bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Case Of Dysfibrinogenemia : Isolation Of The Abnormal, Unclottable Fibrinogen Population
Authors: Jandrot-Perrus M , Aurousseau M H , Josso F 
Published: July 2018

In a 81-year-old healthy woman, gross abnormalities of fibrin formation in routine tests led to the discovery of a dysfibrinogenemia.Abnormal and control fibrinogens were purified in parallel using precipitation by glycine (Kazal) ; final clottability was 95-98 % for the control and 50 % for the patient’s fibrinogen. Electrophoretic behaviour of the fibrinogen momecule, the three chains and the products of fibrin cross-linking by factor XIII a was normal. Functional studies gave the following results :
(i)	delayed coagulation by thrombin, Reptilase and Venacil with gross abnormalities of the clot; (ii)	inhibition of coagulation of normal fibrinogen ; (iii) poor fibrin monomer aggregation (opacimetry) ; (iv) delayed fibrinogen proteolysis by plasmin (SDS-PAGE) . Release of fibrinopeptide A by thrombin was incomplete (RIA).Fibrinogen NH2-terminal residues were found normal, but the presence of ALA-residue in fibrin clot and in the supernatant showed that part of fibrinogen was not clotted, either copolymerized with fibrin or remaining in solution. Gel filtration of the supernatant showed the presence of both soluble complexes and fibrinogen characterized by the elution volume of the peak and NH2-terminal analysis. This fibrinogen population was unclottable by thrombin and inhibited clotting of normal fibrinogen.These preliminary results suggest the existence of a defect on the A-a chain of this abnormal fibrinogen which was called fibrinogen Bondy.
Dibucaine-Activated Platelet Protease(S) Digests GPIb-EDTA Only Partially Inhibits
Authors: Coller Barry S 
Published: July 2018

Local anesthetics have been reported to have several effects on platelets including:	1) inhibition of shape change, the release reaction and aggregation induced by several agents 2) dissolution of cytoskeletal structures and 3) activation of a protease activity which digests proteins of Mr 250,000 and 230,000. It was speculated that the last effect may be due to the Ca++-dependent protease previously described in platelets. I have recently observed that incubation of platelets with 1 mM dibucaine for brief periods of time (15-30 min) resulted in 50-100% enhancement of the initial slope of agglutination induced by either ristocetin or bovine von Willebrand factor (vWf) despite inhibiting the release reaction. If the platelets were formaldehyde-fixed after brief incubation, they also showed the enhancement (control 23 ± 3 U/min (mean ± SEM) and dibucaine 47 ± 6, p < 0.01, n = 7 for ristocetin and 36 ± 7 vs. 65 ± 5, p < 0.01, n= 6 for bovine vWf). Using these platelets, the ristocetin cofactor assay was more sensitive and yet equally specific. If, however, fresh platelets were incubated with dibucaine for > 1 hour, both ristocetin and bovine vWf-induced agglutination became progressively inhibited with almost total inhibition after several hours. This decrease in agglutination was associated with a progressive loss of a glycoprotein with the characteristics of GpIb (Mr 165,000 unreduced and 135,000 reduced) as judged by PAS-stained polyacrylamide gels. The presence of the platelet-impenetrable calcium chelator EDTA (10 mM) only partially prevented the decrease in agglutinability and loss of Gplb. I conclude that:	1. Short term incubation with dibucaine may improve the ristocetin cofactor assay. 2. A dibucaine-activated protease(s) appears to digest Gplb, probably accounting for the decreased agglutination with long incubations. 3. If operating from the outside of the platelet after leakage, at least some of the protease activity is not calcium dependent.
Higher Efficiency In Clot Lysis Rate Of Circulating Plasminogen Activators After DDAVP Infusion Compared To That Of Activators Bound To Clots
Authors: Tran-Thang C , Bachmann F 
Published: July 2018

