Indications For Anticoagulant Therapy Research Articles

Venous thromboembolism in the elderly: introduction and overview.

The indications for anticoagulation therapy, the available agents, and our knowledge about how best to manage such therapy have increased dramatically over just the last few years. Most of the indications for anticoagulation have a much higher prevalence in the elderly than in younger patients. This makes the management of such patients more challenging because the elderly are more prone to thromboembolism, they may be more sensitive to the effects of certain antithrombotic agents, the pharmacokinetics of these agents may be altered by the aging process, the elderly are at a greater risk of major bleeding, and they frequently are taking more medications, a fact that increases the risk of drug interactions. We are very pleased to be able to provide the readers of this journal with a categorized bibliography of some of the best references in this area provided by national authorities in the clinical management of anticoagulation. First, Dr. Fred Anderson, from the University of Massachusetts Medical Center, provides us with selected references that address the epidemiology of venous thrombosis in the elderly. Dr. Anderson is one of the pioneering investigators in this area, and it is his own work that has demonstrated the marked increase in venous thrombosis among elderly hospitalized patients. The second section of bibliographical entries deals with a number of areas related to warfarin use in the elderly. Dr. Ann Wittkowsky, from the University of Washington Medical Center, provides us with an extensive list of selected references that address how the pharmacokinetics and pharmacodynamics of warfarin metabolism in the elderly differs from what is seen in younger patients. Next, Dr. Rebecca Beyth, from Case Western Reserve University, lists key references that examine the increased risk of bleeding related to the use of warfarin in the elderly. Finally, Dr. Philip Hansten, from the University of Washington School of Pharmacy, includes selected citations that cover the critical area of warfarin drug interactions, which is a particular concern in the elderly. The fourth section deals with new information on the use of unfractionated heparin, low molecular weight heparins, and heparinoids. Dr. Spinler and Ms. Evans, from Philadelphia College of Pharmacy and Science at the University of Pennsylvania, in addressing the literature on several new agents, have taken a slightly different approach than that used by the authors in the preceding section on warfarin. First, they provide sources that address the effectiveness of these agents, followed by references on pharmacokinetic differences in the elderly; and they conclude with citations dealing with adverse reactions of these agents in the elderly. Personal communication with these authors indicate that they have concluded that the effectiveness of unfractionated heparin, low molecular weight heparins, and heparinoids in the elderly appear to be comparable with that seen in younger patients for either venous or arterial thromboembolism. They point out, however, that pharmacokinetics differences in the elderly may require a reduction in dosage of unfractionated heparin or low molecular weight heparin. Bleeding risks with these agents appear to be higher in the elderly than in the young, but whether the heparinoids exhibit such pharmacokinetic differences or a higher bleeding risk in the elderly remains to be established. The ~nal section, by Dr. David Green and Dr. Paula Podrazik from Northwestern University, provides selected citations dealing with the rapidly expanding area of antiplatelet therapy in the elderly. Here again, the authors concluded that the organization of information was best managed in a slightly different format. The references they have selected are grouped into ~ve categories: general reviews, drug interactions, pharmacokinetics and pharmacodynamics, adverse reactions, and miscellaneous. As one might expect, within each of the ~ve categories, the selected references are further subdivided according to speci~c antiplatelet agents (i.e., aspirin, dipyridamole, ticlopidine and clopidogrel, glycoprotein IIb/IIIa inhibitors). Again, through personal communication with these authors, they pointed out that the major use of these agents in the elderly is the prevention of myocardial infarction, the treatment of cerebral transient ischemic attacks and ischemic strokes, and in maintaining patency of coronary artery stents. In most cases, lowdose aspirin alone, ticlopidine alone, or the combination has been used. The safety and ef~cacy of a number of potent, new anti-platelet agents in the elderly needs to be examined. The ~nal category of references in this section (“miscellaneous”) provides some interesting reading on nonantithrombotic uses of these agents in

Phacoemulsification and lens implantation in patients treated with aspirin or warfarin

