bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates Of Fibrin Growth As A Predictor Of Acute Myocardial Infarction. A Prospective Blind Study
Authors: Joe Baughman D , Kostis J B 
Published: July 2018

A blind prospective coagulation profile was performed on 147 patients with coronary artery disease (CAD). Theprofile consisted of Prothrombin time (PT), the maximum rate of fibrin production (turbidity) when measuring the PT (PT Vmax), Activated Partial Thromboplastin time (APTT), APTT Vmax, Thrombin time (TT), TT Vmax, Fibrinogen (F), plasma and serum Antithrombin III (At-III), Lysis Time (LT) and Lipoproteins (LP). All clotting times and turbidities were measured using a BioData CP-7; At-III was measured as the loss of thrombin clotting activity; F was measured as the total thrombin clottable protein; LT was measured by a modified CLUE test; LP was measured as a heparin-Mg produced turbidity.During 41 months of follow-up, 12 patients developed a new myocardial infarction (MI), and had significantly higher APTT Vmax (7.46 ± .30U vs. 6.21 ± .09U, p=.0001); PT Vmax (7.83 ± .27U vs. 6.46 ± .10U, p=.0002); TT Vmax (5.33 ± .32U vs. 4.20 ± LOU, p=.0014); and F (339.6 ± 12.2 mg/dl vs. 292.76 ± 4.6 mg/dl, p=.003) than patients who did not. Out of 37 patients with the highest PT Vmax (upper 25%), 27% developed acute MI, while only 2 (1.8%) of the remaining 110 developed MI, giving a risk ratio of 15.4, p=.0001. Similarly, 9 out of 12 infarctions occurred in the upper 25% of APTT Vmax, giving a risk ratio of 8.9, p=0.0004. MI was also predicted by TT Vmax with a risk ratio of 5.9 (p=0.0004) and by fibrinogen with a risk ratio of 4.8 (p=0.0018). No relationship between MI and the other coagulation tests was noted. Thus, 1. rates of fibrin growth may predict the occurrence of MI in CAD, and 2. soluble coagulation parameters are important in the pathogenesis of acute myocardial infarction.
Interventional Radiography In Renal Artery Thrombosis
Authors: Zajko A , Solomon M P , Ring E J , Grossman R A , Barker C F , Perloff L J 
Published: July 2018

Recent reports of successful revascularization of kidneys sustaining prolonged warm ischemia secondary to acute renal artery occlusion prompted the following clinical trial in a renal allograft recipient: During treatment for a mild rejection reaction 19 days after receiving an HLA identical renal allograft, a 30-year old male suddenly developed oliguria with serum creatinine and BUN rising from 2.0-3.4 and 35-61 mg/dl respectively. DTPA technetium and I131 hip- puran scans revealed functional activity and flow limited to the upper pole of the allograft. Arteriography showed multiple intrarenal emboli, a stenotic main renal artery distal to the internal iliac anastomosis, and complete occlusion of the lower pole artery. After transluminal dilatation of the stenosis with a 4 mm balloon catheter, the anastomosis was easily trasversed with coaxial catheters for infusion of streptokinase (5000U/hr) and heparin (800U/hr). Repeat arteriography 12 hours later showed a decrease in the amount of thrombosis. Streptokinase infusion rate was increased to 7500U/hr, and heparin was administered by continuous systemic infusion to maintain the PTT at 45-50. By manipulation of the catheters, thrombi in the major renal artery branches were maneuvered into the already occluded lower pole artery. At 36 hours arteriography revealed reopening of many of the distal occlusions. During this time fibrin degradation products were 10 μg/ml, thrombin time was 64 seconds and fibrinogen level was 235 mg/dl. Although the patient required four weeks of dialysis the urine output was maintained at >1000 ml/day, suggesting polyuric acute tubular necrosis. Five weeks after the occlusive episode, the main renal and upper pole arteries of the allograft were patent and serum creatinine was 3.5 without dialysis.The previously poor results following acute renal artery occlusion in the renal allograft recipient may be improved with early interventional arteriography. This may provide marginal perfusion until surging 1 intervention ensues.
Increased Circulating 6-OXO-PGF1α During Angiotensin II Infusion In Man
Authors: Silberbauer K , Sinzinger H 
Published: July 2018