Clot lysis rate, in presence or absence of vascular activator (VA) during clotting and in the surrounding medium, was studied. The mean fibrinolytic activity of plasma euglobulin fractions (EF) was 0,4 U UK/ml (measured on fibrin plates) in resting volunteers; it increased 6-8 fold ten min after the i.v. infusion of DDAVP (0,4 μg/kg). No activity was detectable in serum EF before and after DDAVP infusion, but, if plasma (10 mM citrate - 5 mM EDTA) was clotted by thrombin and the squeezed clot incubated in 0,017 M acetic acid, most of the activity could be recovered. This demonstrates that VA and intrinsic activator (s)(IA) bind to clots. 125I-fibrinogen labelled plasma and whole blood clots, obtained after DDAVP infusion, when incubated for 3 h at 37 °C in DDAVP serum showed 0% lysis, in normal plasma (containing weak IA activity) 15%, and in DDAVP-plasma 60% lysis. 30% lysis occurred when normal clots ware incubated in DDAVP-plasma. When DDAVP-plasma was clotted with thrombin (10 U/ml) in the presence of 0 to 20 mM Ca++, a striking inverse correlation (r=0,96) was observed between Ca++ concentration and lysis rate. The inhibitory effect of Ca++ may be due to cross-linkage of fibrin or to ↑ binding of α2-antiplasmin to fibrin.These experiments demonstrate that physiological cone, of IA and of VA, bound to the clot during coagulation, do not induce efficient fibrinolysis in the presence of physiological Ca++ cone. Lysis takes place only when additional VA is present in the surrounding medium. This mechanism may be of physiological importance for the hemostasis-fibrinolysis balance in preventing premature lysis of formed fibrin, but assuring gradual fibrinolysis in the presence of ongoing release of VA fran vessel wall endothelium.
Anticoagulant Effect Of A New Potent Heparin In Human After Intravenous Application And The Comparison With Commercially Available Heparin
Authors: Bhargava A S , Wendt H , Günzel P 
Published: July 2018

The anticoagulant effect of a new potent heparin containing 83% high affinity and 17% low affinity fractions was compared with commercial heparin after a single i.v. application in human subjects. 20 male and 20 female normal adult subjects participated in this study. 2 male and 2 female subjects per group were treated intravenously with doses ranging from 18.3–218.3 μg for new potent heparin and 40.3–483.0 μg for commercial heparin per kg body weight. Determinations of thrombin time, whole blood clotting time, activated partial thromboplastin time and plasma heparin levels using factor Xa inactivation assay were performed before and 5, 10, 15, 30 and 60 min after heparin application. The regression analysis and parallel line assay were performed using log dose or double log transformation or log dose and square root transformation of areas under the curve to estimate the relative potencies of the new heparin preparation.The new heparin was 1.5 to 2.0 times more effective than commercial heparin per mg dry weight depending upon the coagulation tests used and the length of observation period. These relative potencies of the new heparin in human is in good correlation with relative potencies determined earlier for the same preparation in different in vitro tests including thrombelastography and in vivo using the dog as an experimental animal. In addition, the determinations of biochemical and the haematological parameters, 24h after application indicated no signs of any adverse effect.
Synthesis And Catabolism Of Human Prothrombin And Pivka-II
Authors: Tsukada H , Takada M R , Tanaka H , Takeuchi T , Gonmori H , Kobayashi N , Maekawa T 
Published: July 2018

The synthesis and catabolism of both prothrombin and PIVKA-II were studied in patients with stable stage of various thromboembolic disorders. Laboratory examinations revealed that their hemostatic and fibrinolytic activities were within normal range. Thirty mg of warfarin was administered orally to patients, which was followed by daily U to 8 mg of warfarin to maintain one stage prothrombin time in therapeutic range. Fifty mg of vitamin K was administered intravenously to these anticoagulated patients. PIVKA-II was determined as prothrombin related antigen in the BaSO^ adsorbed plasma by the method of Ganrot using anti-human prothrombin antibody.After the administration of 30 mg of warfarin, prothrombin clotting activity(FII:C) decreased exponentialy with the half life(T 1/2) of 74 hrs on an average. Rapid increase of PIVKA-II was observed in the early phase of warfarin administration, though in the later phase an increasing tendency slowed down. The changes of PIVKA-II in the early phase could be analyzed easier by following up the changes in the value of (100 - PIVKA-II activity)%. As the progress of time after the administration of warfarin, their values decreased exponentialy with the T 1/2 of 64 hrs on an average. After the administration of vitamin K, FII:C increased rapidly in the initial phase, then slowly returned to normal level. Similarly to the case of PIVKA-II after the administration of warfarin , values of (100 - FII:C activity)% decreased exponentialy with the T 1/2 of 45 hrs on an average. PIVKA-II decreased rapidly after the administration of vitamin K, describing exponential curve with the T 1/2 of 40 hrs on an average.From the results described above, it is suggested that the catabolism of PIVKA-II is much more faster than that of FII:C.
Prothrombin And Abnormal (Des-γ-Carboxy) Prothrombin: Assessment Of Plasma Levels By Ria In Disorders Of Hepatic Vitamin K-Dependent Carboxylation
Authors: Blanchard R A , Furie B C , Kruger S F , Furie B 
Published: July 2018