Purpose: To determine the incidence and nature of hemorrhagic complications in patients having phacoemulsification and foldable intraocular lens (IOL) implantation while taking aspirin or warfarin.Setting: The Jules Stein Eye Institute, University of California at Los Angeles School of Medicine, Los Angeles, California, USA.Methods: This retrospective study reviewed the charts from the practice of 1 ophthalmic surgeon. The type of medication, dosage, indication for anticoagulant therapy, type of incision, type of anesthesia, and intraoperative and postoperative hemorrhagic complications were recorded.Results: Sixty-two patients (82 eyes) taking aspirin and 25 patients (31 eyes) taking warfarin were identified. Seven eyes in the aspirin group (8.5%) and 3 in the warfarin group (9.7%) experienced subconjunctival hemorrhages. Eight of the 10 subconjunctival hemorrhages occurred in eyes with scleral incisions. The remaining 2 occurred in eyes with corneal incisions. No eye developed lid ecchymosis, retrobulbar hemorrhage, hyphema, or suprachoroidal hemorrhage.Conclusion: Phacoemulsification with foldable IOL implantation was performed safely in patients taking aspirin or warfarin. Subconjunctival hemorrhage was the most common hemorrhagic complication.

Prophylaxis of thromboembolic events in congestive heart failure.

In patients with heart failure the incidence of thromboembolism is 0.9-5.5%/year (mean 1.9%/year), but no randomized studies are available to support the indication for anticoagulant therapy in those patients. Atrial fibrillation and previous thromboembolic events seem to be the major risk factors, whereas the effect of ventricular dysfunction has not been independently evaluated; nonetheless several studies suggest that thromboembolism is more likely among those patients with lower ejection fraction and lower peak exercise oxygen consumption. Anticoagulant therapy seems to be indicated also in patients with left ventricular aneurysm with mobile and protruding thrombi. Several studies of patients with dilated cardiomyopathy show that the incidence of thromboembolism ranges from 1.6 to 4.5%/year in patients not treated with anticoagulants, while it is virtually absent in anticoagulated patients. The clinical opportunity of long-term anticoagulant treatment in heart failure patients should be weighted not only on the clinical markers of thromboembolic risk, but also on the relative risk/benefit ratio of the single patient.

Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy.

To review the efficacy and safety of electrical and pharmacologic conversion of atrial fibrillation, strategies for maintenance of sinus rhythm, and the importance of antithrombotic therapy. English-language trials were identified from the MEDLINE database through 1995, bibliographic references, Current Contents, textbooks, and recent abstracts. Randomized trials (including abstracts) were selected. Cohort studies were used if randomized trials were not available. Study design and data were extracted from clinical trials. Statistical analysis of combined data was not appropriate, given the marked variations in study designs and study populations. Cardioversion restores sinus rhythm in more than 80% of patients. In atrial fibrillation of recent onset, pharmacologic regiments have a success rate of 40% to 90%. Sinus rhythm at 1 year is maintained in 30% of patients without antiarrhythmic therapy but in 50% of patients with such therapy. The efficacy and safety of antiarrhythmic drugs relative to one another are not established because trials done to date have been small and cases vary. Successful cardioversion and maintenance of sinus rhythm are most predictable when the duration of atrial fibrillation is brief. Warfarin reduces the incidence of ischemic strokes and emboli in patients with nonvalvular atrial fibrillation from 4.5% to 1.4% per year. Aspirin (325 mg/d) appears to be equally effective in patients younger than 75 years of age who do not have hypertension or a history of thromboembolism or recent heart failure. Although warfarin is more effective than aspirin in preventing embolic strokes in patients older than 75 years of age, it may increase the incidence of hemorrhagic stroke and result in a similar rate of disabling stroke. Cardioversion remains the preferred method with which to re-establish sinus rhythm. Long-term antiarrhythmic therapy is warranted only if recurrences or initial clinical instability are seen; pro-arrhythmic concerns and potential side effects should guide drug selection. Antithrombotic therapy is indicated for all patients older than 60 years of age and in all patients younger than 60 years of age who have clinical evidence of a primary cardiac disorder.

