bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithrombin III Substitution In Acute Hepatic Failure Due To CCl4 Intoxication
Authors: Egbring R , Klingemann H G , Heimburger N , Karges H E , Beule J , Seitz R , Have-mann K 
Published: July 2018

In patients with acute severe hepatic failure the synthesis of clotting factors and inhibitors is considerably diminished. The decrease of clotting factors may be enhanced by liberation of thromboplastic substances from liver cell debris, leading to thrombus formation in the sinusoids and to further cell damage. At the low levels of clotting factors and inhibitors signs of disseminated intravascular coagulation as well as hyperfibrinolysis have been demonstrated. Treatment with heparin to prevent coagulation is insufficient at low levels of antithrombin III (AT III). Therefore, Vogel und Fritsche 1979 suggested the substitution of AT III in these cases.We now report about 3 patients who were admitted to the clinic together with severe signs of liver damage after oral uptake of CCl4
On the day of admission several clotting factors plasminogen and alpha2-antiplasmin were significantly diminished; AT III levels between 25-45% of the norm were found. (Diss. Eckhardt-Klaßnitz). Therefore we started treatment with AT III concentrate from Behringwerke (1000-2000 I.U. daily for 3 to 14 days) and fresh frozen plasma (total volume of 2 1 within the first 3 days).AT III was simultaneously determined by clotting test, a chromogenic substrate test, and immunologically. Hemodialysis was necessary in 2 patients. Unter treatment with AT III and fresh frozen plasma no bleeding tendency occured Though two of the patients showed severe intoxication on admission all could be dismissed with only slight histological signs of liver alterations. Treatment with AT III concentrates, therefore, seems of value in patients with acute yellow liver dystrophy.
Changes In Biologically And Immunochemically Measured Antithrombin III (At III) In Total HIP Replacement With Special Regard To Type Of Thromboembolic Prophylaxis
Authors: Fredin H O , Tengborn L 
Published: July 2018

The plasma levels of AT III were studied in 71 patients operated with total hip replacement. AT III was determined with amidolytic assay using the chromogenic substrate Coatest S-2238 (KabiDiagnostica, Sweden) as well as electroimmunochemically. Samples were drawn before the operation and 4-5 times the first week postoperatively. The results were adjusted to the hematocrit (Hcr) for each sample.The patients were randomly allocated to thromboprophylactic prevention with either Macrodex (Pharmacia, Sweden) or heparin with dihydroergotamine (Sandoz, Switzerland). Phlebography of the operated leg and perfusion/ventilation lung scanning was performed on the 10-14th postoperative day.Results. No difference in the AT III levels were seen in patients who developed postoperatively deep venous thrombosis and/or pulmonary embolism (DVT/PE) as compared to those who did not develop DVT/PE.No decrease of AT III was found postoperatively, when adjusted to HcrThe frequency of DVT/PE did not differ significantly between the two types of thromboembolic prophylaxis.Conclusion. Pre-operative determination of AT III, whether biologically or immunochemically, did not seem to be successful as screening method of patients to develop DVT/PE.
Different Affinities Of Heparin Preparations With Identical Molecualr Weight To Plasma Proteins And Factor Xa
Authors: Harenberg J , Fussi F , Grϋn F , Schlegel A , Mattes K , Zimmermann R , Weber E 
Published: July 2018

