bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Factor XII-Independent Plasminogen Proactivator System Of Plasma Includes Urokinase-Related Activity
Authors: Kluft C , Wijngaards G , Jie A F H 
Published: July 2018

Antibodies to urokinase have been shown to quench part of the fibrinolytic activity of plasma, not involving the extrinsic system. Previously, the intrinsic system has been subdivided into two parts, one dependent and another independent of factor XII, for activation. Both represent approximately 50 BAU activator activity/ml plasma. The aim of this study was to further locate the UK-related activity within the intrinsic fibrinolytic pathways and to delineate its participation in fibrinolysis tests in vitro.Antibodies to UK (AUK) were shown not to quench activities of contact factors such as factor XII, prekallikrein and factor XI in coagulation and chromogenic substrate assays. AUK inhibited in normal plasma, Hageman trait and Fletcher trait plasma a discrete portion of approximately 50 BAU activator activity/ml, apparently the activator activity derived from the factor XII-independent system.Immunoadsorption of plasma with immobilized AUK resulted in a depletion of approximately 50 BAU activator activity/- ml. The contact factors were undisturbed, as were plasminogen and the extrinsic activator. Additions of UK did not restore lost activity, suggesting that AUK has removed the proactivator component.The amount of UK-related activator activity compares to approximately 0.4 IU urokinase activity/ml, and shows a fairly constant level in individuals and is not enhanced by known stimuli for extrinsic activator release.Significant contributions to blood fibrinolytic activity in current assay systems, including the dilute blood clot lysis time method could be demonstrated.
Factor XIII, Tissue Transamidase And Malignancy
Authors: Zuch A , Kloczko J , Bielawiec M , Buluk K , Pilecka E 
Published: July 2018

The aim of the investigation was to compare the activity of factor XIII in patients with malignant neoplasma with the changes in the blood plasma of rats with Guering epitheliomas and to evaluate the effects of this tumour on the activity of tissue transamidase capable of stabilizing fibrin.The investigations were carried out on 125 patients with several neoplasmas and 50 healthy subjects. A significant decrease in f. XIII activity in plasma was found in these patients, as well as decrease in the concentration of free SH groups on which its activity depends. Similar changes In the blood plasma were noted in rats examined 30 days after transplantation of the Guerin tumor. In the organs of these rats a fall in transamidase activity was observed. On the other hand the tumor rich in SH groups contains a very large amount of enzyme which like f. XIII is capable converting fibrin polimer into cross-linking fibrin. Concentration of this transamidase in neoplastic tissue was significant higher than in the tissue of the control animals.Our results suggest that activity of transamidase and SH groups are connected with neoplastic process and that decrease of f. XIII activity in the blood plasma is the result of its consumption during intravascular coagulation initiated by neoplasma.
Purification Of 1- And 0-Gla Prothrombins And Their Differentiation With Normal And Other Dicoumarol-Induced Prothrombins
Authors: Malhotra O P 
Published: July 2018

In normal prothrombin, 10-glutamyl residues present in the amino portion of the molecule are carboxylated to form γ-carboxyglutamic acids (gla). Dicoumarol, an antagonist of vitamin K, induces the production of (partially) acarboxylated atypical prothrombins. In addition to our atypical varieties, viz. 7−,5− and 2-gla prothrombins, we have isolated two more atypical molecules, one containing 1.0±0.1 gla (1-gla prothrombin) and the other approximately 0.25 gla (0-gla prothrombin). These two variants adsorbed onto alumina Cγ-gel (Bio-Rad), similar to 2-gla protein, but were derived from 40 to 50% (NH4)2SO4 saturation. The purified materials, obtained after isoelectric precipitation followed by preparatory polyacrylamide-gel electrophoresis and heparin agarose chromatography, showed a single component by analytical disc-gel electrophoresis both in the presence or absence of sodium dodecyl sulfate (SDS) and contained antigenic activity comparable to that of normal prothrombins.The pI’s of the two variants by column electrofocusing were each 4.835±0.015. Similarly, the two proteins did not reveal any difference in electrophoretic mobility; however, their prothrombin fragments 1 (F1, residues 1-156) did—0-gla F1 moved slower than 1-gla F1. Employing anti (normal) prothrombin sera with Ca2+ , the two, 0− and 1-gla, F1’s produced vaguely visible immunoprecipitates which were definitely lighter than all the other F1’s including 2-gla. These results confirm that not only are multiple forms of atypical prothrombin induced by dicoumarol but also that gla does affect the immunochemical properties of the gla-containing fragment.
Inhibitor Of Factor VII Activation In Multiple Myeloma
Authors: McNutt R A , Penner J A 
Published: July 2018

