bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiplatelet Drugs In Haemodialysis
Authors: Crow M J , Donaldson D R , Roberts T G , Davison A M , Rajah S M 
Published: July 2018

Platelet and fibrin desposition on dialysis membranes remains a significant problem despite systemic heparinisa- tion. In randomised double blind cross-over studies the effect of three antiplatelet drug regimens have been investigated: 1) Placebo, 2) Low Dose Aspirin (ASA) and Dipyridamole (DPM) (110 mg + 75 mg) tds, 3) Standard Dose ASA + DPM (330 mg + 75 mg) tds, 4) Ticlopidine (250 mg) bd.No antiplatelet drugs were given for 21 days prior to each study and the heparin schedule remained unchanged throughout all the studies. Seventeen patients received the ASA + DPM regimens for 7 days and the Ticlopidine regimen for 14 days. Investigations were performed at the last dialysis of each study period and comprised of platelet count pre and post-dialysis, post-dialysis heparin and drug concentrations, scanning electron microscopy (SEM) of the dialysis membrane and in addition platelet aggregation predialysis in the Ticlopidine group.Standard Dose ASA + DPM significantly inhibited the reduction in platelet count during dialysis (p<0.01) and increased the post-dialysis heparin concentration compared to the other regimens (p<0.05). SEM demonstrated that only Standard Dose ASA + DPM produced consistent reduction in platelet and fibrin deposition. Ticlopidine significantly reduced platelet aggregation with ADP (p<0.05). Patient compliance was monitored by serum drug concentrations.This study indicates that Standard Dose ASA + DPM significantly reduces the thrombogenic potential of dialysis membranes, hence improving overall dialysis efficiency. Low Dose ASA + DPM and Ticlopidine show marginal reduction compaired to Placebo. Standard Dose ASA + DPM exerted a deparin-sparing action.
Possible Pathways Of Arachidonic Acid Liberation As Studied With Purified Phospholipases
Authors: Chap H , Perret B , Mauco G , Plantavid M , Laffont F , Simon M F , Douste-Blazy L 
Published: July 2018

Two kinds of informations about arachidonic acid (AA) metabolism in platelet phospholipids (PL) have been obtained from the use of purified phospholipases: 1) Beside the determination of PL sidedness in the plasma membrane, non-lytic degradation by phospholipase A2 + sphingomyelinase C showed that only 6 % of the total platelet AA is localized in the outer surface of the plasma membrane. This heterogeneous distribution is actually a consequence of PL asymmetry, since sphingomyelin and phosphatidylcholine, which predominate in membrane outer leaflet, contain only traces or relatively lower amounts, respectively, of AA than the internal lipids. It is further shown that incubating platelets with free AA specifically labels the large internal pool of AA, whereas the small external pool is renewed by a direct exchange of phosphatidylcholine with plasma lipoproteins. This offers a doublelabelling method allowing to explore the exact role of each AA pool.2) Platelet aggregation by Clostridium welchii phospholipase C produces the same metabolic changes (accumulation of phosphatidic and lysophosphatidic acids) as those induced by thrombin. These observations have led to describe the existence of a cytosolic phosphatidylinositol-specific phospholipase C and a membrane-bound diglyceride lipase. Both enzymes, coupled to diglyceride− (and monoglyceride−) kinase(s), could achieve AA release and (lyso) phosphatidic acid accumulation. Some properties of these enzymes (subcellular localization, calcium and pH dependence, positional specificity) will be presented.
Clinical Application Of Blood Surface Interactions
Authors: Edmunds L H 
Published: July 2018

