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PubMed1988

Anticoagulation clinics and the monitoring of anticoagulant therapy.

Patients attending an anticoagulation clinic were studied to delineate predisposing risk factors for bleeding and thromboembolic episodes. Seventy-three patients were observed for a total of 921.8 patient-treatment months. The mean duration of treatment was 12.6 months (range 3-36 months). No major bleed occurred (a bleed which caused discontinuation of therapy, hospitalization or death). Thirty-two patients had minor bleeding episodes (0.42 bleeds per patient-year of treatment). The average prothrombin time ratio during the third to the sixth month of therapy was predictive of the bleeding risk. There was no association between bleeding and age, sex, indication for anticoagulation therapy or associated illnesses. Four thromboembolic episodes occurred (0.05 per patient-year of treatment), 3 arterial and 1 venous. At the time of the one venous thromboembolic event the prothrombin time ratio was subtherapeutic. In all 3 patients with arterial thromboembolism the mean 3- to 6-month prothrombin time ratio was less than or equal to the lower limit of the recommended range of 1.6-2.5. In our study prothrombin time ratios of 1.3-1.5 for venous thromboembolic disease and 1.6-2.5 for arterial thromboembolic disease were not associated with thromboembolism or major bleeding. Anticoagulation clinics facilitate the close monitoring of patients on oral anticoagulant therapy.

Aged↗
PubMed2001

Practical management of anticoagulation, bleeding and blood product support for cardiac surgery. Part one: bleeding and anticoagulation issues.

There are many challenging problems related to bleeding and anticoagulation in cardiac surgery. Practical guidelines, which are based on available evidence, can help to direct management issues of post-bypass bleeding, perioperative anticoagulation and the use of haemostatic agents. The patient's bleeding history is the most useful preoperative screening test of haemostasis. The input of a haematologist is often valuable in a number of areas, such as preoperative assessment of patients with a significant history of bleeding, or past history of heparin-induced thrombocytopenia, a lupus anticoagulant, or recent venous thromboembolism. Cardiothoracic surgeons, anaesthetists, perfusionists and haematologists can ensure 'best practice' by being actively involved in the development of 'local' transfusion and anticoagulation guidelines, hospital transfusion committee policies, and audits.

Journal Article↗
PubMed2004

Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen.

BACKGROUND: The treatment of patients at increased risk for arterial thromboembolism who require temporary interruption of warfarin sodium therapy is a common clinical problem. We investigated the efficacy and safety of a standardized periprocedural anticoagulation regimen with low-molecular-weight heparin. METHODS: We studied 650 consecutive patients with a mechanical heart valve, chronic atrial fibrillation, or embolic stroke who required interruption of warfarin therapy because of an invasive procedure. Warfarin was stopped 5 or 6 days before the procedure, and patients received subcutaneous dalteparin sodium, 100 IU/kg twice daily, starting 3 days before the procedure. The risk of postprocedural bleeding determined postprocedural anticoagulant management. In patients undergoing a non-high-bleeding-risk procedure who had adequate postprocedural hemostasis, warfarin was resumed on the evening of the procedure, and dalteparin sodium, 100 IU/kg twice daily, was resumed on the next day and continued until the international normalized ratio was 2.0 or more. If postprocedural hemostasis was not secured, the resumption of dalteparin was delayed. In patients undergoing a high-bleeding-risk procedure, warfarin was resumed on the evening of the procedure, but dalteparin was not given after the procedure. RESULTS: Patients were followed up during the preprocedural and postprocedural period for a mean of 13.8 days (range, 10-18 days). In 542 patients who underwent a non-high-bleeding-risk procedure, there were 2 thromboembolic events (0.4%), 4 major bleeding episodes (0.7%), and 32 episodes of increased wound-related blood loss that precluded postprocedural dalteparin administration (5.9%). In 108 patients who underwent a high-bleeding-risk procedure, there were 2 deaths (1.8%) possibly due to thromboembolism and 2 major bleeding episodes (1.8%). CONCLUSIONS: In patients at increased risk for arterial thromboembolism who require temporary interruption of warfarin therapy, a standardized periprocedural anticoagulant regimen with low-molecular-weight heparin is associated with a low risk of thromboembolic and major bleeding complications.