An investigation of a patient with IgG myeloma who developed a clotting abnormality is described. Factor VII activity was 4%. A prothrombin time of 20.4 seconds with control of 11.0 seconds was found in association with normal partial thromboplastin time, factor X level, and a failure to correct with VitaminK and fresh frozen plasma.Methods for characterization were as follows. After defibrination and ammonium sulfate fractionation, plasma globulin portion was further purified on a DEAE ion exchanger. To identify inhibitor, Ig, alpha and beta globulins, myeloma proteins as well as albumin and fibrinogen isolated from patient plasma were incubated with normal plasma for two hours. Inhibitor activity was found in monoclonal antibody fraction. SPA affinity column removed inhibitor activity.To elucidate whether inhibitor was directed against FVII, patient plasma, myeloma proteins, and monospecific xenogeneic antibodies to FVII were compared for their ability to bind 125I FVII. Free from bound forms were separated on a Sephacryl S200 column. Chromatograms indicated absence of binding of patient inhibitor to 125I tracer.Normal and patient plasma were incubated with cephalo- plastin for 2 hours at 37°C. Prolonged recalcification time from 50 to 170 seconds was seen with patient plasma. More significantly, when inhibitor plasma and cephaloplastin were incubated for 2 hours and added to FVII deficient plasma, correction of prothrombin time was evident. Patient plasma not incubated with cephaloplastin failed to correct FVII deficient plasma.We conclude that low activity obtained in the assay system was due to the myeloma protein which inhibited FVII/ thromboplastin interaction rather than an acquired inhibitor directly affecting FVII. It seems likely that the antibody is directed to the functional site of thromboplastin responsible for FVII activation.
Metal Ion-Induced Structural Changes Of Bovine Blood Coagulation Factor X1
Authors: Freyssinet J M 
Published: July 2018

Wheat germ lectin (W.G.A.) has been used as a macromolecular probe to investigate metal ion-induced conformational changes of bovine Factor X1 . The classical precipitin reaction between lectin and glycoprotein only occurs when certain metal ions are present. Precipitin reactions were followed by recording turbidity at 330 nm.It has been verified that W.G.A. lectin activity is insensitive to the presence of either EDTA, Ca(II), Mn(II) or Mg(II). Ca(II) and Mn(II) are able to induce a precipitin reaction between W.G.A. and Factor X1. The reaction is slow at metal ion concentration of 2.5 mM but becomes more rapid when higher divalent cation concentrations are used. Ca(II) and Mn(II) have comparable efficiency, Mg(II) is totally ineffective in promoting such a precipitin reaction. Halftimes of precipitin reactions range from 7 minutes at 2 mM Ca(II) to 0.3 minutes at 100 mM Ca(II). Above 100 mM Ca(II) or Mn(II), increasing metal ion concentration would slow down the reaction ; increasing the ionic strength had a similar effect. Although very slow and weak, the precipitin reaction could still occur at high ionic strength up to 0.8 M. The various conditions that give rise to a precipitin reaction demonstrate that Factor X1 must undergo a cation- catalyzed transit ion which allows binding of lectin to its specific sugar(s). This leads to suggestions on the nature of this structural change. When compared to metal-ion induced protein transition involved in protein-phospholipid binding described in the literature, the difference of divalent cation specificity and active concentration in both of these studies point out that the conformational changes have to be different.
Anticoagulant Effect Isolated From Radix Miltiorrhizae (RSM)
Authors: Stemberger A , Blümel G 
Published: July 2018

