Chronic Anticoagulation Therapy Research Articles

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.

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.

Ximelagatran vs Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation

In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.

Monitoring therapy with oral anticoagulants. Anticoagulation clinics vs assistant physician

Most patients on chronic oral anticoagulant therapy are monitored through anticoagulation clinics, or rather by assistant physicians. Our aim was to compare warfarin anticoagulated patients who were treated with usual medical care (assistant physician) with those treated routinely at an anticoagulation clinic for anticoagulation control. The later was assessed by comparing in both groups of patients the proportion of INRs within the therapeutic range, above 5.0 and below 1.5. The group treated at an anticoagulation clinic achieved better anticoagulation control (both among the patients receiving lower-range anticoagulation therapy and in the patients requiring higher-range anticoagulation therapy) than the group treated with usual medical care.

Herbal remedies and anticoagulant therapy

Herbal remedies, considered to be both safe and effective by most consumers, may interact with conventional drugs. Warfarin, a vitamin K antagonist originally derived from the sweet clover plant, has a narrow therapeutic window which can be monitored using prothrombin international normalized ratios (PT-INR). Many herbs can increase the risk for bleeding when combined with warfarin, either by augmenting the anticoagulant effects of the drug (with increased PT-INR levels) or through intrinsic anti-platelet properties (without altering PT-INR levels). The increased risk for bleeding among such patients may be difficult to predict, especially when formulas which contain many herbs are used. Further research into herb-drug interactions is warranted, as are guidelines for the use of herbal remedies by patients on chronic anticoagulation therapy.

Anticoagulation influences long-term outcome in patients with nonvalvular atrial fibrillation and severe ischemic stroke

Background: Limited data exist regarding long-term prognosis in patients with nonvalvular atrial fibrillation (AF) who have survived a severe, disabling stroke. Objective: The aim of this study was to assess long-term prognosis and its determinants in a prospective case series of stroke survivors with AF and moderate to severe handicap. Methods: From a consecutive series of AF patients with first-ever ischemic stroke, we evaluated prospectively those with moderate to severe disability (grade 4–5 on the modified Rankin Scale) who were treated during a 5-year follow-up period with either warfarin or aspirin. Death and recurrent vascular events were documented. Results: Out of a pool of 438 AF patients, 191 were prospectively assessed. During a mean follow-up of 50.4 months, the cumulative 5-year mortality was 76.7% (95% CI, 69.0–84.3) and the 5-year recurrence rate was 33.7% (95% CI, 23.3–44.1). Cox regression analysis revealed that increasing age, increasing handicap, and aspirin versus warfarin were independent predictors of mortality. Prior transient ischemic attack and aspirin versus warfarin were predictors of vascular recurrence. Anticoagulation was associated with a decreased risk of death (hazard ratio [HR], 0.44; 95% CI, 0.27–0.70; P < 0.001) and recurrent thromboembolism (HR, 0.36; 95% CI, 0.17–0.77; P < 0.01). Conclusion: Our results suggest that chronic anticoagulation therapy may be effective in lengthening survival and preventing recurrent thromboembolism in AF patients who have suffered a severely disabling ischemic stroke.

Periprocedural Management of Anticoagulation in Patients on Extended Warfarin Therapy

Patients receiving chronic anticoagulation therapy pose a clinical challenge when therapy needs to be interrupted for surgical or invasive procedures. Maintaining anticoagulation places them at risk of serious bleeding complications, whereas discontinuing anticoagulation puts them at risk of thromboembolic complications. The main patient groups that may require a periprocedural alternative to oral anticoagulation include patients with prosthetic heart valves, atrial fibrillation, and hypercoagulable states and those with chronic venous thrombosis undergoing surgery. Currently, there is little consensus on appropriate perioperative management of patients on long-term warfarin therapy. This article is an attempt to bring together all the available data on periprocedural bridging to assess the available options for patients undergoing surgical procedures and to provide a rationale for using low-molecular-weight heparins (LMWHs) while individualizing the risks versus benefits in a given patient population.

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.

