Effect of warfarin on the induction and course of experimental endocarditis. (1/1963)

The effect of warfarin treatment on an experimental endocarditis was studied in rabbits. Warfarin had no effect on the induction of a Streptococcus sanguis infection in catheter-induced endocardial vegetations, and the course of this infection was also unaltered. However, warfarin treatment resulted in rapidly progressive bacteremia, probably due to impaired circulation in clearing organs such as the lungs, liver, and spleen. Warfarin also reduced the survival time of the infected rabbits, in which pulmonary edema and extensive lung hemorrhages may have been a contributory factor.  (+info)

Warfarin therapy: evolving strategies in anticoagulation. (2/1963)

Warfarin is the oral anticoagulant most frequently used to control and prevent thromboembolic disorders. Prescribing the dose that both avoids hemorrhagic complications and achieves sufficient suppression of thrombosis requires a thorough understanding of the drug's unique pharmacology. Warfarin has a complex dose-response relationship that makes safe and effective use a challenge. For most indications, the dose is adjusted to maintain the patient's International Normalized Ratio (INR) at 2 to 3. Because of the delay in factor II (prothrombin) suppression, heparin is administered concurrently for four to five days to prevent thrombus propagation. Loading doses of warfarin are not warranted and may result in bleeding complications. Interactions with other drugs must be considered, and therapy in elderly patients requires careful management. Current dosing recommendations are reviewed, and practical guidelines for the optimal use of warfarin are provided.  (+info)

A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. (3/1963)

BACKGROUND: Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. METHODS: In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. RESULTS: A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months. Of 83 patients assigned to continue to receive placebo, 17 had a recurrent episode of venous thromboembolism (27.4 percent per patient-year), as compared with 1 of 79 patients assigned to receive warfarin (1.3 percent per patient-year, P<0.001). Warfarin resulted in a 95 percent reduction in the risk of recurrent venous thromboembolism (95 percent confidence interval, 63 to 99 percent). Three patients assigned to the warfarin group had nonfatal major bleeding (two had gastrointestinal bleeding and one genitourinary bleeding), as compared with none of those assigned to the placebo group (3.8 vs. 0 percent per patient-year, P=0.09). CONCLUSIONS: Patients with a first episode of idiopathic venous thromboembolism should be treated with anticoagulant agents for longer than three months.  (+info)

Pregnancy in patients after valve replacement. (4/1963)

This report is based on information obtained from a questionnaire sent to major cardiac centres in the United Kingdom. This produced details of 39 pregnancies in 34 patients after valve replacement. The 39 pregnancies gave rise to 30 healthy babies. The small size of the series probably reflects both the increasing rarity of young women with rheumatic heart disease in this country and the cautious attitude of their cardiologists. This makes it likely that these women represented the best end of the spectrum of cardiac function after valve replacement. Twenty-four pregnancies in 20 women who were not given anticoagulants producted 23 healthy babies and 1 spontaneous abortion. This group comprised 6 patients with free aortic homografts, 1 patient with a fascia lata mitral valve, 1 with a Beall tricuspid prosthesis, 1 with a combined mitral homograft and Starr Edwards aortic prosthesis, and 1 with mitral and aortic frame-mounted fascia lata valves. There were no maternal deaths or thromboembolic complications in this group which included 5 patients who were in atrial fibrillation. Fifteen pregnancies in 14 women who received anticoagulants gave rise to 7 healthy babies. The fetal losses were one stillbirth, one intrauterine death at 34 weeks, and 3 spontaneous abortions; one surviving child has hydrocephalus as a result of blood clot and there were 2 maternal deaths. This group included 13 patients with Starr Edwards valves, 11 mitral and 2 aortic. A patient with a Hammersmith mitral valve was the only one to have been treated with heparin and her valve thrombosed. One patient with a mounted mitral homograft had a cerebral embolus. Nine of these patients were in atrial fibrillation. In 3 additional patients the valve replacement was carried out during pregnancy. Two of the patients survived operation. In one of these who was treated with warfarin the pregnancy well, but there is an increased fetal wastage in patients pregnancy gave rise to a congenitally malformed baby who died in the neonatal period. The baby born to the mother who did not receive anticoagulants has a hare-lip and talipes. Women with artificial valves can tolerate the haemodynamic load of pregnancy well, but there is an increased fetal wastage in patients taking oral anticoagulants. This is probably largely attributable to fetal haemorrhage but there is also a risk of malformation caused by a teratogenic effect of warfarin. Experience gained in non-pregnant patients suggests that withholding anticoagulatns in pregnant patients with prosthetic valves would usually be undersirable but warfarin should be avoided. The advantages of biological valves were apparent in this series.  (+info)