RSM is a well known Chinese medicinal herb traditionally used as (injectable) decoction to improve circulation+. Decoctions of the root* showed a prolongation of the aPTT and this effect was further characterized.Standardized RSM decoctions were ultrafiltrated using step by step the following membranes: 300.000 MW, 100.000 MW, 50.000 MW, 5.000 MW, 1.000 MW , 500 MW. The effect of these fractions on blood coagulation was studied in routine tests like thrombin time and aPTT. With chromogenic substrates the inhibitory effect was elucidated on the Xa− and thrombin level after exogen or endogen activation of the coagulation system.The most potent fraction has a molecular weight of 5.000 daltons with a high anti-Xa and anti-thrombin effect. Using partly purified Xa and thrombin preparations inhibition of these enzymes was independent from antithrombin III. Activation of plasminogen as reported elsewhere was not detectible. In contrast an antiplasmin effect could be demonstrated. The chemical nature of the inhibitor(s) is under investigation.
Viscoelastic Studies Of Coagulation: Cell-Plasma Interactions
Authors: Mitchell J , Zuckerman L , Vagher J P , Caprini J A 
Published: July 2018

In order to examine the cell-plasma interactions during coagulation, a thrombelastograph was modified to measure two viscoelastic properties of blood: rigidity (G) and rate of stress relaxation (S). Citrated whole blood was collected from healthy donors and centrifuged to obtain platelet-rich and platelet-poor plasma and washed red cells. The blood was reconstituted at varying hematocrits (HCT) and platelet counts (PLT) and coagulation was initiated by adding CaCl2. Factor XIII (FXIII) activity was inhibited with glycine ethyl ester (GEE). In normal blood, the rigidity increases rapidly after 6-8 min following addition of CaCl2 with a rate constant (kG) of 8.2 min and a saturated rigidity (Gsat ) of 22.3×l03 dyn/cm2 . S decreased in a biphasic minner: the first phase (ΔS1) lasting about 15 min and accounting for a 70% fall in S and with a rate constant (ks1) of 6.7 min; the second phase (ΔS2) from 15 min on with a 15% drop in S and with a rate constant (ks2) of 71.4 min. Increasing PLT resulted in a linearly increasing G up to 31×l03 dyn/cm2 for 3×105 cells/mm3. Increasing HCT had no effect on Gsat , but increased kG linearly for 10<HCT<50%. Inhibition of FXIII activity by GEE had no effect on G, but inhibited ΔS2 while kS2 was linearly dependent on GEE concentration. In cell-free plasma, ΔS1 was about 80% in 10 min with virtually no ΔS2. With the inclusion of even a small number of platelets, ΔS1 and ΔS2 returned to that found in normal blood.It was concluded that platelets change the configuration of fibrin in the clot and alter the kinetics of orientation and crosslinking. Red cells have little mechanical influence but do seem to have some procoagulant activity.
Determination Of Reaction Time Changes Per Time Unit In Clot Assays
Authors: Popović Lj 
Published: July 2018

Changes in reaction time of clot assays are usually expressed only in time units, which fails to indicate the extent of the increase or decrease of the reaction time of the tested specimens against that of the basic sample. Reaction time increases of, e.g. , 6 seconds in tested samples, compared to basic sample reaction times of 12 and 24 seconds respectively, signify an increase twice as large in the first as in the second instance.Changes in reaction time of clot assays can be expressed as the increment or decrement of the reaction time per time unit. This amount of increase or decrease (positive or negative alteration of reaction time, T
a
) can be expressed as the quotient of the difference between the reaction times of the tested (T
x
) and basic (To) samples and of the basic sample, e.g. in seconds per second, T
a
=T
x
-To/To. A test sample reaction time 6 seconds longer than basic sample reaction times of 12 and 2k seconds would mean an increase of 0.5 and 0.25 seconds per second, respectively.Reaction time changes of tested samples against that of the standard sample (T
std
) can be calculated in a similar way, T
a
=T
x
-T
std
/T
std
.It can be assumed that this parameter reflects the intensity of the increase or decrease of reaction time per time unit. The quotient of the tested and basic samples can be considered as the coefficient of the increase or decrease of the total reaction time (CT=T
x
/To).
A Simple Quantitative Methodology For The Analysis Of In Vitro Blood Coagulation Profile Kinetics
Authors: Palmason C , Hewitt L A , Harris C 
Published: July 2018