Anticoagulation clinics and the monitoring of anticoagulant therapy

Patients attending an anticoagulation clinic were studied to delineate predisposing risk factors for bleeding and thromboembolic episodes. Seventy-three patients were observed for a total of 921.8 patient-treatment months. The mean duration of treatment was 12.6 months (range 3–36 months). No major bleed occurred (a bleed which caused discontinuation of therapy, hospitalization or death). Thirty-two patients had minor bleeding episodes (0.42 bleeds per patient-year of treatment). The average prothrombin time ratio during the third to the sixth month of therapy was predictive of the bleeding risk. There was no association between bleeding and age, sex, indication for anticoagulation therapy or associated illnesses. Four thromboembolic episodes occurred (0.05 per patient-year of treatment), 3 arterial and 1 venous. At the time of the one venous thromboembolic event the prothrombin time ratio was subtherapeutic. In all 3 patients with arterial thromboembolism the mean 3- to 6-month prothrombin time ratio was less than or equal to the lower limit of the recommended range of 1.6–2.5. In our study prothrombin time ratios of 1.3–1.5 for venous thromboembolic disease and 1.6–2.5 for arterial thromboembolic disease were not associated with thromboembolism or major bleeding. Anticoagulation clinics facilitate the close monitoring of patients on oral anticoagulant therapy.

Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy

Among 617 hospitalized patients who started long-term anticoagulant therapy, major bleeding developed before discharge in 28 (5 percent) and minor bleeding in another 38 (6 percent), with daily incidence rates of 0.4 and 0.5 percent, respectively. The most common site of bleeding was gastrointestinal, and one patient died from bleeding. Four independent risk factors for major in-hospital bleeding were identified and weighted using multivariate discriminant analysis in a randomly chosen group of 411 patients: (1) co-morbid conditions other than the indication for anticoagulant therapy (specific signs of heart, liver, or kidney dysfunction, cancer, and severe anemia); (2) the use of heparin to begin therapy in patients age 60 years or older; (3) the intensity of therapy (measured by the maximal prothrombin time or partial thromboplastin time); and (4) liver dysfunction that worsened during treatment. These findings were validated in an independent testing group of 206 patients; the risk factors identified 151 patients at low (1 percent) risk of major bleeding, 33 at moderate (6 percent) risk, and 22 at high (23 percent) risk. The accuracy and clinical impact of this prediction rule should be evaluated further in other hospitals.

Drug Spotlight on Anticoagulants

The Drug Spotlight turns on anticoagulants, because the appropriate use of these agents could prevent a substantial number of the 50,000 deaths caused by venous thromboembolism annually in the United States. Experts may differ on some of the indications for anticoagulant therapy, the method of administration, and the duration of therapy. Nonetheless, it is important to determine how the use of anticoagulants in your hospital measures up to the ideas presented by Dr. Stanford Wessler, on page 757 and the opinions expressed in the other scientific reports presented in the other journals participating in the program. Listed below are suggestions for studies of anticoagulant therapy. Your pharmacy and therapeutics committee should gather data on one or more of these subjects or on some other aspect of anticoagulation. The analysis of your data might lead to more effective use of anticoagulants and to a reduction in morbidity and mortality from venous

The choice of an oral anticoagulant

Some of the indications for anticoagulant therapy remain controversial, but they are widely used for the prevention and treatment of thrombosis and embolism after surgery1 and after myocardial infarction,2 in patients with atrial fibrillation, and in those with transient cerebral ischaemia.3 This article discusses the drugs available for long-term use. Those suitable for immediate and short-term use, heparin and arvin, will be discussed in the next issue.

Indications for anticoagulant therapy

The value of anticoagulant therapy is solidly established in the presence of deepvein thrombosis and pulmonary embolism, in the presence of recurrent cerebral ischemic episodes when reparative vascular surgery is not possible, and in postoperative and bedridden patients, at least those with a high risk of pulmonary embolism. There is strongly suggestive evidence for the use of anticoagulants in the presence of recurrent systemic emboli due to mitral valve disease, in patients with valvular prostheses, and in patients immediately following reparative vascular surgery. There is suggestive evidence favoring the use of anticoagulants in progressive strokes in men under 55 for two years after myocardial infarction, and in central retinal vein thrombosis. In all other areas in which they are used, the evidence for the use of anticoagulant drugs remains quite uncertain.

