bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet Activating Properties of Murine Monoclonal Antibodies to β2-Glycoprotein I
Authors: Arvieux J , Roussel B , Pouzol P , Colomb M G 
Published: July 2018

SummaryPreviously developed murine monoclonal antibodies (MAbs) to human β2-glycoprotein I (β2GPI), a plasma protein required for the binding of anti-phospholipid antibodies, were studied for anti-platelet reactivity and influence on platelet function. The six MAbs (IgG1 isotype) tested interacted with both intact and fixed platelets in a β2GPI-dependent manner. Carbamylated β2GPI was still recognized by MAbs but was unable to mediate platelet- antibody binding. MAbs induced aggregation and secretion responses of platelets in platelet-rich plasma (PRP) and whole blood, provided subthreshold concentrations of weak agonists (i.e. ADP or adrenaline) were added. When aggregation in PRP was evaluated by a counting technique instead of turbidometrically, the sole addition of MAbs led to a rapid fall in single platelets. Triggering gel-filtered platelets with MAbs together with β2GPI, but not its carbamylated form, led to platelet activation after a lag time, as monitored by aggregometry, measurements of ATP and β-thromboglobulin secretion and calcium mobilization. F(ab')2 fragments of one of the MAbs failed to activate platelets but inhibited the responses to the whole antibody. This process thus depends on MAbs binding to platelets through both Fab and Fc domains, as confirmed by the suppression of platelet responses upon pretreatment with the anti-FcγRII MAb IV.3. Aggregation and secretion induced by MAbs plus β2GPI did not require exogenous fibrinogen and were variably inhibited in the presence of acetyl salicylic acid, apyrase or Ca2+, depending on the concentrations used for the two proteins. We propose that platelet FcγRII crosslinking that follows a platelet-antibody interaction via the platelet binding protein, β2GPI, may be a new mechanism by which anti-β2 GPI antibodies activate platelets and/or synergize with weak agonists.
A Quantitative Protein S Deficiency Associated with a Novel Nonsense Mutation and Markedly Reduced Levels of Mutated mRNA
Authors: Yamazaki Tomio , Hamaguchi Motohiro , Katsumi Akira , Kagami Kazuo , Kojima Tetsuhito , Takamatsu Junki , Saito Hidehiko 
Published: July 2018

SummaryA 50-year-old Japanese man who had experienced recurrent episodes of venous thrombosis was found to have a hereditary protein S deficiency. The amount of total protein S antigen in plasma was reduced by approximately 50% in the patient and his two sons. DNA sequence analysis revealed a novel nonsense mutation, TAG for Gin 522 (CAG), in exon 14 of the protein S gene. Family studies performed by mutagenic PCR followed by restriction enzyme digestion showed that the proband and his two sons were heterozygous for this mutation. An mRNA-based analysis indicated that transcripts of the mutated allele were markedly reduced in the platelets of the affected individuals. Immunoblot analysis failed to detect the truncated mutant of protein S in the plasma or platelets of affected members. Our results demonstrated that this novel nonsense mutation was responsible for the quantitative deficiency of protein S.
Pre-operative Plasma Levels of Thrombin-Antithrombin III Complexes Correlate with the Development of Venous Thrombosis after Major Hip or Knee Surgery
Authors: Ginsberg Jeffrey S , Brill-Edwards Patrick , Panju Akbar , Patel Ameen , McGinnis Joanne , Smith Frank , Dale Ian , Johnston Marilyn , Ofosu Fred 
Published: July 2018

