Clinical features, diagnosis and outcome of acute portal vein thrombosis.
(73/1963)
The clinical features of acute portal vein thrombosis (APVT) are poorly defined in the literature. The proportion that progress to chronic PVT and the influences of various treatments are unknown. Between 1996 and 1998, nine patients presented to our hospital with varying upper gastrointestinal symptoms. They were found to have APVT by colour flow Doppler ultrasound, which was confirmed by CT scanning. All were tested for procoagulant tendencies and then treated with intravenous heparin for 7 days and warfarin for 3 months. Colour flow Doppler ultrasound or CT was done regularly to assess response to treatment. There was complete resolution of thrombus in five patients. Four patients had procoagulant tendencies identified; of these the thrombus resolved in two cases and in two cavernous transformation occurred. In most cases, the thrombus disperses on heparin and warfarin, although the effect of this therapy is unknown. A randomized trial of thrombolytic therapy may be appropriate, in an attempt to reduce the rate of progression to chronic PVT. (+info)
Sex differences and similarities in the management and outcome of stroke patients.
(74/1963)
BACKGROUND AND PURPOSE: Previous studies have documented sex differences in the management and outcome of patients with cardiovascular disease. However, little data exist on whether similar sex differences exist in stroke patients. We conducted a study to determine whether sex differences exist in patients with acute stroke admitted to Ontario hospitals. METHODS: Using linked administrative databases, we performed a population-based cohort study. The databases contained information on all 44 832 patients discharged from acute-care hospitals in Ontario between April 1993 and March 1996 with a most responsible diagnosis of acute stroke. The main outcomes measured consisted of sex differences in comorbidities, the use of rehabilitative services, the use of antiplatelet therapy and anticoagulants (in elderly stroke survivors aged > or =65 years only), discharge destination, and mortality. RESULTS: Male stroke patients were more likely than female stroke patients to have a history of ischemic heart disease (18.1% versus 15.3%, respectively; P<0.001) and diabetes mellitus (20.1% versus 18. 7%, respectively; P<0.001), whereas female patients were more likely than male patients to have hypertension (33.8% versus 30.0%, respectively; P<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively; P<0.001). There were no sex differences in the usage of in-hospital rehabilitative services. The overall 90-day postdischarge use of aspirin and ticlopidine was similar in stroke survivors aged 65 to 84 years. However, among stroke survivors aged > or =85 years, men were more likely than women to receive aspirin (36. 0% versus 30.7%, respectively; P<0.001) and ticlopidine (9.2% versus 6.8%, respectively; P=0.007). Use of warfarin was similar for the two sexes. Men were more likely than women to be discharged home (50. 6% versus 40.9%, respectively; P<0.001) and less likely to be discharged to chronic care facilities (16.8% versus 25.2%, respectively; P<0.001). The risk of death 1 year after stroke was somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to 0.980; P=0.004). The mortality differences were greatest among elderly stroke patients. CONCLUSIONS: Elderly men are more likely than elderly women to receive aspirin and ticlopidine and equally like to receive warfarin after a stroke. Despite these differences, elderly women have a better 1-year survival after a stroke. (+info)
Assessment of patient capability to self-adjust oral anticoagulant dose: a multicenter study on home use of portable prothrombin time monitor (COAGUCHECK).
(75/1963)
BACKGROUND AND OBJECTIVES: Self-testing and self-monitoring with portable prothrombin time (PT) monitors has been shown to be feasible and safe. However the ability of patients on chronic oral anticoagulant therapy (OAT) to self-adjust their dose without specific training has never been properly evaluated. The aims of this study were to evaluate: 1) the ability of patients on chronic OAT to self-adjust their dose without specific training; 2) the integration of a portable PT monitor (Coagucheck, Roche Diagnostics, Germany) for home use into routine patient care in anticoagulation clinics. DESIGN AND METHODS: A nested case-control study was conducted in four centers of the Italian Federation of Anticoagulation Clinics (FCSA). Patients (n=78) on stable OAT for at least 6 months (cases: 47 men, 31 women, age range: 18-75 years) were enrolled on a volunteer basis after passing an Abbreviated Mental Test and providing informed consent. After three instruction sessions on the use of Coaguchek, subjects performed the PT test at home, communicated the INR results to the Center and suggested the dose adjustment and date for next control as they thought appropriate. However, they were requested to follow the prescription made by the Center. Controls (78 subjects) matched by age (+/- 5 years), sex and therapeutic range with the cases, were selected from among those who attended the anticoagulation clinics and managed by usual care. RESULTS: When compared with the dose prescribed by the Clinic, the dose suggested by warfarin and acenocoumarol users was equal to or within +/- 6% of the mean weekly dose in 80% and 82% of suggestions, respectively. Time spent in the therapeutic range during the study was the same (80%) for cases and controls. INTERPRETATION AND CONCLUSIONS: Selected patients on chronic anticoagulant therapy can acquire a satisfactory ability for self-adjustment of OAT dose without specific training. (+info)
Management of intracranial bleeding associated with anticoagulation: balancing the risk of further bleeding against thromboembolism from prosthetic heart valves.