The study intends to get information on the in vivo comparability of different heparin preparations with the same molecular weight (mean MW 15000). Four heparins (150-154 USP/mg, sodium salt) were applicated s.c. to each of six volunteers randomly at weekly intervalls.The pharmacodynamic effects were controlled on the factor IIa activity (thrombin clotting time), aPTT and factor Xa activity (chromogenic substrate S2222) over 10 hrs by 12 blood samples. On the factor IIa activity no differences were seen between the heparins. The coagulation times of the aPTT first prolonged and then shortened below the initial value after 4-6 hrs indicating an activating of the intrinsic coagulation system. One of the heparins had a higher anticoagulation effect than the other preparations (p < 0.05). For this heparin a more effective anti-Xa-activity was measured (p < 0.05). In vitro no differences of the heparins were registered on the test systems in a range of 0.01-2.0 USP/ml plasma.The data indicate, that heparin preparations with the same MW and the same in vitro activities may have different effects in vivo. They let suppose, that these differences may be mediated by different affinites of the heparins to plasma proteins as AT III or lipoproteinlipase, which might have caused the activation of the intrinsic coagulation system by a realease of phospholipids, and by different affinities of the heparin AT III complexes of each heparin to factor Xa.
Analysis Of Subcutaneous Sodium And Calcium Heparin
Authors: Caprini J A , Vagher J P , Zuckerman L , Mitchell J 
Published: July 2018

Thirteen normal adults were randomized to receive a 15,000 unit subcutaneous injection of sodium (Na-hep) or calcium (Ca-hep) heparin and seven days later the experiment was repeated with the other heparin. The APTT, Thrombin-Calcium clot time (TCCT), Lee-White clot time (LWCT) and Heparin 10-A (10-A) assays were determined prior to the injection and 1,2,6, and 10 hours post-injection. With the Na-hep injection, the APTT, TCCT, and LWCT showed a more rapid onset and persistently greater anticoagulant activity during the 10 hour period with statistically significant prolongations for 1 and 2 hour samples. The 10-A activity was higher in the Ca-hep group with significance at 10 hours. All the test values showed anticoagulant activity 1.5 to 2.0 times the control at 10 hours for both heparin preparations.An additional 13 normal adults were randomized to receive 5000 units of Na-hep or Ca-hep subcutaneously every 12 hours for 4 time intervals and after seven days the other heparin preparation was given. The APTT, TCCT, LWCT, and 10-A assays were determined prior to the initial injection and at 2,6,and 10 hours post injections. All APTT values varied between 1 and 1.4 times control with significant elevation at 6 hours in the Ca-hep group. The 10-A assay showed significant differences throughout the study with greater activity in the Na-hep group.We conclude that subcutaneous injections of 5000 units sodium or calcium heparin are bioequivalent despite minor test differences which are magnified by increasing the subcutaneous dose. Therapeutic levels of heparin are maintained for greater than 10 hours following a single 15,000 unit injection and less than 6 hours for 5000 units of either heparin in normal adults. The lack of correlation of either 10-A with other results and the large standard deviation may indicate lack of sensitivity of this assay, rather than differences between heparin salts.
Heparin Kinetics And Coagulation Studies After Subcutaneous And Jet Injection Of Low-Dose Heparin
Authors: Briel R C 
Published: July 2018

Administration of low-dose heparin by jet injection is regarded as most suitable for both patient and staff. The present study deals with the comparison of plasma heparin levels and various coagulation parameters after s.c. and jet injection (K3-pistol Sandoz) of 5000 IU calcium heparin in 0.2 ml and 5000 IU sodium heparin + 0.5 mg dihydroergotamin (DHE) in 0.7 ml. The injection sites were upper arm, abdcmen or upper leg. Estimations were performed in 10 healthy volunteers each receiving 12 different injections. Heparin level profiles (chromogenic substrate S-2222), AT III activity (S-2238) and concentration (Mancini technique), antifactor Xa (S-2222), antiheparin activity (S-2222), antiplasmin (S-2251), TT, aPTT and TEG r+k were measured.There was a positive and significant correlation between postinjection heparin levels and body weight, preinjection “endogenous heparin”, AT III activity and concentration, and a negative correlation to the antiheparin activity found before injection. Heparin levels were slightly higher after heparin/DHE than after heparin alone, but the differences were not significant. 30 min after jet injection heparin levels were slightly higher than after s.c. injection, while after 1 hr they were similar. After 2 to 3 hrs the highest levels were found, being significantly higher after s.c. injection. After 4 and 6 hrs there were no differences between s.c. and jet injection. TT, aPTT and TEG showed similar behavior patterns. The values were independant of the injection site, upper arm or abdomen with both s.c. and jet injection. They were lower, however, if heparin jet injection was done in the upper leg.Thus, the pretreatment measurement of AT III, endogenous heparin and antiheparin activity with chromogenic substrates may be helpful in the management of an inividualized heparin prophylaxis. After heparin jet injection, altered heparin kinetic has to be considered: a more rapid initial absorption is followed by lower peak heparin levels. The upper leg can not be recommended as injection site for heparin jet injection.
Prophylaxis Against Deep Vein Thrombosis Following Total Hip Replacement Using A Combination Of Heparin And Dihydroergotamine
Authors: Kakkar V V , Fok J , Djazaeri B , Ham R , Fletcher M 
Published: July 2018