Linear accelerator thalamotomy

Background The capability of performing functional radiosurgery lesions in the brain using a dedicated linear accelerator (LINAC) have not yet been demonstrated. This study evaluates modern LINAC technology for the creation of a sharp, small and functionally eloquent lesion in the thalamus. Methods Three patients underwent thalamotomy using a dedicated linear accelerator to radiosurgery, 2 females and 1 male, ages were 52, 53, and 73 years. Two patients presented with unilateral poststroke central pain and 1 with unilateral upper extremity pain secondary to metastatic infiltration of the brachial plexus. Maximal doses varied from 150 to 200 Gy, delivered by a 5-mm diameter collimator and 5 to 8 noncoplanar arcs evenly distributed. Results All patients gained substantial relief of their pain. They were able to reduce their medications and improve their activity levels. The patient with end-stage metastatic disease died of his malignancy 2 weeks after the treatment. One patient presented with recurrence of the pain 4 months after the treatment. No clinical complications were noticed. Conclusions A dedicated linear accelerator is able to perform a precise and circumscribed lesion in the thalamus for pain control. Moreover, it proved to be safe, because no complications were observed. For patients using chronic anticoagulant therapy or with severe disabilities caused by cardiac, pulmonary or malignant diseases, this technique represents an alternative of treatment to radiofrequency thalamotomy.

Motor-Vehicle Collision-Related Death Due to Delayed-Onset Subarachnoid Hemorrhage Associated with Anticoagulant Therapy

Delayed deaths following injury are not rare. Various mechanisms may be responsible for such deaths, including pulmonary thromboembolism, fat embolism, infection, systemic inflammatory response syndrome, and delayed hemorrhage. In the present case, we describe a death due to delayed subarachnoid hemorrhage following a motor vehicle collision, wherein the hemorrhage occurred ten days after the incident, while the patient remained hospitalized for skeletal trauma. At no time prior to the hemorrhage did the victim show any symptoms of brain injury. Autopsy revealed basilar subarachnoid hemorrhage arising from a cerebral cortical contusion. There was no evidence of aneurysm or arteriovenous malformation. A significant underlying contributing factor in the delayed hemorrhage was the victim's chronic anticoagulant therapy, which was required because of a mechanical heart valve.

INTESTINAL AND MULTIVISCERAL TRANSPLANTATION FOR PORTOMESENTERIC VENOUS THROMBOSIS: TECHNICAL CONSIDERATIONS AND THERAPEUTIC EFFICACY

P607 Aims: Splanchnic arterial and venous thrombosis is second most common indication for visceral transplantation. The underlying etiology, disease gravity and extent of thrombosis should guide the decision-making process and influence post-transplant outcome. This study is the first to address the different causes of splanchnic thrombosis, indications for each type of the visceral allograft, and survival outcomes. Methods: Between May 1990 and March 2004, 135 consecutive adult patients received 148 intestinal allografts at the University of Pittsburgh. Of these, 48(36%) were transplanted due to splanchnic thrombosis that was limited to the portomesenteric venous system in 20. Diagnosis was with abdominal imaging studies including visceral angiography. Age ranged from 23 to 65 years with a median of 45. Twelve patients suffered from short gut syndrome prior to transplantation and the remaining 8 required full visceral replacement because of variceal bleeding and hepatic failure. Results: Visceral venous thrombosis was due to protein C, S and anti-thrombin III deficiency in 3, Factor V/II mutation in 2, antiphospholipid antibodies in 3, myeloproliferative disorder in 3 and unknown etiology in the remaining 9 patients. The required intestinal allograft was tailored to intestine alone in 6(30%), combined liver-intestine in 4(20%) and multivisceral in 10(50%) patients. The median operative time (hr) was 12 for intestinal 18 for liver-intestinal, and 15 for multivisceral transplantation with an average blood loss of 4, 14 and 23 units, respectively. The pre-transplant liver functions were preserved in all of isolated intestinal recipients and the allograft venous outflow was drained into the recipient vena cava. In two of these, a splenorenal shunt was performed one year prior to transplant for treatment of gastric varcies in presence of chronic anticoagulation therapy. In 3 out of the 4 combined liver-intestinal recipients, systemic venous drainage of the retained left upper abdominal organs was via non-conventional portosystemic shunts. All of multivisceral recipients had combined extensive portomesenteric and splenic venous thrombosis with diffuse minute collaterals combined with Budd-Chiari(3), diabetes(2), renal failure(2) and hepatocellular carcinoma(1). All recipients were anticoagulated despite hepatic replacement. With a mean follow-up of 23±27 months, 14 recipients were alive with a cumulative survival rate of 79% at 6 months and 67% at 5 years. Causes of patient death were graft failure(1), upper gastrointestinal hemorrhage(1), enteric leak(1) and opportunistic infections(3). All of 14 survivors were free of TPN enjoying unrestricted oral diet 6 months to 8 years after transplantation. Conclusions: Despite disease gravity, inherent technical complexity and associated morbidity, intestinal and multivisceral transplantation are effective therapeutic modalities for patients with symptomatic splanchnic venous thrombosis. Thorough pretransplant evaluation with proper tailoring of the required allograft is mandatory for successful outcomes.