The vitamin K-dependent blood coagulation zymogens contain γ-carboxyglutamic acid (Gla) in their amino terminal domains. The presence of these Gla residues is necessary for the physiologic activation of these zymogens to proteases. The Gla residues are synthesized from glutamic acids on precursor proteins in the liver by a vitamin K-dependent carboxylase. In treatment with vitamin K antagonists or in the presence of vitamin K-deficiency carboxylation is impaired and des-γ-carboxy forms circulate in the blood. We have developed specific RIAs for human prothrombin (NPT) and for des-γ-carboxy human prothrombin (APT) to evaluate the levels of these species in human plasma. These plasma assays measure only NPT despite the presence of APT or only APT despite the presence of NPT.These results suggest that total prothrombin synthesis is decreased in patients treated with warfarin and in patients with intrinsic liver disease compared to normals or to vitamin K-deficient patients. APT is not a component of normal plasma (>0.03 g/ml). However APT is present in 90% of the patients with intrinsic liver disease. In ten patients with liver disease in whom samples were obtained before and after vitamin K administration APT persisted in the plasma. This indicates impaired vitamin-K-dependent car-boxylation in these disorders. We feel that the patterns of plasma NPT and APT in these disease states are characteristic and may prove useful in identifying and distinguishing liver disease from disorders of PT biosynthesis.
Dosage-Efficacy Relationship In Single-Dose Replacement Therapy For Acute Bleeding Episodes In Hemophilia
Authors: Weiss A E 
Published: July 2018

The cardinal principle of modern therapy for acute bleeding episodes in hemophilia is “early adequate treatment.” To better define “adequate”, the dose-efficacy relationship was studied in treatment of 491 acute hem- arthroses in 14 adolescent and adult severe hemophiliacs by prompt factor concentrate infusion. All treatments were given within 5 hrs after first recognition of bleeding, with the mean delay being 1.9 hrs; 68% were given within 2 hrs, and 86% within 3 hrs. Treatments were given in 3 concentrate dosage ranges:	8-11, 11-15, and 15-18 u/kg. The outcome of treatment was graded as a “success” (S) if bleeding symptoms resolved promptly without need for additional infusions or absence from school or work; “marginal” (M) if treatment was otherwise successful but rebleeding occurred at the same site within 10 days; or “failure” (F) if symptoms persisted and required additional infusions and/or absenteeism. In each dosage range the time from bleed recognition until treatment and the concentrate dosage were not significantly different among the outcome groups. However, there was a highly significant difference (p<0.01) in the efficacy of treatment at the 3 dosage ranges (see table). The success rate increased stepwise, and the failure rate decreased with increasing dosage ranges. Similarly, the frequency of rebleeding decreased with increasing dosage for primary treatment. The 10% failure rate with low doses is in agreement with several reports advocating low doses for early treatment, but the higher success rates and lower failure and rebleeding rates with the higher doses indicate that these parameters and their impact on overall bleeding frequency and concentrate usage must be considered in the determination of “adequate” doses.
Evidence Of Possible Linkage Between Von Willebrand’S Disease (VWD) And 2 Polymorphic Genetic Markers
Authors: Barrow E S , Reisner H M , Namboodiri K K , Elston R C , Graham J B 
Published: July 2018

VWD shows great variability within and between families. In some kindred the affected persons show decreased amounts of an apparently normal VIIIR:Ag. In others, abnormal electrophoretic mobility of VIIIR:Ag has been associated with a defect in the degree of polymerization. Within kindred, expressivity may be so variable that some transmitters have normal laboratory findings. Detection of linkage between VWD and a clearly defined antigenic or biochemical marker might provide the means to make unambiguous diagnoses and to distinguish between the effects of the multiple genes involved in synthesis of VIIIR:Ag.We have examined 4 VWD kindred, using 23 genetic markers. Individuals were classified for VWD using clinical and laboratory data, pedigree information and 2 statistical procedures: D I based on 3 measures of F VIII activity, and D II which also included bleeding time and a subjective index of symptoms. Using D I, a LOD score of 0.66 at a recombination frequency (θ) of 0.20 was found with GPT (glucose pyruvic transaminase). Using D II a LOD score of 0.50 at a θ of 0.25 was found. Most of the evidence of a VWD- GPT linkage was provided by a single kindred. Using D II, evidence suggesting a second linkage was observed between VWD and GLO (glyoxylase) with a LOD score of 1.03 at a 0 of 0.20, all 4 families contributing.The LOD scores reported are suggestive of linkage and warrant further study. Since GLO relates to Chromosome 6 while the chromosomal location of GPT is not known and since GPT and GLO are unlinked, VWD may be genetically heterogeneous, 2 or more loci being involved.Studies to clarify the relationship of VWD to Chromosome 6 are underway using markers known to be linked to GLO.
In Vitro Bleeding Time
Authors: Sawada S , Kimura A , Yoshida Y 
Published: July 2018

