A comparative study between INR and the determination of prothrombin time with the Coaguchek(r) portable coagulometer in the dental treatment of anticoagulated patients.
(9/76)
OBJECTIVE: To assess the usefulness of the Coaguchek(r) portable coagulometer for determining the International Normalized Ratio (INR) in dental practice. STUDY DESIGN: A total of 139 INR determinations were made in 88 patients anticoagulated with acenocoumarol (Sintrom(r)) for thrombotic pathology, based on the habitual laboratory procedure (Sample 1). Posteriorly and prior to dental treatment, INR was again determined using the Coaguchek(r) portable device (Sample 2). Both determinations were subsequently compared to evaluate possible significant differences between them, applying the Student t-test for paired data and regression measures. RESULTS: The mean INR in Sample 1 was not significantly different to that recorded with the Coaguchek(r) portable device (Sample 2) (2,31 0,81 versus 2,28 0,82, respectively, t= 0,98; p= 0,32). A statistically significant relation was observed between the two samples (R= 0,92; p< 0,01). CONCLUSIONS: The Coaguchek(r) portable coagulometer is a valid instrument for determining INR in anticoagulated individuals, and constitutes an effective method in application to the outpatient dental treatment of such patients. (+info)
Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol.
(10/76)
The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are associated with hypersensitivity to warfarin and bleeding. The effect of these polymorphisms on sensitivity to acenocoumarol is unknown. Three groups of patients, with low, medium, or high acenocoumarol-dose requirements, were studied. Age influenced the acenocoumarol sensitivity. Bearing the 2C9*3 allele was associated with the need for a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence interval [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele required a low dose. The 2C9*2 allele was associated with a lower acenocoumarol-dose requirement (OR, 2.70; 95% CI, 1.11-6.58) because of a reduced risk of the need for a high acenocoumarol dose (4.8% of the patients in the high-dose group carried the 2C9*2 allele versus 34.1% and 30.2%, respectively, in the medium-dose and low-dose groups). Therefore, carriers of 2C9*3 may need a low initial loading dose of acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2 variant does not seem to be clinically relevant, the drug could be an alternative to warfarin in 2C9*2 carriers. (+info)
Platelet aggregation in different antithrombotic regimens. Possible proaggregant effect of low level oral anticoagulation.
(11/76)
Few trials have studied platelet activity during oral anticoagulation and all show a tendency for platelet aggregation to increase. This adverse effect has also been shown in some patients treated with unfractionated heparin, the so-called white clot syndrome. We studied platelet aggregation in patients with atrial fibrillation enrolled in the NASPEAF study and receiving antiaggregant, anticoagulant and both treatments. METHODS: 15 healthy control subjects (group C) and 99 patients were enrolled, the latter receiving 4 different antithrombotic regimens for platelet aggregation: group 1, 600 mg of the antiplatelet drug triflusal; group 2, anticoagulation for an INR of 2-3; and both treatments with 2 different levels of anticoagulation, mean INR of 1.85 (group 3) and of 2.15 (group 4). The same amounts of the agonists ADP, arachidonic acid and collagen were used in all tests. For statistical analysis we used the interval in min, from the addition of the agonist to the beginning of aggregation and the % of aggregation at 5 and 8 min. RESULTS: After arachidonic acid was given, the interval to the beginning of aggregation was shorter in group 2 than in group C: 0.6 +/- 0.21 and 1.1 +/- 1.2, and in both was significantly shorter than in the other three receiving antiplatelet drugs alone: group 1 = 1.58 +/- 1.4 or combined with anticoagulants: group 3 = 1.7 +/- 1.7 and group 4 = 2.4 +/- 2.1. The % of aggregation at 5 min, in groups C, 2, 1, 3 and 4 was respectively 48 +/- 24, 43.2 +/- 19, 29.6 +/- 17, 34.8 +/- 22 and 23.2 +/- 22.5. The data showed significantly increased platelet activity in groups C and 2 compared to groups 1, 3 and 4. Group 3 with a low anticoagulation level (mean INR = 1.85) showed a tendency to greater platelet activity than group 1 and 4 with p value = 0.08. CONCLUSIONS: The antiplatelet drug triflusal alone or combined with a therapeutic level of anticoagulation effectively reduces platelet aggregation and is not influenced by anticoagulant treatment. A low level of anticoagulation (INR < 2) shows a tendency to increase platelet activity. (+info)
Intracranial bleeding: epidemiology and relationships with antithrombotic treatment in 241 cerebral hemorrhages in Reggio Emilia.
