bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged Bleeding Time of Chediak-Higashi Cats Corrected by Platelet Transfusion
Authors: Cowles B E , Meyers K M , Wardrop K J , Menard M , Sylvester D 
Published: July 2018

SummaryCats with the Chediak-Higashi syndrome (CHS) have a platelet storage pool deficiency (SPD). Ten CHS cats were transfused with a concentrate of 51Cr-labeled platelets prepared from normal donor cats. Gne hour after transfusion, the donor platelet count in CHS recipient cats was 40,000-60,000/μl. Bleeding time before transfusion was 9.1 ± 3.0 min. When donor platelet count in CHS cats was 50,000/μl, bleeding time was 1.7 ± 0.2 min. Bleeding time of normal cats was 1.4 ± 0.3 min. Bleeding time increased to 3.3 ± 0.2 min and to 5.3 ± 0.2 min when the platelet count was 30,000/μl, and 15,000/μl, respectively. The close inverse relationship between bleeding time and number of donor platelets in CHS cats (r = —0.92), suggests that prolonged bleeding time is due to a platelet abnormality, that platelet transfusion can effectively correct prolonged bleeding time in an animal model of platelet SPD and that CHS cats may be an appropriate animal model to evaluate hemostatic capabilities of transfused platelets.
Platelet Interaction with Collagen Fibrils in Flowing Blood
Authors: Baumgartner Hans R. 
Published: July 2018

SummaryThe subendothelial surface of rabbit aorta and α chymotrypsin-digested subendothelium were exposed to anticoagulated human blood in an annular flow chamber. The wall shear rate was similar to that observed in large arteries (830 sec–1) and exposure times varied from 2½ to 40 min.The platelet reactive substrate of α chymotrypsin-digested subendothelium consists of a three-dimensional meshwork of collagen fibrils which form islands of variable size and height in a matrix of virtually unreactive elastin. Collagen-induced aggregation in the aggregometer was similar with or without prior α chymotrypsin-digestion of a highly dispersed preparation of fibrillar collagen. The rate of platelet adhesion was decreased on the fibrillar collagen of α chymotrypsin-digested subendothelium as compared to intact subendothelium. On the other hand the rate of aggregation was increased once platelets adhered to the fibrillar collagen. Mural thrombi (aggregates) disappeared on subendothelium whereas they grew progressively on the fibrillar collagen. Thus the fibrillar collagen of α chymotrypsin-digested subendothelium appears to be a more thrombogenic surface. It is suggested that physical (loose three-dimensional meshwork versus a comparatively solid surface) and/or chemical (number of platelet reactive sites per unit surface area) differences between the two surfaces may explain the platelet-surface-interaction patterns which are characteristic for each surface.
Intermittent Plasminogen-Streptokinase Treatment of Deep Vein Thrombosis
Authors: Scully M. F , Lane D. A , Sagar S , Thomas D. P , Kakkar V. V 
Published: July 2018

SummaryThe fibrinolytic response of 12 patients receiving single daily infusions of 600,000 units of streptokinase (SK) and 90 mg of plasminogen for the treatment of DVT has been studied. The mean plasminogen concentration was maintained throughout the treatment period (4–6 days) at between 20–40 % the initial value, while mean circulating plasmin concentration rose to only about twice initial plasma levels. The degradation of fibrinogen as indicated by a fall in clottable fibrinogen and rise in serum FDP varied appreciably from patient to patient. In 9 patients fibrinogen did not fall below 1 mg/ml and serum FDP rose to greater than 1 mg/ml. Limited fibrinogenolysis occurred in 2 patients, while in another patient who bled there was immediate and extensive depletion to below 0.5 mg/ml. The beneficial clinical results obtained with this regimen (Kakkar et al. 1975), which produces only limited systemic plasminaemia, suggest that thrombolysis may be facilitated by higher levels of plasminogen than those maintained during conventional SK treatment.
Oxygen-Induced Consumptive Coagulopathy and its Enhancement by Lead Acetate
Authors: Kiesow L. A , Shapiro S , Lindsley B. F , Bless J. W 
Published: July 2018

