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At least 163 records · Page 9Linked to original sources
PubMed1990

Comparison of test methods for the lupus anticoagulant: international survey on lupus anticoagulants-I (ISLA-1).

Six lyophilized plasma samples were sent to 20 "expert" laboratories for assessment of lupus anticoagulant (LA). Four samples contained pooled LA of graded potency mixed with aged normal plasma. One contained LA plus cephalin phospholipid and one contained a nonspecific venom anticoagulant. Sixteen methods were used overall with some participants using up to 8 methods. Results were scored in regard to the known potencies of LA in the samples and other known induced defects. Activated partial thromboplastin time (APTT) tests used by most participants for preliminary screening were relatively sensitive, but non-specific. Platelet or phospholipid neutralization procedures (PNP) appeared to be sensitive and specific but showed a non-linear response to increased LA content. Kaolin clotting time (KCT) tests showed the most sensitive response to increased LA content but the weaker LA were not scored as abnormal by most laboratories as the samples may have contained platelet fragments. Other commonly used tests such as the tissue thromboplastin inhibition (TTI) test and the dilute Russell's viper venom test (DRVVT) were carried out somewhat inconsistently. The variability in performance of tests in different laboratories indicates that standardization of methodology is urgently required. Generally it seemed that most clotting tests were "bypassed" by the addition of phospholipid to a known LA-positive sample in apparently direct proportion to their sensitivity. Sample preparation, especially prevention of contamination with activated platelets is a vital preliminary part in the assay of LA.

Autoantibodies↗
PubMed1990

Bleeding times in rats treated with heparin, heparin fragments of high and low anticoagulant activity and chemically modified heparin fragments of low anticoagulant activity.

A template bleeding time study in the rat was undertaken to see if it is possible to correlate bleeding times with the molecular weight, anticoagulant activity or chemical composition of heparin or heparin-derived compounds. Heparin from porcine intestinal mucosa (PM-heparin) and from bovine lung (BL-heparin) as well as heparin fragments from these sources were compared. Heparin fragments of low anticoagulant activity were prepared by affinity chromatography on immobilized antithrombin as well as by chemical modification. A heparin fragment of high affinity for antithrombin (HA-fragment) caused a marked and dose-dependent increase in bleeding time while the corresponding heparin fragment with low affinity for antithrombin (LA-fragment) had a marginal and non-dose dependent effect on the bleeding time. Similar results were also obtained with PM-heparin with high and low affinity for antithrombin. A high anti-FXa activity was not always correlated with a marked bleeding tendency. Provided that a fragment was devoid of activated partial thromboplastin time (APTT) activity, it was not possible to provoke a bleeding time of 20 min or longer, although the compound was administered at a dose of 1,088 U/kg (anti-FXa activity). On the other hand, a N-acetylated chemically oversulphated heparin fragment, with a very low anti-FXa activity (1 U/mg) and with an APTT activity of 34 U/mg, caused a bleeding time of 20 min or longer in 70% of the animals after injection of the same number of APTT units, 1,088 U/kg. These data indicate that the APTT activity is a better and more sensitive indicator of the bleeding than is the anti-FXa activity.

Acetylation↗
PubMed1969

Assessment of short-anticoagulant administration after cardiac infarction. Report of the Working Party on Anticoagulant Therapy in Coronary Thrombosis to the Medical Research Council.

This report describes the design and results of a controlled trial of anticoagulant drugs in the treatment of patients admitted to hospital suffering from acute myocardial infarction. A total of 1,427 patients were allocated at random to therapy with high-dosage or low-dosage anticoagulants. The high-dosage regimen was 36 hours of heparin administration and phenindione in doses to maintain the thrombotest level between 10 and 20%. The mean phenindione dosage was 72 mg./day. The low-dosage regimen consisted of 1-mg. tablets of phenindione. Therapy was continued for 28 days.There was no significant reduction in the mortality in the high-dosage group. Among the 712 patients allocated to high dosage 115 (16.2%) died before the 29th day of the trial. Of the 715 patients allocated to low dosage 129 (18%) died. This difference between these mortality rates could have occurred by chance.There was a significant reduction in the frequency of clinically evident thromboembolic complications (systemic artery occlusion, leg vein thrombosis, and pulmonary embolism) among patients in the high-dosage group. This did not, however, materially affect the difference in mortality from all causes.