(12/76)
BACKGROUND AND OBJECTIVES: Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs. DESIGN AND METHODS: We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs. RESULTS: We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p < 0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and by age (p < 0.0001). INTERPRETATION AND CONCLUSIONS: Careful selection of patients and prevention of traumatic events are the main candidate mechanisms to reduce intracranial bleeding in patients being treated with AC and AP drugs. (+info)
Relationship between international normalized ratio values, vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment.
(13/76)
BACKGROUND AND OBJECTIVES: In vitro studies have shown that the rate of prothrombin activation is linearly related to the concentration of factor II (FII) in the assay system, suggesting a key role of prothrombin levels in the expression of the antithrombotic activity of oral anticoagulant treatment (OAT). We investigated the in vivo relationship between prothrombin activation and vitamin K-dependent clotting factor levels during the early and steady phases of OAT in patients and in healthy volunteers. DESIGN AND METHODS: The changes in international normalizezd ratio (INR) and in the plasma levels of FVII, FX, FII, protein C (PC) and prothrombin fragment 1.2 (F1+2) induced by OAT were monitored over 9 days in 10 patients not on heparin starting warfarin after heart valve replacement (HVR) and in 9 healthy volunteers submitted to an 8-day course of warfarin treatment. FII and F1+2 plasma levels were also measured in 100 patients on stable oral anticoagulant treatment with INRs ranging from 1.2 to 6.84. RESULTS: Because HVR patients had subnormal FVII, FX and FII levels after surgery, INR values > 2.0 were attained already 24 hours after the first warfarin dose. In healthy volunteers, INR values greater than 2.0 were first observed after 72 hours. Nadir levels of FVII, PC, FX and FII were reached between 40 and 88 hours in HVR patients and between 72 and 192 hours in healthy volunteers. The FII apparent half-disappearance time (t/2) was 99 hours in HVR patients and 115 hours in healthy volunteers (p = ns). In HVR patients there was no normalization of initially elevated F1+2 levels until day 7 with an apparent t/2 of 132 hours. In healthy volunteers, a decrease to subnormal F1+2 levels was observed by day 8 of treatment (apparent t/2 = 107 hours). In both HVR patients and healthy volunteers, FII and PC levels were independent predictors of the changes in F1+2 levels (p = 0.0001). In patients on stable OAT, only FII levels were independent predictors of the variation in F1+2 levels (p = 0.0001). INTERPRETATION AND CONCLUSIONS: During the early phase of oral anticoagulant treatment in vivo prothrombin activation is a function of the balance between FII and PC levels and is not significantly prevented until nadir levels of FII are obtained. This provides an explanation for the requirement of overlapping heparin and oral anticoagulant treatment for at least 48 hours after the achievement of therapeutic INR values in patients with thromboembolic diseases. In addition, in vivo prothrombin activation is a function of FII levels rather than INR values also in patients on stable oral anticoagulant treatment. (+info)
Pharmacogenetics of acenocoumarol: cytochrome P450 CYP2C9 polymorphisms influence dose requirements and stability of anticoagulation.
