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PubMed1981

An assessment of an amidolytic assay for factor VII in the laboratory control of oral anticoagulants.

A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and a chromogenic substrate assay for factor VII in the assessment of laboratory control of oral anticoagulants in short-term and long-term patients. Opportunity was also taken to compare the findings with parallel results obtained with the venous Thrombotest technique and a specific clotting assay for factor VII. There was good agreement between the amidolytic factor VII assay, using a method modified from Seligsohn et al (1978) with the Quick test using BCT and Thrombotest in 60 long-term patients. Tests in 53 patients within the first 3 weeks of starting oral anticoagulant administration gave less satisfactory agreement between the above amidolytic method and the conventional tests. In contrast, there was a good correlation between the two conventional tests in both groups and also between the clotting and amidolytic factor VII method. Although the results are an improvement on previous, less satisfactory correlations between the BCT prothrombin time method and amidolytic assays for factor II and X, the present study indicates the limitations of a specific clotting assay versus a broad spectrum extrinsic clotting test in oral anticoagulant control. While not warranting the routine use of the chromogenic assay for factor VII in place of the prothrombin time using BCT, the factor VII amidolytic assay offers a limited but dependable guide to dosage in long-term patients. The complexity of the technique in its present form militates against its adoption for routine anticoagulant control in hospital laboratories.

Acenocoumarol↗
PubMed1987

Protein C response to induction and withdrawal of oral anticoagulant treatment.

Protein C activity and antigen levels have been related to clotting activities of factors VII and X during the induction and withdrawal periods of oral anticoagulant treatment. Both factor VII and protein C activities fell rapidly during induction but factor VII showed a more rapid and much more marked depression than protein C. In contrast, reductions in factor X were much slower. Protein C antigen, although depressed rapidly at the initiation of treatment, did not subsequently fall to the same degree as protein C activity. The ratio of activity to antigen became progressively smaller. On discontinuation there was a reversal of the pattern but with two important differences. Firstly, there was evidence of an excessive rise ('rebound') of factor VII compared with the steady state levels in these patients; and secondly there was a surprisingly slow return of protein C to normal levels after the oral anticoagulant was withdrawn (levels were still below normal on day 4). These observations lend support to gradual withdrawal of oral anticoagulants after a period of long-term administration. The results suggest that after discontinuation of long-term anticoagulants patients may have increased coagulability up to four days.

Acenocoumarol↗
PubMed1988

The reliability of international normalized ratios during short-term oral anticoagulant treatment.

The reliability of the international normalized ratios (INR) system in the induction phase of coumarin administration has been studied in 15 serial patients over the first 7-40 days of treatment (mean 13.1). The INR results obtained with a variety of thromboplastin reagents have been compared with those obtained with the WHO second primary IRP, BCT/253. A wide divergence of INR values was observed with the various thromboplastins on each day of testing. INR values cannot therefore be relied upon with some of these reagents in the early days of anticoagulant treatment. This probably arises from the difference in responses of the thromboplastins to depression of vitamin K-dependent clotting factors. Consistent deviations from the IRP suggested that additional error may be due to inaccurate calibration of their products by the manufacturers. When the slopes of the sensitivity of the individual reagents to clotting factors II, VII and X were compared, however, results overall more closely approximated to those of the IRP when the INR were substituted for simple prothrombin ratios.

Acenocoumarol↗
PubMed1993

Haemorrhagic bullae induced by oral anticoagulants.

A 77-year-old patient developed haemorrhagic bullae on her fingers 30 months after initiation of anti-coagulation treatment with warfarin sodium for chronic atrial fibrillation and mitral insufficiency. The bullae resolved 10 days after discontinuation of the medication. Two weeks after initiation of sintrom, (3-alpha-(4-nitrophenyl)-beta-acetylethyl-4-hydroxy coumarin), the lesions recurred and resolved again upon cessation of the drug. This adverse skin reaction has not been hitherto reported.