COMPARISON OF EFFICACY OF 3 AND 12 MONTHS' ANTICOAGULANT THERAPY AFTER MYOCARDIAL INFARCTION: A Controlled Clinical Trial

In a controlled clinical trial 208 patients with myocardial infarction were randomised into two groups. The patients in group A were given anticoagulant treatment for 3 months, the patients in group B for 12 months. All the patients were under 70 years of age and had not previously had a myocardial infarction. 10 patients were withdrawn from the investigation for different reasons, leaving 101 patients in group A and 97 in group B. The comparability between the two groups was found to be good. The intensity of the treatment was moderate. The average mean prothrombin-proconvertin value per week was 24·8% in both groups in the first 3 months, and 22·4% in group B during the whole 12 months. In group A 9 patients had 11 reinfarctions, 4 sudden deaths occurred, and the mortality was 6·9%. In group B there were 5 reinfarctions, 7 sudden deaths, and a mortality of 8·3%. There were 3 extracardiac thromboembolic episodes in group A and none in group B. None of these episodes proved fatal. 1 patient died of subarachnoidal hæmorrhage. No statistically significant difference between the groups with regard to death-rate or reinfarction-rate could be demonstrated. There was no difference in the results between patients over and under 60 years of age. The investigation supports the opinion that following myocardial infarction there is no indication for anticoagulant therapy beyond the first 3 months with moderate intensity of treatment as used in this study.

Pelvic thrombophlebitis in the puerperal and postoperative gynecologic patient: Obscure fever as an indication for anticoagulant therapy

Pelvic thrombophlebitis in the puerperal and postoperative gynecologic patient: Obscure fever as an indication for anticoagulant therapy

An evaluation of anticoagulant therapy.

Abstract 1.1. During the past decade the indications for anticoagulant therapy have been clarified. They are listed herein. 2.2. In view of the reduction in both death rate and in the incidence of thromboembolic complications following coronary thrombosis with myocardial infarction with the use of anticoagulants in mild and moderately severe cases, the position that their use should be reserved solely for those patients who are severely ill at onset does not appear justified. This because, despite apparent mildness during the first day or two of the disease, the future course is difficult or impossible to predict with certainty and because the first complication may produce death, more serious illness or permanent disability. 3.3. Recent evidence favors the increased use of anticoagulants during more severe periods o congestive heart failure. 4.4. Newer anticoagulants are now rapidly being developed which generally can be classified as acting similarly to heparin or to dicumarol. 5.5. The clinical facts regarding each of the better known anticoagulants, including their advantages and disadvantages, have been outlined. 6.6. More complete experimental studies should be carried out before crystalline trypsin should be released for general clinical use. 7.7. The final decision whether to use anticoagulants or not, and which ones to use in a specific patient, must rest with the physician responsible for his care. 8.8. Among the important factors to be considered in making this decision are: (1) The diagnosis and condition of the patient; (2) the presence of any coincidental problem requiring caution or contraindicating their use; (3) the sound evidence indicating anticoagulant therapy under these particular circumstances; (4) the qualities of the specific anticoagulants under consideration; (5) the availability of accurate prothrombin and coagulation time tests; (6) the availability of vitamin K and K 1 , and transfusions for emergency use; and, perhaps of greatest importance, (7) the conscientiousness, and skill in this particular field, of the physician who is responsible for their use.

Incompatibility of lumbar block and anticoagulant therapy.

Temporary paralysis of the lumbar sympathetic ganglions by means of a paravertebral injection of procaine hydrochloride is enjoying a well-earned measure of popularity both as a therapeutic test and as a means of treatment. Paravertebral blocks are commonly used to determine the degree of vasospasm in the legs and, thus, to discover how much relief can be expected from lumbar sympathectomy. Paravertebral block is almost a specific treatment for femoral thrombophlebitis (milk-leg). It is important to note, however, that the indications for paravertebral sympathetic block often coincide with the indications for anticoagulant therapy. This is an important item to consider because, while the indications for use of paravertebral procaine injections may coincide with the indications for anticoagulant therapy, the simultaneous use of these procedures is fraught with great danger. In other words, paravertebral blocks should never be done in patients who are receiving anticoagulant therapy. This conflict in therapeutic agents

A fundamental consideration of anticoagulant therapy.

THE fundamental problem in all anticoagulant therapy is to maintain a decreased coagulability of the blood until the danger of thrombosis is past. Since as yet there is no adequate clinical test to demonstrate a thrombotic tendency, the indications for anticoagulant therapy are essentially statistical, being limited to cases in which experience has shown a high incidence of thrombosis. This varies from almost certain further thrombosis and embolism, with the patient showing frequent recurrences of these vascular accidents, to the definite but low incidence for general postoperative cases. Although anticoagulant therapy is essential for the first type of patient, it . . .