Venous thromboembolism is a frequent and important complication of total hip replacement. Changes in blood coagulability and stasis in the deep veins of the lower limb are major factors in the pathogenesis of deep vein thrombosis (DVT). Prophylactic efforts aimed at changes in coagulability have met with little success in this group. Dihydroergotamine mesylate (DHE), a potent venoconstrictor acting mainly on the capacitance vessels of the limbs is capable of doubling the velocity of venous flow and should minimise stasis.Four hundred and six patients undergoing total hip replacement were investigated for the efficacy of a combination of heparin (5000IU) and DHE (0.5mg) given 8 hourly subcutaneously in the prevention of postoperative venous thromboembolism. High risk patients were scanned using the I125-labelled fibrinogen uptake test and all patients under went bilateral ascending phlebography on the 14th postoperative day unless there was clinical or isotopic evidence necessitating earlier investigation.There were 117 DVT (28.8%), 19 (16.4%) of which were bilateral. Three pulmonary emboli (0.7%) occurred, one of which was fatal. Prophylaxis was discontinued in 6 patients (1.5%) because of postoperative bleeding and wound haematoma developed in 23 patients (5.7%) - 6 of which required evacuation.Heparin and DHE combination in prophylaxis represents a considerable improvement over the use of heparin alone (52% incidence DVT) and Aspirin (80%).
Sex Difference In Heparin Induced Platelet Aggregation In whole Blood
Authors: Kohanna F , Ransil B , Smith M A , Salzman E W 
Published: July 2018

The Clay Adams Ultraflo-100 cell counter coupled with the Nuclear Data 60 pulse-height analyzer permits detection of platelet aggregates in whole blood. Its high resolution recognizes lesser degrees of aggregation than can be seen in PRP by conventional aggregometry. Platelet aggregates are manifested by a drop in number of single platelets. We used this device to study platelet aggregation induced by beef-lung heparin in whole blood.Blood was drawn by venepuncture into a syringe containing either heparin (10 u/ml, n=15) or tri-sodium Citrate (0.130 M, n =7). Samples were gently rocked at 37° for 0, 1, 2, 3, 5, 10 and 30 minutes and then fixed in buffered formaldehyde.Platelet counts of both sexes in citrated whole blood decreased linearly over time (males:n=4; females: n=3; 12% decrease at 30 min. in both). Platelet counts in heparinized blood at time 0 for both males and females were oimodally distributed. Subsequent changes in platelet count also suggested bimodality, with high and low responders (HR and LR) in each sex, corresponding to the bimodal grouping of initial platelet counts. Males exhibited an exponential decay in concentration of single platelets within the first 5 minutes;, counts at 30 minutes fell 31% (HR, n=3) and 23% (LR,n=4) respectively. Females (both HR and LR) demonstrated a biphasic early response with a deep minimum at 2 ininutes (HR=45% decrease, n=4; LR= 26% decrease, n=4) followed by rapid partial disaggregation by 3-5 minutes and subsequent exponential-like decayHeparin and DHE combination in prophylaxis represents a considerable improvement over the use of heparin alone (52% incidence DVT) and Aspirin (80%).Results suggest a profound effect of heparin on platelet aggregation in whole blood, which is markedly different in males and females. The explanation for the sex difference is not known.
Analysis Of Heparin Monitoring
Authors: Caprini J A , Rabadi S J , Vagher J P , Mitchell J 
Published: July 2018