Blood coagulation profilers graphically display the kinetic events which lead to in vitro clot formation. Their potential usefulness in patient monitoring is evident, but at the present time is limited by the lack of a standard data analysis procedure. The present study demonstrates a simple, quantitative, approach to profile analysis.The profile curve was comprehensively defined in terms of seven easily determined parameters. The average value for each parameter was determined from extensive testing of commercial coagulation control plasmas (n=100), human female volunteer plasmas (n=30), and pooled female plasmas (n=5). Where control and human parameter values were significantly different, correction factors, were calculated to “normalize” the commercial plasma values. The “normalized” commercial plasma parameters could then be used as a highly reproducible reference standard with which a patient’s profiler could be statistically tested for abnormalities.Profiles of third trimester of pregnant women (n=11) were compared with the reference standard as a positive test of the procedure to identify hypercoagulable states. Similarly profiles of newborn babies (n=10) and factor deficient patients (n=7) were compared as a positive test of the procedure to identify hypocoagulation. The results indicate that the analytical procedure applied to the blood profiles are valid, and may be of use in the clinical setting.
A Laboratory Case Report Of “Hypercoagulation Syndrome” Following Eight Weeks Of Estrogen Replacement Therapy
Authors: Palmason C , Shams S , Harris C 
Published: July 2018

A preliminary study was designed to identify if estrogen replacement therapy (E.R.T.) could be correlated with any progressive alterations in blood coagulation function. A total of thirty post menopausal women were assigned to treatment groups and monitored monthly for six months. This presentation relates the laboratory findings of one 55 year old woman who developed significantly altered blood coagulation parameters after two months on conjugated estrogens equine (1.25 mg/day).Routine biochemistry, F.S.H. levels, haematology, and eight standard coagulation tests were done. However, prothrombin time (P.T.), and partial thromboplastin times (P.T.T.), were done on a Coagulation Profiler (T.M.). Assessment of coagulation function was affected through comparison of the patients present P.T. and P.T.T. profiles with pretreatment and reference standard profiles. All aspects of the patient’s coagulation kinetics were altered significantly, in the direction of hyper-coagulation (p< 0.001) with the exception of the P.T. time alone, which was unchanged. Platelet aggregation was impossible, due to spontaneous aggregation during pre-test standing, fibrinogen and euglobulin lysis levels were also raised. The patient reported breast engorgement, abdominal distension and calf tenderness. Two months following E.R.T. discontinuation, the patient’s blood coagulation parameters had all returned to pretreatment levels.The case is discussed within the context of an hypercoagulation syndrome resultant upon an idiosyncratic response to estrogen therapy.
Rebound Phenomenon After Discontinuation Of Oral Anticoagulant Therapy?
Authors: Harenberg J , Haas R , Zimmermann R 
Published: July 2018

Duration and discontinuation of oral anticoagulant therapy in the prophylaxis of recurrent thrombembolic diseases is often discussed. After stopping of the therapy an elevated incidence of rethromboses are observed. Therefore we determined fibrinopeptide A (FPA) as the most sensitive parameter of thrombin activity in vivo in patients treated with phenprocoumon in order to get information on the effectivity of the oral anticoagulant therapy and on the rebound phenomenon after discontinuation of the treatment.In 136 outpatients a significant relation between FPA and the effectivity of the anticoagulant therapy was observed: 2.7 ng/ml plasma (mean, thrombotest values < 5%), 3.5 ng/ml (5%-15%) and 4.1 ng/ml (>15%, p < 0.01). Normal FPA were 1.4ng/ml. In 11 patients with low FPA the oral anticoagulants were discontinued. FPA was determined in weekly intervalls. Within four weeks a continous increase of FPA from 1.6 ng/ml (median) to 3.8 ng/ml was observed. After eight weeks FPA was 8.2 ng/ ml (p < 0.05). The in vitro release of FPA after 10 min incubation of blood increased from 3.4ng/ml to 72 ng/ml after eight weeks (p < 0.05, normal release up to 5 ng/ml).The data indicate the clinical relevance and the different therapeutic implications of the determination of FPA in patients treated with phenprocoumon. They further give the first criterion, which outlines the effectivity of an oral anticoagulation therapy by reducing the thrombin activity in vivo. They give some evidence for a rebound like phenomenon after discontinuation of the oral anticoagulant treatment.
Hypercoagulability In Acute Esophageal Variceal Bleeding
Authors: Hiller E , Hegemann F , Riess H 
Published: July 2018