Angiotensin II(A II) is able to stimulate phospholipase A2. This enzyme initiates the arachidonic acid cascade. Previously we have shown that All enhances the PGI2 release from rat aortic rings and rat kidneys.We, therefore, wondered if All infusion in man might influence the plasma concentrations of 6-OXO-PGF1α (RIA in unextracted plasma), the stable metabolite derived by nonenzymatic conversion from PGI2. Fourteen patients with normal blood pressure, who were tested to assess left ventricular function by radionuclide angiography, received All (2-l,5μg/min for 15 minutes i.v.). During the rise of blood pressure (x:125/80mmHg to 157/102mmHg)6-OXO-PGF1α increased significantly (2p<0.01). Fifteen minutes after All termination the blood pressure returned to prevalues(x:125/82mmHg) and 6-OXO-PGF1α dropped. In one patient saralasin, a competitive inhibitor of All, had no direct effect on 6-0X0-PGF1α (0.1μg,1μg and 10μg saralasin/kg b.w./min, each dosage was infused for 15 minutes).The released vasodilator PGI2, as measured by 6-OXO-PGF1α generated in the vessel wall and in the kidney, might antagonize the vasoconstriction caused by AII.
In Vivo Platelet Activity In Young Patients With Cerebral Ischemia And Mitral-Valve Prolapse
Authors: Scharf R E , Hennerici M , Bluschke V , Schneider W 
Published: July 2018

Recent studies have demonstrated a sixfold higher incidence of mitral-valve prolapse (MVP) in young patients with cerebral ischemia compared to an age-matched control population. To examine whether there is a pathogenetic relationship between MVP and cerebral ischemia, we studied 47 patients (12 males, 35 females) under 45 (mean age 35.4 ± 6.6) years with transient ischemic attacks (TIA) and stroke who had failed to show a cause from extracranial Doppler examination, cranial computerized tomography and cerebral angiography. In vivo platelet activity was evaluated by measuring the B-thrcmboglobulin (β-TG) concentration in the platelet poor EDTA-theophylline-PGE1-plasma using the Amersham RIA kit.The β-TG levels of the patients (54.9 ± 31.4, x ± SD ng/ml) were significant higher than those of an age- and sex-matched control group (n=40, 19.7 ± 6.4 ng/ml, p<0.001) MVP was demonstrated in 28% of the patients (13 of 47) in contrast to 7.5% of the controls (3 of 40). The difference of the β-TG levels of patients with MVP (n=13, 52.9 ± 25.5 ng/ml) and of patients without MVP (n=34, 55.7 ± 33.7 ng/ml) was not significant (p < 0.40). There was no correlation bet ween duration or extent of the neurological deficit and the individual β-TG level.Our results confirm that the incidence of MVP is higher in young patients with cerebral ischemia of unknown cause than in asymptomatic young people. The significantly elevated plasma β-TG concentrations in the patients' group nay indicate an increased platelet activity in vivo. There was io significant difference between β-TG levels of patients tfith and without MVP. Thus, MVP can not be the cause for the altered platelet activity.
Release Of Lyso-PAF-Acether From Platelets
Authors: Benveniste J , Le Couedic J P 
Published: July 2018

The release of PAF-acether from platelets, stimulated by thrombin or the ionophore A 23187, is now well-documented. PAF- acether, 1-O-alky 1-2-ace tyl-sn-glyceryl-phosphorylcholine, may represent the molecular intermediate for the third pathway (i.e. non-ADP, non-thromboxane A2~dependent) of platelet aggregation. We now report the release from stimulated platelets of the non-ace ty la ted compound, l-0-alkyl-2-lyso-sn-glyceryl-3-phos- phorylcholine (lyso-PAF-acether). We have already published the structural identification of this molecule released from blood leukocytes.Washed rabbit platelets (5 x 108/ml) were incubated in Tyrode’s for up to 7 min in the presence of 2.5 uM ionophore or 2.5 U/ml thrombin. PAF-acether was measured by aggregation of washed aspirin-pretreated rabbit platelets in the presence of ADP scavengers. Lyso-PAF-acether was measured by the same method after its chemical acetylation into PAF-acether, followed by treatment with lipase from Rhizoppus arrhizus. Results are given in g/ml, by comparison to known amounts of totally synthetic PAF-acether. PAF-acether and lyso-PAF-acether were released with similar kinetics, reaching a maximum at 5 min. Maximal releases of PAF- acether were 79.0 ± 16.9 and 12.4 ± 8.5 ng/ml (mean ± 1 SD) and that of lyso-PAF-acether were 2.6 ± 0.6 and 1.9 ± 0.8 ug/ml, i.e. about 4 uM, for the ionophore (3 exp.) and thrombin (7 exp.) respectively. PAF-acether directly released from platelets and that obtained through acetylation of lyso-PAF-acether maintained their aggregating activity after treatment with the lipase, thus behaving like the leukocyte-derived compound.The release of lyso-PAF-acether implies the activation of a phospholipase A2 acting on a membrane alkyl-ether phospholipid. Biosynthetic incorporation of acetate into platelet PAF-acether has been reported. Therefore, lyso-PAF-acether may be an intermediate for PAF-acether synthesis ; also potent biological activities of lyso-PAF-acether can be anticipated.
Influence Of An Orally Active Thromboxane Synthesis Inhibitor On Platelet Function In Man
Authors: Walter E , Zimmermann R , Lehle R , Weber E 
Published: July 2018