Blood contact with non-endothelial cell surfaces activates Factor XII and platelets. Clinical applications of temporary or permanent devices placed within or in series with the circulation are limited by this fact. Depending upon whether or not coagulation is inhibited, thrombosis or blood injury occur.In recent years improvements have been made in vascular prostheses, heart valves and assist devices. PTFE (Gortex) prostheses as small as 4 mm in diameter have been successfully used in selected high-flow applications such as aorto-pulmonary shunts. Improved mechanical heart valves have reduced the tendency of .valve thrombosis and possibly late emboli, but long-term anticoagulation is still required for patients with aortic bioprostheses and some patients with mitral xenografts. Development of durable relatively thromboresistant materials has led to wide and successful application of the intra-aortic balloon with few thromboembolic complications. Improved designs and development of durable, relatively thromboresistant materials have advanced experimental left ventricular assist devices to the stage of limited clinical application.When coagulation is inhibited by heparin, extracorporeal perfusion systems injure formed and unformed blood elements. Platelets particularly are activated with the result that platelet function is depressed and postoperative bleeding times are prolonged after perfusion with either membrane or bubble oxygenator systems. Currently clinical trials using prostacyclin to protect platelets during the period of bypass are underway. Bleeding consequences of platelet dysfunction and heparin continue to limit clinical application of long-term extracorporeal perfusion applications for cardiac and respiratory assistance.
Definition And Evaluation Of A Therapuetic Range For The Control Of Oral Anticoagulant Treatment By Chromogenic Assays
Authors: Bertina R M , Loeliger E A 
Published: July 2018

The evaluation of the usefullness of chromogenic assays in the control of oral anticoagulant treatment, often is hampered by the rather poor correlation between the new parameter and the reference one (Prothrombin Time determination) within the therapeutical range. This means that before large scale double blind prospective studies can be started, it should be checked that the use of the experimental method will not result in unacceptable deviations in prescribed dosage.From 150 patients (each within therapeutic zone for more than 3 months) blood/plasma was analysed by at least 2 different chromogenic assays (FII, FX) and by the reference method (PT determination); the selection of patients was such to get an equal distribution over the total therapeutic range (2.0-5.0 in terms of proposed International Calibrated Ratio - ICR); on basis of these results a therapeutic range was defined for each of the experimental methods.Next it was checekd to what extent the use of the experimental method would result in differences in prescribed dosages (when compared with the reference method) a. in 100 of the abovementioned patients at subsequent control periods, b. in previously stable patients with a PT < lower limit or > upper limit of the therapeutic zone, and c. in patients starting oral anticoagulant treatment (outclinic patients and hospitalized patients).During the study the precision of the different chromogenic assays was checked using two lyophilized pooled patient plasmas.
Kinetics Of Factor Viii Inhibitors In Three Non-Hemophiliac Patients
Authors: McClellan S L , Hussey C V , Fobian J E , Pisciotta A V 
Published: July 2018

Factor VIII (VIII) inhibitors were isolated from the gamma globulin fraction of the plasmas of three non-hemophilic patients. One of these patients is thought to have acquired the inhibitor secondary to Hodgkin’s disease while the other two were apparently drug-related. These patients presented without significant prior replacement therapy and showed elevated levels of von Willebrand factor (VIIIVW-R) as measured by Ristocetin aggregation of fixed washed platelets and elevated levels of antigenic VIII (VIIIAGN) using a CELIA technique. The procoagulant VIII (VIIIAHF) activities, however, ranged from 12-20% of normal activity (one-stage method) and the inhibitors were present in levels of 6-50 Bethesda Units/ml of plasma.The kinetics of the interaction between these inhibitors and VIII were studied to further characterize the inhibitors. In vitro inactivation of VIII by the inhibitors demonstrated a two-step kinetic model similar to that proposed by Biggs. Iii vivo neutralization of transfused VIII appeared to follow the same model. The high levels of VIIIAGN and VIIIVW-R in the presence of low levels of VIIIAHF suggest binding of the inhibitor to the procoagulant moiety. Further, two-step inactivation of the procoagulant activity suggests binding of more than one molecule of inhibitor near rather than at the active procoagulant site which results in increasing stearic inhibition of the active site. This is in contrast to simple direct binding of a single molecule of inhibitor as described with bimolecular second order kinetics.Finally, the presence of high levels of VIIIAGN with markedly attenuated VIIIAHF activities implies relatively slow clearance of the inhibitor-VIII complex.
Ristocetin Induced Platelet Factor 3 Availability, A Possible New Tool In The Diagnosis Of Von Willebrand’S Disease
Authors: Muszbek L , Losonczy H , Hársfalvi B , Nagy I 
Published: July 2018

