Chronic Oral Anticoagulation Research Articles

Observance of Antiplatelet Therapy after Stent Implantation in Patients under Chronic Oral Anticoagulant Treatment

Patients undergoing coronary stenting must take dual antiplatelet therapy during a variable period. The combination of chronic oral anticoagulants (COA) with antiplatelet therapy has been related to an increased risk of hemorrhage. The aim of this study was to evaluate the level of the antiplatelet therapy observance in those patients and the incidence of adverse events after 1 year. Patients with prior COA treatment with coronary lesions suitable for stenting were included. Clinical assessment was performed on admission, with follow-up at 1, 6, and 12 months. Antiplatelet and COA treatment, adverse cardiac events, and hemorrhagic episodes were registered. A total of 70 patients were included. Mean age was 70.5 +/- 8.7 years. The most common cause of COA was atrial fibrillation. Conventional stents were used in 40% and drug-eluting stents (DES) in 60%. Treatment at discharge was: ASA + clopidogrel + COA 64.2%, ASA + clopidogrel 25.4%, COA + clopidogrel 7.5%, and COA + ASA 3%. Observance of antiplatelet and COA therapy at 1-6-12 month follow-up after conventional stent was: COA 73.1-70.8-69.6%; ASA 92.3-75.4-65.2%; clopidogrel 92.3-62.5-43.5%. In patients receiving DES, it was: COA 76.9-78.9-80.6%, ASA 79.5-65.8-55.7%, and clopidogrel 94.9-84.2-61.1%. Dual antiplatelet therapy in patients with DES over these periods was taken in 79.5-51.4-27.8%, respectively. The incidence of adverse events was minor bleeding 11.4%, major bleeding 8.6%, myocardial infarction 4.3%, stent thrombosis 1.4%, and death 12.8%. There is a great variability in the treatment prescribed at discharge. Low observance with dual antiplatelet therapy has been detected in these patients, particularly after DES implantation, and they present a very high rate of complications in the follow-up.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Stent Implantation in Patients Taking Chronic Oral Anticoagulation

The purpose of this study was to evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation (AC) with warfarin is recommended. The optimal antithrombotic strategy after percutaneous coronary intervention (PCI) for patients receiving AC is unclear. Consecutive patients who underwent stent implantation and were discharged on triple therapy (defined as the combination of aspirin and thienopyridines and AC) were analyzed. Of the 127 patients with 224 lesions, 86.6% were men, with a mean age of 69.9 +/- 8.8 years. Drug-eluting stents (DES) were positioned in 71 (55.9%), and bare-metal stents (BMS) were positioned in 56 (44.1%) patients. Atrial fibrillation (AF) was the main indication (59.1%) for AC treatment. The mean triple therapy duration was 5.6 +/- 4.6 months, and clinical follow-up was 21.0 +/- 19.8 months. During the triple therapy period, 6 patients (4.7%) developed major bleeding complications; 67% occurred within the first month. No significant differences between DES and BMS were observed in the incidence of major (5.6% vs. 3.6%, respectively, p = 1.0) and minor (1.4% vs. 3.6%, respectively, p = 0.57) bleeding and mortality (5.6% vs. 1.8%, respectively, p = 0.39). A significant difference was observed in favor of DES in target vessel revascularization (14.1% vs. 26.8%, p = 0.041). While receiving triple therapy, major bleeding occurred in 4.7% of patients; one-half of the events were lethal, and most occurred within the first month.

Hemorrhagic and Thromboembolic Complications after Bariatric Surgery in Patients Receiving Chronic Anticoagulation Therapy

