bluuebunny/crossref_metadata_2025_split huggingface dataset:
INACTIVATION OF HEPATITIS VIRUSES AND HIV IN PLASMA AND PLASMA DERIVATIVES BY COMBINED TREATMENTWITH β-PR0PI0LACT0NE/UV-IRRADIATION
Authors: Stephan W , Dichtelmüller H , Prince A M , Gürtler L , Deinhardt F 
Published: June 2019

A combined treatment of plasma andplasma derivatives by β-Propiolactone (β-PL) /UV-irradiation is inuse at Biotest for the preparation ofthe virus safe serum preserve Bisekd® and coagulation factor concentrates.The efficacy of this sterilization procedure has been demonstrated for HAV(> 8.2 log10), HBV ( 7.0 log10) and HNANB (> 4.5 log10). As HIV has become a major problem tne inactivation of HIV by β-PL/UV in human plasma was tested. Pooled human plasma was spiked with 104.2 infectious units per ml of the Gallo strain of HIV/ HTLV-III and sterilized with 0.25 % β-PL, 60 min at pH 7.2 and subsequently UV-irradiated (4 × 20 W). After treatment with β-PL alone orβ-PL/UV no infectious HIV was detectable by reverse transcriptase assay in inoculated H-9 cultures after 14 days of cultivation (> 4.2 log10 inactivation). When the virucidal efficacy of ft-PL and UV was tested separately, β-PL inactivated > 3.5 log10, UV-irradiation another 2.5 log10 of HIV, as demonstrated by immunofluorescence tests in H-9 cultures 27 daysafter inoculation.When cryoprecipitate/F VUI-concentrate was sterilized by ft-PL and UV, > 4.5 log10 of HIV were inactivated by UV and > 3.5 log10 by α-PL. The results indicate, that the combined treatment by β-PL/UV inactivates all potentialtiters of HIV, which can be expected inscreened and pooled human plasma orcryoprecipitate, used for the preparation of virus safe plasma derivatives.
VIRAL SAFETY OF SOLVENT/DETERGENT-TREATED AHF IN PATIENTS WITH HEMOPHILIA
Authors: Horowtz M S , Hilgartner M W , Lipton R A , Rooks C , Horowitz B 
Published: June 2019

The safety of an Antihemophilic Factor concentrate (Factor VIII-SD) treated with the organic solvent tri(n-butyl) phosphate (TNBP) and sodium cholate is being assessed with respect to transmission of non-A, non-B hepatitis virus (NANBHV) and human immunodeficiency virus (HIV). TNBP/cholate treatment has been previously shown to inactivate at least 10,000 infectious doses each of hepatitis B virus (HBV) and NANBHV using a chimpanzee model, and 30,000 tissue culture infectious doses of HIV.Patients enrolled in the study have had no previous exposure to blood products made from plasma pools, although some have received small quantities of single-donor products. They have normal alanine amino transferase (ALT) levels and no markers of prior HIV infection and have all been vaccinated against HBV. Each has been treated, as required, with an individual lot of Factor VIII-SD prepared at the New York Blood Center by an FDA-licensed procedure. ALT levels and HIV antibody have been monitored bi-weekly for two months and monthly until the end of six months. Seven patients who have received 475 -20,000 units of AHF(total units 38,255, median dose ∽3400 units) have been followed for at least three months. There has been no indication in these patients ofinfection with either NANBHV or HIV. An eighth patient who had an elevatedALT level prior to enrollment was followed for HIV antibody only. He remains HIV antibody negative through fivemonths of follow-up. Six additional patients have entered the study, but have not yet required treatment or have been followed for only a short time. These results suggest that the risk of virus infection associated with the use of AHF concentrates is significantly diminished by solvent/detergenttreatment.
COMPARISON OF VARIOUS AMI DOLYTIC HEPARIN ASSAYS: REPORT OF A COLLABORATIVE STUDY
Authors: Sternberger A , Haas S , Breddin K , Blümel G 
Published: June 2019