Ristocetin induced platelet aggregation (RIPA) is a highly valuable technique in the laboratory diagnosis of von Willebrand’s disease (vWD) and together with the estimation of bleeding time, F VIII procoagulant activity and F VIII related antigen in most cases it makes also division of vWD into phenotypic subgroups possible. We have shown that ristocetin makes platelet factor 3 available and ristocetin induced platelet factor 3 availability (RIPF3) similarly to RIPA also depends on a plasma factor. In the present paper it was examined if RIPF3 can be applied as a laboratory test in the diagnosis of vWD. PRP from normal controls, patients with various release defects and von Willebrand patients was incubated and continuously stirred with ristocetin or phys. saline and after 20 min the RW clotting times were determined. RIPF3 activity was expressed as the ratio of the clotting times obtained following incubation with phys. saline and ristocetin.In healthy controls and patients with release defect (n=21) this ratio was higher than 1.5, and in most cases between 1.8-2.5. In patients with vWD (n=10) the ratio was well below 1.5 (with one exception it ranged between 0.95-1.2). In 9 of the lO patients the absence or strong diminution of RIPA and RIPF3 showed close paralellism. In one patient only the slope of first vawe of ristocetin aggregation was decreased while at the same time an almost total inhibition of RIPF3 could be observed. The results indicate that RIPF3 is a valuable quantitative diagnostic test in von Willebrand disease. It can be used if expensive aggregometer is not available and it may also have an importance as additional test to RIPA in the division of vWD into subgroups. An attempt was made to develop this test further by using chromogenic substrate for the measurement of RIPF3.
Crossed Concanavalin A Affinoimmunoelectrophoresis Of Factor VIII - Related Antigen In Whole Plasma
Authors: Krauss J S , Sheard M 
Published: July 2018

Normal human factor VIII is precipitated by the lectin concanavalin A (con A). In order to study this interaction pooled normal plasma has been subjected to crossed affinoimmunoelectrophoresis with con A in the first dimension and commercial antiserum to factor VIII in the second dimension. Both decreased anodal migration and decreased precipitin height of the factor VIII - related antigen (FVIIIR:ag) confirmed the precipation of FVIIIR:ag by con A.This technique, performed in conjunction with crossed immunoelectrophoresis (CIEP) of FVIIIR:ag, should prove useful in the analysis of von Willebrand disease (vWd) variants whose FVIIIR:ag has decreased carbonhydrate and, therefore, is poorly precipitated by con A.
Presence Of Complement Factor C4 And HMW Kininogen In Prothrombin Complex Concentrates
Authors: Steinbuch M , Pejoudier L , Boffa M C 
Published: July 2018

The protein contaminants of prothrombin complex preparations obtained by adsorption onto ion exchangers and namely DEAE-Sephadex were studied.Among them a high amount of C4 accompanied by some C4- binding protein was noticed. Certain preparations contain as much as 20 times the normal plasma concentration of C4. This complement component is able to form an anaphylatoxin. Its molecular integrity has been checked by immunoelectrophoresis and rocked electrophoresis. Its degradation by several enzymes is shown.The clotting component concentrates contain also high amounts of kininogen. The enrichment of high molecular weight (H.M.W.) kininogen is comparable to the one observed for C4. Its presence was assessed with an antiserum specific for this protein and the ability of the kininogen to supply kinin was checked on guinea pig ileon.The potential thrombogenicity of prothrombin complex preparations has been attributed to contact factors. It is shown in this study that factor XII and its derivatives as well as PK can be easily removed during the processing of the fraction. However, kininogen displays the same affinity for the ion exchanger than the clotting components.
Incomplete Fibrin Formation And Highly Elevated Factor XIII Levels In Multiple Myeloma
Authors: Klingemann H G , Egbring R , Heimburger N , Havemann K 
Published: July 2018