(14/76)
BACKGROUND AND OBJECTIVES: Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarinic metabolism. Variant alleles, CYP2C9*2 and CYP2C9*3, have been related to decreased enzymatic activity, but their clinical relevance in acenocoumarol metabolism has not been established. We investigated CYP2C9 polymorphisms in relation to acenocoumarol dose requirement, stability of anticoagulation and bleeding. DESIGN AND METHODS: CYP2C9 genotyping was performed in 325 acenocoumarol-treated patients (INR target between 2.0 and 3.0) and in an additional group of 84 patients with repeated bleeding. RESULTS: Patients with the wild-type CYP2C9*1/*1 genotype (n=169) required a higher maintenance dose of acenocoumarol (17.1 8.7 mg/week) than did patients with the CYP2C9*2 (14.6 6.4 mg/week, p<0.05, N=97) or the CYP2C9*3 allele (11.2 6.2 mg/week, p<0.001, n=59). Out of 170 patients requiring a low-dose of acenocoumarol (70 years (OR=3.73, 95%CI=2.29-6.08, p<0.001), and the CYP2C9*3 allele (OR=4.75, 95%CI=2.36-9.55, p <0.001). Carriers of CYP2C9*3 spent less time within the therapeutic range (64.7 23.1%) than did patients with the CYP2C9*1/*1 genotype (75.1 22.0%, p<0.01), and more frequently had an INR >4.5 at the initiation of treatment (43.9% vs.11.6%, p<0.001), but did not show repeated bleeding more frequently (19.0% vs.15.5%, p=NS). INTERPRETATION AND CONCLUSIONS: CYP2C9*3 is related to lower acenocoumarol dose requirements, a higher frequency of over-anticoagulation at the initiation of therapy and an unstable anticoagulant response. (+info)
A placebo-controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol.
(15/76)
AIM: To evaluate pharmacokinetic and pharmacodynamic interactions between tamsulosin and acenocoumarol. METHODS: Twelve healthy volunteers received tamsulosin 0.4 mg or placebo once daily for 9 days in a double-blind, cross-over study. On day 5 of each study period, a single 10-mg oral dose of racemic acenocoumarol was administered. RESULTS: The ratios (point estimates (90% confidence intervals)) of values in the presence and absence of tamsulosin were: AUCPT 1.01 (0.98, 1.03); maximum prothrombin time (Ptmax) 0.99 (0.94, 1.05); AUC (R)-acenocoumarol 1.02 (0.90, 1.16), and AUC (S)-acenocoumarol 1.03 (0.89, 1.20). Both combinations, tamsulosin and placebo with acenocoumarol, were well-tolerated. CONCLUSIONS: Multiple doses of tamsulosin had no effect on the pharmacokinetics or pharmacodynamics of a single high dose of acenocoumarol. (+info)
Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol.
(16/76)
OBJECTIVES: To evaluate the incidence of thromboembolic and haemorrhagic events in a cohort of patients with mechanical heart valves who had to withhold acenocumarol and were treated with enoxaparin. DESIGN: Observational prospective study. SETTING: In hospital; after discharge, and follow up by telephone call. PATIENTS AND METHODS: All consecutive patients with mechanical heart valves admitted to the authors' hospital between May 1999 and January 2002 who had to interrupt treatment with acenocumarol and were treated with enoxaparin as an alternative to other methods were enrolled. In each patient, the following characteristics were prospectively determined: the reason for interrupting acenocumarol, demographic data, estimated global risk for thromboembolic events, international normalised ratio before starting enoxaparin treatment, number of days taking enoxaparin, and mean level of anti-Xa activity during treatment. All patients were followed up through clinical history during the hospitalisation and by telephone after discharge to detect thromboembolic events. MAIN OUTCOME MEASURE: Presence of thromboembolic or haemorrhagic events. RESULTS: 82 patients were identified and followed up for a mean of 2.8 months (range 1.5-3.5 months) after discharge. 61 of them (74%) had one or more associated thromboembolic risk factors. Acenocumarol was interrupted (to perform an invasive procedure in 74 patients and because of haemorrhagic complication in 8) an average of 11.2 days (range 3-40 days). Most patients received the standard enoxaparin dose (1 mg/kg at 12 hour intervals). Mean (SD) anti-Xa activity was 0.58 (0.3) IU/ml (median 0.51). There were 8 minor and 1 major bleeding events during enoxaparin treatment. No thromboembolic complications were clinically detected during hospitalisation or during follow up (95% confidence interval 0% to 3.6%). CONCLUSIONS: Enoxaparin may be an effective and relatively safe substitute anticoagulant for patients with mechanical heart valves who must withhold acenocumarol. (+info)