Forty-six thrombosis patients were treated for a total of 437 days with continuous pump infusion heparin therapy. A bolus injection (50 units heparin/kg body weight) was followed by continuous infusion (14.2 units/kg/hour). The patients were randomized into 3 groups, daily coagulation profiles performed, and heparin dose adjusted by the following criteria: 1. no daily dose change unless indicated by clinical symptoms; 2. daily dose adjusted to yield an APTT 1.5 to 2X control; 3. daily dose adjusted to yield a negative TEG index.Group 2 received the most heparin, had the highest body weight, and greater incidence of minor bleeding ( + hemo- test urine and/or stool)(5 point drop in hematocrit).APTT values over 100 sec were seen in 44.4% of patients without bleeding and 52.5% with bleeding complications. Unmeasurable TEG graphs (SLT) were seen in 14.8% of patients without bleeding and 57.9% with bleeding. However, the combination of APTT over 100 sec and SLT were associated with 87.5% incidence of bleeding.The safety of continuous infusion heparin therapy is seen by the 2.2% incidence of major recurrent thrombosis and 2.2% major bleeding with or without laboratory monitoring. The combination of APTT and TEG was predictive of bleeding in 87.5% of cases. The TEG graph can be used to detect activated samples eliminating inconsistent APTT results.
The Influence of Sex Hormones on Rat Platelet Sensitivity to Adenosine-Diphosphate
Authors: Orchard M A , Botting J H 
Published: July 2018

SummaryThe sensitivity of rat platelets to the aggregating agent adenosine-diphosphate (ADP) was studied. Platelets from male and female rats demonstrated comparable sensitivity. Neither ovariectomy nor castration altered platelet sensitivity to ADP. However platelets from mock-operated female, but not mockoperated male rats were less sensitive. Administration of physiological doses of l7β-oestradiol to ovariectomised rats reduced platelet sensitivity. Administration of l7β-oestradiol to mock operated female rats increased platelet sensitivity to ADP. The results suggest that physiological amounts of oestrogen induce a loss of platelet sensitivity following surgery or stress, whereas higher concentrations of oestrogens increase platelet sensitivity.
In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue II. Effects of a Heparin Analogue
Authors: Schmitz-Huebner U , Asbeck F , Loo J van de 
Published: July 2018

SummarySSHA, a semi-synthetic heparin analogue, and sodium heparin from porcine intestinal mucosa were injected subcutaneously into six healthy volunteers over a period of three days in a cross-over trial. Before injection and 2, 4, 6, 8 hrs afterwards, the heparin like activity was measured with the APTT, the anti-Xa clotting test and two chromogenic substrate assays. The results show that SSHA mediates both anti-Xa and antithrombin activities in vivo. A comparison between the effects of SSHA and heparin is problematical due to the heterogeneity of different heparin preparations. Low doses of the analogue (45 mg s. c.) induced proportionally higher and longer lasting anti-Xa activities than higher doses (90 mg s. c.). Repeated injections of SSHA twice daily led to increasing effects on two tests for heparin-like activity, whereas two other tests remained unchanged. Both drugs were tolerated equally well, side effects were not detected. Clinical studies are required to demonstrate whether SSHA is similar or superior to low-dose heparin for use in thrombosis prophylaxis.
Purification and Partial Characterization of Draculin, the Anticoagulant Factor Present in the Saliva of Vampire Bats (Desmodus rotundus)
Authors: Apitz-Castro Rafael , Béguin Suzette , Tablante Alfonzo , Bartoli Fulvia , Holt John C , Hemker H Coenraad 
Published: July 2018