Acenocoumarol↗
PubMed2004

Non-fatal major bleeding during treatment with vitamin K antagonists: influence of soluble thrombomodulin and mutations in the propeptide of coagulation factor IX.

BACKGROUND AND OBJECTIVES: The key complication of treatment with vitamin K antagonists (VKAs) is bleeding. The major determinant of VKA-induced bleeding is the intensity of anticoagulation. Individual patient characteristics may also influence bleeding risk. In addition, soluble thrombomodulin (s-TM) levels and mutations in the propeptide of factor (F)IX are important candidate risk factors in this respect. PATIENTS AND METHODS: A matched case-control study was designed to search for risk factors that predict bleeding during VKA treatment. We selected cases that had experienced major bleeding during treatment with VKA and matched controls without bleeding complications from the databases of two Thrombosis Services. The controls were matched for indication of treatment, age, gender, type of anticoagulant used and whether or not treatment with VKA was stopped. DNA and plasma were stored of all cases and controls. RESULTS AND CONCLUSIONS: In total 110 patients and 220 controls consented to participate. The results indicate that s-TM levels, measured by ELISA, may be a risk indicator for bleeding [crude odds ratio 3.25 for the highest quartile vs. the lowest quartile (95% confidence interval 1.40, 7.51)]. Three novel mutations, determined by direct sequencing, in the gene portion encoding the propeptide of FIX were identified that do not seem to play an important role in bleeding risk during treatment with VKAs.

Acenocoumarol↗
PubMed2005

Poor anticoagulation quality in the first 3 months after unprovoked venous thromboembolism is a risk factor for long-term recurrence.

BACKGROUND AND AIM: Several factors are associated with an increased risk of recurrent venous thromboembolism (VTE). The aim of the study was to investigate whether the quality of oral anticoagulation therapy (OAT) is a long-term risk factor for recurrence of VTE after OAT interruption. METHODS AND RESULTS: A total of 297 patients (170 males) with a recent acute unprovoked VTE episode were prospectively monitored during OAT in our anticoagulation clinic and followed up for 21 months after OAT interruption. Recurrent events were recorded in 42 subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt-y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT duration. Subjects experiencing recurrence after OAT interruption had spent significantly more time at markedly subtherapeutic international normalized ratio (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR) during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95% confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P = 0.003) at univariate and multivariate analysis, respectively] in those who spent more time (upper quintile) at INR values <1.5, being especially evident in the first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI 1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P = 0.056)] analysis when the entire OAT period was considered. Subjects in the upper quintile of time spent at INR values <1.5 had significantly higher D-dimer values when OAT was stopped and after 3 months. CONCLUSIONS: The amount of time that subjects with an acute unprovoked VTE event spend at near-normal INR values (<1.5) during the first 3 months of treatment is associated with higher D-dimer values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrence.

Acenocoumarol↗
PubMed1997

Internal cardioversion of chronic atrial fibrillation in patients.

Transvenous internal cardioversion of chronic AF using a right atrium (RA) coronary sinus (CS) vector requires more energy than cardioversion of paroxysmal AF. Chronic AF is not terminated in 25% of patients using biphasic shocks up to 10 J. We therefore evaluated efficacy, safety, and tolerability of internal cardioversion using a "unipolar" configuration (RA to skin patch) and biphasic shocks in patients with long-lasting AF and different heart disease. In each patient, biphasic R wave synchronous shocks were delivered between a large defibrillating surface area electrode in the RA and a skin patch in the left prepectoral position. Defibrillation protocol started with a test shock of 0.4 J. Shocks were repeated and increased until termination of AF or a maximum of 34 J. Sedation was used when the patient described the shock as painful. This study included 11 patients with a mean age of 67 +/- 8 years (range 56-83). AF duration was > or = 1 month in all patients with a mean duration of 11 +/- 11 months (range 2-36). Underlying heart disease was present in all patients and the mean left atrial dimension was 43 +/- 9 mm (range 26-57). AF was terminated in 10 of 11 patients (91%) with a mean delivered energy of the successful shocks of 18.7 +/- 8.7 J (median energy 16.9 J; range 7.3-32.5) and a mean leading edge voltage of 564 +/- 129 V. The mean shock impedance at the defibrillation threshold was 71 +/- 13 omega (range 59-103). A total of 131 shocks were delivered without any complication and proarrhythmia episodes. We conclude that low energy "unipolar" internal cardioversion is a simple, safe, and effective technique for termination of chronic AF in patients with heart disease. The procedure is often tolerated under light sedation.

