in megakaryocytes as a lineage and maturation specific protein, we studied the GPV expression at the protein level by using a novel monoclonal antibody (1D9) recognizing GPV. Flow cytometric and immunohistochemical analysis indicated that GPV was detected on the surface and in the cytoplasm of only the megakaryocytes in bone marrow aspirates. In a megakaryocytic cell line UT-7, GPV antigen increased after treatment with phorbol-12-myri-state-13-acetate (PMA). These data indicate that only megakaryocytes specifically express the GPV protein among hematopoietic cells and that the expression of GPV increases with differentiation of the megakaryocyte as GPIb-IX complex.
A Single Base Pair Deletion in the Promoter Region of the Factor IX Gene Is Associated with Haemophilia B
Authors: Hall Adrian J , Chuansumrit Ampaiwan , Peake Ian R , Winship Peter R 
Published: July 2018

SummaryPatients with the haemophilia B Leyden phenotype show a distinct pattern of factor IX expression characterized by a post-pubertal increase in FIX levels and the remission of clinical symptoms in adult life. This phenotype has previously been linked to single base mutations within transcription factor binding sites in a region of ∼40 bp around the major start point of transcription of the FIX gene. Here we report a novel mutation in this region within the transcription factor C/EBP binding site at +1 to +18. The mutation is a single base pair deletion from a triplet of thymine residues at +6 to +8. We show that the extent to which this mutation disrupts the binding of C/EBP to its binding site is less marked than the disruption caused by the +13 A→G mutation of FIX Norwich (1). This correlates with age-matched phenotypic data we have available for the patient reported here and that of FIX Norwich.
Recombinant Versus High-sensitivity Conventional Thromboplastin: A Randomized Clinical Study in Patients on Oral Anticoagulation
Authors: Finazzi Guido , Falanga Anna , Galli Monica , Cortelazzo Sergio , Remuzzi Andrea , Barbui Tiziano 
Published: July 2018

SummaryA prospective, randomized, double-blind clinical trial was carried out in a single center to compare the clinical and laboratory quality of oral anticoagulant therapy monitored with recombinant tissue factor (RTF) or with a sensitive, human-derived, conventional thromboplastin (CT) in the PT test. Seven hundred and fifty-seven consecutive patients receiving oral anticoagulation for various indications were randomized to RTF (n = 379) or CT (n = 368) for 6 months. Total follow-up was 167 and 153 patient-years for RTF and TP groups respectively. Fifty-six bleeding events were observed: 31 in the RTF group and 25 in the TP group. The incidence of bleeding was 18.5 and 16.5% pt-yrs for RTF and TP patients respectively (n.s.). The event-free follow-up curves were not significantly different between the two groups. The laboratory quality of oral anticoagulation was evaluated with the “last check in file” method: therapeutic INR was found in the same propor-tipn of RTF and TP patients (70.2% vs 68.8%). Our study shows that RTF is as effective as a sensitive, conventional thromboplastin for monitoring oral anticoagulation.
Recombinant Variants of Tissue-type Plasminogen Activator Containing Amino Acid Substitutions in the Fibronectin Finger-like Domain and the Kringle 1 Domain
Authors: Yahara Hitoshi , Matsumoto Keiji , Maruyama Hiroyuki , Nagaoka Tetsuya , Ikenaka Yasuhiro , Yajima Kazuyoshi , Fukao Hideharu , Ueshima Shigeru , Matsuo Osamu 
Published: July 2018