One of the authors, A.Kimura,et al. reported the technique called “in vitro bleeding time” using fresh pig skin and the heparinized animal blood (BLOOD 54:6 1347-1357). The system was used to measure both the normal hemostasis of swine and to investigate what causes abnormal hemostasis in the von Willebrand animals. Author modified this system to use dried pig skin and heparinized normal(n=62) and abnormal hemostatic human blood(n=20). Heparinized human whole blood at constant hydrostatic pressure was allowed to flow through a 5mm incision in the dried pig skin (LYODERM, ARMOUR PHERMACEUTICAL CO.) in the flow cell(HELLI- GE CO.), shown in the figure. Exuded blood was drawn by the proportionning pump and hemolized with distilled water. The hemoglobin concentration was measured and recorded by the automatic electrophotometer. The time elapsed from the start of flow to the cessation was measured as in vitro bleeding time. In vitro bleeding time was 7.6±3.6(mean±SD) minutes in normal.In von Willebrand’s disease and Hermansky-Pudlak syndrome in vitro bleeding time was prolonged.
Platelet Volume Measurements: The Importance Of Anticoagulation
Authors: Thompson C B , Diaz D D , Quinn P G , Lapins M , Kurtz S B , Valeri C R 
Published: July 2018

Recent advances in electrical cell sizing have made mean platelet volume (MPV) routinely available in most clinical laboratories. To study the importance of anticoagulation on platelet size stability, blood was collected in 7 different anticoagulants and stored at room temperature for up to 8 hours. Platelet counts and platelet sizing were performed using whole blood on a Coulter S+ and using platelet-rich plasma on a Coulter H4 Channelyzer. The results suggest that both calcium chelation and acidification were required to inhibit platelet shape change and aggregation. Electrolyte composition, pH, and tonicity of the anticoagulant all influenced the stability of the MPV. As a result of these studies, an anticoagulant combining ACD and Na2EDTA at a pH of 5.0 and an osmotic strength of 308 m0sm/1 was used to study platelet volume and counts in whole blood on a Coulter S+ used in the hematology laboratory of our hospital. Platelet counts with ACD-Na2EDTA anticoagulant were no different from routine Na2EDTA platelet counts and exhibited 2.9% error in reproducibility and a 4.4% variability over the 8 hours of storage. Mean platelet volumes were reproducible to within 3% and had less than 1% variability over the 8 hours of storage. Platelets anticoagulated with ACD-Na2EDTA remained discoid in shape and could be shown to undergo a shape change on stimulation with ADP up to at least 8 hours after collection, when the pH was adjusted to 7.4 and the Ca++ concentration restored.These data demonstrate that platelet count and platelet volumes remained stable in blood collected in ACD-Na2EDTA anticoagulant for up to 8 hours at room temperature. In 52 volunteers studied, an inverse correlation (r=.72, p<0.001) was observed between platelet count and MPV, suggesting that the circulating platelet mass may be a more important indicator of platelet homeostasis than either the platelet count or the mean platelet volume alone.
A Platelet Aggregometer With Automatic Data Processing
Authors: Blasberg P , Wurzinger L J , Mussler K , Myrenne H , Schmid-Schönbein H 
Published: July 2018