Adult↗
PubMed1995

Laboratory identification of lupus anticoagulants: results of the Second International Workshop for Identification of Lupus Anticoagulants. On behalf of the Subcommittee on Lupus Anticoagulants/Antiphospholipid Antibodies of the ISTH.

Lupus anticoagulants (LAs) are antibodies that interfere with phospholipid dependent coagulation reactions in vitro. This workshop was designed to provide the participants with an experience in identification of LAs, to evaluate different criteria for mixing studies, to assess the performance of recently introduced confirmatory studies and to assess the performance of two potential surrogate LA control plasmas. The results demonstrate that there continues to be significant variation in the sensitivity and responsiveness of APTT reagents to the presence of LAs, confirming the need for more than one screening assay before the presence of a LA can be ruled out. In this workshop, the best distinction between factor deficiency and inhibitors was obtained using a 1:1 mix of normal plasma with patient plasma and the criterion defining correction as shortening of the APTT to within 5 s of the APTT of pooled normal plasma. A 4:1 mix of patient to normal plasma did not work well in distinguishing factor deficiency from inhibitors. The platelet neutralization procedure, DVV confirm and StaClot LA all gave positive results with the LA samples. False positive platelet neutralization procedures were seen with the samples from patients on oral anticoagulants and a factor V inhibitor. False positive StaClot LA results were obtained with high titer factor VIII inhibitors. Both of the potential surrogate plasmas gave variable results with multiple assays; they can not be recommended for routine use at present.

Humans↗
PubMed1977

Comparative pharmacokinetics of coumarin anticoagulants XXIX: Elimination kinetics and anticoagulant activity of (S)-(-)-warfarin in rats before and after chronic administration.

The kinetics of elimination and the anticoagulant effect of (S)-(-)-warfarin were determined in adult male rats before and after daily drug administration for 13 days. There was a small but statistically significant (p less than 0.05) decrease in the body clearance of (S)-(-)-warfarin (from 4.84 to 4.37 ml/hr/kg) and an increase in the serum free fraction of racemic warfarin (added to serum in vitro) from 0.00850 to 0.0107 (p less than 0.05). The concentration of (S)-(-)-warfarin in serum at which the synthesis rate of prothrombin complex activity is one-half of the pre-warfarin rate increased from 0.532 to 0.655 microgram/ml on the average (p less than 0.05).

Animals↗
PubMed1990

The anticoagulant effect of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-6-hydroxyhexylamine, another amino-estrogen with prolonged anticoagulant effect.

The anticoagulant and estrogenic effects of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-6-hydroxyhexylamine, are described. A single subcutaneous injection of hexolame in adult and infant male mice produced dose-dependent increases in blood clotting time which could be observed even after 2 days. In ovariectomized mice, hexolame produced vaginal cornification (estrogenic response). The data suggested that if used in the treatment of prostatic cancer, hexolame, like prolame, would not induce cardiovascular accidents. It could also be useful in the prevention of thrombosis.

Amino Alcohols↗
PubMed2002

[Oral anticoagulant treatment: practical aspects and significance of anticoagulant clinics].

Vitamin K antagonists (VKA) decrease the synthesis of the active forms of four coagulation factors (factors II, VII, IX, X) and three inhibitors (proteins C, S, Z). There are VKA having a short half life (Sintrom, Pindione) and VKA having a long half life (Apegmone, Previscan, Coumadine). The treatment is monitored by the INR which in the majority of the indications must range between two and three. The first INR is usually performed 36 to 72 h after starting the treatment. There are a number of drug interactions. The rate of major bleedings range from 1.1 to 4.9 for 100 patient-year according to the published studies. Since around 600,000 patients are treated by VKA in our country, the absolute number of serious bleeding is high (> or = 17,000 per year). Anticoagulant clinics are structures aimed to instruct the patient and to advise the general practitioner to monitor the treatment, using computer assisted methods. It has been reported that these structures reduce the incidence of bleeding and of thrombotic events by 3 to 4 times.

Acenocoumarol↗
PubMed1996

Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm. Sulfated fucose branches on the polysaccharide account for its high anticoagulant action.