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetic-ally, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-like domain (finger domain) or at the kringle 1 domain (K1 domain). The finger modified variant, t-PA N37S.S38V.G39V.R40E. A41F.Q42S had about a 6.0-fold higher plasma half-life in vivo than wild-type t-PA. Two variants with modifications in the K1 domain, t-PA G161R.K162R.S165W and t-PA N115P, showed an improved kinetic parameters and a 2.2-fold higher plasma half-life in vivo than wild-type t-PA, respectively. To create a recombinant variant of t-PA with a higher enzymatic activity and a further prolonged half-life in vivo, the genes containing each modifications were joined and expressed in animal cells. The two variants, t-PA N37S.S38V G39V.R40E.A41F.Q42S.G161R.K162R.S165W and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N 115P, were purified from conditioned media and their biochemical, pharmacokinetic and thrombolytic profiles were investigated. Although the variant t-PA N37S.S38V.G39V.R40E.A41F.Q42S.G161R.K162R.S165W demonstrated an impaired enzymatic activity compared to the wild:type t-PA, the half-life of the variant, t-PA N37S.S38V.G39V.R40E.A41F.Q42S. N115P, following intravenous bolus injection in rabbits was considerably longer than that of finger-domain modified variants. Human plasma clot lysis assay estimated the fibrinolytic activity of both variants to be about 2.0-fold less effective than that of the wild-type t-PA. In the rabbit jugular vein clot lysis model, doses of 1.0 and 0.0625 mg/kg were required for about 70% lysis in the wild-type t-PA and t-PA N37S.S38V.G39V.R40E.A41F.Q42S.N115P, respectively. These findings suggested that the variant in this study can be used at a lower dosage in a single bolus injection.
Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta
Authors: Gjesdal Knut , Pepper Duncan S. 
Published: July 2018

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.
Effects of t-AMCHA and EACA on the Plasma Kallikrein System
Authors: Nakahara Masao 
Published: July 2018

SummaryVaried amounts of t-AMCHA or EACA added to non-contact fresh dog plasma generates kininogenase and TAME esterase activities. These phenomena may be abolished by prior addition of lima bean trypsin inhibitor. t-AMCHA or EACA had no effect on partially purified kallikrein, but had a significant inhibitory influence on plasma kininase. The generation of prekallikrein activator with t-AMCHA was ascertained by gel filtration on a Sephadex G-100 column. The blood kinin level increased about 50% one hr after administration of t-AMCHA. It is suggested from these results that t-AMCHA may initiate the true activation of the kallikrein system by activating the Hageman factor.
Heparin Therapy during Cardiopulmonary Bypass in Children Requires Ongoing Quality Control
Authors: Andrew Maureen , MacIntyre Brian , MacMillan James , Williams William G , Gruenwald Colleen , Johnston Marilyn , Burrows Fred , Wang Elaine , Adams Margaret 
Published: July 2018

SummaryHeparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 ± 40 vs HT: 418 ± 26, Mean ± SEM, p <0.01). 94% of all HC ACT values were above 450 s compared to only 27% of HT ACT values. If HT ACT values had been used for patient monitoring, all patients would have received more heparin to achieve ACT values above 450 s. The two machines reported similar ACT values when heparin was added in vitro to whole blood (0.1-5.0 units/ml), (HC: Y = 98X + 104, r2 = 0.93 HT: Y = 82X + 109, r2 = 0.94). Heparin concentrations in our patients following a bolus of 300 U/kg of heparin, but prior to CPB were 3.2 ± 0.07 units/ml. Following the initiation of CPB, heparin concentrations decreased to 1.3 ± 0.05, reflecting, in part, hemodilution by the pump prime (1 U of heparin/ml). In contrast to the in vitro results, there was no relationship between ACT values measured by either machine and plasma heparin concentrations in ex vivo samples. Finally, plasma concentrations of 8 coagulation proteins measured prior to CPB and following CPB were decreased by 27-55%, predominantly reflecting the final dilution by CPB. In conclusion: 1) HT and HC machines cannot be used interchangeably in pediatric patients without risk of altering clinical practice in an uncontrolled fashion; and 2) ACT values from children on CPB correlate poorly with heparin concentrations, likely due to hemodilution. Optimal use of anticoagulant therapy during CPB in children requires further study in clinical trials and ongoing quality control.
Effect of Isotretinoin on Endogenous Tissue-Type Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor 1 (PAI-1) in Humans
Authors: Wallnöfer A E , van Griensven J M T , Schoemaker H C , Cohen A F , Lambert W , Kluft C , Meijer P , Kooistra T 
Published: July 2018