SummaryFrom the saliva of the vampire bat Desmodus rotundus, we isolated an unknown anticoagulant protein which we have named draculin. Its molecular mass as determined by non-reduced SDS-PAGE is about 83 kDa. The reduced polypeptide shows a slower migration. HPLC in a molecular sieve matrix yields a single, symmetrical peak corresponding to 88.5 kDa. Isoelectric focusing shows an acidic protein with pI = 4.1–4.2. Aminoacid analysis is compatible with a single chain polypeptide of about 80 kDa. Cyanogen bromide cleavage yields a single 16-aminoacid peptide, corresponding to the amino-terminus of the native molecule. Draculin inhibits the activated form of coagulation factors IX and X. It does not act on thrombin, trypsin, chymotrypsin and does not express fibrinolytic activity. The inhibition is immediate and not readily reversible, with a stoichiometry of about two molecules of draculin per molecule of factor IXa or Xa. Surprisingly, the inhibitory activity against either factor is not affected by the presence of the other. Draculin binds quantitatively to either immobilised factor Xa or factor IXa. Our preliminary interpretation is that there are two forms of draculin that hardly differ in structure. Both bind to factor Xa and to factor IXa but one form inhibits factor Xa and the other inhibits factor IXa.When added to plasma, draculin increases the lag phase as well as the height of the peak of thrombin generation.
Evaluation of Recombinant Human Factor IX: Pharmacokinetic Studies in the Rat and the Dog
Authors: Keith James C , Ferranti Thomas J , Misra Bibhu , Frederick Thomas , Rup Bonita , McCarthy Kyle , Faulkner Robert , Bush Larry , Schaub Robert G 
Published: July 2018

SummaryThe pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine™, a purified human plasma-derived factor IX, after single 100 IU/kg IV doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine™ were 4–5 μg/ml. The mean plasma half-lives were 13.2 ± 1.6 h for rhFIX and 13.3 ± 1.6 h for Mononine™. Dogs also received rhFIX (40 IU/kg IV, daily) for 28 days or Mononine™ (40 IU/kg IV daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine™ (40 IU/kg) dogs.
Diagnostic Value of a New Sensitive Membrane Based Technique for Instantaneous D-Dimer Evaluation in Patients with Clinically Suspected Deep Venous Thrombosis
Authors: Leroyer Christophe , Escoffre Martine , Moigne Emmanuelle Le , Grimaux Marc , Cagnioncle Olivier , Oger Emmanuel , Bressollette Luc , Abgrall Jean-François , Amiral Jean , Mottier Dominique 
Published: July 2018

SummaryBackground: Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). Aim: To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. Methods: A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. Results: 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 ± 3.4% (95% Cl), and specificity is 36.6 ± 6.9%. Positive predictive value is 67.7 ± 4.8% and negative predictive value is 76.1 ± 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. Conclusion: This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.
The Identification and Significance of a Thr→Pro Polymorphism in Kringle IV Type 8 of Apolipoprotein(a)
Authors: Prins J , Lues F R , van der Hoek Y Y , Kastelein J J.P , Bouma B N , van Rijn H J.M 
Published: July 2018

SummaryElevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant independent risk factor for the development of atherosclerosis. Interindividual levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for sequence polymorphisms in the K.IV coding domain, we identified a polymorphism predicting a Thr→Pro substitution located at amino acid position 12 of kringle IV type 8 of apo(a). The functional and clinical significance of this polymorphism was analysed in a case-control study and by comparing the in vitro lysine binding characteristics of the two Lp(a) subtypes.The case-control study (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender matched normolipidemic controls) revealed an overall allele frequency for the Thr12-→Pro substitution in kringle IV type 8 of 14% and a negative association between presence of the Pro12-subtype and symptomatic atherosclerosis (p <0.03). The in vitro lysine binding studies, using Lp(a) isolated from subjects homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine-Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for immobilised plasmin degraded des- AA-fibrin (DesafibTM-X) was also comparable for the two subtypes, however a decreased maximal attainable binding (Bmax) for immobilised desafibTM-X was observed for the Pro12-subtype Lp(a).