Medical liability risk avoidance: a case for adopting the International Normalized Ratio (INR) system. (5/1963)

Since bleeding is a common adverse effect associated with the oral anticoagulant warfarin, maximizing the therapeutic potential of this drug requires close laboratory monitoring. The International Normalized Ratio (INR) is a system that has been developed to improve and standardize the assessment of the intensity of oral anticoagulation therapy. Clinical information and medicolegal arguments supporting the adoption of this system are reviewed. The potential for improvement in patient outcomes and minimization of medical liability favors the adoption of the INR system.  (+info)

Strategy for balancing anticoagulation and hemostasis in aortocoronary bypass surgery: blood conservation and graft patency. (6/1963)

The minimal effective dose of aprotinin on hemostasis under normothermic perfusion, the influence of anticoagulant therapy on graft patency, and the thromboembolic and hemorrhagic events were investigated after aortocoronary bypass graft operation (CABG). One hundred CABG patients under normothermic perfusion were randomly divided into the following groups: (1) coumadin plus acetylsalicylic acid (ASA) (n=32); no aprotinin used during cardiopulmonary bypass (CPB); (2) minimal-dose, 10(6) KIU during CPB, aprotinin used, followed by ASA and coumadin (n=36); and (3) very low-dose, total of 2x10(6) KIU before CPB and during CPB; aprotinin used; anticoagulation therapy with heparin early after surgery and followed by replacement with ASA and coumadin (n=32). The patency of arterial grafts was 100% in all groups. The patency of vein grafts was 95-98% and there was no difference among the groups. The blood loss was significantly reduced in both aprotinin groups (groups 2 and 3) compared to the coumadin plus ASA group, although no difference existed between the 2 aprotinin groups. Postoperative thrombotic and hemorrhagic events were not observed in any group. From this study, it was concluded that 10(6) KIU aprotinin in pump-prime-only followed by oral ASA and coumadin was the recommendation from the benefit/cost consideration.  (+info)

Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. (7/1963)

OBJECTIVES: The purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent. BACKGROUND: Gravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients. METHODS: Forty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage < or = 5 mg and > 5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently. RESULTS: A total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were > 5 mg had 22 fetal complications, whereas those taking a dose < or = 5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; p < 0.7316). CONCLUSIONS: There is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation.  (+info)

Risk assessment and anticoagulation for primary stroke prevention in atrial fibrillation. (8/1963)

BACKGROUND AND PURPOSE: Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF). METHODS: A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated. RESULTS: The mean+/-SD age of 234 patients was 67.1+/-11.8 years, and 122 (52%) were women. Clinical risk factors were present in 74 of 80 patients (92%) aged >75 years compared with 99 of 154 patients (64%) 75 years of age, and was associated with clinical risk factors in all patients. Eligibility for anticoagulation was seen in 72 of 154 (47%) to 105 of 154 (68%) patients aged 75 years, regardless of criteria used (P<0.01). Warfarin was being used in 55 of 105 patients (51%) 75 years (P<0.001). Anticoagulation was being undertaken in 7 of 49 patients (14%) +info)