SummaryThe exposure of rats to 100% oxygen at 1 atmosphere leads to a prolongation of prothrombin times and activated partial thromboplastin times. This development is associated with a consumption of factor XII, VIII, and VII activities and with the appearance of fibrin monomers and fibrinogen degradation products. Lead acetate enhances all oxygen-induced changes of the coagulation systems drastically. The O2 survival time of chicks which are naturally deficient in factor XII is greatly increased over that of rats and is not affected by lead acetate. Oxygen survival times of rats suffering from chronic respiratory disease (CRD) are also significantly increased when compared with normal rats. It appears that consumptive coagulopathy and disseminated intravascular coagulation are early events in oxygen exposure, and that their development is accelerated by lead ions.
Evaluation of a New Anti-Fibrinogen-Coated Latex Particle Agglutination Test in the Measurement of Serum Fibrin Degradation Products
Authors: Marder Victor J. , Cruz Genuina O. , Schumer Bruce R. 
Published: July 2018

SummaryA new latex particle agglutination test (FIBROTEX®) has been compared with the Thrombo-Wellcotest® and the tanned red cell hemagglutination inhibition immunoassay (TRCHII) for sensitivity to purified fibrinogen and plasmic degradation products and for reactivity with 31 normal sera and 170 sera from patients with thrombotic disorders. The latex particles in the FIBROTEX® are coated with antibodies against fibrinogen and fragment E (anti-FE), in contrast with the anti-fragment D and anti-fragment E antibodies which coat the latex particles of the Thrombo-Wellcotest® (anti-DE). The relative sensitivities of the TRCHII and the anti-FE and anti-DE latex tests were, respectively, 0.5, 2.5 and 7.5 μg/ml for fibrinogen; 0.5, 0.5 and 4.0 μg/ml for fragment X; and 1.25, > 30 and 8.0 μg/ml for fragment D. Compared with anti-DE, the anti-FE particles demonstrated fewer false-positive results with sera and urines of normals and higher titers, fewer false negatives and better overall correlation with the TRCHII results (r = 0.89 vs. 0.75) on pathologic sera. The FIBROTEX® is simple and rapid (5 minutes) and provides a more sensitive and accurate determination of serum fibrin degradation products than the Thrombo-Wellcotest®.
Prevention of Platelet Adhesion and Aggregation by a Glutardialdehyde-Stabilized Heparin Surface
Authors: Olsson P , Lagergren H , Larsson R , Rådegran K 
Published: July 2018

SummaryA stable heparinized surface was prepared by sequential treatment of polyethylene with water solutions of hexadecylamine hydrochloride, heparin and glutardialdehyde. In order to explain the “non-thrombogenic” properties of this surface, it was evaluated with regard to prevention of platelet adhesion and aggregation.Human heparinized blood (2 and 10 IU/ml) with 51Cr-labelled autologous platelets was rotated for 60 minutes in untreated and heparin-treated circular tubings. The surface area/blood volume ratio was varied and an air-blood interface was present. In untreated tubings, platelet adhesion and aggregation increased in proportion to the size of the surface area/blood volume ratio, irrespective of the heparin concentrations of the blood. In the heparin-treated tubings, there was no measurable platelet adhesion to the surface and no platelet aggregation in the blood. The difference between the heparinized and the untreated surfaces with regard to platelet adhesion was discernible even after 10 minutes storage of stagnant blood.It is concluded that platelet adhesion and aggregation induced by exposure of blood to a foreign surface in an in vitro experimental model can be prevented by a stable heparin coating of the surface.
Kinetic Parameters of Platelet Aggregation as an Expression of Platelet Responsiveness
Authors: Rossi Ennio C , Louis Gerlinde 
Published: July 2018

SummaryThe kinetics of platelet aggregation induced by collagen and by ADP were studied. The maximum aggregation (ΔLTmax) and the ADP and collagen concentrations required to produce half-maximum aggregation (Kd) were determined using platelets obtained from normal individuals, individuals who ingested aspirin and individuals whose platelet-rich plasma (PRP) demonstrated spontaneous aggregation. The Kd and ΔLTmaxfor ADP-induced platelet aggregation were variable and markedly affected by the citrate concentration. Conversely, kinetic parameters of collagen-induced aggregation were more reproducible and less affected by citrate. The Kd for collagen in platelet aggregation was increased following aspirin ingestion and decreased in samples of PRP that demonstrated spontaneous aggregation. These results suggest that kinetic parameters of platelet aggregation may be useful to express the responsiveness of platelets.
Ethanol-Induced Microaggregate Formation in Pig and Rabbit Blood
Authors: Elmér Olle , Göransson Göran , Saku Motonori , Bengmark Stig 
Published: July 2018

