bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrinolytic Response to Venous Occlusion and Fibrin Fragment D-Dimer Levels in Normal and Complicated Pregnancy
Authors: Ballegeer V , Mombaerts P , Declerck P J , Spitz B , Van Assche F A , Collen D 
Published: June 2018

SummaryThe fibrinolytic response to venous occlusion was assessed in 29 women with normal or complicated pregnancy, by measurements of total t-PA and free t-PA with specific ELISAs. The release of t-PA from the vessel wall was 11±9 ng/ml in nonpregnant women (mean ± SD, n = 6) but was markedly reduced throughout pregnancy. Following venous occlusion, free t-PA increased by 12 ± 11 ng/ml in non-pregnant women but remained below the detection limit of 2 ng/ml towards the end of pregnancy. A markedly reduced t-PA release with absence of free t-PA was also observed during late pregnancy in patients with insulin-dependent diabetes mellitus, intra-uterine growth ietaida-tion and pre-eclampsia.Plasma levels of fragment D-dimer of cross-linked fibrin were measured with a specific FITS A in 79 pregnant women. D-dimer levels were 129 ± 36 ng/ml (mean ± SD, n = 8) in non-pregnant women and increased to 400 ± 170 ng/ml (n = 25) and 440 ± 220 ng/ml (n – 22) during the second and third trimester of pregnancy respectively. Significantly higher levels than observed in uncomplicated third trimester pregnancies were found in 3 out of 6 diabetic and in 2 out of 7 pre-eclamptic women.It is concluded that the t-PA release after venous occlusion is significantly reduced during pregnancy. In addition, released t-PA is rapidly inhibited. The levels of fragment D-dimer increase during pregnancy, suggesting that, notwithstanding the marked impairment of the fibrinolytic response to venous occlusion, the fibrinolytic system remains functionally active.
Intranasal and Intravenous Administration of Desmopressin: Effect on F VIII/vWF, Pharmacokinetics and Reproducibility
Authors: Lethagen S , Harris A S , Sjörin E , Nilsson I M 
Published: June 2018

SummaryA comparison was made of intranasal administration of 300 μg desmopressin (DDAVP) by spray, with intravenous administration of 0.2, 0.3 and 0.4 μg DDAVP/kg in 10 healthy volunteers. The effect of DDAVP was measured on F VIII/vWF complex and on plasminogen activator release. In addition, plasma levels of DDAVP were determined using a specific and sensitive radioimmunoassay. Moreover, the reproducibility of the spray effect in 10 healthy volunteers was tested after administration of 300 μg DDAVP intranasally by spray on 5 different occasions.Plasma levels of DDAVP showed a clear dose-response with the maximum levels at 0.4 μg/kg i.v. The effect of the spray approximated the 0.2 μg/kg response. However, the maximum response in both F VIII/vWF complex and plasminogen activator release was obtained after 0.3 μg/kg i. v. The response to 0.4 μg/kg i. v. was not significantly different from the response to 0.3 μg/kg indicating that maximum stimulation was reached with 0.3 μg/kg. There was no correlation between plasma levels of F VIII/vWF and DDAVP indicating that the biological response to DDAVP is subjected to saturation kinetics.The reproducibility of the effect of the spray dose on VIII : C was 21% (c.v.) and 27% for the intra-individual and interindividual variation, respectively, and compared favorably with intravenous administration.Intranasal DDAVP (300 μg) is as effective as 0.2 μg/kg intravenously and provides an accurate, reproducible and convenient alternative to parenteral administration.
Plasma Prekallikrein Activity in Patients with Total Hip Arthroplasty
Authors: Hoffmann J J M L , Kortmann J H J P M 
Published: June 2018