A new aggregometer was designed to meet the following requirements: A) a uniform well defined shear rate throughout the whole PRP sample, B) two different shear rates - one favourable for platelet aggregation (PA) - one to subject already formed aggregates to high shear to test aggregate stability, C) a modular set up to extend the aggregometer easily from 1 to 4 channels, D) automatic processing and documentation of all aggregation data.I.	The aggregation moduls: Each aggregation modul contains a Couette-viscometer (500 μl PRP required). The outer cylinder (a disposable plastic vial) is rotated to induce shear rates in the range of 40s-1 and 4000s-1. For measurement of PA each channel is equipped with a He-Ne laser which radiates a light beam through the sample. Transmitted (It) and scattered (Is) light is measured by independent photodiodes and from the ratio Is/It+Is turbidity of the test sample is estimated. The moduls are thermostatised to 37°C. 1 to 4 moduls are supplied by one motor-gear box (1:100) unit. 2.	The data processing unit: The data processing unit is controlled by an OEM-microcomputer, which allows an on line display and storage of the actual turbidity values during the whole experiment. At the end of each experiment the aggregation curve is calculated and may be plotted on a x,t- recorder. The area under the curve and the lag phase of PA is estimated. In addition the whole experimental run is controlled and documented by the printer equipped microcomputer using the interactive high level language BASIC.The aggregometer consists mainly of two parts:
The described aggregometer exhibits the following advantages: the use of a uniform low shear rate enables one to observe spontaneous PA and to reduce the concentrations of PA-inducing agents (e.g. 5×10-7m ADP) compared to conventional aggregometers whereas the stability of already formed aggregates can be tested with the high shear rate. Furthermore the evaluation of all data (PA, integral of PA, lag time) is done automatically.
The Natural History Of Hemophilic Factor VIII-Antibodies: Differences In The Half Disappearance Time Following Anamnestic Rise
Authors: Lechner K , Krinninger B , Niessner H , Nowotny Ch , Thaler E , Deutsch E 
Published: July 2018

In 12 severe hemophiliacs with an antibody to factor VIII of the high responder type antibody activity was followed over a treatment free period of at least three months up to seven years, following 30 factor VIII treatments. After reaching the peak level the antibody titer declined exponentially with a median half disappearance time of 36 days within in a period of 2 - 7 months. There was a considerable variation of the half disappearance time among patients and even in the same patient. Particularly inter - esting were two patients who showed an unusually short half disappearance time of 5 and 9,5 days,respectively. On the other hand, in one patient the half disappearance time after three stimulations was between 67 and 98 days.In five patients a biexponential disappearance curve was observed. In these patients after a first component of rapid decline (as described above) a second slower component was observed. The half disappearance time of this second component was between 92 - 480 days (median 200 days). In one patient eventually a plateau was reached. The transition of the first to the second component occured 2-7 months after stimulation, when the antibody level had fallen to 2 - 30 % of the peak level. Biexponential curves were observed only in patients with peak levels of more than 300 BU/ml. However, only a single rapid component was observed in one patient with peak levels of 470 BU/ml. Hemophilic factor VIII antibodies are heterogenous with regard to their behaviour in vivo. These differences have to be taken into account if therapeutic decisions have to be made.
An Inhibitor Selectively Directed Against Factor VIII-AHF In A Patient With Von Willebrand’S Disease (vWD)
Authors: Castella A , Miller J L , Neuberg R W , Friedman H S 
Published: July 2018

We have studied a 17 month old boy with previously diagnosed vWD who presented with intracerebral hemorrhage. There was a history of excessive bleeding from circumcision, after corrective surgery for pyloric stenosis, and from an upper lip cut. He had received multiple units of cryoprecipitate from the first month of life until the present admission. Work-up demonstrated prolonged bleeding time and prolonged PTT, normal prothrombin time, thrombin time, and platelet aggregation with ADP, epinephrine and collagen. Ten days after cessation of factor VIII replacement therapy he had undetectable F VIII-AHF, F VIII-Ag of 86% by the Laurell technique and F VIII-RCo of 18%. We could demonstrate a time- dependent inhibitor directed against F VIII-AHF measuring 92 Bethesda units. In mixing studies with normal plasma, little or nor inhibitory activity directed against F VIII-RCo could be identified. The patient’s platelets showed increased ristocetin-induced platelet aggregation (RIPA) at doses as low as 0.5 mg/ml.There was no evidence of a bleeding disorder in the maternal side of the family. All of the paternal family members studied showed prolonged bleeding times, decreased F VIII-RCo, and increased RIPA with low doses of ristocetin, findings similar to those patients recently characterized as having type IIb vWD. Although other members of the patient’s family had previously received cryoprecipitate replacement therapy, no inhibitors appear to have developed in these persons.Factor VIII inhibitors in vWD are uncommon, with those reported usually showing little or no inhibition of F VIII-AHF. These findings appear to represent a unique pattern of inhibitor development that may be related to a molecular variant of vWD in this patient.