Several studies have shown that elevated levels of circulating thromboxane and a decreased capacity of the vessel wall to synthesize prostacyclin do occur in patients with cardiovascular diseases and in diabetes. In contrary to the effect of aspirin, selective inhibition of thromboxane synthesis of the platelets would preserve the production of prostacyclin. This selectivity is offered by UK-37, 248, a new imidazole derivative.In 11 patients with cardiovascular diseases and en -hanced platelet aggregation a single dose of 100 mg UK-37,248 was tested. Before and 1, 2, 4, 6 and 24 h after intake, blood pressure, pulse, bleeding time were controlled, and blood was taken for in-vitro platelet aggregation and for measurements of plasma as well as serum TXB2 . The plasma TXB2 -level decreased from 130.9±14.2 pg/ml to 85.7±4.6 pg /ml (p< 0.005) after 6 h. Serum TXB (319.3±31.4 ng/ml) was lowest 1 h after drug intake (32.9±5.9 ng/ml, p< 0.001). 5 h later the level was still significantly decreased (182.1±24.3 ng/ml,p<0.005). The drug had no influence on blood pressure and pulse rate in the lying as well as standing position. Bleeding time was minimally prolonged in 7 patients, the mean prolongation was about 10 %. No effect could be observed on spontaneous, ADP-and co11agen-induced platelet aggregation.The inhibition of thromboxane synthesis in man by UK-37,248 after a single dose of 100 mg could very well be demonstrated. There was no or only a minimal effect on platelet aggregation and bleedingtime. Evaluation of long-term administration is needed.We thank Dr. Tyler, Sandwich, for TXB2-measurements.
Inhibition Of Human Tissue Plasminogen Activator By Human Plasma : No Evidence For A Specific Antiactivator
Authors: Korninger C , Collen D 
Published: July 2018

Human tissue plasminogen activator (TPA) was highly purified (one-chain or two-chain form) from the culture fluid of a melanoma cell line and labeled with 125
Gel filtration of mixtures of human plasma with trace amounts of labeled and 10 to 1,000 units/ml of unlabeled TPA revealed formation of two radioactive complexes with apparent Mr of 150,000 and 800,000, which were devoid of lytic activity of fibrin plates. These radioactive complexes were precipitated (90 and 63 percent) by antisera against α2 antiplasmin (α2AP) and α2-macroglobulin (α2M) respectively, but not by antisera against other known plasma protease inhibitors. In plasma specifically depleted in α2AP formation of the complex with Mr ≃ 150,000 did not occur, whereas removal of α2M abolished formation of the complex with Mr ≃ 800,000. The initial rates of formation of these two complexes in plasma were very similar to those obtained with mixtures of TPA and 1 μM α2AP or 3.5 μM α2M respectively. Complex formation was completely abolished by blocking the active site serine of TPA.In purified systems TPA was inhibited by α2AP with a rate constant of 140 M-1s-1 and by α2M with a rate constant of 30 M-1s-1. These rate constants correlate well with the rate of formation in plasma of the Mr ≃ 150,000 complex and the Mr ≃ 800,000 complex respectively.All these data indicate that TPA is slowly inhibited in human plasma by α2AP (tl/2 ≃ 60') and by α2M (tl/2 ≃ 120'). We found no evidence for the existence of another significant inhibitor in plasma. Both the one-chain and two-chain forms of TPA behaved very similarly in all experiments.
Delayed Elimination Of Fibrin From The Lungs In Rats Treated With The Primary Fibrinolysis Inhibitor α2-Antiplasmin
Authors: Carlin G , Einarsson M , Saldeen T 
Published: July 2018