Adult↗
PubMed1995

Efficacy and safety of combined anticoagulant and antiplatelet therapy versus anticoagulant monotherapy after mechanical heart-valve replacement: a metaanalysis.

We performed a metaanalysis of five randomized controlled trials to compare the efficacy and safety of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulants alone after prosthetic heart-valve replacement. The combined regimen reduced embolism and overall mortality by approximately 67% (pooled odds ratio [OR] 0.33; 95% confidence interval [CI] 0.16 to 0.69; p = 0.0032) and 40% (OR 0.60; 95% CI 0.32 to 1.12; p = 0.11), respectively, but increased the risk of hemorrhage by approximately 65% (OR 1.65; 95% CI 1.15 to 2.39; p = 0.0069) and of major gastrointestinal hemorrhage by approximately 250% (OR 3.47; 95% CI 1.43 to 8.40; p = 0.0058). It is estimated that for every 1.6 patients who had their stroke prevented by combination therapy, there was an excess of one major gastrointestinal bleed. This metaanalysis suggests that the benefits derived from the enhanced antithrombotic potential of combined therapy outweigh the toxic effects resulting from the enhanced anticoagulant potential of this regimen.

Administration, Oral↗
PubMed2006

A new plastic collection tube made of polyethylene terephtalate is suitable for monitoring traditional anticoagulant therapy (oral anticoagulant, unfractionated heparin, and low molecular weight heparin).

To improve the safety of blood collection, plastic tubes have been developed but various interactions with the coagulation system and/or antithrombotic drugs were reported with the first generation of such tubes. The aim of this multicentre study was to compare hemostasis test results measured in evacuated plastic tubes made of polyethylene terephtalate (VenoSafe, Terumo Europe) and in siliconized glass tubes containing the same citrate concentration (0.129 M). In addition, the impact of aging of the plastic tube was investigated by collecting blood samples in tubes at 8 months and at 1 month before expiry. Blood was drawn in 3 centres from untreated patients (n=269), patients on oral anticoagulant treatment (OAT, n=221), and patients treated with either unfractionated heparin (UFH, n=73) or a low molecular weight derivative (LMWH, n=48). Prothrombin time (PT) or INR, activated partial thromboplastin time (APTT) and anti-FXa activity were locally performed, when applicable. In untreated patients and in patients on OAT, PT and APTT values were found statistically shorter (p<0.05) when evaluated in plastic tubes than in glass tubes, except when PT was evaluated using a human thromboplastin. Surprisingly, significantly longer APTT and higher anti-FXa activities were obtained when blood from patients on UFH was drawn in plastic than in glass tubes. However, none of the differences had any clinical relevance (Bland-Altman analysis). In patients on anticoagulant treatment, there was no effect of aging of the plastic tubes. These results suggest that the plastic tube VenoSafe is suitable for coagulation testing both in untreated subjects and more interestingly in patients on traditional anticoagulant therapy during the whole shelf life indicated by the manufacturer.

Anticoagulants↗
PubMed1998

Multicentre randomised study of computerised anticoagulant dosage. European Concerted Action on Anticoagulation.

BACKGROUND: The demand for anticoagulant treatment is increasing. We compared the benefits of computer-generated anticoagulant dosing with traditional dosing decided by experienced medical staff in achieving target international normalised ratios (INRs). METHODS: In five European centres we randomly assigned 285 patients in the stabilisation period and stabilised patients to the computer-generated-dose group (n=137) or traditional-dose group (n=148). Centres had a specialist interest in oral anticoagulation but no previous experience with computer-generated dosing. The computer program calculated doses and times to next visit. Our main endpoint was time spent in target INR range (Rosendaal method). FINDINGS: For all patients combined, computer-generated dosing was significantly beneficial overall in achieving target INR (p=0.004). The mean time within target INR range for all patients and all ranges was 63.3% (SD 28.0) of days in the computer-generated-dose group compared with 53.2% (27.7) in the traditional-dose group. For the stabilisation patients alone, computer-generated doses led to a non-significant benefit in all INR ranges (p=0.06), whereas in the stable patients the benefit was significant (p=0.02). INTERPRETATION: The computer program gave better INR control than the experienced medical staff and at least similar standards to the specialised centres should be generally available. Clinical outcome and cost effectiveness remain to be assessed.