SummaryStudy objective. To determine whether levels of thrombin-antithrombin III (TAT) in plasma, taken two weeks pre-operatively, predict the development of deep vein thrombosis (DVT) in patients undergoing major hip or knee surgery.Design. Prospective cohort.Setting. Tertiary-care referral centre, university-affiliated hospital.Patients. Ninety eight consecutive patients undergoing elective hip or knee surgery.Intervention. All eligible consenting patients were seen in a preoperative clinic two weeks prior to surgery and had blood taken for measurement of plasma TAT level. After surgery, they received a combination of unfractionated heparin 5000 Units 12-hourly subcutaneously, and antiembolism stockings (TEDS), as prophylaxis against DVT. Contrast venography was performed prior to discharge, and according to the results, patients were classified as having proximal (popliteal and/or more proximal) DVT (n = 12), calf DVT (n = 7) or no DVT (n = 79).Measurements and Results. The mean TAT level was significantly higher in patients who developed DVT (5.7 μg/l) than in those who did not (4.1 μg/l), p = 0.035. Using cut-points of 3.5 and 5.5 μg/l for the TAT level, patients could be categorized as high, intermediate, and low risk for the development of DVT. The proportion of patients with TAT levels of ≥3.5μg/l who developed calf or proximal DVT was significantly higher than the proportion of patients with TAT levels of <3.5 μg/l who developed calf or proximal DVT (p = 0.02). The proportion of patients with TAT levels >5.5 μg/l who developed proximal DVT was significantly higher than the proportion of patients with TAT levels of ≤5.5 μg/l who developed proximal DVT (p = 0.03).Conclusions. This study demonstrates that pre-operative TAT levels correlate with the risk of developing DVT after major orthopedic surgery. Further studies are needed to determine the reason(s) for this observation and whether rational recommendations about prophylaxis and screening for DVT can be made based on the results of a pre-operative TAT level.
Endothelial Haemostatic Factors May Be Associated with Mortality in Patients on Long-term Anticoagulant Treatment
Authors: Brännström Mats , Jansson Jan-Håkan , Boman Kurt , Nilsson Torbjörn K 
Published: July 2018

SummaryThe aim of the present study was to test if long-term mortality could be predicted by endothelial derived haemostatic variables in a population with high morbidity due to thromboembolic disease. Plasma samples were drawn from 212 out-patients treated with oral anticoagulants, at the beginning of the study, and analyzed for mass concentration of tissue plasminogen activator (tPA) and its inhibitor (PAI-1), and von Willebrand factor. In the course of 3.8-year follow-up 45 patients died, including 38 vascular deaths. We found that all-cause mortality was significantly associated with increased levels of vWF and tPA. For vascular mortality there was a significant association with all three haemostatic variables (tPA, PAI-1, vWF). For vWF there was a 3-fold increase in total and vascular mortality in the highest quartile compared to the lowest quartile. There were 27 vascular deaths in the group of patients with a tPA-value above the median compared to 11 in those with a tPA below the median. In multivariate Cox regression analysis (including: age, sex, smoking habits, body mass index, diabetes mellitus, hypertension, tPA, PAI-1, and vWF), vWF and smoking were independently significantly associated with all-cause mortality, and tPA and age with vascular mortality. Endothelial derived haemostatic variables are predictors of total and vascular mortality in patients treated with oral anticoagulants.
Pharmacokinetics and Tolerability of Factor XIII Concentrates Prepared from Human Placenta or Plasma: a Crossover Randomised Study
Authors: Brackmann H H , Egbring R , Ferster A , Fondu P , Girardel J M , Kreuz W , Masure R , Miloszewski K , Stibbe J , Zimmermann R , Krzensk U , Hoos A 
Published: July 2018

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.
Pharmacokinetics of Heparin in Healthy and Obese Subjects and in Combination with Dihydroergotamine
Authors: Beermann Björn , Lahnborg Gordon 
Published: July 2018

SummaryHeparin (5000 IE s.c., 5000 IE i v, 200 IE/kg i v) was given to healthy volunteers without and with 0.5 mg dihydroergotamine (DHE) i v to test whether DHE influences the kinetics of heparin. The anticoagulant (200 IE/kg) was also administered to obese subjects. Heparin was assayed using a chromogenic substrate for activated factor X.The plasma levels of heparin did not differ whether given concomitantly with DHE or not. Halflife of heparin was also uninfluenced of DHE demonstrating that the beneficial effect of DHE on postoperative thromboembolism is not caused by interaction with the pharmacokinetics of heparin.The plasma levels of heparin were significantly higher in the obese subjects than in the normal ones. The halflife of the drug averaged 2.13 h in the obese subjects and 1.36 h in the normal subjects (p<0.02). It was concluded that the heparin dosage should be calculated in terms of estimated ideal weight.
The Immunological Characterization of Human Antibodies to Factor VIII Isolated by Immuno-Affinity Chromatography
Authors: Kavanagh M L , Wood C N , Davidson J F 
Published: July 2018