Patients with the adult respiratory distress syndrome after trauma (the delayed microembolism syndrome) show fibrin deposition in the lungs and delayed elimination of this fibrin. This delayed elimination of fibrin has been supposed to play a key role in the pathogenesis of this syndrome.In the present investigation we have studied the effect of treatment with purified α2-antiplasmin on the elimination of fibrin from the lungs in rats with thrombin-induced intravascular coagulation. The amount of α2-antiplasmin injected was chosen as to simulate the posttraumatic increase of this inhibitor in man.Methods. Labelled fibrinogen was injected into a tail vein 24 hours before the experiment. Human α2-antiplasmin, 1.2 mg corresponding to the normal amount in about 12 ml human plasma, dissolved in 1 ml saline was injected into a tail vein 3 minutes before the thrombin injection. Thrombin, 350 NIH units/kg was injected during 5 minutes into a tail vein. The rats were killed 5 or 35 minutes after the end of the thrombin injection and the amount of fibrin in the lungs was determined.Results. Rats not given α2-antiplasmin showed heavy fibrin deposits determined from radioactive incorporation in the lungs 5 minutes after the thrombin injection. Thirty-five minutes after the thrombin injection most of the fibrin had disappeared from the lungs. Rats given α2-antiplas-min showed the same amount of fibrin in the lungs 5 minutes after the thrombin injection whereas the fibrin amount in the lungs 35 minutes after the thrombin injection was not significantly reduced.The results may argue for the increase of α2-antiplasmin being of importance for the delayed elimination of fibrin seen in patients in the posttraumatic phase.
Partial Primary Structure Of Human α2-Antiplasmin
Authors: Lijnen H R , Wiman B , Van Hoef B , Collen D 
Published: July 2018

α2-Antiplasmin (α2AP), the main physiological inhibitor of plasmin in human plasma, is a single–chain glycoprotein with a molecular weight of 67,000 consisting of about 510 amino acids and containing 13 percent carbohydrate.A tryptic digest on 400 mg of reduced, carboxymethylated and citraconylated purified α2AP was performed. Peptides were separated by combinations of ion exchange chromatography, gel filtration and high performance liquid chromatography, and sequenced using the manual Edman degradation. Some peptides were further digested in order to establish overlaps. At the time of submission of this abstract we have sequenced 7 out of the approximately 21 arginyl peptides completely (each between 3 and 21 residues) and are working on the others. At present we have about 200 residues of sequence. Here we only report the stretches of 10 amino acids or more, which may be useful to compare the structure of α2AP with that of other serine protease inhibitors.
Preparation Of Antithrombin, High Activity Heparin And A Heparin-Antithrombin Complex By A Rapid Two-Step Affinity Method
Authors: Jordan R , Zuffi T , Fournel M , Schroeder D 
Published: July 2018

The tight binding affinity of antithrombin for heparin makes possible a relatively selective purification scheme based on salt elution from heparin-Sepharose. We have found, however, that purity can often be greatly increased if the elution is carried out with soluble heparin instead. This heparin can be removed from the antithrombin, either in whole or part, by a second affinity step on Concanavalin A Sepharose. The antithrombin, which binds to the matrix through its glycosidic moieties, retains its ability to bind heparin at physiological ionic strengths. Thus, the complex of antithrombin and heparin is readily isolated free of unbound heparin species. The complex can be eluted intact with low ionic strength buffers containing sugars which compete for binding to the lectin. Alternatively, the high activity heparin (400–500 units/mg) can be obtained separately by a 1 M NaCl wash which is then followed by a carbohydrate wash to obtain the purified antithrombin.We have made certain preliminary biochemical and anticoagulant characterizations of these materials. Not unexpectedly, both the high activity heparin and its complex with antithrombin show significantly greater in vitro potency in comparison to unfractionated heparin. In vivo anticoagulant efficacy, as evaluated in a rabbit infusion model, confirmed the in vitro findings and further suggests some potential therapeutic benefit may be derived from infusion of a preformed heparin-antithrombin complex.
Familial Antithrombin III Deficiency Associated With Recurrent Arterial Thromboembolism
Authors: Hale C S , Mattson J C , Zuhlke J A 
Published: July 2018