SummaryIncreased microaggregate formation was found after mixing ethanol with blood from pig and rabbit in vitro, measured with Swank’s Screen Filtration pressure method. Final ethanol concentrations were in the range found in ethanol-intoxication in man. No rise in SFP was noticed when plasma with 10,000 platelets/μl was used. It is therefore doubtful that altered plasma proteins caused the rise in SFP. It is suggested that if a direct effect of ethanol upon platelet aggregation exists in vivo, it may be of importance in acute ethanol intoxication and in chronic alcoholism.
Effects of Thrombin, Chymotrypsin and Aggregated Gamma-Globulins on the Proteins of the Human Platelet Membrane
Authors: Podolsak B 
Published: July 2018

SummaryAnalysis of platelet membrane proteins and glycoproteins by SDS Polyacrylamide gel electrophoresis was carried out before and after treatment with thrombin. Extended incubation with thrombin (in the presence of EDTA or adenosine, which inhibit aggregation) produced extensive changes in the bands observed. With incubation times of a few minutes however, the changes were restricted to a glycopeptide, GP IV (approx. 90,000 Daltons) and one or two polypeptides of low molecular weight, in particular polypeptide 16 (approx. 23,000 Daltons). At 0–3° C only polypeptide 16 was still hydrolyzed.Chymotrypsin, which does not activate platelets, attacked glycopeptides I, II, III but no changes were apparent in GP IV and polypeptide 16. When chymotrypsin-treated platelets were further incubated with thrombin, only GP IV and one to two low molecular weight polypeptides, especially polypeptide 16, were affected. As polypeptide 16 appears to be an integral membrane component it is possible that it, either by itself or in combination with GP IV, represents the primary thrombin substrate involved in platelet activation.Aggregated IgG, which also activates platelets, does not modify the membrane glycoproteins but does change the low molecular weight region in particular band 16.
Spectrophotometric Determination of Factor Xa Generation in Factor IX Concentrates
Authors: Pepper D. S , Banhegyi D , Howie Ann 
Published: July 2018

SummaryPrevious work from this department, concerned with testing the potential thrombogenicity of therapeutic factor IX concentrates, demonstrated that following recalcification of factor IX concentrates thrombin was generated within 3-30 minutes of incubation (Sas et al. 1975). The test developed (known as the TGt 50 test) is a two-stage assay and was thus found to be time consuming, tedious and tended to become inaccurate with long incubation periods and a large number of samples. A semiautomatic version of the test is reported in which the synthetic peptide Bz-ILE-GLU-GLY-ARG-pNA (S-2222) is added to recalcified, diluted factor IX concentrate in the micro-cuvette of a multiple sample recording spectrophotometer. Information can be obtained on (a) the amount of Xa (if any) present prior to recalcification (b) the initial amount of Xa formed and (c) the time taken to activate all factor X to Xa. Direct graphical interpretation shows a number of qualitative differences between commercial preparations, but by either of the criteria (b) or (c) above, it is possible to place the different products into “activated” and “non activated” groups such that both the Xa generation times and TGt 50 tests identify the same two groups of products. This agreement also indicates that the TGt 50 test is independent of the intrinsic factor V levels in the various concentrates.
Factor V Leiden: An Additional Risk Factor for Thrombosis in Protein S Deficient Families?
Authors: Koeleman B P C , Rumpt D van , Hamulyák K , Reitsma P H , Bertina R M 
Published: July 2018

SummaryWe recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible for Activated Protein C resistance) among symptomatic protein C deficient probands (19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia in six protein C deficient families. Here, we report the results of a similar study in protein S deficient probands and families. Among 16 symptomatic protein S deficient probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence is significantly different from that in the normal population, and is probably caused by the selection of probands for familial thrombosis and protein S deficiency. In 4 families, the segregation of the FV Leiden mutation and the protein S deficiency could be studied. In sibships where both abnormalities were segregating, the percentage of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects with only the FV Leiden mutation, and two out of the three subjects with only protein S deficiency had developed thrombosis. These results indicate that in the families presented here the combination of the FV Leiden mutation and the protein S deficiency is associated with a high risk for thrombosis. A reliable estimate of the penetrance of the single defects is not possible, because the number of individuals with a single defect is too low.
A Higher than Expected Incidence of Factor VIII Inhibitors in Multitransfused Haemophilia A Patients Treated with an Intermediate Purity Pasteurized Factor VIII Concentrate
Authors: Peerlinck Kathelijne , Arnout Jef , Gilles Jean Guy , Saint-Remy Jean-Marie , Vermylen Jos 
Published: July 2018