SummaryNine human antibodies to factor VIII were isolated from haemophilic plasmas by affinity chromatography and gel filtration and six were subsequently subjected to immunological characterization. Three partially purified preparations were similarly characterized. Eight of the antibodies were characterized as being exclusively IgG and one preparation was found to contain IgM. Seven of the antibodies contained only a single light chain type, four being of type lambda and three of type kappa. Two antibody preparations contained both kappa and lambda light chains. In four of the preparations, only a single heavy chain sub-class could be demonstrated, three of IgG3 and one of IgG4. Of the remainder, three were a mixture of IgG3 and IgG4 sub-classes and one contained both IgG2 and IgG4. IgG sub-classification could not be achieved with the IgM-containing preparation. These results demonstrate a restricted heterogeneity of light and heavy chains in human antibodies to factor VIII.
Influence of ω-Aminoacids on the Activation of the First Component of Complement at Low Ionic Strength
Authors: Takada Yumiko , Takada Akikazu 
Published: July 2018

SummaryCl, the first component of human complement, was activated to Cls by diluting human plasma in a solution of low ionic strength. The addition of lysine and its related aminoacids to plasma resulted in inhibition of Cl activation, α, ω-diaminoacids such as lysine and ornithine were most effective and ω-aminoacids such as 6 aminohexanoic acid were far less effective. Tranexamic acid which is most potent in inhibition of fibrinolysis among those aminoacids was least effective in the inhibition of Cl activation, ω-aminoacids or their analogues hardly inhibited Cls which had already been activated.
Permeability Enhancing and Chemotactic Activities of Lower Molecular Weight Degradation Products of Human Fibrinogen
Authors: Sueishi Katsuo , Nanno Shigeru , Tanaka Kenzo 
Published: July 2018

SummaryFibrinogen degradation products were investigated for leukocyte chemotactic activity and for enhancement of vascular permeability. Both activities increased progressively with plasmin digestion of fibrinogen. Active fragments were partially purified from 24 hr-plasmin digests. Molecular weights of the permeability increasing and chemotactic activity fractions were 25,000-15,000 and 25,000 respectively. Both fractions had much higher activities than the fragment X, Y, D or E. Electron microscopic observation of the small blood vessels in rabbit skin correlated increased permeability with the formation of characteristic gaps between adjoining endothelial cells and their contraction.These findings suggest that lower molecular weight degradation products of fibrinogen may be influential in contributing to granulocytic infiltration and enhanced permeability in lesions characterized by deposits of fibrin and/or fibrinogen.
Contribution of Plasma Proteinase Inhibitors to the Regulation of Activated Protein C in Plasma
Authors: Marlar Richard A , Kressin David C , Madden Renee M 
Published: July 2018

SummaryActivated protein C (APC), a serine protease, is regulated in plasma by protease inhibitors. This study was undertaken to determine the role of the major plasma inhibitors in regulating APC in plasma. Kinetic analysis and specific immunoassays for APC-inhibitor complexes were used to determine the inhibitors that form complexes with APC. Of the eight plasma inhibitors investigated, four interact with APC: protein C inhibitor (PCI), α1-proteinase inhibitor (PI), α2-antiplasmin (AP) and C1 esterase inhibitor (C1 Inh). The second order rate constants are: 1.3 × 104 M−1 s−1 (PCI); 15 M−1 s−1 (PI); 410 M−1 s−1 (AP); and <6 M−1 s−1 (C1 Inh), with a relative effectiveness of each inhibitor to inactivate APC in plasma: 49:36:15:<1, respectively. PCI, PI and AP are the major inhibitors of APC in plasma. Low concentrations of APC will be inhibited by PCI with PI and AP playing a secondary role. However, as increasing APC is generated, PI and AP begin to play more important roles as the PCI is consumed.
Relations between Activation and Inhibition of Fibrinolysis in the Walls of Human Arteries and Veins
Authors: Hegt Vincent Noordhoek 
Published: July 2018

SummaryFrom systematic studies of both the activation and the inhibition of fibrinolysis in human blood vessels, data which provided insight into the fibrinolysis antagonism along and across the human vessel wall were obtained.The capacity for fibrinolysis initiated by plasminogen activator in sections of human arteries and veins as demonstrated by the fibrin sfide technique differed greatly along and across the vessel walls. Inhibition of plasmin fibrinolysis in these blood vessels as detected by the fibrin slide sandwich technique was present at sites of low fibrinolytic activity, while inhibition was absent in areas showing strong fibrinolysis. Fibrinolysis was related to endothelial cells, while inhibition of fibrinolysis was brought about by smooth muscle cells. The results indicate that differences in endothelial fibrinolysis may be the result of differences in inhibition of fibrinolysis caused by variations in the number of smooth muscle cells present locally. A systemic decrease in endothelial fibrinolysis observed in endotoxin shock, hyaline membrane disease and a Waterhouse-Friderichsen syndrome appeared to be associated with a systemic increase in inhibition of fibrinolysis not related to smooth muscle cells.
The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study
Authors: Tinlin Shawn , Webster Sandra , Giles Alan R 
Published: July 2018