Acenocoumarol↗
PubMed1995

The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats.

The effects of Danshen (Salvia miltiorrhiza), a popular traditional Chinese medicinal herb on the pharmacokinetics and pharmacodynamics of R- and S-warfarin stereoisomers were studied in rats. After a single oral dose of racemic warfarin (2 mg kg-1), treatment with oral Danshen extract (5 g kg-1, twice daily) for 3 days significantly altered the overall pharmacokinetics of both R- and S-warfarin and increased the plasma concentrations of both enantiomers over a period of 24 h and the prothrombin time over 2 days. At steady-state levels of racemic warfarin (0.2 mg kg-1 day-1 for 5 days) the 3-day treatment of Danshen extract (5 g kg-1, twice daily) not only prolonged the prothrombin time but also increased the steady-state plasma concentrations of R- and S-warfarin. The results indicate that Danshen extracts can increase the absorption rate constant, area under plasma concentration-time curves, maximum concentrations and elimination half-lives, but decreases the clearances and apparent volume of distribution of both R- and S-warfarin. The pharmacokinetic and pharmacodynamic interactions of warfarin during co-treatment with Danshen extract observed in this study indicate an explanation for the clinically observed incidents of exaggerated warfarin adverse effects when traditional Chinese medicinal herbs or herbal products such as Danshen and Danggui (observed in a previous study) were co-administered.

Acenocoumarol↗
PubMed1978

Oral anticoagulants controlled by the British comparative thromboplastin versus low-dose heparin in prophylaxis of deep vein thrombosis.

The British comparative thromboplastin (BCT) was used to monitor the effectiveness of oral anticoagulants in preventing deep vein thrombosis (DVT) in patients undergoing major gynaecological surgery. All patients were screened for DVT with the use of the (125)I-fibrinogen scan.One hundred and forty-five patients aged 40 years or more were randomised into three groups. Group 1 received oral anticoagulant (nicoumalone) treatment, stabilised over five days before surgery and continuing into the second postoperative week. The other patients served as two contrast groups and were managed on a double-blind basis. Group 2 received a subcutaneous low-dose regimen of heparin calcium. Group 3 received subcutaneous saline. Eleven of 48 patients in the saline group, three of 49 patients in the heparin group, and three of 48 patients in the oral anticoagulant group developed DVT as judged by (125)I-fibrinogen scanning. The incidences in groups 1 and 2 were significantly lower than in the saline group. The falls in haemoglobin concentration and incidence of haemorrhage were similar in all three groups.The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin were equally effective in preventing deep vein thrombosis in a moderate-risk group. Immediate preoperative prothrombin ratios of 2.0-2.5 and postoperative ratios of 2.0-4.0 with the BCT gave adequate protection without increased haemorrhagic risk.

Acenocoumarol↗
PubMed1979

Interaction between anticoagulants and contraceptives: an unsuspected finding.

To assess the effects of oral contraceptives on anticoagulant treatment the prothrombin times of 12 patients were measured while they were taking both drugs simultaneously and while they were taking only anticoagulants. The mean prothrombin time ratio was significantly higher when patients were taking both drugs than when they were taking only anticoagulants and their doses of anticoagulant were significantly lower. During both periods most of the prothrombin values remained in the therapeutic range. These findings suggest that, contrary to the common belief that oral contraceptives diminish the effects of anticoagulants, contraceptives in fact potentiate the action of the anticoagulants.

Acenocoumarol↗