SummaryThe behaviour of the contact system was studied in 40 patients with total hip arthroplasty, by measuring plasma prekallikrein, spontaneous kallikrein activity and factor XII. In the literature it had been shown that patients with complications from this operation had decreased prekallikrein and increased kallikrein activity (M. Nakahara. Acta orthop scand 1982; 53: 591-6). In the present study, comprising patients with and without pain and proven loosening of the hip prosthesis, these findings could only partially be confirmed. Patients with a loosened prosthesis had significantly lower prekallikrein (mean 0.78 ± 0.28 U/ml; p <0.01) than patients without problems, but no detectable kallikrein activity in plasma. Patients with pain but no loosening had normal prekallikrein (1.04 ±0 0.26 U/ml) and also no demonstrable kallikrein activity. Factor XII was normal in all patient groups. It is concluded that decreased prekallikrein is limited to patients with a loosened hip prosthesis, with or without pain.
F VIII Subunits: Purification and Antigenic Properties
Authors: Nordfang Ole , Ezban Mirella , Hansen Jan J 
Published: June 2018

SummaryFactor VIII-Light Chain (FVIII-LC) and FVIII-Heavy Chain (FVIII-HC) were purified from human plasma by the use of immunosorbents containing monoclonal antibodies or human inhibitor antibodies. FVIII-LC was subsequently isolated in essentially pure state by cation exchange chromatography. The preparations obtained contained 50 ng of protein for each unit of FVIII-LC antigen (FVIII-LC: Ag).Affinity purified FVIII-LC and FVIII-HC preparations containing less than 0.3% of the opposite subunit were added in FVIILC inhibition assay of hemophilia A inhibitor antibodies. FVIII-LC was able to fully block the inhibitor activity in 6 out of 7 hemophilia A plasmas and partially block the inhibitor activity of one plasma. FVIII-HC only blocked FVIILC inhibiting antibodies form the plasma that was not fully blocked by FVIII-LC. It is suggested that FVIII-LC can be used for immunotherapy of the patients whose FVIILC inhibiting antibodies are directed towards FVIII-LC.When FVIII-LC was coupled to Sepharose at a concentration of 4800 units of FVIII-LC: Ag per ml Sepharose, 0.2 ml of the immunosorbent was able to bind 900 Bethesda units from 100 ml hemophilia A inhibitor plasma. This opens the possibility to remove FVIII inhibitor antibodies from circulation by extracorporeal immunotherapy with FVIII-LC coupled to Sepharose.
Continuous High-Dose Factor VIII for the Induction of Immune Tolerance in Haemophilia A Patients with High Responder State: A Description of Eleven Patients Treated
Authors: Scheibel E , lngerslev J , Dalsgaard-Nielsen J , Stenbjerg S , Knudsen J B ,   The Danish Study Group
Published: June 2018

SummaryEleven severely affected haemophilia A patients (aged 6-42 y) with F VIII : C inhibitor (high responders) were treated with highdose F VIII in order to eliminate the inhibitors. The patients comprise Danish high responder patients treated during the period 1977-1985.In all patients the inhibitors decreased significantly. In six, the inhibitor apparently disappeared (detection limit 0.4 Bethesda Units per ml) (BU/ml), in four patients a low level inhibitor of 0.4-1.4 BU/ml persisted. One patient is still on high-dose ;schedule. The duration of high-dose treatments ranged from less than one month up to 18 months. In all patients the tendency to spontaneous bleedings vanished when a measurable VIII : C level appeared in the post-infusion sample. The inhibitor suppression has allowed for extensive physical training and rehabilitation orthopaedic surgery. The patients are now able to conduct a normal haemophilic life on self-administered prophylactic doses of F VIII.
Requirement for Thrombin Receptor Occupancy During Platelet Secretion Under Aggregating and Non-Aggregating Conditions
Authors: Koike Kazuo , Holmsen Holm 
Published: June 2018