A polysaccharide isolated from the body wall of the sea cucumber Ludwigothurea grisea has a backbone like that of mammalian chondroitin sulfate: [4-beta-D-GlcA-1-->3-beta-D-GalNAc-1]n but substituted at the 3-position of the beta--glucuronic acid residues with sulfated alpha--fucopyranosyl branches (Vieira, R. P., Mulloy, B., and Mourão, P. A. S. (1991) J. Biol. Chem. 266, 13530-13536). Mild acid hydrolysis removes the sulfated alpha--fucose branches, and cleaved residues have been characterized by 1H NMR spectroscopy; the most abundant species is fucose 4-O-monosulfate, but 2,4- and 3, 4-di-O-sulfated residues are also present. Degradation of the remaining polysaccharide with chondroitin ABC lyase shows that the sulfated alpha-L-fucose residues released by mild acid hydrolysis are concentrated toward the non-reducing end of the polysaccharide chains; enzyme-resistant polysaccharide material includes the reducing terminal and carries acid-resistant -fucose substitution. The sulfated alpha-L-fucose branches confer anticoagulant activity on the polysaccharide. The specific activity of fucosylated chondroitin sulfate in the activated partial thromboplastin time assay is greater than that of a linear homopolymeric alpha-L-fucan with about the same level of sulfation; this activity is lost on defucosylation or desulfation but not on carboxyl-reduction of the polymer. Assays with purified reagents show that the fucosylated chondroitin sulfate can potentiate the thrombin inhibition activity of both antithrombin and heparin cofactor II.

Animals↗
PubMed1994

Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation.

OBJECTIVES: A high frequency of asymptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) has been reported, but information about the outcome of the patients with PE remains sparse. The aims of the present study were to assess the prevalence of silent PE in patients with symptomatic, venographically proven DVT, and to evaluate the natural history of silent PE. DESIGN: Consecutive patients from one centre of primary care were included in a randomized, open study with blinded control. All patients gave written, informed consent. SUBJECTS: Eighty-seven consecutive patients with venographically proven DVT and with a perfusion-ventilation lung scintigraphy performed within 48 h of the DVT diagnosis were included. On the 10th and 60th days the lung scintigraphy was repeated in 80 and 60 patients, respectively. All the patients were followed for 3 months in the out-patient clinic. INTERVENTIONS: All patients were ambulated from the first day and were allocated randomly to no anticoagulant (non-AC) therapy or to AC therapy with intravenous heparin infusion for at least 6 days and oral AC therapy for 3 months. RESULTS: Forty-three of these patients had a high probability lung scintigraphy for PE. Distal vein and femoral vein thrombosis embolized in 33 and 53% of patients, respectively. The progression rate after 60 days was 3% in both the AC and the non-AC group and after 10 days the rates were 13 and 8%, respectively. CONCLUSIONS: A high frequency of silent PE in patients with DVT both above and below the knee is demonstrated. AC treatment did not influence the resolution rate of PE or the rate of clinical PE in a 3-month follow-up period.

Adolescent↗
PubMed2005

Meta-analysis of trials comparing oral anticoagulation and aspirin versus dual antiplatelet therapy after coronary stenting. Clues for the management of patients with an indication for long-term anticoagulation undergoing coronary stenting.

The combination of oral anticoagulation (OAC) and aspirin was the antithrombotic treatment initially adopted after coronary stenting (PCI-S). Although dual antiplatelet therapy with aspirin and a thienopyridine subsequently proved safer and more effective, OAC and aspirin combination is still used in patients with an indication for long-term OAC undergoing PCI-S. The absolute (AR) and relative (RR) risk of cardiac events and hemorrhagic/vascular complications of OAC and aspirin versus antiplatelet therapy were evaluated in a meta-analysis of four historical clinical trials. In 2,436 patients, the RR of a 30-day primary composite endpoint of death, myocardial infarction and the need for revascularization was significantly reduced by antiplatelet therapy (RR 0.41; 95% CI 0.25-0.69), whereas the RR of stent thrombosis (RR 0.26; 95% CI 0.06-1.14) and major bleeding (RR 0.36; 95% CI 0.14-1.02) was not statistically different. The 30-day AR of death, myocardial infarction, need for revascularization, major bleedings and vascular complications with OAC and aspirin were 0.65, 3.8, 4.2, 6.4 and 6.6%, respectively. In conclusion, due to the low AR of adverse events, the combination of OAC and aspirin appears an acceptable treatment after PCI-S in patients in whom long-term OAC is deemed mandatory.