Administration, Oral↗
PubMed2001

To anticoagulate or not to anticoagulate patients with cardiomyopathy.

The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class declines. The interactions of aspirin and ACE inhibitors have been best evaluated for the hemodynamic effects. There may be additional factors hitherto not studied. The hemodynamic effect of ACE inhibitors may be more important in NYHA classes III and IV than in less symptomatic patients. Warfarin use has clear indications for patients in atrial fibrillation with mechanical prosthetic valves, in hypercoagulable states, and with a previous history of embolization. Aspirin is inexpensive and commonly available, but its use must be evaluated and articulated by the prescribing physician. The current multicenter prospective trials will provide much needed guidance on this subject. The ongoing trials do not have a placebo arm, however, indicating a consensus among clinicians that patients with cardiomyopathy should be on an antiplatelet or anticoagulant drug until further data emerge.

Anticoagulants↗
PubMed2002

Inhibition of factor VIIa/tissue factor with nematode anticoagulant protein c2: from unique mechanism to a promising new clinical anticoagulant.

Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent (K(i) = 10 pM) inhibitor of the factor VIIa/tissue factor complex (fVIIa/TF) that involves the pre-requisite binding to either zymogen or activated factor X (fX) prior to the formation of the final quaternary complex with fVIIa/TF. The formation of the binary complex with circulating fX governs the pharmacokinetic profile of rNAPc2 in humans, resulting in a prolonged elimination half-life of >50 h. The clinical antithrombotic potential of rNAPc2 has been evaluated in a phase-II trial in which the incidence of deep-vein thrombosis was reduced over 50% compared to historic controls with low-molecular-weight heparin in patients undergoing knee replacement surgery. A second phase-IIa trial demonstrated the safety of rNAPc2 and the significant suppression of thrombin generation in patients undergoing elective percutaneous coronary intervention treated with standard anticoagulant and antiplatelet therapies. Overall, rNAPc2 is a unique inhibitor of the fVIIa/TF complex and a promising new clinical anticoagulant.

Anticoagulants↗
PubMed2000

Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates.

We have characterized the structure of a sulfated d-galactan from the red algae Botryocladia occidentalis. The following repeating structure (-4-alpha-d-Galp-1-->3-beta-d-Galp-1-->) was found for this polysaccharide, but with a variable sulfation pattern. Clearly one-third of the total alpha-units are 2,3-di-O-sulfated and another one-third are 2-O-sulfated. The algal sulfated d-galactan has a potent anticoagulant activity (similar potency as unfractionated heparin) due to enhanced inhibition of thrombin and factor Xa by antithrombin and/or heparin cofactor II. We also extended the experiments to several sulfated polysaccharides from marine invertebrates with simple structures, composed of a single repeating structure. A 2-O- or 3-O-sulfated l-galactan (as well as a 2-O-sulfated l-fucan) has a weak anticoagulant action when compared with the potent action of the algal sulfated d-galactan. Possibly, the addition of two sulfate esters to a single alpha-galactose residue has an "amplifying effect" on the anticoagulant action, which cannot be totally ascribed to the increased charge density of the polymer. These results indicate that the wide diversity of polysaccharides from marine alga and invertebrates is a useful tool to elucidate structure/anticoagulant activity relationships.

Animals↗
PubMed2006

Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants.