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.
Multi-Center Study of Thromboplastin Calibration Precision – Influence of Reagent Species, Composition, and International Sensitivity Index (ISI)
Authors: Besselaar A M H P van den , Bertina R M 
Published: July 2018

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.
Effect of Heparin on Thrombin Inhibition in the Microcirculation
Authors: Nydahl S , Frebelius S , Swedenborg J 
Published: July 2018

SummaryDisappearance of thrombin enzymatic activity was measured during recirculation through the microvasculature in a rat Langendorff heart preparation. This resulted in a 50% loss of thrombin from the recirculating solution. No increased loss of thrombin could be demonstrated if a mixture of antithrombin III and thrombin was recirculated, compared to thrombin alone. If, however, a heparin/thrombin mixture was recirculated, a 90% loss of thrombin could be demonstrated. Pretreating the microvasculature with large amounts of heparin resulted in recovery of antithrombin III in the recirculated heparin solution. At a subsequent recirculation with a heparin/thrombin mixture the loss of thrombin was decreased to the control level, as seen when recirculation with thrombin alone was performed. It is concluded that disappearance of thrombin enzymatic activity from a solution when recirculated through the microcirculation can be considerably increased if recirculated together with heparin, which probably reacts with endogenous antithrombin III on the vessel wall. The disappearance of thrombin in the absence of heparin was, however, unaffected by antithrombin III. The latter finding is compatible with the hypothesis that, in the microcirculation, antithrombin III/glycosaminoglycans play only a minor role for inhibition of thrombin coagulant activity and that thrombin binds mainly to thrombomodulin.
Spontaneous Atrial Thrombosis in Aged Syrian Hamsters II. Hemostasis
Authors: Dodds W. Jean , Raymond Sharon L. , Moynihan Ann C. , McMartin Donald N. 
Published: July 2018

SummaryCoagulation and fibrinolysis were studied in a colony of aged Syrian hamsters with spontaneous atrial thrombosis, and the results are consistent with concomitant consumption coagulopathy. In comparison to age- and sex-matched hamsters from the same colony, those with atrial thrombi had significantly prolonged prothrombin and partial thromboplastin times, reduced levels of factors II, VII, VIII and X activities and plasminogen; and concentrations of fibrinogen-fibrin split products in excess of 80 μg/ml. Hematocrits of the thrombosed animals were significantly decreased, total plasma proteins were increased, leukocyte counts were within normal limits, and platelet counts were about half those of the controls. Thrombosed hamsters had significantly reduced plasma albumin content, increased γ1-, β-, and γ-globulins, and reduced A/G ratios.Aged sick hamsters without demonstrable thrombi also had reduced coagulation and fibrinolytic activities and platelet counts, but their fibrinogen levels were markedly elevated, and fibrinogen-fibrin split products were either absent or present in trace amounts. This suggests an earlier and/or less acute form of the thrombotic process.
Antithrombin III and Heparin Inactivation in Thrombin Involving Reactions
Authors: Marciniak Ewa 
Published: July 2018

SummaryThe inhibitory capacity of antithrombin III (AT III) was measured by a quantitative method independent of the velocity of inhibition. When AT III was in excess of thrombin in plasma or in purified system the capacity of inhibitor decreased quantitatively in proportion to the amount of thrombin neutralized. Heparin present in reaction together with thrombin invariably induced a more extensive utilization of inhibitor than thrombin alone. The extent of this additional loss of inhibitory capacity was to a limited degree related to the concentration of heparin. Heparin itself was neutralized in thrombin-AT III reaction losing its anticoagulant property in proportion to the amount of thrombin bound by inhibitor. This quantitative neutralization of heparin occurred not only when the anticoagulant participated in thrombin-AT III binding but also when heparin was added to a medium containing a preformed thrombin-AT III complex. These results suggest that acceleration of binding and increased utilization of binding capacity are the two regular effects of heparin on thrombin-involving reactions of AT III. Both of these effects may be abolished by quantitative binding of heparin to thrombin-AT III complex.