Administration, Oral↗
PubMed1987

Effect of oral anticoagulant treatment on plasma and serum antithrombin III: a study on 172 patients at different levels of anticoagulation.

Antithrombin III (AT III) functional levels are much lower in serum than in plasma; during oral anticoagulation this difference is reduced. Plasma and serum of 172 patients taking vitamin K antagonists were tested for AT III antigen and both AT III heparin cofactor and anti-Xa heparin cofactor. Crossed immunoelectrophoresis of AT III on heparin-agarose was also carried out in plasma and serum. The patients were divided into four groups: (1) international normalized ratio (INR) 9.3-4.1, n = 25; (2) INR 4.0-2.5, n = 73; (3) INR 2.4-2.0, n = 40, and (4) INR 1.9-1.5, n = 34. 66 healthy subjects were used as controls. Plasma levels of AT III antigen, AT III heparin cofactor, and anti-Xa heparin cofactor were the same in all groups. In all groups all serum AT III parameters were higher than in controls; crossed immunoelectrophoresis of AT III on heparin-agarose indicated that this finding was due to a lower formation of complexed AT III in serum. AT III heparin cofactor serum values were the same whatever the INR over a large range (9.3-1.5); the highest anti-Xa heparin cofactor serum levels were noted in the groups treated more intensely (groups 1 and 2).

Administration, Oral↗
PubMed1999

[Major thromboembolic complications during oral anticoagulant therapy. Importance of level of anticoagulation].

PURPOSE: The incidence of major thromboembolic complications in patients on oral anticoagulant therapy (OAT) and the correlation of this with the intensity of the OAT and the INR level at the time of the episode have been assessed in our study. PATIENTS AND METHODS: We have carried out a retrospective study including 1350 patients with an overall follow-up period of 6432 patient-years. The mean INR level throughout OAT and at the time of the mayor thromboembolic event were considered. The statistical analysis was performed by means of a survival analysis test. RESULTS: The incidence of major thromboembolic complications found in our study was 1.18/100 patient-years. Those patients with a mean INR below the therapeutic range showed significantly a higher risk (3.31 times higher) of suffering from some sort of major thromboembolic complication. Mean INR level at the time of the event was 1.9 and 47% of those patients had an INR level < 2 at the time of the thromboembolic complication. CONCLUSIONS: The probability of suffering a major thromboembolic complication for those subjects on OAT increases as the INR falls below the therapeutic range; therefore we must pay special attention to this factor in order to avoid any further recurrences.

Administration, Oral↗
PubMed2000

[Secondary anticoagulant prophylaxis with low molecular heparins or oral anticoagulants and bone mineral density].

A broad spectrum of indications for low molecular weight heparin (LMWH) requires an assessment of side effects especially during prolonged administration. There are common risk factors for venous thromboembolism (VTE) and osteoporosis; heparin is "the drug of choice" for VTE treatment. The aim of our study was to assess the effect of treatment and prophylaxis with LMWH (enoxaparine sodium) and oral anticoagulant (acenocoumarol) for bone structure. Material consists of in- and outpatients. 49 densitometries were performed in 31 patients (in 15 cases double examination). We observed a decrease of bone mineral density in comparison to the initial examination in most cases: mean change of bone mass for examined areas was 3.05%.

Acenocoumarol↗
PubMed1986

[New results concerning the effectiveness of therapy of chronic glomerulonephritis. Results of cytostatics-anticoagulants-aggregation inhibitors, cystostatics-anticoagulants-aggregation inhibitors-prednisone and cystostatics-prednisone therapy, derived from a retrospective study].

The indication and effectiveness of the immunosuppressive therapy of chronic glomerulonephritis is now as ever controversial. As a result of a retrospective therapy study in an at least one-year therapy with cytostatics, thrombocyte aggregation inhibitors and anticoagulants (CAA-therapy, n = 27), additional prednisone therapy (CAAP-therapy, n = 95) and cytostatic-prednisone therapy (CP-therapy, n = 33) we find favourable results for the CAA/CAAP-therapy in the nephrotic syndrome and glomerulonephritides with distinct clinical exacerbation also in sclerosations in histology. Clinically inactive nephritides with exclusive urinary findings and sclerosations cannot be influenced therapeutically.

