bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association of Platelet and Red Cell Count with Platelet Impedance Changes in Whole Blood and Light-Scattering Changes in Platelet Rich Plasma: Evidence from the Caerphilly Collaborative Heart Disease Study
Authors: Sharp Dan S , Beswick Andrew D , O'Brien John R , Renaud Serge , Yarnell John W G , Elwood Peter C 
Published: July 2018

SummaryThis epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet “function” as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet “sensitivity” as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.
Effect of Peptides on the Inactivation of Tissue Plasminogen Activator by Plasminogen Activator Inhibitor-1 and on the Binding of Tissue Plasminogen Activator to Endothelial Cells
Authors: Wittwer A J , Sanzo M A 
Published: July 2018

SummaryThe effectiveness of tissue plasminogen activator (tPA) in thrombolytic therapy is dependent upon the rate at which therapeutically administered tPA reaches the clot site and the proportion of that tPA which is enzymatically active. Interactions between tPA and its main plasma inhibitor (PAI-1) and between tPA and the endothelial cells lining blood vessels are two factors which may limit efficacy. In an attempt to identify the regions of the tPA molecule involved in these interactions, we have examined a series of synthetic peptides with amino acid sequences corresponding to different regions of the tPA molecule for their ability to protect tPA from inactivation by PAI-1 and for their ability to reduce the binding of tPA to endothelial cells. Three peptides were identified which were especially effective at maintaining tPA activity in the presence of PAI-1 and three others were found which had a lesser effect. These same peptides were also found to inhibit the binding of tPA to endothelial cells. This suggests that the same regions of the tPA molecule are involved in both processes. None of the peptides inhibited the binding of tPA to fibrin. These peptides may serve as models for the development of agents for enhancing the activity of both endogenous tPA and of tPA administered in thrombolytic therapy.
Low Incidence of Antibodies to Recombinant Human Tissue-Type Plasminogen Activator in Treated Patients
Authors: Reed B R , Chen A B , Tanswell P , Prince W S , Wert R M , Glaesle-Schwarz L , Grossbard E B 
Published: July 2018

SummarySera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was a predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients’ serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.
Venostasis but not DDAVP Infusion Provokes the Plasma Fibronectin Increase
Authors: Letowska M , Bykowska K , Sablinski J , Lopaciuk S , Kopeć M 
Published: July 2018

SummaryPlasma fibronectin (pFN), von Willebrand factor antigen (vWf: Ag), factor VIII procoagulant activity, fibrinogen, euglobulin lysis time (ELT) and hematocrit were determined in healthy blood donors before and after venostasis as well as after intravenous infusion of l-deamino-8-D-arginine vasopressin (DDAVP). Both venostasis and DDAVP provoked an increase in vWf : Ag and shortening in the ELT. In contrast, venostasis only but not DDAVP induced an increase in pFN levels which was statistically significant with and without correction for a concomitant hematocrit increment. The results indicate that there is a distinct difference in the patterns of venostasis and DDAVP mediated release of proteins from the vessel wall.
Von Willebrand Factor Antigen Is Less Sensitive than Ristocetin Cofactor for the Diagnosis of Type I von Willebrand Disease -Results Based on an Epidemiological Investigation
Authors: Rodeghiero Francesco , Castaman Giancarlo , Tosetto Alberto 
Published: July 2018

SummaryRecently, in an epidemiological investigation involving 1,218 children aged 11-14, we demonstrated that the prevalence of von Willebrand’s disease, based on a low ristocetin cofactor activity (RiCof) in children with a personal and/or family history of hemorrhage, was at least 1% (Blood 1987; 69: 454). All the diagnosed cases had multimeric patterns typical of type I von Willebrand’s disease (vWd). Since standardization of RiCof is difficult and the test is not easily performed in a clinical laboratory, we measured von Willebrand factor antigen (vWf: Ag) in all available unthawed plasma samples of previously investigated children by ELISA, to assess the relative sensitivity of this more simple test for diagnosing vWd.Separate normal ranges were calculated by non-parametric methods for 0 and non-0 subjects, and for children and adults, since values were higher in non-0 subjects and in children.Taking into account the 90% confidence interval around the lower limit of the normal range, 7 (50%) of the 14 cases diagnosed by RiCof were detected by vWf: Ag. Furthermore, two new cases would have been diagnosed by vWf: Ag, leading to a relative Ag/ RiCof global sensitivity of 64%. A similar figure was obtained when the two tests were compared in the group of relatives of the affected children.In conclusion, measurement of vWf: Ag seems to be definitely less sensitive than the RiCof assay for detecting patients with vWd, even in type I patients, and RiCof remains the test of choice for screening for vWd in hemorrhagic patients.
Effect of Soluble and Immobilized Plasmin on Fibrinogen and Platelets
Authors: Senatore F , Shankar H , Ho C H , Avantsa S , Allon M , Posteraro R 
Published: July 2018