Perioperative management of bariatric surgical patients receiving chronic anticoagulation requires an understanding of potential hemorrhagic and thromboembolic risks. The aim of this study is to evaluate hemorrhagic and thromboembolic complications in morbidly obese patients who are on oral anticoagulation treatment and subsequently undergo laparoscopic bariatric surgery. The medical records of all laparoscopic Roux-en-Y gastric bypass (LRYGB) patients from June 2001 to March 2006 were retrospectively reviewed. In addition, data of patients who received chronic anticoagulation therapy with Coumadin and underwent laparoscopic Roux-en-Y gastric bypass was analyzed. Clinical parameters included length of hospitalization, hemorrhagic complications, thromboembolic complications, conversion rate, reoperation, and blood transfusion. During the study period, 1,700 consecutive patients underwent bariatric surgery for the treatment of morbid obesity. Of these, 21 patients were treated with chronic oral anticoagulation; 3 of the 21 (14%) had hemorrhagic complications: one patient had intraluminal hemorrhage and two patients had intraabdominal hemorrhage. Two patients required blood transfusion, and one patient underwent surgical reintervention. None of the 21 laparoscopic operations were converted to open procedures. There were no postoperative mortalities, and there were no thromboembolic events in this series. Laparoscopic bariatric surgery can be performed relatively safely in morbidly obese patients who are treated with chronic oral anticoagulation. Even in the presence of bleeding, patients can be successfully treated without the need for reoperation.

Anticoagulation for mechanical heart valves: a role for patient based therapy

Anticoagulation management issues following mechanical cardiac valve replacement revolve around target levels for chronic oral anticoagulation. While these levels are important, they are only one aspect of a follow-up process that should be individualized to each patient with a mechanical cardiac valve and coupled with patient education, risk factor modification, and long-term follow-up. It is difficult to separate patient related risk factors, those traditional risk factors that markedly increase the incidence of potential valve related events (i.e., atrial fibrillation), and yet other more subtle non-traditional risk factors for thromboembolism (i.e., smoking and hypertension) that contribute to events. These also require management during the post-operative period and long-term follow-up. There are also different risk factors for anatomic valve position. The aortic valve is the safest of all the anatomic positions regarding valve related events. The mitral valve is at higher risk and the tricuspid valve is the most risky anatomic position. Anticoagulation related hemorrhage is the most dangerous event for mortality and morbidity in the aortic position, thromboembolism in the mitral position, and valve thrombosis in the tricuspid position. Each of these requires different degrees of patient modification and target levels for anticoagulation. Additionally, low risk patients with aortic valve replacement may not require anticoagulant therapy at all. Rather, treatment with modern, highly potent platelet inhibiting drugs may be effective after a period of sewing ring endothelialization under the protection of antithrombotic therapy. Each of these aspects and risk factors is discussed, as well as the call for prospective randomized trials treating low risk patients with anti-platelet drugs versus warfarin anticoagulation.

Barriers to Anticoagulation in Patients With Atrial Fibrillation

See related article, pages 227–230. Atrial fibrillation (AF) is not a benign cardiac arrhythmia but instead confers a 5-fold increased risk of stroke compared with age-matched people in sinus rhythm.1 AF patients also have a worse outcome after stroke, with elevated mortality and stroke recurrence rates,2 longer hospital stays,3 and lower discharge rates to their own homes.3 Current estimates suggest that AF afflicts ≈2.2 million Americans,4 whereas in the United Kingdom ≈740 000 individuals are thought to have AF,5 with >46 000 new cases being diagnosed each year.6 Given the increasing prevalence of AF and the associated thromboembolic complications, there are significant numbers of patients who require chronic oral anticoagulation (OAC). Current guidelines7,8 recommend that AF patients at moderate to high risk of stroke should be commenced on chronic anticoagulation with a vitamin K antagonist (VKA). These recommendations are based on data from meta-analyses of 13 randomized controlled trials which have demonstrated significant reductions in stroke9,10 and mortality10 with the use of warfarin. Despite the overwhelming evidence of the benefit of warfarin thromboprophylaxis in patients with AF, such therapy remains significantly underused. OAC care varies considerably from country to country and physicians tend to undertreat more than overtreat.11,12 Physicians’ dilemma of whether to prescribe warfarin is reflected in the recent Euro Heart Survey of AF patients, which revealed that only 67% of patients eligible for VKAs were actually prescribed it,13 although actual ‘real-life’ prescription of OAC may be significantly lower than this. So, why are eligible patients with AF not prescribed OAC? Warfarin itself is plagued by a number of inherent problems, the most important being the narrow therapeutic international normalized ratio (INR) window (target INR 2.5, range 2.0 to 3.0) which must be maintained, given that …

Abstract 2356: Dual Antiplatelet Therapy following Percutaneous Coronary Intervention with Stent Implantation in Patients on Chronic Oral Anticoagulation

Objectives: To evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation (AC) with warfarin is recommended. Background: It is well established that antiplatelet therapy with aspirin ad thienopiridines is required following percutaneous coronary intervention (PCI) with stent implantation. Some patients have also indication for long-term AC. The optimal antithrombotic strategy following PCI in such patients is unclear. Methods: All consecutive patients who underwent PCI with stent implantation discharged on triple therapy (defined as the combination of aspirin and thienopyridines and AC with warfarin) were analyzed. Results One-hundred and twenty-seven patients with 224 lesions: 86.6% males, mean age 69.9±8.8 years were included in the study. Drug-eluting stents (DES) were positioned in 71 (55.9%) and bare metal stent (BMS) in 53 (41.7%) patients. Atrial fibrillation (AF) was the main indication (59.1%) for AC treatment, followed by prosthetic valves (12.4%) and mural left ventricular (LV) thrombus (9.1%). Average risk of thromboembolic events in the subgroup with AF was 1.79 ± 1.23 according to CHADS2 score. The mean triple therapy duration was 5.6±4.6 and clinical follow-up 21.0±19.8 months. During the triple therapy period, 6 patients (4.7%) developed major bleeding complications; 67% of which occurred within the first month. No significant differences between DES and BMS were observed in the incidence of major (respectively 5.6% vs. 3.8%, p=1.0) and minor bleeding (respectively 1.4% vs. 3.8%, p=0.57) and mortality (respectively 5.6% vs. 1.9%, p=0.39). Four patients died in DES group: 3 of major bleeding complications and one of ischemic stroke. The only death in the BMS group was due to subarachnoid hemorrhage. A significant difference was observed in favor of DES in target vessel revascularization (14.1% vs. 28.3%, p=0.041). Conclusions: While on triple therapy, major bleeding complications occurred in 4.7% of patients, half of them were lethal and most (67%) occurred within the first month.

Clinical and Echocardiographic Markers of Mortality Risk in Patients With Atrial Fibrillation

Atrial fibrillation (AF) is independently associated with increases in cardiovascular and all-cause mortality. Although cardiovascular co-morbidities predict stroke risk in AF, their relation with mortality has not been well described. To identify clinical and echocardiographic markers of mortality in patients with AF, 524 patients with AF underwent transesophageal echocardiography from August 2000 to March 2005. Clinical risk factors for systemic thromboembolism were determined for each patient. A CHADS2 (congestive heart failure, hypertension, age>75 years, diabetes, and previous stroke or transient ischemic attack) score ranging from 0 to 6 was calculated for each patient. Transesophageal echocardiographic reports were reviewed for the presence of left atrial spontaneous echocardiographic contrast, left atrial thrombus, the left ventricular ejection fraction, aortic arch atheroma, and the presence and severity of mitral regurgitation. Mortality data were obtained from the Social Security Death Master File. Univariate and multivariate models were structured to assess which variables predicted mortality. In a multivariate model, a history of heart failure, age>75 years, the absence of systemic anticoagulation with warfarin, the presence of left atrial spontaneous echocardiographic contrast, and greater than moderate mitral regurgitation were independent predictors of mortality. Increasing CHADS2 score was also an independent predictor of mortality. A CHADS2 score of 5 or 6 was associated with a >50-fold increase in mortality compared with patients with CHADS2 scores of 0. In conclusion, a history of heart failure, age>or=75 years, the absence of chronic oral anticoagulation, a CHADS2 score>0, and greater than moderate mitral regurgitation are independent predictors of mortality in patients with AF.

Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheter (TCC) thrombosis

Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A, 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p < 0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p < 0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05). VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No patient showed any bleeding events. Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.

Thienopyridines in Percutaneous Coronary Interventions: Standard Procedures and High Risk Subsets

Due to the significant clinical and economic consequences of subacute stent thrombosis and the use of more complex devices (brachytherapy, drug eluting stents) in a variety of clinical situations (i.e. acute coronary syndromes), initiation and duration of a combined antiplatelet therapy using aspirin and a thienopyridine drug has become an issue of ongoing discussion in interventional cardiology. This review will provide a short introduction into the pathophysiology of stent thrombosis before standard procedures and critical issues on the use of thienopyridines in the setting of coronary interventions are discussed. Furthermore, clinically relevant issues that are not clearly covered by recommendations or guidelines like thienopyridines after coronary interventions in patients on chronic oral anticoagulation are also addressed.

“Bridging” and Mechanical Heart Valves

Mechanical heart valves require anticoagulation to prevent valve-associated thrombosis and thromboembolic stroke. Oral vitamin K antagonists such as warfarin are prescribed universally; however, oral agents do not act immediately and usually require at least 5 days to achieve a therapeutic effect. Article p 564 Measurement of the prothrombin time, which is standardized by reporting the result as the international normalized ratio (INR), assesses the anticoagulant effect of warfarin. For most mechanical heart valves, the target INR ranges between 2.0 and 3.5. In the postoperative cardiac surgical setting, patients are usually started on low doses of warfarin because they tend to have impaired hepatic metabolism and suboptimal nutritional status. Even with low initial doses of warfarin, mechanical heart valve replacement patients are susceptible to excessively high INRs.1 This known exaggerated initial response to warfarin after heart valve replacement can lead to the habitual prescription of such low warfarin doses that warfarin as monotherapy may not achieve a stable and therapeutic INR for weeks after its initiation. To minimize the delay in achieving therapeutic anticoagulation, a “bridging” anticoagulant is prescribed. The “bridge” is administered parenterally, thereby providing an immediate anticoagulant effect. Traditionally, the “bridging” agent has been unfractionated heparin (UFH). More recently, physicians tend to select low-molecular-weight heparin (LMWH), even though few studies exist to validate the efficacy and safety of either LMWH or UFH in this setting. The rationale for shunning UFH has been to avoid the known perils and inconveniences of its use as a continuous peripheral intravenous infusion. UFH is rarely administered in an immediately therapeutic dose because of fear of precipitating bleeding complications. Especially in postoperative mechanical valve replacement patients, there is reluctance to follow the high dosing requirements for initial bolus and infusion regimens published in standardized nomograms. Instead, UFH is usually started in cautious small …

Ximelagatran, the Oral Anticoagulant of the Future An Evidence Based Review

This article presents the available data on Ximelagatran, a novel oral direct thrombin inhibitor and explores its therapeutic potential Recent large clinical trials have evaluated the efficacy and safety of this anticoagulant compared to the standard anticoagulation therapy with warfarin and heparins in several thrombotic disorders. These trials provide strong evidence for the efficacy and safety of ximelagatran in the following clinical indications; the prevention of venous thromboembolism after knee or hip replacement, the treatment of deep venous thrombosis, and prevention of stroke in patients with atrial fibrillation. Further evaluation of this promising oral anticoagulant is warranted in other thrombotic cardiovascular disorders requiring chronic oral anticoagulation therapy such as in patients with prosthetic heart valves, intracardiac thrombi, dilated cardiomyopathy, after myocardial infarction and post percutaneous coronary interventions.

LAPAROSCOPIC RENAL-ADRENAL SURGERY IN PATIENTS ON ORAL ANTICOAGULANT THERAPY

Patients requiring chronic anticoagulation are theoretically at increased risk for hemorrhage or thromboembolism perioperatively. Experience with laparoscopic renal/adrenal surgery in patients on chronic warfarin is limited. We assessed hemorrhagic/thromboembolic complications in this group of patients. The records of 787 patients undergoing laparoscopic renal/adrenal surgery were retrospectively reviewed. A total of 25 patients on chronic oral anticoagulation with warfarin were identified. The indications for warfarin therapy as well as perioperative management were reviewed. Clinical parameters, including operative time, estimated blood loss, hemorrhagic/thromboembolic complications and transfusions, were documented and compared with those in patients not receiving chronic anticoagulation. Atrial fibrillation (56% of cases) and a prosthetic mitral valve (28%) were the most frequent indications for chronic anticoagulation. Bridging anticoagulation with unfractionated heparin was the most frequent management method (68% of cases). Patients with anticoagulation were older (p <0.001) and hospitalized longer (<0.001) than those without anticoagulation. Operative time, estimated blood loss and the conversion rate were not significantly different between the groups. However patients on chronic warfarin significantly more often required transfusion (24% vs 5.2%, p <0.005) and had more postoperative bleeding episodes (8% vs 0.9%, p <0.05) than patients not on chronic anticoagulation. No thromboembolic events occurred in the anticoagulated group, while 3 occurred in the nonanticoagulated group (p = 1). Laparoscopic renal/adrenal surgery in patients requiring chronic anticoagulation therapy can be performed safely. The risk of intraoperative bleeding is not increased, although the incidence of postoperative bleeding as well as transfusions is higher.

Basilar Dolichoectasia with Clot Formation and Subarachnoid Haemorrhage

PATIENT 1 See Fig. 1. A 71-year-old hypertensive man on clopidogrel for a previous heart attack experienced a mild brainstem ischaemic stroke, followed by progressive hearing loss. 17 months later,...

Nonpharmacologic stroke prevention in atrial fibrillation

Atrial fibrillation is associated with significant mortality and morbidity. The burden of morbidity in atrial fibrillation is mostly due to stroke, one of the major causes of death and the leading cause of long-term disability. Although highly effective in prevention of thromboembolic stroke, several factors limit utilization of chronic oral anticoagulation therapy. Eradication of atrial fibrillation and restoration of effective atrial contraction by surgical methods, or recently, by percutaneous catheter ablation methods, are two attractive approaches for stroke prophylaxis. Surgical exclusion of the left atrial appendage has generated considerable interest in the past decades and it is now performed routinely during mitral valve surgery in many centers. Recently, minimally invasive and percutaneous methods for the exclusion of left atrial appendage have been introduced. Currently, these approaches are being evaluated in ongoing trials. This review will discuss the current status of nonpharmacologic methods in the prevention of stroke in atrial fibrillation.

Patients’ perceptions regarding oral anticoagulation therapy and its effect on quality of life

ABSTRACTObjective: Anticoagulation clinics have improved the time spent within therapeutic range and decreased hemorrhagic complications and costs in chronic oral anticoagulation. Whether these benefits correlate to patients’ quality of life (QOL) remains to be determined. The impact of patients’ perceptions about anticoagulation on QOL has not been evaluated. The objective of this study was to evaluate prospectively patients’ perceptions and quality of life in patients chronically anticoagulated.Research design and methods: A cross-sectional study was designed to investigate the prevalence of positive and negative perceptions about oral anticoagulation therapy (OAT) and to identify vulnerable groups. Patients anonymously completed the SF-36 survey and a questionnaire that focused on patients’ perceptions of protection from thrombotic complications or fear of haemorrhage due to the anticoagulation. We related those perceptions to the General Health SF-36 score, to the patient's characteristics, the absolute bleeding risk (i.e. intended International Normalized Ratio [INR]), duration of therapy and medical attention.Results: One thousand patients were included and 905 questionnaires evaluated. Most patients felt protected and better since the beginning of therapy (71.5% and 61.5%, respectively). Patient characteristics associated with negative perceptions were; female sex (Odds Ratio [OR] 1.58, 95% Confidence Interval [CI] 1.06–2.36, p = 0.01); patients with less than 1 year of therapy (OR 2.16, 95% CI 1.34–3.48, p = 0.006); those not satisfied with medical attention (OR 2.86, 95% CI 1.53–5.18, p = 0.0001); and those that modified their lifestyle (OR 2.75, 95% CI 1.49–4.91, p = 0.0002). Patients with a lower bleeding risk (INR 2.0–3.0) had more negative perceptions than those with a higher risk. Patients with negative perceptions achieved the lowest score in the SF-36 survey. Haemorrhages did not affect patients’ perception or QOL.Conclusions: Patients’ perceptions correlated with QOL. We were able to identify patient characteristics associated with poor QOL and thus the group of patients whose negative perceptions most warranted special attention from their clinicians.

Does Chronic Oral Anticoagulation With Warfarin Affect Durability of Endovascular Aortic Aneurysm Exclusion in a Midterm Follow-up?

To evaluate the effect of oral anticoagulation on durability of endovascular aortic aneurysm repair (EVAR). Retrospective review was conducted of 182 consecutive EVAR patients (169 men; mean age 75.3 years, range 53-89) between 1999 and 2003. Patients on warfarin anticoagulation (WA, n=21; International Normalized Ratio of 2 to 3) were compared against a control group (CG) with no postoperative anticoagulation (n=161). Death, aneurysm rupture, and reintervention were considered primary endpoints; endoleaks, endograft migration, and aneurysm remodeling were secondary endpoints. Mean follow-up was 16.3+/-12.6 months. One-year mortality was 6.6% (9.5% WA versus 6.2% CG); overall mortality was 14.3% (p=0.414). No aneurysm rupture occurred. At 1, 2, and 3 years, respectively, cumulative reinterventions (20%/20%/20% WA versus 12%/15%/20% CG; p=0.633) and endoleak rates (25%/25%/25% WA versus 17%/22%/34% CG; p=0.649) were comparable. In both groups, most completion endoleaks resolved (42.9% WA versus 74.4% CG; p=0.474), but few de novo endoleaks did (0% WA versus 12.8% CG; p=0.538). Anticoagulation did not affect mean time to aneurysm sac shrinkage (1.3+/-0.3 WA versus 1.4+/-0.1 years CG; p=0.769). After EVAR, anticoagulation appears safe and does not significantly alter mortality, risk for rupture, or the incidence of reintervention. Early endoleaks appear more common in anticoagulated patients, but anticoagulation does not preclude spontaneous endoleak resolution nor does it increase late endoleak rates. Irrespective of the anticoagulation status, early but not late endoleaks usually sealed spontaneously. Observing type II endoleaks appears safe in the absence of aneurysm enlargement.

The Influence of Prior Oral Anticoagulation Therapy on the Anticoagulant Effect of Low Molecular Weight Heparin.

Low Molecular Weight Heparins (LMWHs) have been suggested by the ACCP as an alternative to UFH for the anticoagulation of patients on chronic oral anticoagulation therapy (OAT) with warfarin. However, the optimal way to manage these patients remains to be established particularly for high-risk patients who require any type of general surgery or urgent invasive PCI procedures.The purpose of this study is to evaluate the LMWH point-of-care (POC) HEMONOXTM assay (Edison, NJ) in patients on chronic OAT. This clot-based test uses rTF reagents and the Hemochron Jr. Signature+ system. The Hemonox clotting time (CT) was analyzed at baseline and at peak response post enoxaparin treatment.Following IRB approval, blood samples from patients on chronic OAT (5 to 20 years, n=13) were evaluated with the Hemonox assay within 12– 18 hours of their last warfarin dose, patients were evaluated weekly for 4 –12 consecutive weeks. In vitro enoxaparin dose response was evaluated by adding 1 U/ml to blood samples obtained from the OAT patients. In supplemental clinical evaluation, 2 PCI cases on OAT were performed at Newark Beth Israel Medical Center, Newark, NJ. Patients were anticoagulated during their PCI procedure with enoxaparin at a final IV dose of 0.5 mg/kgHemonox CT baseline response was patient specific and the same response profile was obtained for each patient on OAT who underwent consecutive weekly testing. The majority of patients on OAT (9/13; 69%) exhibited elevated Hemonox baseline CT (150–350 secs) when compared to the previously reported range for PCI patients without prior OAT (baseline CT < 100 secs in 100% of cases, Mean = 71.2 ± 9.0, n= 39). Three patients on OAT (23%) showed CT≤150 secs, and only one patient (8%) yielded a baseline < 100 secs. When the blood of the patient with baseline < 100 sec (baseline value = 70 secs) was spiked in vitro with 1 U/ml enoxaparin, the Hemonox CT was 339 secs which was comparable with the peak response (386 and 308 secs; anti-Xa activity = 0.70 ± 0.01 U/ml; concentration of enoxaparin in the circulation = 0.77± 0.13) observed in the PCI patients receiving enoxaparin (0.5 mg/kg IV) and with a prior OAT who showed similar baseline values. Spiked samples from clinic patients with Hemonox baseline > 150 secs were > 700 secs.Our results demonstrate that prior to administration of LMWH, baseline monitoring may be helpful in patients on OAT to alert clinicians to appropriate alterations of enoxaparin dosing and target anticoagulation times due to the influence of warfarin.

Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols

Purpose The potential association between vitamin K intake and coagulation instability has been explored primarily in case reports and small, retrospective, uncontrolled studies. We prospectively evaluated the effects of dietary vitamin K intake on anticoagulation parameters. Methods In an observational protocol, clinical characteristics and vitamin K intake, assessed semiquantitatively, were evaluated in 39 outpatients who made 230 visits to our anticoagulation clinic. In a randomized crossover protocol, 12 patients with stable anticoagulation underwent 4-day in-hospital dietary interventions, 1 to 2 weeks apart, providing a 500% increase and an 80% decrease in vitamin K intake relative to the baseline level. Results Univariate analysis of the observational data demonstrated a progressive, statistically significant inverse association between the vitamin K intake score and different levels of anticoagulation. Multivariate logistic regression analysis showed that vitamin K intake was independently associated with both overcoagulation and undercoagulation. In the randomized protocol, the international normalized ratio increased from 2.6 ± 0.5 at baseline to 3.3 ± 0.9 at day 7 ( P = 0.005) in subjects on the vitamin K–depleted diet and decreased from 3.1 ± 0.8 at baseline to 2.8 ± 0.6 at day 4 ( P = 0.04) in those on the vitamin K–enriched diet. Conclusion Our prospective data strengthen the concept that the interaction between vitamin K and coumarin is a clinically relevant, major independent factor that interferes with anticoagulation stability.

Oral Anticoagulation in Clinical Medicine for Venous and Arterial Thrombotic Indications

Oral anticoagulant therapy is used increasingly for the prevention and treatment of thromboembolic complications from vascular disease on the basis of accumulating evidence of its effectiveness in many clinical indications. In the last few decades important developments have been achieved in laboratory and clinical monitoring of treated patients, leading to more appropriate therapy and improved safety. As a result, the number of patients on chronic oral anticoagulation has increased dramatically in recent years. However, the underutilization of this effective therapy is still a pervasive problem. Both fear of complications, especially bleeding, and the practical difficulties associated with this demanding therapy are frequent concerns of physicians, preventing wider use of this treatment in many patients who would benefit from it.

Bleeding risk factors in chronic oral anticoagulation with acenocoumarol.

We studied major bleeding complications, death related to hemorrhage, and tried to identify predisposing factors for bleeding in outpatients treated with acenocoumarol. We evaluated 811 outpatients attending a specialized anticoagulant therapy unit. The intended INR range was 3.5-4.5 for mechanical heart valve replacement (N= 384) and 2.0-3.0 for other indications (N= 427). The variability of INR for the total follow-up and the 2 months before the hemorrhage was calculated. The total follow-up was 1,963.26 years with 27,321 control tests. We observed 47 major bleeding episodes, including 2 fatal (central nervous system hemorrhages), in 37 patients. 49.5% of the patients had underlying diseases. The rate of major and fatal hemorrhage was 2.39 and 0.10 episodes per 100 patients year, respectively. Hemorrhagic complications were more frequently observed in patients with a more intense intended range (8.2% in the INR 3.5-4.5 group vs. 1.5% in the 2.0-3.0 INR group). The risk of major bleeding increased in patients with an achieved INR higher than 6 and in those with higher INR variability during follow-up. The estimated probability of bleeding also increased with time: it was 0.102% at 78 months, and at the beginning of therapy it was 0.006% and 0.007% at 1 and 4 months, respectively. The intensity of anticoagulation and the deviation of the INR from the target are the most important risk factors for bleeding in patients taking acenocoumarol. Monitoring the variability of INR can help identifying patients predisposed to bleeding. However, the screening for underlying disease should always be performed.