The authors performed a controlled study to compare commercially available amidolytic heparin assays based on anti-Xa or anti-I la systems. All participants (see below) were provided with the same batch of all heparin preparations and reagents including homogenous plasma preparation. In addition plasma was spiked with the various unfractionated (n=2) as well as lmwh- (n=5) and heparinoid preparation (n=l). The four university laboratories analyzed all heparin preparations that are registered or used in clinical trials in FRG (n=8). The two testkit producers analyzed registered heparin preparations and the heparin producer their brand only. The study was recently completed and the data analysed and collected. The first evaluation revealed that the amidolytic anti-I la assay is insensitive for lmwh and heparinoids. Determination of unfractionated heparins is not accurate below 0.5 units of the corresponding standard. The Xa-methods are more sensitive for lmwh and heparinoids, however these methods also reveal a high standard deviation. Estimation of concentrations below 0.5 units of all tested heparin preparations is questionable.The authors are indented for active cooperation to Prof. Dr. K. Andrassy (Med. Univ. Heidelberg), Dr. M. Biegholdt (MIDY LABAZ), Dr. G. Dertinger (Sandoz AG), Dr. VJ. Feller (Braun Melsungen AG), Dr. P. Friberger (Kabi Vitrum Stockholm), Dr. P. Hell stern (Univ. Klinik Homburg), Dr. D. G. Meulemann (Organon Scientific Development Group), Dr. X. Muller (Nordmarkwerke), Dr. Zimmer (Boehringer Mannheim GmbH).
CIRCADIAN CHANGES IN THE ANTICOAGULANT EFFECT OF HEPARIN. PHARMACODYNAMIC AND PHARMACOKINETIC EFFECT
Authors: Decousus H A , Scully M F , Reynaud J , Arnaud-Crozat E , Boissier C , Barral R , Queneau P , Reynaud J , Parker C , Kakkar v v 
Published: June 2019

Six patients, with thromboembolic arterial disease, were prospectively studied to assess the influence of the time of injection of a constant dose of calcium heparin (Choay ), given subcutaneously, on the level of heparin measured by APTT and anti-Xa assay. For each patient, the initial dose of heparin was adjusted by APTT 6h after a morning injection to 1.5 and 2.5 times control. Dose was then kept constant. Four randomized times of injection were tested (8am, 4pm, 8pm and 12pm), in each patient acting as his own control. Blood was sampled via a cannula, at Oh, 2h, 3h,4h,5h,6h, 8h, lOh and 12h after injection. The mean APTT and anti-Xa values for the evening injections (8pm and 12pm) were higher than for the morning injection (8am), at 2h until lOh after injection. These differences were significant (analysis of variance:p<0.001) and reached almost 30 seconds for mean APTT values measured 4h, 5h and 6h after injection. For the afternoon injection (4 pm) the mean APTT and anti-Xa values were intermediate but significantly different from all the other times of injection (analysis of variance: p<0.01).Blood was sampled also on two consecutive days at 12am and 12pm from eight patients receiving heparin subcutaneously for treatment of DVT (administered at 6am and 6pm respectively). Heparin levels by APTT, TT and three antifactor Xa methods (Heptest, Hepaclot, Chromogenic) were significantly higher at night than morning (analysis of variance p<0.005). Cosinor analysis confirmed these results are consistent with circadian variation as we have previously reported after continuous infusion of UF heparin (Br. Med. J., 1985, 290, 341-344). The observed variation was found to be a resultant of a pharmacodynamic effect (circadian variation in assay response to heparin) and pharmacokinetic effect (circadian variation in 99m Tc-heparin clearance). Such circadian variation should be taken into account when deciding heparin dosage.
THE EFFECT OF SHEAR ON OLIGOMER FORMATION; EFFECTIVE REMOVAL OF MONOMERS
Authors: Berk H R 
Published: June 2019

Fibrin polymerization has been found to be influenced by shear flow conditions (Puryear,1980). In order to determine which mechanisms are responsible for theeffect reported it is necessary to look at the various stages in fibrin polymerization. It is known that the enzymatic attack of thrombin on fibrinogen is not influenced by shear (Sellers,1981). The next step, which is investigated in this study, is the oligomer-early protofibril stage.Fibrinogen (human, Kabi) is reacted with thrombin (human, Sigma) under Couette flow conditions (volume-averaged shear 0-250sec-l) in a pH 6.8, 4mM CaC12, HEPES buffered solution (I. S.-.15). The reaction time is chosen so that 6% of fibrinopeptide A (FPA) is released. The reaction is stopped by a 1,6 hexandiol-hirudin solution. The effect of shear on oligomer population is measured using large angle 1ightscattering techniques.In order to predict theoretical shear effects on oligomer formation, it is important to be able to predict the population size. This is done using Jamney’s (1983) predictions, for early reaction time, assuming q=16. Given a size distribution it is possible to apply low Reynold’s number hydrodynamic and Smoluchowski1 s( coagulation theories to predict possible shear affects.Hydrodynamic theory predicts no effect of shear on oligomer formation; Peclet numbers are too small. Smoluchowski coagulation theory, on the other hand, predicts that for oligomer sized particles in the shear range studied, orthokinetic (shear induced) coagulation becomes more important than peri kinetic (Brornian) coagulation.Results obtained from Zimm analysis show a dramatic increase in molecular weight, compared to the stagnant case, in the shear region corresponding to where orthokinetic coagulation dominates. The higher the thrombin concentration, the more extreme and earlier (i.e. lower shear) these effects are felt. After a peak is reached in molecular weight there is a sudden drop. This is caused by monomer exhaustion which shifts the population to a more homogeneous type. The concept of orthokinetic coagulation is important physiologically since it is advantageous to incorporate monomers onto fibers as quickly as possible.
COMPARISION OF THE DETECTION OF LUPUS ANTICOAGULANTS USING THREE DIFFERENT METHODS AND THE PRESENCE OF ANTI-CARDIOLIPIN ANTIBODIES
Authors: Criel A , Gilbert B , Van Hoof A , Hidajat M , Louwagie A 
Published: June 2019

Lupus anticoagulant (LAC) is an antibody directed against phospholipids which prolongs in vitro clotting assays. Several detection methods have been described; however all give some different results. Recently ELISA and RIA assays have been developed which detect IgG and IgM anti-cardiolipin antibodies. The aim of our study was to compare three different LAC tests with an ELISA anti-cardiolipin test. The tests used were : kaolin clotting time (KCT or Exnertest), tissue thromboplastin inhibition test (TTI or Schleider test), activated partial thromboplastin time using a 50, 100, 200 fold dilution of the phospholipid preparation (APTT dilution test), and an IgG and IgM anti-cardiolipin ELISA test. 114 samples of patients suffering from diseases known to be accompanied with LAC antibodies (auto-immune diseases, recurrent abortion, thromboembolism, etc.) were studied. Positivity with one of the tests was found in 45 patients (39%). Patients with the diagnosis of SLE or otherimmune diseases showed the highest positivity (56%) whereas those with thromboembolism, recurrent abortion etc. were only positive in 27%.Among these 45 positive patients the TTI was positive in 41 cases (91 %);however in 10 cases (24 %) this was the only positivity found. The KCT test and the APTT dilution test were both positive in 18 cases (40 %). Anti-cardiolipin antibodies were found in 21 patients (47 %): IgG only in 12 (27 %), IgM only in 5 (11 %), both IgG and IgM in 2 (4 %); in 19 of these 21 patientsthe TTI was also positive.In our study the TTI test seems to be the most sensitive test but possibly also the test with the highest aspecific positivities. IgG and IgM anti-cardiolipin antibodies were less frequently found than expected.
FIBRINOLYTIC ACTIVITY AND OTHER COAGULATION PROTEINS IN PATIENTS WITH LUPUS ANTICOAGULANT
Authors: Borrell M , Fontcuberta J , Muñiz E , Grau E , Oliver A 
Published: June 2019

Patients with lupus anticoagulant (LA) is a group with recognised risk of thrombosis. In order to study the possible causes of this tendency, we have studied the fibrinolytic activity and some other coagulation parameters considered as thrombotic markers in a group of 12 patients with LA. Half of them had presented thrombotic disease and/or recurrent abortions. 3 patients presented systemic lupus erythematosus and in the other 9 we couldn't detect any connective tissue disorder. The following tests were performed: tissue plasminogen activator (t-PA) activity, t-PA antigen, t-PA inhibitor, fibrin plates with and without kaolin, -antiplasmin, plasminogen, prekallikrein, antithrombin III, protein C, protein S. The results were analysed comparing the values obtained in LA group with respect to normal values, and among the LA group between patients who had suffered from thrombotic disease and those who did not.The results obtained did not show significant differences between control group and LA patients except in t-PA activity which was found decreased in LA group: 1.86±0.89 versus 3.0±0.94 in control group (meantstandard deviation). Among this group there were no differences between patients who had suffered from thrombotic disease and those who didn’t.From these results we suggest that unpaired t-PA activity may contribute but not be the only responsible factor for the dvelopment of thrombosis in these patients.
INCREASED THROMBIN GENERATION DURING COLLECTION OF BLOOD FROM DONORS TAKING ORAL CONTRACEPTIVES (OC)
Authors: Skjønsberg O H , Kierulf P , Engebretsen L F , Gjønnes G , Godal H C 
Published: June 2019

450 ml blood was drawn into Fenwal PVC-bags from 26 OC-users and 28 non-users. The groups were comparable with regard to sex, age, smoking habits and blood collecting time. Thrombin generation was estimated as the fibrinopeptide A (FPA) concentrations in the bags immediately after ending the donations. The blood was also analyzed following storage at 4°C for 24 hours.Subsequent to donation, the median FPA level in the control group was 4.2 (range 1.8-18.9) and in the OC-group 7.5 (range 2.2-113.7) (p°0.05), reflecting a more pronounced thrombin generation during collection of blood from OC-users. The level of prekallikrein (PKK) was also higher in blood drawn from OC-users (97.0% (73-128) in the control group versus 121.5% (79166) in the OC-group (p°0.001)), as was the level of FVIII:C, the latter difference was, however, not significant (p=0.06). The A T-111 concentrations were similar in the two groups.No cold promoted activation could be observed following storage of the bags at 4°C for 24 hours, neither was any change observed in the levels of FPA, PKK or AT-III. There was no difference between the groups with regard to decay of FV111: C upon storage.We conclude that thrombin generation is more pronounced during collection of blood from donors taking OC. Only some of the OC-users seem to generate appreciable amounts of FPA (19% above 30 ng/ml), and it is important to notice that all bags containing alarmingly high levels of FPA were drawn from women taking OC.
PROTEIN C AND PROTEIN S LEVELS IN TALL GIRLS TREATED WITH ETHINYL -OESTRADIOL
Authors: Huisveld I A , Greven E C G , Bouma B N 
Published: June 2019

Increased levels of several coagulation factors and reduced levels of anti thrombin III (ATIII) have been observed in adults on oestrogen medication and in girls who were treated for excessive tallness with high doses of ethinyloestradiol (E2). In females using oral contraceptives an additional effect on the protein C system has been reported. In our study we evaluated the effect of e-thinyloestradiol treatment (0.1-0.3 mg, administered for at least 6 months) in 14 tall girls (age 14 + 2 yr and height 179 + 4 cm). 13 girls of comparable age (13 + 2 yr) and height 175 + 7 cm) served as controls. Protein C, protein S, C4-binding protein as well as Factor II, plasminogen and ATIII antigen levels were determined by rocket immunoelectrophoresis. ATI11 heparin cofactor ami do-lytic activity was assessed using S2222. Protein S antigen not in complex with C4b-binding protein (PSfree), was assayed in the supernatant plasma after selective precipitation of the protein S-C4b-binding protein complex with PEG 8000. Complete separation of free protein S and PS-C4b-bp complex was verified with crossed immunoelectrophoresis. Results were expressed as % of a normal pool. In the group of girls who were being treated with ethinyl oestradiol (E2-users) significantly higher levels (P<0.001) were observed for protein C (126 ± 29 vs 88 ± 10 in the controls), Factor II (109 ± 18 vs 81 ± 12 in the controls) and plasminogen (131 ± 19 vs 85 ± 9 in the controls). Protein S (58 ± 10 vs 97 ± 8 in the controls) and PSfree (54 ± 11 vs 88 ± 11 in the controls) were sig nificantly reduced (P<0.001) in the E2-users. Only a slight reduction was observed in ATIII antigen levels (95 ± 16 vs 104 ± 9 in the controls) and in the ATIII heparin cofactor activity (105 ± 14 vs 104 ± 9 in the controls). No difference between E2-users and controls was observed in the C4b-binding protein levels (111 ± 25 vs 114 ± 33).Results indicate that treatment of tall girls with high doses of synthetic oestrogens is associated with in vitro signs of hypercoagulability quite comparable to those observed in adult females. However, in contrast to observations made in adults no thromboembolic complications have been reported in juvenile subjects on E2-medication implying additional (aqe-related) variables in the qe-nesis of thrombosis.
EVALUATION OF COMMERCIAL PROTEIN C ASSAYS
Authors: Morrien-Salomons M M , Sturk A , Huisman M V , Borm J , Büller H R , ten Cate J W 
Published: June 2019

Plasma protein C inactivates the activated coagulation factors V and VIII. The assay of protein C is important, because a protein C deficiency is associated with a thrombotic tendency. We therefore evaluated 5 commercial assays in 49 normal volunteers, 48 patients suspected of deep vein thrombosis (DVT) of the leg but with negative impedance plethysmography (IPG), and 52 patients with DVT proven by IPG. The assays were rocket electrophoresis (Merz and Dade antibody), ELISA (Boehringer Mannheim), 2 chromogenic activity assays (Behringwerke and Kabi) and a clotting assay (Behringwerke). Coumarin therapy was used by 13 DVT positive, and 3 DVT negative patients. Results are presented in the table.TABLE: In correlation 1 and 2, the assay results all non-coumarin treated individuals (n = 133) were compared with rocket electrophoresis and ELISA resp.In the non-coumarin treated patients, both in the DVT positive and in the DVT negative patient group one protein C deficiency was detected by all assays.Based upon the large assay VC (ROCKET) and normal range (B. CLOT), and poor correlation of the assays with the ELISA (ROCKET, B. CLOT) we conclude that the ELISA, B.CHROM and K.CHROM are to be preferred. However, as B.CHROM does not need a plasma absorption step it is somewhat preferable for activity assays.
A New Type of Congenital Dysfibrinogenemia (Fibrinogen Tokyo) with Defective Stabilization of Fibrin Polymers
Authors: Samori T. , Yatabe M. , Ukita M. , Fujimaki M. , Fukutake K. 
Published: June 2019

A new type of congenital dysfibrinogenemia characterized by abnormal stabilization of fibrin polymers under the normal concentration of plasma factor XIII and normal thrombin time has been discovered in Tokyo.The molecular abnormality of this abnormal fibrinogen are shown by an anodal immunoelectrophoretic mobility and an abnormal pattern of D fragment in fibrinogen degradation products by plasmin digest on Immunoelectrophoresis and crossimmunoelectrophoresis.However, the plasma fibrinogen level of this case measures always in the normal range, when immunological methods or thrombin dependent methods are used, and the decreased level of plasma factor XIII is indicated by the use of assay methods based on clotlysis.
A Series of Extremely Potent Thrombin-Inhibitors Newly Synthetized
Authors: Okamoto S. , Hijikata A. , Kikumoto R. , Tonomura S. , Tamao Y. 
Published: June 2019