SummaryThe requirement for receptor occupancy in thrombin-induced secretion in human platelets has been studied. When increasing concentrations of thrombin were added to gel-filtered platelets containing a constant, high concentration of hirudin, dense granule secretion was initiated at lower thrombin concentrations than those required for α-granule secretion and aggregation; acid hydrolase secretion required higher concentrations. A 62-fold excess of hirudin produced abrupt stop of dense granule secretion and a-granule secretion when added to non-aggregating (no stirring) platelets shortly after thrombin; it had no affect after these secretory process had reached about 30% of their maximal values. Acid hydrolase secretion was, however, abruptly stopped by hirudin at any stage. When the platelets were allowed to aggregate, the three secretory processes increased their rates and were abruptly stopped by hirudin at any stage. Aggregation (optical) occurred slower than dense granule and α-granule secretion, and was reversed by hirudin when added before it had reached 30% of its maximum.It is concluded that a-granule secretion, like dense granule secretion, only requires a short receptor occupancy to be completed, in contrast to the requirement for sustained occupancy for acid hydrolase secretion. α-Granule secretion might, however, require longer occupancy than dense granule secretion. Aggregation is believed to potentiate secretion through close cell contact and the secretion processes were inhibited by hirudin through hirudin’s effect on aggregation.
Shortening of Bleeding Time by 1-Deamino-8-Arginine Vasopressin (DDAVP) in the Absence of Platelet von Willebrand Factor in Gray Platelet Syndrome
Authors: Pfueller Sharron L , Howard Margaret A , White James G , Menon Chandrasekhara , Berry Elizabeth W 
Published: June 2018

SummaryThe Gray platelet syndrome is a rare disorder characterised by the absence of platelet a-granules and their contents. We describe a new patient and the effects of infusions of l-deainino-8-aiginine vasopressin (DDAVP). The patient had a prolonged skin bleeding time and his platelets had reduced numbers of a-granules, increased vacuolation and reduced retention on glass beads. Flatelet von Willebrand factor antigen (vWf:Ag) was undetectable and levels of platelet fibrinogen, p-thioniboglobulin, platelet factor 4 and thrombospondin were reduced. All tests of plasma coagulation factors were normal, including Factor VIII (F. VIII: C), vWf: Ag, ristocetin cofactor (R: CoF) and botrocetin cofactor. Platelet ATP, ADP, platelet albumin, surface membrane glycoproteins and 14C-serotonin uptake were also normal. Infusions of DDAVP increased plasma F.VIII:C, vWf:Ag and R.CoF and sliuitened the bleeding time un two occasions. This suggests that DDAVP shortens the bleeding time by releasing vWf: Ag and/or other proteins from cellular storage sites other than the platelet.
A Multi-Centre Study to Evaluate Method Dependency of the International Sensitivity Index of Bovine Thromboplastin
Authors: Peters R H M , van den Besselaar A M H P , Olthuis F M F G 
Published: June 2018

SummaryIn The Netherlands, a particular coagulometer method for prothrombin time (PT) determination with reduced sample and reagent volumes is used by 62% of the laboratories controlling oral anticoagulant therapy. This “micro-method” has been calibrated against the manual tilt-tube technique for PT determination by six Dutch laboratories. Each laboratory tested 20 fresh normal blood samples and 60 fresh patient blood samples using both methods with the same batch of bovine thromboplastin reagent, according to a detailed protocol. Both methods were comparable as to their precision, but PTs measured by the micromethod were significantly prolonged (p <0.001, Student’s t-test) as compared to the manual method. This effect is stronger for samples of normal subjects than for patients’ samples. It was assumed that the International Sensitivity Index (ISI) of the bovine thromboplastin for the manual method was 1.00 in each laboratory. The ISI-values of the bovine thromboplastin for the micro-method determined by the six laboratories ranged from 1.00 to 1.07 (mean 1.03, SD 0.03). Our results indicate that any other laboratory, using this thromboplastin and the micromethod, should obtain accurate assessment of the International Normalized Ratio from their own mean normal PT and an ISI which is 3% higher than the ISI supplied by the thromboplastin manufacturer for the manual tilt-tube method.
Impaired Fibrinolysis as an Essential Contribution to Thrombosis in Patients with Lupus Anticoagulant
Authors: Tsakiris D A , Marbet G A , Makris P E , Settas L , Duckert F 
Published: June 2018

SummaryLupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p <0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.
Induction of Endothelial Cell/Macrophage Procoagulant Activity: Synergistic Stimulation by Gamma Interferon and Granulocyte-Macrophage Colony Stimulating Factor
Authors: Zuckerman Steven H , Surprenant Yvonne M 
Published: June 2018