SummaryThe effect of isotretinoin on fibrinolysis was investigated in 10 healthy, male volunteers in a randomized, double-blind, crossover-designed study. Isotretinoin (40 mg) was administered in the morning and in the evening for 5 days. t-PA, u-PA and PAI-1 antigen and activity in plasma were measured every morning at 9 a.m. on days 1 to 4 and every 3 hours over 24 hours on day 5. Isotretinoin treatment had no significant stimulatory effect on endogenous t-PA antigen and activity in morning plasma samples nor on their circadian variation. Also, u-PA antigen levels did not change after isotretinoin treatment. Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment. After treatment with isotretinoin a significant rise of fasting triglyceride plasma levels was observed as compared to placebo. The study shows that isotretinoin has no clinically significant effect on endogenous fibrinolysis.
Demonstration of Rickettsia Conorii-Induced Coagulative and Platelet Activation in vivo in Patients with Mediterranean Spotted Fever
Authors: Davì Giovanni , Giammarresi Carlo , Vigneri Sergio , Ganci Antonina , Ferri Claudio , Di Francesco Letizia , Vitale Giustina , Mansueto Serafino 
Published: July 2018

SummaryEndothelial injury in vivo induced by Rickettsia Conorii, the etiologic agent of Mediterranean Spotted Fever (MSF) has been recently demonstrated. We sought to determine whether platelet and/or coagulative activation in vivo can be demonstrated in the acute phase of MSF, through measurements of a major metabolite of thromboxane (TX) in the urine (1 1-dehydro-TXB2) and of plasma prothrombin fragment 1+2, whose levels reflect activation of prothrombin to thrombin. Moreover, we measured plasma endothelin-1 as marker of endothelial dysfunction. Our results provide biochemical evidence for the occurrence of TXA2-dependent platelet activation and thrombin generation in vivo, together with endothelial dysfunction. These phenomena could account for clinical manifestations of MSF, such as vasculitis and focal microthrombus formation. These results could also provide a rationale for testing the efficacy of aspirin or heparin in reducing the prothrombotic status of Rickettsiae diseases.
Primary Prevention of Coronary Arterial Thrombosis with the Factor Xa Inhibitor rTAP in a Canine Electrolytic Injury Model
Authors: Lynch Joseph J , Sitko Gary R , Lehman E Dale , Vlasuk George P 
Published: July 2018

SummaryThe antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 μg/kg/min continuous infusion) or heparin (200 U/kg bolus followed by 2 U/kg/min continuous infusion) were started 60 min prior to the initiation of LCX coronary artery electrolytic injury (150 μA continuous anodal current). All 6/6 saline-treated control animals developed occlusive thrombi at 49.8 ± 13.6 min after the initiation of vessel injury, and possessed a residual thrombus mass of 20.7 ± 3.3 mg. In the rTAP treatment group, 4/6 preparations developed occlusive thrombi, but with times to thrombosis delayed significantly compared to both the saline control as well as to the heparin treatment group (202.7 ± 28.9 min; p <0.01 to both saline and heparin groups). The remaining 2 rTAP-treated preparations remained patent despite the continued electrical stimulation of the coronary vessel for 5 h. Residual thrombus mass in the rTAP treatment group was reduced markedly compared to the saline control group (4.4 ± 1.0 mg; p <0.01). Heparin infusion resulted in a modest but statistically insignificant delay in occlusive LCX coronary artery thrombosis compared to saline controls, with all 6/6 heparin-treated preparations occluding at 79.7 ± 16.5 min after the initiation of vessel injury. Residual thrombus mass in heparin-treated animals, however, was reduced compared to saline controls (9.4 ± 1.4 mg; p <0.01). These results support a pivotal role for fXa in the process of arterial thrombosis, as well as the feasibility of inhibiting fXa as an effective strategy for the primary prevention of arterial thrombosis.
Acquired Haemophilia: Functional Study of Antibodies to Factor VIII
Authors: Allain J P , Gaillandre A , Frommel D 
Published: July 2018

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.
Acute and Chronic Changes in Platelet Volume and Count After Cardiopulmonary Bypass Induced Thrombocytopenia in Man
Authors: Martin J F , Daniel T D , Trowbridge E A 
Published: July 2018

SummaryPatients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.