In some patients suffering from multiple mye - loma a defect in fibrin formation has been suggested as one cause for bleeding tendency. However nothing is known about the commoness of this disorder or about the correlation to factor XIII activity.As pointed out in this investigation the defect in fibrin formation, as proven in SDS-PAA electrophoresis, is due to a lack of α- chain polymerization in 5/11 patients with IgG - myeloma and 2/5 with IgM paraproteinemia. No disturbed fibrin formation could be observed in IgA myeloma (n=6). Factor XIII concentration of subunit A and to a smaller extent of subunit S (Laurell technique) were highly elevated in all cases with regular fibrin formation. Comparable values were obtained measuring the transamidase activity as incorporation of C 14 labelled putrescin into casein. Levels up to 600 % of normals could be evaluated. In contrast all patients with a lack of α- chain polymerization had a factor XIII activity within the normal range. Addition of factor XIII concentrate to plasma with defective fibrin formation led in 5 out of 7 cases to a partial crosslinking of α - monomers. A complete α- chain polymerization could not be achieved, even when high concentrations of factor XIII were used. We conclude that in some cases paraproteins can inhibit the factor XIII activity and prevent its action on fibrin. Patients, who are able to produce factor XIII, especially the active part subunit A in excess, can achieve a regular fibrin formation. Treatment with factor XIII in case of bleeding should be taken into consideration.
In Vitro Comparison Of Activated & Nonactivated Prothrombin Complex Concentrates (PCC)
Authors: Lazerson J , Abildgaard C F , Harrison J 
Published: July 2018

In order to determine whether any in vitro test is related to clinical efficacy of PCC we compared nonact ivated PCC (Konyne-Cutter, Proplex-Hyland; Prothromplex- Immuno) with activated PCC (Autoplex-Hyland, FEIBA-Immuno, Antiinhibitor Correctional Concentrate (AlCC)-Cutter). The non-activated partial thromboplastin time (NAPTT), factor VIII correctional activity (FVIIICA) by the Hyland method, and factor VIII inhibitor bypassing activity (FEIBA) by the Immuno method were performed on all PCC according to the manufacturer’s specifications, utilizing their reagents. The results are reported as averages as interlot differences were minimal.No differences in results were obtained in FVIIICA assay of Autoplex whether inhibitor plasma or noninhibitor (factor VIII deficient) plasma was used as substrate, in contrast to the FEIBA assay where substitution of noninhibitor plasma resulted in a threefold decrease in final units of FEIBA (i.e. 5 units vs 16 units).It is concluded that the non-activated PCC contain 1/3 to 1/2 the factor VIII correctional activity of the activated PCC and that the NAPTT depending on the dilution selected is only a poor correlate of either. The relationship of the assays to clinical efficacy remains unknown.
Identification Of Thrombin In Human Serum By Iso- Tachophoresis
Authors: Principe D Del , Biancini G , D’Arcangelo C , Mancuso G , Persiani M , Menichelli A 
Published: July 2018

We investigated the nossibility of detection of thrombin in blood by analytical isotachophoresis. This technique is a relatively new electrophoretic method for separation of different ions. At the equilibrium the ions move with the same speed and are spaced into consecutive zones between the leading and terminating electrolytes according to their mobilities. The instrument used for analytical isotachophoresis was equipped with an UV and thermal detectors. The leading was MES, Ammediol, hydroxypropylmethyl cellulose 0.25%, pH 9.2; the terminating was EACA, Ammediol, adjusted with Ba(OH2) to pH 10.8. Carrier ampholytes,pH 3.5-8 range were employed as spacers.Free thrombin was not detected by analytical isotachophoresis in 30 normal sera, while it was demonstrated in 2 children with laboratory and clinical evidence of DIC.Our data show that the detection of free thrombin by isotachophoresis is due to an in vivo decrease of the serum neutralizing capacity following either an enzyme excess or an inhibitor loss.The isotachophoresis allows the assay of microquantities of sample(2 μl)in short time(15-20 min) and may reveal itself useful in clinical diagnosis.
Permeability Enhancing And Chemotactic Activities Of Lower Molecular Weight Degradation Products Of Human Fibrinogen
Authors: Tanaka K , Sueishi K 
Published: July 2018

