The management of coumarin-induced over-anticoagulation Annotation.
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Kyphoscoliosis surgery is frequently associated with major blood loss and coagulation disorders. A patient with juvenile rheumatoid arthritis, heart valve prosthesis and respiratory restrictive syndrome, was submitted to surgical correction of kyphoscoliosis. Current drug therapy included digitalis, oral anticoagulant and nonsteroidal anti-inflammatory drugs. After careful preoperative evaluation, oral anticoagulant and nonsteroidal anti-inflammatory drugs were discontinued (five and ten days before surgery, respectively), and intravenous heparin was introduced and maintained until two h before surgery. Bacterial endocarditis prophylaxis was obtained with ampicillin (50 mg.kg-1) and gentamicin (1.5 mg.kg-1). Anaesthetic management followed a general, balanced technique and the use of invasive monitoring devices. Clotting times were kept within the normal range--prothrombin time between 13 s and 14 s; partial thromboplastin time between 28 s and 30 s. Surgery was straightforward. The patient remained ventilated for 24 h and intravenous morphine (6 micrograms.kg-1.h-1) was used for nurse controlled analgesia. Afterwards, this was changed for patient controlled analgesia. Intravenous heparin was restarted 12 h after surgery and there were no complications postoperatively. Keeping the patient without anticoagulant therapy during this kind of surgery, was the less harmful option, taking into consideration that haemorrhage is inevitable and thromboembolism is a potential, though serious risk.
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The Omniscience prosthetic heart valve has been clinically evaluated in 44 patients operated on between January and July, 1981. There were 23 aortic valve replacements (AVR), 18 mitral valve replacements (MVR) and 3 double valve replacements (DVR). Mean age was 48 +/- 11 years. Preoperatively, 61% patients were in New York Heart Association (NYHA) functional class IV, 36% in class III and 2% in class II. The hospital mortality rate was 4.5%. Actuarial freedom from thromboembolic events was 97.4 +/- 2.6% (3 1/2 years of follow-up). Postoperatively, 93% of the patients were in NYHA class I and 7% in class II. There were 7 cases of periprosthetic leak requiring reoperation (6 AVR, 1 MVR) for an overall incidence of 6.3% per patient year. In all these cases the causative factor was considered to be the Dacron sewing ring. All patients survived the reoperation. The actuarial survival rate was 93.9 +/- 5.9% for AVR and 93.7 +/- 6.1% for MVR. These data would suggest that the Omniscience prosthesis represents an acceptable device for heart valve replacement, except for the high incidence of periprosthetic leakage, related to the Dacron sewing ring. Recent modification of the valve-construction including a Teflon sewing ring may avoid the relatively high rates of periprosthetic leakage following implantation of this mechanical valve.
A case of a arachnoidal cyst with intracystic bleeding and subdural haematoma is reported. The association of an arachnoidal cyst in the middle cranial fossa with a subdural haematoma or intracystic bleeding is emphasised. The diagnosis of such lesions, the nature of the pathology and therapy are discussed.
BACKGROUND: The optimal intensity of oral anticoagulant therapy for patients with mechanical heart valves (i.e., the level at which thromboembolic complications are effectively prevented without excessive bleeding) is not known. We attempted to determine the optimal intensity by calculating the incidence of both complications at different levels of anticoagulation. METHODS: Data were collected on all patients with mechanical heart valves who have been seen at four regional Dutch anticoagulation clinics since 1985. The primary outcome events were episodes of thromboembolism or major bleeding. The intensity-specific incidence of each type of event was calculated as the number of events that occurred at a certain intensity of anticoagulation (expressed in terms of the international normalized ratio [INR]) divided by the number of patient-years during which the INR was at this level in the total patient population. RESULTS: A total of 1608 patients were followed during 6475 patient-years. Cerebral embolism occurred in 43 patients (0.68 per 100 patient-years) and peripheral embolism in 2 (0.03 per 100 patient-years). Intracranial and spinal bleeding occurred in 36 patients (0.57 per 100 patient-years) and major extracranial bleeding in 128 (2.1 per 100 patient-years). The optimal intensity of anticoagulation, at which the incidence of both complications was lowest, was achieved when the INR was between 2.5 and 4.9. CONCLUSIONS: The intensity of anticoagulant therapy for patients with prosthetic heart valves is optimal when the INR is between 2.5 and 4.9. To achieve this level of anticoagulation, a target INR of 3.0 to 4.0 is recommended.
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BACKGROUND: Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. METHODS: Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). RESULTS: During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. CONCLUSIONS: In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
BACKGROUND: The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. METHODS: We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years. RESULTS: The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02). CONCLUSIONS: Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).
OBJECTIVES: The purpose of this study was to determine the optimal intensity of oral anticoagulation in patients who participated in a randomized trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery. METHODS: The distribution of patient-time spent in international normalized ratio (INR) classes of 0.5 INR unit was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischemic and hemorrhagic events were calculated as the ratio of the number of events at a certain INR category and the total patient-time spent in that class. The relationship between INR class and event rates was quantified by rate ratios calculated in a Poisson regression model. RESULTS: In 1326 patients (mean age, 69 years) 41,928 INR measurements were recorded in 1698 patient-years. Patients spent 50% of the total time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%) was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the incidence of ischemic events (n = 154, INR data on event available in 49%) decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major bleeding (n = 123, INR data on event available in 65%) increased significantly by a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9 ischemic and 2.9 hemorrhagic) per 100 patient-years. CONCLUSIONS: The target range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation intensity and is safe for the prevention of ischemic events in patients after infrainguinal bypass graft surgery.
A prospective randomized study involving 101 patients undergoing total hip replacement was performed to find out whether prophylactic anticoagulation starting 4 days before the operation was more effective than starting on the eve of the operation. The postoperative level of anticoagulation was set at an INR of 2.1. There was no difference between the two groups in the incidence of proximal localized deep venous thrombosis. Blood loss did not depend on the level of peroperative anticoagulation. There were no postoperative hemorrhagic complications. No fatal pulmonary embolism occurred during the study. After discontinuation of the oral anticoagulants because of a negative venogram, nonfatal pulmonary embolism occurred in 3 out of 55 patients. A plea is made for low-dose anticoagulation for 3 months after total hip arthroplasty.
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A Normotest (NT)-Thrombotest (TT) discrepancy is claimed to reflect the presence of coumarin-induced inhibitors or intravascular coagulation, or both. The results of this study indicate, however, that a significant NT-TT discrepancy is also present in all plasmas from patients who have congenital coagulation disorders of the prothrombin complex. None of these patients had received an anticoagulant or showed any sign of intravascular clotting; nevertheless the discrepancy observed was similar to that found in plasmas of coumarin-treated patients: average values were 0.437 and 0.450, respectively. As no inhibitor was present in the congenital coagulation disorders, except in hemophilia BM, the phenomenon does not appear to be specific for coumarin plasma. This indicates that the NT/TT discrepancy is a non-specific phenomenon that does not seem to provide any additional information about coumarin-treated patients compared with that obtainable by means of a simple prothrombin time test.
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