SummaryInflammatory mediators such as endotoxin can stimulate the expression of procoagulant activity on both endothelial cells and macrophages while the monokines Interleukin 1, IL-1, and Tumor Necrosis Factor, TNF induce procoagulant activity on endothelial cells. Incubation of murine peritoneal macrophages with suboptimal concentrations of endotoxin results in a two fold increase in procoagulant activity. Macrophages incubated with gamma interferon, IFN γ, or Granulocyte-Macrophage Colony Stimulating Factor, GM-CSF, for 16 hours prior to endotoxin stimulation demonstrated a synergistic increase in procoagulant activity. A synergistic increase in procoagulant activity was also observed with primary cultures of human umbilical cord endothelial cells incubated with recombinant human IFN γ for 16 hours prior to endotoxin, TNF, or IL-1 stimulation. Human GM-CSF had no stimulatory effect on endotoxin or monokine induced endothelial cell procoagulant activity. The augmentation of macrophage and endothelial cell procoagulant activity by IFN γ and GM-CSF may provide a novel explanation for the role of these cytokines in acute and chronic inflammation.
Demonstration of Ac-Arg-Gly-Asp-Ser-NH2 as an Antiaggregatory Agent in the Dog by Intracoronary Administration
Authors: Shebuski R J , Berry D E , Bennett D B , Romoff T , Storer B L , Ali F , Samanen J 
Published: June 2018

SummaryThis study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100–400 mM, acute platelet dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NHz otr collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.
Risks to the Fetus of Radiologic Procedures Used in the Diagnosis of Maternal Venous Thromboembolic Disease
Authors: Ginsberg Jeffrey S , Hirsh Jack , Rainbow Andrew J , Coates Geoffrey 
Published: June 2018

SummaryThe diagnosis of suspected venous thromboembolic disease during pregnancy is problematic because of the fear of fetal irradiation with routine diagnostic procedures. In order to develop rational guidelines, we have calculated levels of radiation exposure to the fetus for the common diagnostic procedures and conducted a literature review to examine the fetal risks associated with these levels of radiation. A small increase in the relative risk of childhood cancer is suggested by a literature review of outcomes following low dose (less than 5 rads), in utero radiation exposure. With careful use of the available procedures, a diagnosis of venous thrombosis is possible with fetal radiation exposure of less than 0.50 rads and a diagnosis of pulmonary embolism is possible with fetal radiation exposure of less than 0.05 rads. The risk of such exposure is small, both in relative and absolute terms.
Measurement of Aspirin Concentrations in Portal and Systemic Blood in Pigs: Effect on Platelet Aggregation, Thromboxane and Prostacyclin Production
Authors: Bochner F , Siebert D M , Rodgers S E , McIntosh G H , James M J , Lloyd J V 
Published: June 2018

SummaryLow doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration : time profile between pigs. After 50 mg single dose the ratio of the arterial : portal area under the plasma concentration versus time curve (AUC) was 0.63 ± 0.08 (mean ± SE, n = 6). In three pigs which received all three dosage regimens, the arterial : portal AUC ratios were 0.48 ± 0.05 after 50 mg single dose, 0.52 ± 0.02 after 100 mg single dose and 0.47 ± 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/ 106 platelets) induced by this stimulus decreased from 536 ± 117 before aspirin to 57 ± 14 after aspirin (mean ± SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1α (ng/disc after 10 min incubation), was 1.66 ± 0.28 (mean ± SE, n = 4) in untreated pigs and 0.95 ± 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.
Epitope Localization of Anti-Factor VIII Monoclonal Antibodies Determined by Recombinant peptides
Authors: Ware Jerry , Toomey John R , Stafford Darrel W 
Published: June 2018