Fibrinogen degradation products were investigated for leukocyte chemotactic activity and enhancement of vascular permeability. Fragments X, Y, D and E, and non-dialysable lower molecular weight degradation products were fractionated from plasmin digests of human fibrinogen by gel filtration, zone electrophoresis and ion exchange chromatography. They were assayed for chemotactic activity for human granulocytes by the modified Boyden chamber and for vascular permeability increasing activity in rabbit skin injected intravenously with pontamine blue.Both activities increased progressively with plasmin digestion of fibrinogen. 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 and E. The low molecular weight break down product with chemotactic activity showed the highest activity in rabbit skin in vivo as well. Granulocytic infiltration was most prominent 6-12 hr after intradermal injection and apparent even at an intradermal dose of 0.5/μg. Permeability enhancement of the active fraction reached to its muximum level at 5-10 min and was dose-dependent. Electron microscopic observations of the small blood vessels in rabbit skin correlated an increased permeability with the formation of characteristic gaps between adjacent endothelial cells and their contraction. Carbon particles used as a tracer passed into the vascular walls through these intercellular gaps.These observations add more support for the hypothesis that lower molecular weight degradation products of fibrinogen may be influential in contributing to granulocytic infiltration and enhanced permeability in lesions associated with deposits of fibrin and/or fibrinogen.
Fibrinogen In Liver Cirrhosis. Sialic Acid Content Of Fibrinogen In Moderate And Severe Cirrhosis And Relation To Thrombin Time
Authors: Palareti G , Poggi M , Coccheri S 
Published: July 2018

An increased content in sialic acid in the carbohydrate moiety of fibrinogen (fibrinogen sialic acid, FSA) as described in a number of different liver patients has been accounted for the polymerization defect often found in conditions of liver damage.In 22 cases of liver cirrhosis divided into “moderate” (n = 11) and “severe” (n = 11) according to standardized criteria, FSA was measured with the method of Warren after purification of fibrinogen with β-alanine and glycine, and expressed in mg per 100 mg of fibrinogen.In the whole group of cirrhotics FSA was 0.79 mg ± 0.17 (controls n = 10, FSA 0.70 mg ± 0.13, p > 0.05). However, FSA was markedly increased in “severe” cases (0.90 mg ± 0.16) both vs controls (p < 0.001) and vs “moderate” cases (0.69 mg ± 0.10, p < 0.005). Thrombin time (TT) although prolonged in cirrhotics (p < 0.001) was not significantly different between the subgroups. FSA correlated inversely with fibrinogen level (p < 0.01) but did not correlate with TT.These results show that the increase in FSA is a feature of severe liver cirrhosis especially in presence of a low fibrinogen level. Although probably involved in the polymerization defect, this increase alone cannot properly explain the prolongation of TT which is known to occur also in absence of serum FDP.
Lyophilized, Reconstituted Human Plasma-, A Better Substrate Than Purified Fibrinogen For Thrombin Activity Assay
Authors: Brosstad F , Godal H C 
Published: July 2018

The clotting time of purified fibriiwgen/thrcinbin mixtures is regularly used for assay and standardization of thrcmbin activity. However, considerable batch-tobatch variations as well as difficulties in obtaining precise determination of the visual gel point are nharasteristics of purified fibrinogen preparations, making them suboptimal for these purposes. In contrast, thrombin (1 NIH U) clotting time of pooled, human citrated plasma varies only insignificantly from batch to batch,and the readability of the gel point and storage stability at -20°C are excellent . For a more general use of pooled plasma as substrate for thrcnibin assay a lyophilized specimen would obviously be more practicable. To study this, pooled citrated hunan plasma was either lyophilized directly, or subsequent to dialysis against 0.2M citrated buffer pH 7.4 and reconstituted to original volume with water after storage at either +20°C or -20°C for varying periods of time.Conclusion: Only plasma dialysed prior to freeze-drying shewed a pH and a thrombin clotting time identical to that of unprocessed plasma. Such lyophilized plasma can be kept at rocm temperature for at least 1 year (our present limit of observation) wihtout any sign of deterioration, and represent a premising alternative to presently used thrombin substrates.