SummaryPlasmin was immobilized on collageno-elastic tubes (CET) using carbodiimide as the cross-linking agent. The effects of plasmin-CET grafts and corresponding soluble plasmin on fibrinogen, thrombin-mediated fibrinogen activation, and platelet activity, were investigatedThere was a significant increase in fibrinogen deposition on plasmin-CETs over non-plasmin (i.e. control) CETs. Furthermore, exposure of fibrinogen to plasmin CETs enhances its deposition to control grafts situated downstream. Plasmin-bound CETs retained higher platelet deposition when preliminarily coated with fibrinogen. Finally, plasmin exerted a positive effect on thrombin-mediated fibrinogen activation at low plasmin concentrations. A mechanistic hypothesis aimed at interpreting this
finding is proposed.
A Comparison of General Anesthesia and Regional Anesthesia as a Risk Factor for Deep Vein Thrombosis Following Hip Surgery: A Critical Review
Authors: Prins Martin H , Hirsh Jack 
Published: July 2018

SummaryWe evaluated the evidence in support of the suggestion that the risk of deep vein thrombosis after hip surgery is lower with regional than with general anesthesia. A literature search was performed to retrieve all articles which reported on the incidence of postoperative thrombosis in both fractured and elective hip surgery. Articles were included if the method of anesthesia used was reported and if they used mandatory venography. Based upon the quality of study design the level of evidence provided by a study was graded.In patients who did not receive prophylaxis there were high level studies in elective and fractured hip surgery. All studies showed a statistically significantly lower incidence of postoperative deep vein thrombosis with regional anesthesia (relative risk reductions of 46-55%). There were no direct comparative studies in patients who received prophylaxis. However, between study comparisons did not show even a trend towards to lower incidence of postoperative thrombosis with regional anesthesia.
Two Daily Subcutaneous Injections of Fragmin as Compared with Intravenous Standard Heparin in the Treatment of Deep Venous Thrombosis (DVT)
Authors: Bratt Göran , Åberg Wiveca , Johansson Margareta , Törnebohm Eva , Granqvist Staffan , Lockner Dieter 
Published: July 2018

SummaryIn a prospective, randomized, open study 119 consecutive patients with phlebographically verified deep venous thrombosis (DVT) of the leg (36% distal and 64% proximal) were treated either with a low molecular weight heparin (Fragmin, Kabi-Vitrum) subcutaneously (120 anti-FXa U/kg) twice daily or standard heparin (SH) as continuous intravenous infusion (480 IU kg−1 day−1). The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2-0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection. The SH dose was modified to prolong the APTT 2-3 times.Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 ± 12.1 to 15.7 ± 12.7 in the Fragmin group and from 16.9 ± 12.0 to 14.4 ± 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings.After 22 ± 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups.We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.
ARIC Hemostasis Study -II. Organizational Plan and Feasibility Study
Authors: Wu K K , Papp A C , Patsch W , Rock R , Eckfeldt J , Sharrett R 
Published: July 2018

SummaryIn our previous paper, we reported the development of a blood collection and processing system (BCPS) suitable for the ARIC multicenter hemostasis study. As an additional step of preparation for the ARIC study, we incorporated this BCPS into an organizational plan to increase efficiency and minimize errors. We initially designed organizational trays for blood collection tubes and aliquot tubes and developed a coordinated step-by-step plan for the orderly processing of blood samples. Once the plan was considered workable, we carried out a pilot study to test the feasibility of this integrated organizational plan. Included in the pilot study were 95 healthy subjects randomly selected from 4 ARIC field centers, whose age and gender were comparable to those projected for the ARIC population. We determined the time lapse of filling the first tube as an index of blood flow. The overall mean time-lapse was 23 s (S.D. = 5). There was no significant difference among the field centers. We also determined the entire time lapse required for completing the sample processing. The total processing time was always less than 60 min. By performing the processing of samples in pairs, all the samples from two subjects could be completely processed in 70 min. This greatly increased the efficiency of field center operation. We evaluated the potential in vitro hemostasis activation by measuring plasma Β-thromboglobulin and platelet factor 4 levels. The geometric means of both proteins were comparable to our previously reported results. Fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C and activated partial thromboplastin time were analyzed. All the hemostatic measurements exhibited no shift of the values. We conclude that the organizational plan together with the BCPS facilitate the incorporation of hemostasis measurements into the ARIC study. It should be valuable as a general guide for other multicenter studies measuring hemostatic factors.
Prevention of Reocclusion by MCI-9038, a Thrombin Inhibitor, Following t-PA-lnduced Thrombolysis in a Canine Model of Femoral Arterial Thrombosis
Authors: Mellott Michael J , Connolly Thomas M , York Sally J , Bush Larry R 
Published: July 2018

SummaryWe compared a selective thrombin inhibitor (MCI-9038; Argatroban), a thromboxane A2 (TXA2) receptor antagonist (L-670,596) and a serotonin-2 receptor antagonist (ketanserin) for their ability to hasten clot lysis and delay reocclusion in a canine model of femoral arterial thrombosis. Occlusive thrombosis was induced by insertion of a thrombogenic copper coil. Femoral arterial blood flow velocity (FABFV) was monitored directly and continuously by Doppler flowmetry. Thrombolysis was induced with tissue plasminogen activator (t-PA; 0.8 mg/kg, i.v.), starting 60 min after thrombotic occlusion and continued for 90 min. Ten minutes after occlusion, dogs received an intravenous infusion of either vehicle, MCI-9038 (10 Μ;g kg−1 min−1), ketanserin (0.1 mg/ kg bolus plus 5 pg kg−1 min−1), D670,596 (1 mg/kg bolus plus 17 pg kg−1 min−1) or a combination of D670,596 and ketanserin. All infusions were discontinued 1 h after stopping the t-PA, and were followed by a 30 min observation period. The times to thrombolysis were similar for all treatments (mean ± SEM = 47 ± 3; all groups). MCI-9038 prevented reocclusion, defined as permanent cessation of FABFV during the hour after stopping the t-PA. All dogs receiving MCI-9038 reoccluded within 30 min after stopping its infusion (71 ± 3 min). Reocclusion occurred in all other dogs, except one vehicle-treated dog and a second dog that received L-670,596 plus ketanserin. Vehicle-treated dogs reoccluded within 23 ± 8 min. Reocclusion was not delayed significantly by ketanserin, L-670,596 or the combination of the two. Thus, in this model, MCI-9038 prevented reocclusion, suggesting that thrombin may be an important mediator of arterial rethrombosis after t-PA-induced thrombolysis.
A Comparative Study of Three Methods for the Visualization of von Willebrand Factor (vWF) Multimers
Authors: Ledford M R , Kent J W , Civantos F 
Published: July 2018

SummaryThis study was performed to compare three visualization methods for the detection of vWF multimers: autoradiography (125I), electroblot with a horseradish peroxidase system (BLOT-HRP), and an avidin-biotin peroxidase system (AV-BIO). Each method was evaluated according to: 1) ability to visually detect bands and subbands thereby identifying von Willebrand’s disease (vWD) subtypes and normals, 2) reagent availability, 3) cost, and 4) time requirements. Additionally, resolvability was evaluated utilizing low, intermediate, and high resolution gels prepared with both low and high gelling temperature agaroses with subsequent visualization by the three detecting systems.With intermediate resolution gels, our results showed that all three visualization methods could discern pathologic patterns from normal. In addition, the avidin-biotin peroxidase system demonstrated the best band discreteness with low resolution gels used to detect unusually high molecular weight multimers. With high resolution gels used for subtyping type II vWD, we found the internal band structure was best demonstrated using LGT agarose and the electroblot horseradish peroxidase system.
Behçet Syndrome Associated with Protein S Deficiency
Authors: Chafa O , Fischer A M , Meriane F , Chellali T , Sternberg C , Otmani F , Benabadji M 
Published: July 2018

SummaryBeçget syndrome is a multisystem disorder characterized by ocular, mucocutaneous, articular, gastrointestinal and neurologic abnormalities. We report here an unusual case of Beçget syndrome, characterized by the importance of the thrombotic events(7 phlebitis of both legs and resection of two toes). Additional manifestations of the Beçget syndrome occurred only 10 years after the first thrombotic episode. The oldest daugther of the propositus and his brother suffered also from thrombophlebitis; this familial history of thrombosis led to the performance of a haemostatic study. A congenital protein S deficiency was found in the propositus and in three of his children. Normal protein S levels were found in nine unrelated patients with Beçget syndrome. Thus this observation suggests that, when thrombotic manifestations are the first and major symptom of Beçget syndrom, an additional cause of thrombosis has to be investigated.
Production and Therapeutic Use of a Factor XI Concentrate from Plasma
Authors: Bolton-Maggs P H B , Wensley R T , Kernoff P B A , Kasper C K , Winkelman L , Lane R S , Smith J K 
Published: July 2018

SummaryFactor XI deficiency is an uncommon bleeding disorder usually manifested by excessive bleeding after surgery or trauma. Until recently the only effective therapy has been fresh-frozen plasma (FFP) infusion. We describe the efficacy and safety of a new factor XI concentrate produced from human donor plasma by a modification of the method used for antithrombin III concentrate. The mean recovery of factor XI in the circulation measured on 62 occasions was approximately 91% of the injected dose, and the mean half-disappearance-time was 52 h. The concentrate was used for 31 invasive procedures in 30 patients, including 16 patients who had a definite bleeding tendency on previous occasions, with normal haemostasis being achieved in all but 1. Only 1 patient (previously experiencing allergy to FFP) experienced adverse effects during infusion. Monitoring of liver function tests and viral antibody status in suitable patients has shown no evidence of transmission of hepatitis viruses, HIV-1 or parvovirus B19.We conclude that this concentrate provides effective treatment for patients with factor XI deficiency. Preliminary results suggest safety from virus transmission, but this needs to be established in further studies of previously untreated patients.
Characterization of Three Alboaggregins Purified from Trimeresurus albolabris Venom
Authors: Peng Manling , Lu Weiqi , Kirby Edward P 
Published: July 2018

SummaryAlboaggregins (AL-A, AL-B, AL-C) isolated from Trimeresurus albolabris snake venom represent a new family of proteins which bind to platelet glycoprotein lb (GPIb). These alboaggregins were purified to homogeneity with ion exchange HPLC (Mono-Q column) and hydrophobic HPLC (TSK Phenyl-5PW column). On SDS-polyacrylamide gel electrophoresis, apparent molecular weights of AL-A, AL-B and AL-C were 52 kDa, 26 kDa, and 121 kDa respectively, under nonreducing conditions. Upon reduction, each alboaggregin showed two types of chains with apparent molecular weights in the range of 15-20 kDa. All three alboaggregins agglutinated formalin-fixed platelets. Agglutination activities and binding of labeled alboaggregins to GPIb were specifically inhibited by the monoclonal antibody AK2 which is directed against the 45 kDa N-terminal region on GPIb, but not by monoclonal antibodies against other epitopes on GPIb. 125I-alboaggregin binding to platelets was not altered by the presence of thrombin. Alboaggregins did not bind to GPIIb/IIIa. Alboaggregins were competitive inhibitors for 125I-bovine vWF binding to platelets. Mutual competition studies between AL-A, AL-B and AL-C for the binding of labeled bovine vWF and AL-B to platelets demonstrated that AL-B and AL-C had a significantly higher affinity than AL-A.
Low Molecular Weight Heparin Therapy: Is Monitoring Needed?
Authors: Boneu B 
Published: July 2018

SummaryRecent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces,the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH.Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several . meta-analyses indicate comparable risk while any overdose unaccept-ably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required. In the treatment of established DVT, considering the haemorrhagic risk of LMWH, the risk of undertreating the patient and the absence of large clinical trials comparing the advantages of monitoring the dose or not, it might be useful to check anti Xa activity at least once at the beginning of the treatment but the need for this initial check remains to be established. Because a large proportion of patients will be in the desired range, dose adjustments will be far less frequent than for UH.