In 15 patients with acute esophageal bleeding selected parameters of hypercoagulability were determined at frequent intervals during intensive care treatment. Estimation of soluble fibrin monomer complexes (SFMC) by gel filtration of plasma samples which were purified by ß-alanine precipitation allowed the determination of the relative amount of SFMC (percentage of SFMC in relation to the total fibrinogen content in plasma). Antithrombin III (AT III) activity was determined photometrically using the chromogenic substance S-2238 and immunologically by one dimensional immunelectrophoresis. Fibrin split products (FSP) were estimated by the staphylococcal clumping test.Increased levels of SFMC were observed in 10 out of 15 patients on admission. A further increase was noted in most patients in whom bleeding persisted and who needed replacement therapy with blood components. Substitution with prothrombin complex concentrates induced acute DIC in two patients with levels of SFMC up to 24 %. AT III was decreased to levels of 30-50 % in 8 patients during the acute illness. A discrepancy between the functional and immunological AT III value was noted in some instances but more often both values were very low.High levels of SFMC in addition to levels of AT III of less than 50 % reflect a serious state of hypercoagulability with a very poor prognosis for the patients. Clotting factor concentrates may be especially thrombogenic in these patients with impaired clearing activity. Fresh frozen plasma and AT III concentrates provide an appropriate source of the most important clotting factors.
Clinical Spectrum Of The Lupus Anticoagulant In Pediatrics
Authors: Sternbach M S , Reece E L , Esseltine D , Macdonald E 
Published: July 2018

Hemostatic mechanisms were investigated in two patients: one had deep vein thrombosis, the other one bled after a tooth extraction. Standard coagulation methods were used: Coagmate for P.T. and P.T.T., manual water bath methods for thrombin time, factor levels and circulating anticoagulants.An 11 year old girl presented with a deep vein thrombosis of the left ileo-femoral junction. Her P.T.T. was prolonged 66"/30" with the presence of a circulating anticoagulant with Anti-factor XI activity. All other factors, fibrinogen and thrombin time were normal. A.N.A. was + 1/40; D.N.A. binding was + 1/40; complement (C4) was low. An Anti I was positive in a titer of 1/256. The patient was treated with anticoagulants for 6 months.A 10 year old boy had prolonged bleeding following a deciduous tooth extraction. A spleen tip was the only pertinent physical finding. P.T. and P.T.T. were markedly prolonged (P.T. 16"/11"; P.T.T. 50"/30"). A circulating anticoagulant with Anti-factor XI and XII activity was detected. The patient’s clot dissolved completely at 4°C for 2 hours (while being stable for 48 hours at 37°C and 20°C). The patient had a + A.N.A., a + anti-D.N.A., and a positive direct Coombs’ with anti-N specificity. Hematuria, cylindruria, and proteinuria were also present. Following prednisone therapy, the circulating anticoagulant and the positive Coombs’ disappeared.These cases illustrate that the lupus anticoagulant may be present with either thrombotic or hemorrhagic manifestations.
Antithrombin III Infusion During Fulminant Hepatic Failure
Authors: Braude S , Arias J , Hughes R D , Canalese J , Gimson A E S , Williams R , Scully M F , Kakkar V V 
Published: July 2018

The antithrombin III (ATIII) levels in 17 patients with fulminant hepatic failure due to viral hepatitis or paracetamol overdose were found to be 25.8%±SD 12.80 of normal on admission. The levels did not correlate with eventual survival or death and remained essentially unchanged for up to 7 days.In an attempt to assess the role of the low levels of AT III during the course of hepatic failure and in relation to treatment by charcoal haemoperfusion we have infused patients with commercially purified ATIII. Preliminary measurements of ATIII (chromogenic substrate method) were made and ATIII infused to achieve a plasma concentration of 50 to 70%. Infusion was by an initial bolus of 1500-2000 units followed by up to 500 units every 6 hours. To date 3 patients in Grade IV hepatic coma have been treated, one died 1 day after admission and the other two survived. In the latter the return of the prothrombin time to normal was similar to that in patients without the addition of ATIII. In one of the survivors the platelet count did not fall, suggesting ATIII may have had a protective effect on platelet consumption. There was also an indication, that there was a more uniform and better response to heparin anticoagulation during haemoperfusion than found previously without ATIII infusion.Further patients will be treated to evaluate whether AT III substitution can reduce the consumptive coagulopathy and platelet destruction which occurs in the course of fulminant hepatic failure.