Inhibition of tissue factor pathway inhibitor type 1 (TFPI) is one of the mechanisms by which lupus anticoagulants (LA) may upregulate tissue factor (TF) activity. We wanted to examine whether purified immunoglobulin G (IgG) from patients with LA may interfere with the ability of TFPI to inhibit ex vivo TF-induced thrombin generation. The endogenous thrombin potential (ETP) in pooled normal plasma (PNP) supplemented with IgG from either patients with LA or controls was determined in the absence or presence of recombinant TFPI (rTFPI). In the presence of a heparin neutralizer, the ETP was also determined in plasmas from patients with LA and controls before and after heparin injection in order to quantify the anticoagulant effect of heparin-releasable TFPI in vivo. Compared with IgG from controls (n = 14), IgG from patients with LA (n = 28) induced a wide range of enhancing or inhibitory effects on the ETP in PNP. The response to rTFPI in PNP with IgG from patients with LA correlated inversely with thrombin generation (r(s) = 0.637, P = 0.0003). Correspondingly, the relative inhibition of ETP in postheparin plasmas was smaller for patients (n = 11) than for controls (n = 9) (32% vs. 68%, P = 0.007). Our findings support the hypothesis that TFPI anticoagulant activity is inhibited in some patients with LA.

Adult↗
PubMed1985

The mechanism of action of oral anticoagulants and its consequences for the practice of oral anticoagulation.

A short review on the discovery of the relation between vitamin K and the synthesis of clotting factors and on the development of anticoagulant therapy is given. The procoagulant activity induced by vitamin K resides in the postribosomal modification of N-terminal glutamic acids in gamma-COOH glutamic acids. The mode of action of oral anticoagulants is explained. The concentration-effect relations and the choice of an oral anticoagulant is discussed.

Administration, Oral↗
PubMed2003

Low incidence of hemorrhagic complications of oral anticoagulant therapy in patients with atrial fibrillation in the daily practice of an anticoagulation clinic.

BACKGROUND: Over the last years, the use of oral anticoagulant treatment (OAT) has increased dramatically, principally for the prevention of embolic stroke in patients with atrial fibrillation. This study was aimed at evaluating the efficacy and safety of the management of OAT in a real-practice situation. METHODS: Nine hundred and three consecutive unselected patients, 250 of whom with atrial fibrillation, referred for the control of OAT to the Anticoagulation Clinic of the University of Florence were studied. The total follow-up period was 1679 patient-years. RESULTS: The rate of major bleeding events was 0.8 per 100 patient-years in atrial fibrillation patients. In patients with a target INR > or = 3 a significantly higher rate of bleeding (p = 0.02) with respect to patients with a target INR < 3 was observed. CONCLUSIONS: A low incidence of complications may be obtained even in elderly atrial fibrillation patients on OAT followed in an Anticoagulation Clinic specifically devoted to this management.

Acenocoumarol↗
PubMed1976

[The anticoagulant property of a lipoid anticoagulant and the mechanism of its influence on hemocoagulation].

A lipoid anticoagulant (LA) from human brain tissue was shown to possess a higher anticoagulant activity than previously obtained preparations. It has been established that out of four phospholipids present in LA, only phosphatidyl serine inhibits the coagulant activity of plasma. In isolated hemocoagulating systems LA and phosphatidyl serine were shown to inhibit prothrombin conversion catalyzed by thrombokinase and to exert the antithrombic action in the system thrombin--fibrinogen. Kinetic study of phosphatidyl serine- and LA-induced inhibition of thrombine formation and the thrombine--fibrinogen reaction by conjugated inhibition. Similar kinetic behaviour, observed upon inhibition of both processes by phosphatidyl serine and LA suggest that phosphatidyl serine is a main anticoagulant agent of LA.

Anticoagulants↗
PubMed2005

[Thromboembolic and haemorrhagic complications in patients treated with anticoagulants after artificial heart valve replacement. Risk factors dependent on quality of anticoagulant treatment].