Preclinical readiness testing of the arrow international CorAide left ventricular assist system

Background Left ventricular assist system technologies are currently being developed as effective alternatives to cardiac transplantation. In this study, in vivo testing of the Arrow International CorAide left ventricular assist system was conducted to determine its preclinical readiness based on demonstrated system performance and biocompatibility. Methods Arrow International CorAide blood pump assemblies were implanted in 7 calves for 1-month (n = 4) and 3-month (n = 3) durations without the use of chronic anticoagulation therapy. Hemodynamic performance, physiologic pump control, end-organ function, and device-related adverse events were evaluated during the studies and at autopsy. Results Hemodynamics were stable in all cases with a mean pump flow of 4.1 ± 0.8 L/min and a mean arterial pressure of 101 ± 4 mm Hg. In all calves, renal and hepatic function remained normal with no incidence of hemolysis, infection, bleeding, or embolism. The CorAide physiologic control algorithm demonstrated appropriate pump speed and flow adjustments in response to physiologically induced inputs, and the system's external electronic components demonstrated no hardware or software malfunction. All 7 cases were sacrificed electively. Autopsy revealed no sign of end-organ disease on gross and histologic examinations, and no device failure, malfunction, or mechanical wear of the pump blood-bearing surfaces was found. Conclusions The Arrow CorAide left ventricular assist system demonstrated effective pump performance and good biocompatibility with no incidence of device-related adverse events. This system has completed its preclinical readiness testing and is approved for clinical trials in Europe in 2003.

Periprocedural thromboprophylaxis in patients receiving chronic anticoagulation therapy

Patients receiving chronic anticoagulation therapy pose a clinical challenge when therapy needs to be interrupted for surgical or invasive procedures. Maintaining anticoagulation places them at risk for serious bleeding complications, whereas discontinuing anticoagulation puts them at risk of thromboembolic complications. Most patients can undergo dental procedures, cataract surgery, and diagnostic endoscopy without discontinuing anticoagulation. The main patient groups that may require a periprocedural alternative to oral anticoagulation (periprocedural thromboprophylaxis or bridging) include patients with prosthetic heart valves, atrial fibrillation, and hypercoagulable states and patients with chronic venous thrombosis who are undergoing surgery. Currently, there is little consensus on the appropriate perioperative treatment of patients on long-term warfarin therapy. There are an increasing number of studies that evaluate the benefits of periprocedural bridging with low-molecular-weight heparin (LMWH) in place of unfractionated heparin (UFH). An advantage of LMWH over UFH is that perioperative conversion from warfarin therapy with LMWH can be carried out in the outpatient setting, which is more convenient for patients and is cost effective. As with the use of UFH, there are reports of maternal thromboembolic complications with LMWHs in pregnant women with mechanical heart valves. This review brings together the available data on periprocedural bridging to assess the available options for patients on long-term warfarin therapy who are undergoing surgical procedures. It provides a rationale for using LMWHs while individualizing the risks versus benefits in a given patient population.

Safety, Effectiveness, and Efficiency: A Web-Based Virtual Anticoagulation Clinic

Information systems that include Web-based technology can provide clinical decision support in care processes that can be algorithmically described. Long-term oral anticoagulation with warfarin is one such care process. THE VIRTUAL ANTICOAGULATION CLINIC: A clinical decision support tool was developed using evidence-based guidelines from the extant medical literature on the indications for and management of therapy with warfarin. Training modules for physicians and support staff were implemented, and patients were prospectively enrolled in the "virtual anticoagulation clinic" when they began taking warfarin or when they returned for routine follow-up under the usual care model. Designated warfarin coordinators managed the virtual anticoagulation clinic under physician supervision. Following the adoption of the virtual anticoagulation clinic, uniform improvement in time in therapeutic range was observed in each participating practice, with those practices using it the longest equaling or exceeding results reported from formally organized warfarin clinics. Major adverse events were observed only in patients who were not managed in the manner suggested by the virtual anticoagulation clinic. A Web-based solution to chronic anticoagulation therapy offers an inexpensive, safe, and significantly more effective alternative to the usual care model.