A 28-year-old male with a strong family history of thromboembolic disease sustained three arterial thromboembolic occlusions during a 7 mo. period. The patient had antithrombin III (AT III) levels of 19.2 mg/dl (N=17-30 mg/dl) by RID and an immediate (heparin activated) antithrombin level of 77% (N=88-120%). Crossed IEP showed normal electrophoretic mobility of the patient's AT III. Of 30 family members tested, 10 demonstrated decreased AT III by both immunologic and functional assays. Two children of the propositus and three children of the sister of the propositus were tested and none were found to be abnormal. Because of the unusual presence of arterial thrombotic events in this family, platelet function studies were performed on the propositus and on two AT III deficient family members. A 19-year-old brother of the propositus, with no history of thrombotic events but with 13 mg/dl AT III and 83% activity had normal platelet aggregation studies and demonstrated no evidence of hyperaggregability with suboptimal concentrations of aggregating agents. He did, however, demonstrate a slight increase in platelet adhesion in a collagen adhesion assay. The second family member, a 65 year-old aunt of the propositus with 13.7 mg/dl AT III and 75% activity was on Coumadin at the time of evaluation of platelet function. Platelet aggregation and adhesion studies were normal in this individual. The propositus was also tested while on Coumadin and showed no abnormality of platelet aggregation, no hyperaggregability and no increase in platelet adhesion.In view of our experience, we recommend screening for AT III deficiency in patients with unexplained recurrent arterial thromboembolism as well as those with venous thromboembolism, especially if the family history is suggestive.
On The Pharmacology Of Hirudin
Authors: Markwardt F 
Published: July 2018

Hirudin, the anticoagulant substance obtained from medicinal leeches, was isolated and chemically characterized by us 20 years ago. In order to estimate the potential therapeutic effect, its pharmacodynamic and pharmacokinetic properties were studied in animal experiments. Pure hirudin is well tolerated and, except its anticoagulant effect, it proved to be a pharmacologically inert substance. According to its physico-
chemical properties as a polypeptide ( MW 7600) it is not absorbed enterally in active form and does not penetrate the skin. After parenteral administration hirudin distributes in extracellular fluid. It is eliminated with a half-life of 70 min and 80 % are excreted in unchanged form through the kidneys.The specific inhibition of thrombin by hirudin in the blood prevents not only fibrinogen conversion but also the thrombin-catalyzed activation of other clotting factors and platelets. The antithrombotic effect was demonstrated in experimental animals (rat, rabbit, dog). The incidence of venous clotting thrombi induced by stasis and of arterial deposition thrombi induced by lesion of the vessel wall was prevented. Of special importance is the effect of hirudin to prevent
microthrombosis in DIC induced by infusion of thrombin or endotoxin. In this case hirudin is superior to heparin.Pre-clinical testing showed that hirudin is a potential antithrombotic agent.
Kinetic Study Of Factor X (FX) : Potential Value For The Initiation Of Oral Anticoagulant Treatment
Authors: Fiessinger J N , Aiach M , Nussas C , Capron L 
Published: July 2018

FX has been claimed to be of clinical relevance in monitoring long term treatment with anticoagulants. The aim of this investigation was to study the behaviour of FX at the beginning of the treatment.Seventeen patients under heparin therapy received a daily dose of 3 mg of Acenocoumarol. Blood samples were obtained at 1, 2, 4, 6, 8 days (Dθ - 8), after starting the treatment. Heparin was stopped when prothrombin time (PT) was less than 40 per cent of normal value. FX was evaluated using an automated amidolytic method. Factor VII (FVII) and PT were measured in a clotting assay.The disappearance of FX from plasma could be fitted to an exponential decay pattern during 6 days in 17 patients, 8 days in 11 patients. Concerning FVII, the exponential decay was limited to the first 2 days, then a stable level was reached. The decrease rates of FVII and FX during the first two days were correlated (r = 0,76). The regression line In (FX) = f (D) calculated from D0, D1, D2 could be used for predicting FX concentration at or D8. A highly significant linear correlation existed between the observed and predicted levels (D8 : r = 0,97) (D6 : r = 0,92).These results suggest that FX amidolytic assay could be useful for monitoring the initiation of anticoagulant treatment. The decrease rate of FX could be a valuable guide for an early determination of the maintenance dose of anticoagulant.
Intra-Operative Antithrombin III, Plasminogen And α2 Antiplasmin Behaviour
Authors: Büller H R , Henny Ch P , Ritzen M , Kahlé L H , ten Cate J W 
Published: July 2018

Previously we reported that major surgery induces a marked but transient decline (30%) of antithrombin III (AT III) and plasminogen (PLG) in the first post-operative days .α2AntiPlasm: in (α2AP) alone decreases on the day of operation. In tne study presented we focused on the intra-operative behaviour of AT III, PLG and α2AP in order to establish whether the decrease is gradual or that even lower values are reached during surgery, in different groups of patients. AT III was studied as a marker of activation of the coagulation system and PLG and α2AP as indicators of fiorinolytic activity. Blood samples were taken pre-operatively, every thirty minutes intra-operatively, and within one hour after surgery.The observations were related to hematocrit, blood loss, transfusion and duration of surgery. It is concluded that major surgery is associated with a profound decline of AT III, PLG and α2AP, which may play an important role in the development of intra operative thrombosis.