SummaryIn order to define the epitopes recognized by anti-coagulation factor VIII (FVIII) monoclonal antibodies, we have constructed a recombinant DNA epitope library from random fragments of the FVIII cDNA. The characterization of 33 different clones producing recombinant antigens in the expression vector, λgt11, has identified the epitopes for six different anti-FVIII monoclonal antibodies. The antigenic determinant for each antibody was defined by the overlapping or shared DNA sequence of multiple immunoreactive clones. One weak inhibitor of FVIII coagulant activity binds within the gly701 ser750 sequence of the FVIII sequence. An antibody which recognizes the amino-terminus of FVIII heavy-chain (within trp14 - tyr46) does not inhibit FVIII activity. Two non-neutralizing antibodies both map within residues asp807 - ser817 while two other non-neutralizing antibodies bind within lys1673 - pro1688. The general usefulness of this strategy for mapping FVIII antigenic determinants is discussed.
Methylene Blue Enhances Lateral Association of Fibrin Resulting in Rapid Gelation and Thick Fiber Formation
Authors: Carr Marcus E , Powers Patrick L 
Published: June 2018

SummaryMethylene blue (MB) has been suggested as a therapeutic alternative for heparin reversal in patients sensitive to protamine. We investigated the impact of MB on the assembly and structure of thrombin induced fibrin and plasma gels. MB (1,600 μg/ml) reduced the thrombin clotting time (TCT) of plasma by 30% and of purified fibrinogen by 46%. Above 1,600 μg/ml, TCTs were prolonged due to MB mediated fibrinogen precipitation. The presence of 5 mM CaCl2 masked the effect of MB in both purified and plasma systems and lowered the threshold for MB-induced purified fibrinogen precipitation to 800 μg/ml. MB shortened the lag phase prior to thrombin-induced turbidity increase, and enhanced final gel turbidity. The fibrin fiber mass/length ratio increased from 5.2 to 13.1 × 1013 dalton/cm in purified fibrin gels and from 3.2 to 10.4 × 1013 dalton/cm in plasma gels as the MB concentration increased from 0 to 200 μglml. Due to the photooxidant effect of MB on fibrinogen, rapid time-dependent loss of fibrinogen clottability was obvious at low MB concentrations (50 to 400 μg/ml). At high MB concentrations, intense MB light absorption partially protected fibrinogen within the sample. Accurate measurements could only be made, however, when MB was added just prior to thrombin and the assays were performed in the dark. While erythrocytes may reduce the impact of MB photooxidation in whole blood, plasma samples must be shielded from light if reproducible results are to be obtained.
Defibrinogenation by Arvin Reduces Air-Drying-lnduced Arteriosclerosis in Rat Carotid Artery
Authors: van Pelt-Verkuil E , van de Ree P , Emeis J J 
Published: June 2018

SummaryThe effects of lowering plasma fibrinogen levels by Arvin injections have been investigated in a rat model of arteriosclerosis. In this model air-drying-induced endothelial denudation of the left carotid artery results in myointimal lesion development. Arvin (2 × 50 Units/kg) was given at 4 and 2 hours prior to surgery, reducing plasma fibrinogen levels at surgery to about 20%. Fibrinogen levels then normalized within 24 hours. Myointimal lesion development was evaluated morphometrically at 14 days after surgery. Statistical analysis of the morphometric data showed that defibrinogenation had resulted in significantly smaller myointimal lesions. Low plasma fibrinogen levels might thus be considered a negative risk factor for intimal smooth muscle cell proliferation in this model.
Influence of Whole Blood on Standard Curve for Heparin Measurement - Possible Heparin Binding by Red Cells
Authors: Melissari E , Thye C , Scully M F , Kakkar V V 
Published: June 2018

SummaryMeasurement of heparin ex vivo is usually with reference to standard curve prepared with a “spiked” normal human plasma pool (NHP). When the calibration curve was prepared by addition of heparin to whole blood before plasma separation, although the linear relationship was maintained the slope was increased in comparison to the classical standard calibration curve. It is concluded that the preparation of the calibration curve by addition of heparin to NHP may give erroneously high heparin levels in treated patients’ plasma, leading perhaps to inappropriate dosage. It was also observed that when heparin was added to blood of different haematocrit (prepared by addition of washed RBC to plasma) and plasma prepared, the subsequent APTT was decreased with the fall in haematocrit; suggesting that the laboratory monitoring of heparin treatment should take into account the patient’s haematocrit.