SummaryIn May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation.Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII.This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials.
Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion
Authors: Krulder J W M , de Boer A , van den Besselaar A M H P , Cohen A F , Schoemaker H C , Briët E , Meinders A E 
Published: July 2018

SummaryThe objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning.In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.
Clearance of Recombinant Tissue Factor Pathway Inhibitor (TFPI) in Rabbits
Authors: Palmier Mark O , Hall Lori J , Reisch Celeste M , Baldwin Margaret K , Wilson Alan G E , Wun Tze-Chein 
Published: July 2018

SummaryThe pharmacokinetics of recombinant tissue factor pathway inhibitor (TFPI) after an intravenous bolus injection was studied in rabbits. Clearance of TFPI was followed by measurement of the radioactivity of the 125I-labelled compound in the whole plasma or the trichloroacetic acid precipitate and by quantitation of the functional TFPI activity of the unlabelled compound using a tissue factor-induced coagulation assay. When iodinated TFPI was used, the ratios of the trichloroacetic acid precipitable counts vs. that of the whole plasma was about 1 in the first 10 min after TFPI injection, but this ratio gradually decreased to less than 0.5 after 2 h. This result suggested that the iodinated TFPI in the plasma was partially degraded after prolonged circulation in the animal. When unlabelled TFPI was used, the clearance of TFPI activity from the plasma exhibited bi-exponential elimination kinetics with a rapid alpha phase half-life $$(t
1/2α) of 2.3 min, and a terminal beta phase half-life $$(t
1/2β) of 79 min. The plasma clearance was 4.2 ml kg–1 min–1. The tissue distribution of intravenously administered 125I-TFPI in the rabbit was studied using whole-body autoradiography. At 3 min after dosing, significant levels of TFPI were apparent in the liver, kidney, and other highly blood perfused tissues. Signficant levels of 125I-TFPI-derived radioactivity were also apparent in the liver and kidney at 30 min after intravenous administration. The localization within the liver demonstrated a mottled appearance, suggesting regions of higher uptake within the liver. In the kidney, the outer cortex consistently revealed the highest activity.
Coagulation Factor IXa Binding to Activated Platelets and Platelet-Derived Microparticles: A Flow Cytometric Study
Authors: Hoffman Maureane , Monroe Dougald M , Roberts Harold R 
Published: July 2018

SummaryFactor IX plays a central role in blood coagulation, since it can be activated by either XIa (intrinsic pathway) or tissue factor-VIIa (extrinsic pathway). Activated factor IX (IXa), in a surface-bound complex with factor Villa, then activates factor X. Platelets provide the catalytic surface upon which this Xase complex is assembled in vivo. We have used flow cytometry to examine binding of factor IXa to thrombin-activated platelets in the absence of added Villa. Platelet-bound IXa and platelet protein GPIb were detected by indirect immunofluorescence staining followed by two-color flow cytometric analysis. Microparticles were identified by their light scattering characteristics. Two binding sites for factor IXa were detected. The high affinity binding site saturated at about 10 nM, with a K
d of 1.6 nM. A second binding curve, with a K
d of about 100 nM, was observed at higher concentrations of IXa. The high affinity factor IXa binding sites comprise about 7% of the total factor IXa binding. Binding to both sites was dependent on the presence of calcium. Thus, we conclude that factor IXa, in addition to its high affinity binding, has a calcium-dependent low affinity association with activated platelets and microparticles. Sims et al. have shown that binding sites for a different coagulation factor, factor Va, are concentrated on microparticles relative to platelet membrane proteins, such as GPIb. GPIb is distributed on platelets and microparticle in proportion to plasma membrane surface. At 100 nM factor IXa, 1–3% of the total bound factor IXa was associated with microparticles, as was a similar proportion of the total GPIb. However, at 10 nM IXa, factor IXa binding to microparticles was concentrated about 2-fold relative to GPIb staining. Thus, the high affinity factor IXa binding site is concentrated on microparticles to a small degree, while the low affinity binding site is not.
Desmopressin Has No Beneficial Effect on Excessive Postoperative Bleeding or Blood Product Requirements Associated with Cardiopulmonary Bypass
Authors: Prost D de , Barbier-Boehm G , Hazebroucq J , Ibrahim H , Bielsky M C , Hvass U , Lacombe C , Français J L , Desmonts J M 
Published: July 2018

SummaryCardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 µg/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time.Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar.The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII :C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII: C levels were slightly higher in desmopressin-treated patients at 90 min, the difference was not significant. Thrombin-antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformely in both groups.We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding.