bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adsorption of Blood Coagulation Factors II, VII, IX and X from Human Plasma to Aluminium Hydroxide
Authors: Swart A. C. W , Klaassen B. H. M , Bloys-van Treslong-De Groot C. H. F , Hemker H. C 
Published: June 2018

SummaryThe influence of pH, adsorption time, ionic strength, buffer type and plasma concentration on adsorption and elution of the factors of the prothrombin complex from normal human ACD plasma onto A1(OH)3 is investigated. Reproducible small differences are found between the behaviour of the four factors II, VII, IX, and X.
Intravenous Infusion of a Standardised Coagulation Active Phospholipid Complex in Uremic Coagulation Deficiency
Authors: Schimpf K.l , Hanf-Hoppe H.-W , Immich H 
Published: June 2018

SummaryInfusion for 90 min of 10 ml brain lipid extract brought thrombin generation and prothrombin consumption levels in uremic patients to normal for 3 h. After quick injection of the same doses (within 3 min) the effect lasted less than l1/2h. Control subjects produced hypercoagulability with the same treatment. The results of these clinical experiments, obtained with 12 subjects, were shown by analysis of variance to be statistically significant.
Fibrinogen Troyes - Fibrinogen Metz
Authors: Soria J , Soria C , Samama M , Poirot E , Kling C 
Published: June 2018

SummaryTwo new cases of congenital dysfibrinogenemia have been discovered. In the first case, “Fibrinogen TROYES”, the abnormality is characterized by a prolonged thrombin clotting time, the defect being due to abnormal aggregation of fibrin monomers. There is no tendency towards excessive bleeding. The abnormality is found to be present with the same intensity in one of the patient’s brothers and one of his sisters.In the second case, “Fibrinogen METZ”, the abnormality is more pronounced, since, even in the presence of very high thrombin concentrations no clotting occurs. The abnormality is due to a defect in the release of fibrinopeptides, on addition of thrombin. The patient’s blood contains only abnormal fibrinogen. The plasma recalcification time is more prolonged than in the whole blood clotting time. The abnormality is present in both parents in heterozygote form, a milder form than in the patient who is homozygous. The patient has a moderate bleeding tendency, the parents being normal in this respect.
Induction of Immunotolerance in Hemophilia for High Titre Inhibitor Eradication: A Long-Term Follow-Up
Authors: Mariani G , Solinas S , Pasqualetti D , Ghirardini A , Verani P , Buttó S , Lopez M , Moretti T 
Published: June 2018

SummaryThree hemophiliacs with high titre inhibitor were treated with a medium-high FVIII dose schedule (100 IU/kg bw daily) with the aim of inducing the immunotolerance. These patients were followed-up extensively concerning their immunological status and HIV serology. In all of them the inhibitor disappeared and normal FVIII kinetics were obtained after 22, 15 and 29 months. After eradication of the inhibitor, no recurrence took place in any of the patients. All the patients were HIV Ab positive before the beginning of the treatment. In one of them CD4+ cells fell progessively 32 months after the treatment was started, a fullblown AIDS showed up, and the patient died 5½ years after the beginning of the treatment. In the second and third patient the CD4+ cells varied widely but remained >400/μl during the whole immunotolerance treatment. The latter two patients are AIDS and ARC free so far, but patient No. 2 developed a mild-to-severe thrombocytopenia.Considering the high cost of the treatment and the possibility that such an intensive administration of FVIII concentrates might worsen the immunological status of patients, this therapeutic procedure should only be applied with caution.
Abnormal Typical Pattern of Platelet Function and Thromboxane Generation in Unstable Angina
Authors: Zahavi M , Zahavi J , Schafer R , Firsteter E , Laniado S 
Published: June 2018

SummaryPlatelet aggregation (PA), platelet thromboxane B2 (TXB2) generation and 14C 5-hydroxytryptamine (5HT) release were studied in 13 patients with unstable angina, and compared to 14 patients with stable angina and 16 healthy controls. A typical pattern, distinct in 4 aspects from stable angina patients or controls, was observed in the unstable angina patients. ADP or collagen induced shape change was 3-4 times greater, the extent of epinephrine induced PA was nil or very low, the extent of collagen induced 14C 5HT release was also reduced while collagen induced platelet TXB2 generation was increased in spite of a reduced extent of PA. The extent of ADP or collagen induced PA was also significantly reduced. These results indicate a platelet membrane abnormality occurring presumably during contact of the circulating platelets with a non-occlusive thrombus observed at sites of ruptured plaques in unstable angina patients. Since also the pattern (20-30% overlap with control values) was distinct from that of stable angina patients, it might indicate an active thrombotic process.Plasma β-thromboglobulin (βTG) and TXB2 levels and serum TXB2 generation were also studied in the cardiac patients and controls and in another 10 patients with advanced peripheral occlusive arterial disease (POAD). Plasma βTG and TXB2 levels were slightly elevated in the unstable angina patients and markedly elevated in the POAD patients. Serum TXB2 generation was, however, elevated in the stable angina patients (p <0.002) and more so in the unstable angina patients (p <0.001) compared to controls or to POAD patients. This was presumably mediated through enhanced thrombin generation. These results suggest that the measured plasma βTG variable in the unstable angina patients is not useful in the assessment of in vivo platelet activation. It is presumably reflecting the sum of local enhanced platelet activation (at sites of ruptured plaques) and of reduced function of the “defective” circulating platelets. The ability of the platelets of unstable angina patients to generate large amounts of TXB2 if occurring in vivo might induce an intense coronary vasospasm.
Arterial Thrombosis Associated with Immune Thrombocytopenia: Presence of a Platelet Aggregating IgG Synergistic with Thrombin and Adrenalin
Authors: Jackson Shaun P , Jane Stephen M , Mitchell Christina A , Fernando Cortizo W , Hau Lena , Pfueller Sharron L , Salem Hatem H 
Published: June 2018

SummaryWe report the case of a 50-year-old lady who presented with arterial thrombosis in the setting of thrombocytopenia. Investigations confirmed the diagnosis of idiopathic thrombocytopenic purpura. A spontaneous platelet aggregating factor (SPAF) was isolated from the immunoglobulin fraction of the patient's plasma. The isolated IgG irreversibly aggregated platelet-rich plasma and washed platelets, an effect abolished by pretreating the platelets with aspirin. The activity of the IgG was greatly enhanced by subaggregatory concentrations of thrombin and adrenalin and was localized to the F(ab')2 of the molecule. Plasmapheresis in combination with anti-platelet therapy resulted in an increase in the patient's platelet count, reduced platelet aggregating activity of plasma and significant clinical improvement.We suggest that the presence of this platelet aggregating IgG contributed to the development of thrombosis in our patient and postulate that a similar factor may explain the paradox of thrombosis observed in a select group of thrombocytopenic patients.
Factors of the Extrinsic Pathway of Blood Coagulation in Tumour Associated Macrophages
Authors: Ádány Róza , Kappelmayer János , Berényi Ernö , Szegedi Andrea , Fábián Erzsébet , Muszbek László 
Published: June 2018

SummaryDespite the growing evidence implicating intratumoural fibrin formation in the progression of malignant tumours, the origin of coagulation factors that participate in extravascular clotting has not been elucidated. Using immunohistochemical methods we attempted to detect and localize clotting factors of extrinsic pathway in different human malignant tumours. Coagulation factors II, V, VII and X (FII, FV, FVII and FX) were detected in a huge number of cells showing spindle-shaped or stellate morphology. By double immunohistochemical labellings it was demonstrated that cells containing these clotting factors express monocyte/macrophage differentiation marker antigens recognized by Leu M3, Ki M7 and DAKO-macrophage monoclonal antibodies, i.e. they represent monocyte-derived, phagocytic tumour associated macrophages (TAMs). These findings suggest that TAMs can be viewed as clot cells, which in addition to the initiation of extravascular clotting by expressing procoagulant activity can also provide all the components necessary for the extrinsic thrombin formation.
Extrinsic Pathway Inhibitor in Elective Surgery: A Comparison with other Coagulation Inhibitors
Authors: Sandset P M , Høgevold H E , Lyberg T , Andersson T R , Abildgaard U 
Published: June 2018

SummaryExtrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of anti thrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.
Evaluation of Coagulometric Assays in the Assessment of Protein C Anticoagulant Activity; Variable Sensitivity of Commercial APTT Reagents to the Cofactor Effect of Protein S
Authors: D'Angelo Silvana Viganó , Gilardoni Felicia , D'Angelo Armando 
Published: June 2018

SummaryIn vivo expression of protein C activity is dependent on the availability of the activated protein C (APC) cofactor protein S. In the clinical laboratory, measurement of protein C anticoagulant activity is mostly performed in modified APTT assays. We have evaluated 13 commercial APTT reagents for their sensitivity to the cofactor effect of protein S by comparing APC-dependent clotting time prolongations in normal plasma and in protein S depleted plasma. In normal plasma, the sensitivities of the APTT reagents to the anticoagulant effect of APC were markedly different and correlated with the sensitivity of reagents to factor V and VIII. Reagents containing soy phosphatides appeared more sensitive than reagents containing phospholipid of animal origin. Analysis of dose-response curves obtained in normal plasma distinguished one group of reagents showing clotting time prolongations linearly related to the APC concentrations, a second group showing a log-linear relationship and a third group showing a log-log relationship. In protein S depleted plasma, sensitivity of APTT reagents to APC was in general proportional to that observed in normal plasma. However, for some reagents dose-response curves were qualitatively different in normal and in protein S depleted plasma. With all the APTT reagents, APC-dependent clotting time prolongations corresponding to 30-80% of APC anticoagulant activity observed in normal plasma, were observed in protein S depleted plasma. At variance, in a modified Xa one-stage clotting assay, negligible clotting time prolongations were observed in protein S depleted plasma, indicating that over 90% of the APC anticoagulant activity was protein S dependent in this assay system. Dilution of a relative insensitive APTT reagent effectively increased its sensitivity to the cofactor effect of protein S, suggesting that different phospholipid content and/or composition might be responsible for the different sensitivity of APTT reagents to protein S.These results question the validity of APTT based assays for the identification of qualitative protein C abnormalities with defective interaction with protein S.
The Effect of Some Instruments for Prothrombin Time Testing on the International Sensitivity Index (ISI) of Two Rabbit Tissue Thromboplastin Reagents
Authors: Poggio Marina , Besselaar Antonius M H P van den , Velde Edo A van der , Bertina Rogier M 
Published: June 2018

SummaryTwo commercial rabbit tissue thromboplastins were calibrated against the International Reference Preparation for rabbit thromboplastin (coded RBT/79) by one laboratory using the manual technique, a semi-automatic electro-mechanical coagulometer and three different automatic photo-optical instruments. The calibration of the two reagents was performed in three and two different exercises, respectively, and showed good reproducibility of the procedure. The purpose of calibration is providing a formula for the assessment of the International Normalized Ratio (INR) for patients receiving oral anticoagulants. The World Health Organization (WHO) model for thromboplastin calibration leads to the equation INR = RISI, in which R is the prothrombin time ratio and ISI the International Sensitivity Index of the calibrated thromboplastin/instrument system. This equation was adequate for one reagent, but not for the other when it was used in combination with the four instruments. At therapeutic intensities of anticoagulation, the deviation from the WHO-model observed for the second reagent was clinically insignificant. The WHO model was fully adequate when the second reagent was used with the manual technique. For both thromboplastins, there were statistically significant differences in ISI between the four instruments. The largest difference-amounting to approximately 10%-was observed between two photo-optical instruments. The order of instruments with increasing ISI was the same for the two reagents. It is recommended that thromboplastin manufacturers specify the instruments used for calibration of their reagent.
Protein C Inhibitor from Human Plasma: Characterization of Native and Cleaved Inhibitor and Demonstration of Inhibitor Complexes with Plasma Kallikrein
Authors: Laurell Martin , Stenflo Johan 
Published: June 2018

SummaryProtein C inhibitor (PCI) was purified from human plasma using immunoaffinity chromatography and heparin Sepharose chromatography, a method that allowed the purification of active and inactive inhibitor. PCI purified from outdated plasma was inactive and either in complex with plasma kallikrein or proteo-lytically degraded. Sequence analysis of cleaved PCI and of complexes between PCI and activated protein C or urokinase identified the previously recognized inhibitor cleavage site Arg354-Ser355. Two additional cleavage sites were observed in the modified inhibitor i.e. Arg357-Leu358 and Arg362-Leu363 which probably represent secondary cleavage of the inhibitor. Furthermore the sequence analysis of the inhibitor, whether purified from fresh or outdated plasma, revealed that it was microheterogeneous in the NH2-terminus as a result of cleavage by a trypsin like enzyme(s).
The Incidence and Clinical Significance of Amiodarone and Acenocoumarol Interaction
Authors: Caraco Yoseph , Chajek-Shaul Tova 
Published: June 2018

SummaryAcenocoumarol sensitivity index (ASI) was calculated in 36 patients receiving amiodarone and acenocoumarol concomitantly, by dividing the acenocoumarol daily dose (μg kg−1 day−1) by the prothrombin ratio expressed as International Normalised Ratio (INR). It was found to be significantly lower (4.2 ± 0.3 pg kg−1 day−1) than the ASI (11 ± 0.6 μg kg−1 day−1) determined in 35 patients in the control group, who received acenocoumarol and not amiodarone. In 15 patients, ASI was 13.2 ± 1.4 and 4.2 ± 0.6 μg kg−1 day−1 before and after initiation of amiodarone therapy, respectively. In 5 patients, ASI was 6.2 ± 0.6 μg kg−1day−1, while patients were receiving both medications, and 28.1 ± 6.1 μg kg−1 day−1 following discontinuation of amiodarone therapy. ASI determined while patients were on both medications was not affected by the presence of mild impaired renal or liver function. In 7 patients treated with both drugs concomitantly, severe bleeding diathesis developed. It is concluded that amiodarone augmented the anticoagulant effect of acenocoumarol in all patients receiving both drugs. An initial reduction of acenocoumarol daily dose by 50% and further adjustment of acenocoumarol dose according to daily prothrombin ratio is recommended. It is also suggested that acenocoumarol dose should be adjusted after cessation of amiodarone therapy.
The Nature of Synergy between Tissue-Type and Single Chain Urokinase-Type Plasminogen Activators
Authors: Fry Edward T A , Mack David L , Sobel Burton E 
Published: June 2018

SummaryEnhancement of thrombolysis with combinations of tissue-type and single chain urokinase plasminogen activators (t-PA and scu-PA) has been demonstrated in vivo but has not been seen consistently in vitro. This study was designed to characterize interactions between t-PA and scu-PA with respect to rate of and extent of thrombolysis in vitro and to delineate mechanisms responsible. Combinations of t-PA and scu-PA at selected concentrations synergistically enhanced thrombolysis in vitro compared with thrombolysis induced by either activator alone. Enhanced thrombolysis did not occur at the expense of fibrin specificity since the extent of fibrinogenolysis and consumption of α2-antiplasmin were significantly less with synergistic combinations of t-PA and scu-PA compared with equi-effective concentrations of either activator alone. Attenuation of complex formation of t-PA and two chain u-PA (tcu-PA), formed from scu-PA, with plasma proteins did not appear to contribute to enhancement of thrombolysis as assessed by fibrin autography. Binding of 125I-t-PA to thrombi was increased by 27% at 1 hr and by 21% at 2 hr in the presence of scu-PA (p <0,001 for both). Conversion of scu-PA to tcu-PA was enhanced when thrombi were exposed to scu-PA in the presence of t-PA. Results of this study indicate that t-PA and scu-PA at selected concentrations enhance thrombolysis in vitro synergistically without compromising fibrin specificity. Enhanced binding of t-PA to thrombi in the presence of scu-PA and enhanced conversion of scu-PA to tcu-PA appear to contribute to synergy between t-PA and scu-PA for thrombolysis.
Effect of Standard Heparin and a Low Molecular Weight Heparin on Thrombolytic and Fibrinolytic Activity of Single-Chain Urokinase Plasminogen Activator In Vitro
Authors: Lourenço D M , Dosne A M , Kher A , Samama M 
Published: June 2018

SummaryThe effect of unfractioned heparin (UH) and low molecular weight heparin (LMWH) (Kabi 2165 - Fragmin®) on in vitro scu-PA thrombolytic and fibrinogenolytic activity was investigated. Thrombolytic activity was evaluated by following lysis of radiolabeled plasma clot immersed in plasma in presence of scu-PA alone or with either form of heparin. A 200 IU/ml scu-PA concentration produced clot lysis within 7 hr. UH or LMWH led to a slightly faster clot lysis which was statistically significant only at the 2nd and 3rd hour. No significant difference could be evidenced between UH and LMWH effect. During clot lysis, plasmin, generated within the clot led to a gradual transformation of scu-PA to tcu-PA, specially after a 4-hr incubation. Appearance of tcu-PA activity in the plasma surrounding the clot was significantly inhibited by either form of heparin. This finding contrasts with results observed in purified systems and suggests the presence of heparin-dependent plasma factor(s) inhibiting tcu-PA formation or its activity. Possible candidates might be anti-thrombin III and PAI-3.No fibrinogen breakdown was observed when plasma was incubated for 7 hr at 37° C in presence of scu-PA alone (200 IU/ ml) or with either form of heparin. However, in presence of a plasma clot, an important fibrinogen breakdown was observed during clot lysis reflecting the action of plasmin and/or tcu-PA generated within the clot, in the surrounding plasma. Fibrinogenolysis was less pronounced in the presence of both heparin preparations possibly as a consequence of the reduction in the tcu-PA level. These results underline the importance of plasma factors in the interaction of heparin with plasminogen activators such as scu-PA.
The Differential Glycosylation of Human Pro-Urokinase from Various Recombinant Mammalian Cell Lines Does Not Affect Activity and Binding to PAI-1
Authors: Sarubbi Edoardo , Nolli M Luisa , Robbiati Federico , Soffientini Adolfo , Parenti Franco , Cassani Giovanni 
Published: June 2018

SummaryHuman chromosomal DNA encoding single-chain urokinase-type Plasminogen Activator (scu-PA, or pro-urokinase) was inserted in an expression plasmid and transfected in human A431, mouse LB6 and CHO cells. LB6 cells were also transfected with a Bovine Papilloma Virus derivative containing the scu-PA gene. Human scu-PA was purified from cell supernatants of recombinant clones and characterized for structure and function.All recombinant scu-PAs are undistinguishable from human urine-derived scu-PA for peptide backbone, but possess a higher sugar content, as revealed by SDS-PAGE analysis after digestion with glycopeptidase F. This difference is partly due to an increased sialic acid content, as shown by analysis of neuraminidase-treated scu-PAs.No difference was found, however, among recombinant and natural scu-PAs in the kinetics of conversion into two-chain active forms (tcu-PAs) by human plasmin, and in the KM and kcat values of tcu-PA activity on the chromogenic substrate S-2444 and on human plasminogen. Also, recombinant and non-recombinant tcu-PAs displayed similar dose-response curves for binding to the endothelial inhibitor PAI-1.In conclusion, the glycosylation pattern of u-PA does not affect its interaction with the plasma proteins directly involved in its fibrinolytic function.