UNLABELLED: Thromboembolic (TE) and hemorrhagic (H) complications are the most significant causes of morbidity and mortality in patients treated with oral anticoagulants (OA) after implantation of artificial valvular prostheses. The risk of complications is dependent on recommended target INR ranges and quality of anticoagulation treatment. We studied 358 patients with a mean age 56.9 +/- 10.3 (who underwent 144 mitral, 172 aortic, 42 both artificial heart valve replacement). The follow up was averaged 36.7 +/- 12.1 month. Linearized incidents of TE events was 2.7%/pty, H events--4.15%/pty. The quality of anticoagulant treatment based on following parameters: averaged INR +/- SD, percentage measurements of INR within the target range 2.5-3.5, within the broad range 2-4 and under 2 and over 5. Average frequency of tests, SD/averaged INR X 100%--was similar in patients with TE and H complications and event free patients. Significant differences were found when a shorter period of time-3 months preceding the TE or H incident was analized compared with the average results of measurements of event free patients. The patients with TE and H complications have statistically significant higher fluctuation ratio than event free patients (respectively: 1.09 -/+ 0.71 and 1.71 -/+ 1.06 vs 0.5 -/+ 0.32, p = 0.04 and 0.02 ) CONCLUSIONS: 1. The risk of TE and H complications was dependent on high fluctuation of INR values in the period of 3 months before the event. 2. The worse control of measurements of INR in the period of 3 months before the event in comparison with yearly values within the recommended target ranges show, that TE and H complications are directly dependent on period of poor INR control.

Adult↗
PubMed1991

Novel anticoagulant peptides from the functional site of human placental anticoagulant protein.

Histidine-containing peptides SHLRKV and DHTLIR, corresponding to placental anticoagulant protein-I (PAP-I) residues 204-209 and 266-271, respectively, are included in the functional site of PAP-I and exhibit anticoagulant activity, but the peptides in which alanine is substituted for histidine do not. However, the peptide KHALKG, corresponding to the region from Lys-97 to Gly-102, did not exhibit an anticoagulant activity, showing that it is not included in the functional site. These findings thus suggest that His-205 and His-267 are involved in the Ca(2+)- or the phospholipid-binding site of PAP-I but that His-98 is not.

Amino Acid Sequence↗
PubMed1989

[The effects of various anticoagulants on blood coagulation: with special reference to false positive lupus anticoagulants].

We studied the effects of heparin, dextran sulphate (MDS), gabexate mesilate (FOY), nafamostat mesilate (FUT-175) and argipidine (MD-805) on APTT, PT, thrombin time (TT) and kaolin-activated PTT (KPTT) with various concentrations of phospholipid for screening of lupus anticoagulants (LA). Heparin, MDS and FUT-175 had a greater effect on APTT than PT. On the contrary, MD-805 had a similar effect on both APTT and PT, which suggests that MD-805 inhibits thrombin generation equally on intrinsic and extrinsic coagulation pathways. Heparin and MD-805 were more effective on TT than MDS, FUT-175 and FOY at high concentrations significantly prolonged TT. But, at even higher concentrations of FUT-175, prolongation of TT was reduced contrary to our expectation. With FOY TT became less prolonged with a passage of time, suggesting time-dependent reduction of its anticoagulant activity. Heparin (0.1-0.2 U/ml) and MDS (0.1-0.3 mg/ml) did not have any effect on KPTT with high concentration of phospholipid, but did FUT-175. It suggests that phospholipid inhibits anticoagulant activity of heparin and MDS. Anti-phospholipid activity of heparin and MDS is similar to that of LA. We concluded that the differentiation of LA from heparin-like inhibitors is needed.

Anticoagulants↗
PubMed1987

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Administration, Oral↗
PubMedDate not supplied

[Sclerosis of varicose veins in patients on anticoagulants. Apropos of the report of 2 patients on anticoagulants].

The article refers to two cardiac patients on anticoagulants, one of them has an aortic valve, the other has had a myocardiac infarction, both have varicose lower members associated with trophic disorders. Cases of sclerotherapy on weak patients using antivitamin K (anti-coagulant solution) are rare. Usually the classic technique of sclerotherapy using Aetoxisclerol (Polydaconol) is used in the treatment of such cases. Both results have been good and without incidence. The concentrations of sclerosant solution are more or less the same those used for patients not on anticoagulant. Taking into account the results of these two cases, we should not as a matter of course refuse treatment to varicose patients on anticoagulants.

Aged↗