(76/1963)
Mechanical heart valves are associated with a risk of thromboembolism and anticoagulation is generally recommended. However, this is inevitably associated with a risk of intracranial bleeding. The case of a patient who sustained an intracranial bleed while taking warfarin for a prosthetic aortic valve and a further two intracranial bleeds while on heparin as an inpatient is discussed and the literature on the management of intracranial haemorrhage in patients on warfarin with prosthetic valves is reviewed. (+info)
Are the current bioequivalence standards sufficient for the acceptance of narrow therapeutic index drugs? Utilization of a computer simulated warfarin bioequivalence model.
(77/1963)
PURPOSE: The purpose of this computer simulation was to determine the likelihood of two bioequivalent (vs. reference) generic warfarin formulations (with varying bioavailability) passing current bioequivalence criteria against each other at varying bioavailability. Methods. A bioequivalence simulation program generated 100 warfarin bioequivalence (BE) studies with 24 patients/study. The reference formulation (R) was assigned a bioavailability of 90%. In these simulations the first generic (G(1)) had a bioavailability that was incrementally decreased from 90%. The second generic (G(2)) had a bioavailability that was incrementally increased from 90%. The bioequivalence testing was performed initially as G(1 )vs. R, then G(2) vs. R, and finally G(2) vs. G(1). The tests were performed according to current criteria for therapeutic index drugs. RESULTS: 5400 BE studies with a total of 129,600 subjects and 2,462,400 sampling times were simulated. When G(1) vs. R was compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 88% or less. When G(2) vs. R were compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 113% or greater. When Generic 2 and Generic 1 were compared fewer than 80% of studies passed when the relative AUC(0-t) ratios deviated from the reference by 7% or more. DISCUSSION Despite limitations this simulation indicates that two bioequivalent (vs. reference) generic warfarin products may not be bioequivalent to each other. Alternative methods of assessing bioequivalence are needed when more than one generic of narrow therapeutic index drug exists on the market. (+info)
Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment.
(78/1963)
Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-type CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, chi(2) = 17.985, P =.001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the 2C9*2 allele in patients with a maintenance dose of 1. 5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy. (Blood. 2000;96:1816-1819) (+info)
A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its orthologs in mice and humans.
(79/1963)
The locus underlying hereditary resistance to the anticoagulant warfarin (symbol in the rat, Rw) was placed in relation to 8 positionally mapped gene-anchored microsatellite loci whose positions were known in the genome maps of the rat, mouse, and human. Rw segregated with the markers Myl2 (zero recombinants) and Itgam, Il4r, and Fgf2r (one recombinant each) during linkage analysis in a congenic warfarin- and bromadiolone-resistant laboratory strain of rats. Comparative ortholog mapping between rat, mouse, and human placed Rw onto mouse chromosome 7 at about 60 to 63 cM and onto one of the human chromosomes 10q25.3-26, 12q23-q24.3, and 16p13.1-p11. (Blood. 2000;96:1996-1998) (+info)
Preoperative haemoglobin and warfarin response.
(80/1963)
There is a narrow line between the benefits and risks of anticoagulant therapy. Many factors influence a patient's response to warfarin, and careful monitoring is required to ensure that the therapeutic level of anticoagulation is achieved. The purpose of this retrospective review was to examine the relationship between the postoperative response to warfarin and the preoperative level of haemoglobin. The results showed that lower preoperative levels of haemoglobin are associated with an increased response to warfarin (p = 0.01). (+info)