Starting with the simple arginine derivatives having weak thrombin-inhibitory activity, ca. 320 chemical compounds were designed and synthetized by the authors, in such a way as increasing the inhibitory activity by stepwise chemical modifications. The extremely potent inhibitors thus obtained are described.These inhibitors are chemcially naphthalene-sulfonyl-arginine derivatives, the basic structure being composed of three functional sub-units and designed, to reflect the part of fibrinogen peptide to be split by thrombin.One of the representatives, dansyl-arginine-ethyl-piperidine amide, inhibited 50% of thrombin activity at 0.1 μM when 5 μM fibrinogen was substrate. Similar result was also obtained when benzoyl-Phe-Val-Arg-pNA was substrate. The mode of inhibition was found competitive.The inhibitors suppressed the platelets aggregation due to thrombin satisfactorily. However, the inhibition on plasmin, reptilase or trypsin was far weaker, indicating the very high selectivity to thrombin. Their relatively low toxicity led the authors to extend the studies toward the animal experiments and results obtained will be reported elsewhere.
Common Action of Inducers and Inhibitors of Aggregation on Phosphorylation of Surface Localized Ca-Binding Protein
Authors: Booyse F. M. , Marr J. , Tomlinson D. , Yang D. G. , Rafelson M. E. 
Published: June 2019

Analysis of intact 32P-labeled platelets by SDS-polyacrylamidegel electrophoresis shows the presence of only a single phosphorylated protein. This phosphoprotein has been isolated, has a subunit molecular weight of 11,100, is surface localized (lactoperoxidase-125 Iodine labeling) and binds 1 mole of Ca2+ per mole of phosphorylated subunit. The γ-32ऩ from (γ-32P) ATP is specifically incorporated as 0-phosphoserine by a cAMP-dependent protein kinase.The phosphorylated state and hence the Ca-binding of this protein is maintained by membrane associated cAMP-dependent protein kinase phosphorylation and phosphoprotein phosphatase dephosphorylation. Thrombin, collagen, histone and ADP competitively inhibit phosphorylation and Ca-binding by serving as protein kinase acceptors. Epinephrine, serotonin and ristosetin induce dephosphorylation and abolish Ca-binding by activating the phosphoprotein phosphatase. PGEl5 ATP, cAMP increase phosphorylation and Ca-binding by activating the protein kinase ; aspirin and EDTA increase phosphorylation and Ca-binding by inhibiting the phosphoprotein phosphatase. In 3 cases of Glanzmann’s thrombasthenia, increased phosphorylation and Ca-binding was due to decreased phosphoprotein phosphatase activity-activity was restored the addition of ristosetin. A common phosphorylation-dephosphorylation mechanism for the action of inducers and inhibitors on Ca-mobilization and platelet activation will be presented.
A New Fibrinogen Anomaly: Fibrinogen Buenos Aires
Authors: Buraschi J. A. , Sack E. S. , Quiroga E. , Hendler H. 
Published: June 2019

Report of a familial defect of fibrinogen in a 42 year old woman and in one of her siblings. The defect in the boy produced different abnormalities. She had a lifelong hemorrhagic tendency and deffective wound healing and only slight prolongation of the thrombin time. She had normal fibrinogen levels (tested by several methods) and normal coagulation factors (including Factor XIII). Both fibrinolytic mechanism and platelet function were normal. Plasmatic antithrombin III activity was normal whereas its serum activity was increased. The bleeding time was moderately prolonged and clot retraction impaired. The thromboelastogram showed reduction of the “ma.” and plasma polymerization was deficient. These last two abnormalities were partially corrected by transfusions of fresh plasma. Aggregation of fibrin monomers was also deficient whereas fibrinopeptide release was quantitatively normal. The abnormal fibrinogen has increased immunoelectrophoretic mobility and an abnormal sedimentation pattern.Her son had a markedly prolonged thrombin time with bovine thrombin whereas with the human enzyme the test was moderately abnormal. Plasma polymerization was absent and sedimentation cooefficient increased. Reptilase time was normal. The abnormal fibrinogen is tentatively designated fibrinogen Buenos Aires, since its possible identity with other abnormal fibrinogen has not been excluded.