Anticoagulants↗
PubMed1975

[Comparative studies with various anticoagulant stabilizer combinations for the preservation of blood specimen in leukosis diagnosis. II. Testing the application possibilities of new anticoagulant stabilizer combinations for the hematologic diagnonsis of leukosis].

The anticoagulant Chelaplex III in aqueous solution with two new stabilizers (methenamine and tannin) was tested for the preservation of blood samples, together with another combination composed of oxalic acid and methenamine solution. The eventual aim was to test their suitability for use with blood specimens dried in the tube, but this was not done in the present experiments. It was shown that a combination of 5% oxalic acid with 36% methenamine was at least as good as the conventional Chelaplex III-formaldehyde combination for inhibiting coagulation, and it was relatively cheap.

Animals↗
PubMed2002

Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature.

We report a severe hemorrhagic disorder in two pediatric patients with lupus anticoagulant (LA) associated to acquired factor II (prothrombin) deficiency. In both patients, hemorrhagic symptoms resolved after corticosteroid therapy. Serial coagulation studies showed that Staclot LA assay was more sensitive than DVVconfirm and Staclot PNP tests to confirm the presence of LA when associated with severe factor II deficiency. Both patients had non-neutralizing anti-prothrombin antibodies and their titers inversely correlated with factor II activity (r = -1.0, P < 0.0001). Associated findings in these patients included positive immunologic tests for systemic lupus erythematosus, a positive anti-cardiolipin antibody, and anti-beta(2) GPI antibodies in one case. Our findings point out the difficulty in diagnosing LA associated with acquired factor II deficiency and suggest that, in confirmation of its phospholipid dependency, the inclusion of a source of normal human plasma in the test sequence to correct for any factor deficiency and a confirmatory step utilizing hexagonal (II) phase phospholipids may be crucial to the diagnosis of LA in some patients with LA-hypoprothrombinemia syndrome.

Adolescent↗
PubMed2000

The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathway.

Recent research has revealed a number of links between inflammation and coagulation. The protein C anticoagulant pathway appears to be the major pathway involved in the cross-talk between inflammation and coagulation. Studies indicate that inflammatory mediators can downregulate key components of the pathway through transcriptional control, proteolytic inactivation and oxidant damage. In turn, in vivo and in vitro studies have revealed mechanisms by which the components of the pathway may inhibit inflammatory responses. These include inhibition of cytokine responses to endotoxin, inhibition of leukocyte attachment to the activated endothelium and inhibition of thrombin and factor Xa generation in the microcirculation where both enzymes can lead to endothelial cell activation, further potentiating the inflammatory response. The ability of the protein C system to modulate both inflammation and coagulation may explain i part why specific defects in the pathway appear to be associated with both arterial and venus thrombosis.

Activated Protein C Resistance↗
PubMed1990

Detection of lupus like anticoagulant: current laboratory practice in the United Kingdom. The Lupus Anticoagulant Working Party.

Various tests have been advocated for the detection of lupus like anticoagulants (LA) and related antiphospholipid antibodies, but there is no agreement on the most appropriate laboratory approach. Two hundred and fifty five of 433 hospital centres in the United Kingdom responded to a questionnaire. Many different tests were reported to be in use for screening for LA with considerable variation in plasma preparation, choice of reagent, and methodological details. Three freeze dried plasmas were subsequently assessed for the presence of LA by 183 laboratories. While 92% correctly identified a strong inhibitor and 91% a negative control, only 65% correctly identified a weak inhibitor. Pronounced variations in the suitability of commonly used reagents in the activated partial thromboplastin time test (APTT) were noted and important methodological features were identified in the kaolin clotting time, dilute thromboplastin time, and dilute Russell's viper venom time tests. It is concluded that careful plasma preparation, with avoidance of platelet contamination, use of a suitable test in addition to the APTT, and attention to methodological detail are essential for the reliable identification of LA, a clinically important inhibitor.

Autoantibodies↗