Long-term outcome of infrainguinal bypass grafting in patients with serologically proven hypercoagulability

The purpose of this study was to test the hypothesis that the long-term outcome of infrainguinal bypass grafting in patients with congenital or acquired hypercoagulability is inferior to the results in patients without documented clotting disorders. The study was a retrospective analysis of consecutive patients from January 1994 to January 2001. Five hundred eighty-two infrainguinal bypass grafts were created in 456 patients. Indication for surgery was limb-threatening ischemia in 84%; prosthetic conduits were implanted in 38%. Seventy-four grafts were created in 57 patients with one or more serologically proven hypercoagulable states, including heparin-induced platelet aggregation (n = 37), anticardiolipin antibodies (n = 11), lupus anticoagulant (n = 8), protein C or S deficiency (n = 7), antithrombin III deficiency (n = 3), and factor V Leiden mutation (n = 1). Patients with hypercoagulability were younger (63 +/- 2 years versus 69 +/- 1 years; P =.007), more likely to have undergone prior revascularization attempts (38% versus 21%; P =.003), and more likely to have chronic anticoagulation therapy after surgery (46% versus 25%; P =.001). After 5 years (median follow-up, 19 months), patients with hypercoagulability had poorer primary patency (28% +/- 7% versus 35% +/- 5%; P =.004), primary assisted patency (37% +/- 7% versus 45% +/- 6%; P =.0001), secondary patency (41% +/- 7% versus 53% +/- 6%; P =.0001), limb salvage (55% +/- 8% versus 67% +/- 6%; P =.009), and survival (61% +/- 8% versus 74% +/- 4%; P =.02) rates. Multivariate analysis identified only prosthetic conduit choice (P =.0001), hypercoagulability (P =.0003), and limb salvage indication (P =.01) as independent predictors of graft failure. Patients with serologically proven hypercoagulability have inferior long-term patency, limb salvage, and survival rates after infrainguinal bypass. The high prevalence rate (13%) of diverse hypercoagulable states in this patient population supports serologic screening, especially in referral practices.

Perioperative considerations in the patient with a left ventricular assist device.

Perioperative considerations in the patient with a left ventricular assist device.

Prothrombotic States that Predispose to Stroke.

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

Candidates for prostatectomy who require chronic anticoagulant therapy present a major perioperative management problem due to the threat of significant hemorrhage associated with surgery and the risk of thromboembolism associated with discontinuation of the anticoagulants. We evaluated prospectively a perioperative routine using low molecular weight heparin substitution to allow safe discontinuation of prophylactic oral anticoagulants in patients undergoing transurethral resection of the prostate. We treated 20 patients on chronic oral anticoagulant therapy who required prostatectomy for bladder outlet obstruction according to a prospective protocol based on exchange of the oral anticoagulants with perioperative injections of low molecular weight heparin and resumption of oral anticoagulants early postoperatively. The safety and efficacy of this regimen were assessed in comparison to a control group comprised of 20 randomly selected nonwarfarin treated patients who underwent prostatectomy during the same period. The need for blood transfusions and mean number of units transfused did not significantly differ between the 2 groups. Due to persistent hematuria routine removal of the catheter was possible only in 9 of 20 patients (45%) in the heparin group compared to 18 of 20 (90%) in the control group. Average catheterization and hospitalization period in the heparin group was 3.2 days and 4.2 days respectively, compared to 2.1 and 2.1 days in the control group, respectively (p <0.01). No long-term hemorrhagic or thromboembolic complications were noted at 3 months postoperatively. Despite longer hospitalization in the heparin treated group, our substitution protocol is safe and effective.

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

The Efficacy and Safety of Perioperative Low Molecular Weight Heparin Substitution in Patients on Chronic Oral Anticoagulant Therapy Undergoing Transurethral Prostatectomy for Bladder Outlet Obstruction

Potential impact of therapeutic warfarin treatment on type II endoleaks and sac shrinkage rates on midterm follow-up examination

Objective: Successful endovascular aortic aneurysm repair depends on exclusion and spontaneous thrombosis of the aneurysm sac. The need for chronic postoperative anticoagulation therapy could limit the applicability of this technology with delay or prevention of sac thrombosis resulting in endoleak formation and altered remodeling of the aneurysm sac. The purpose of this study was the determination of whether chronic therapeutic anticoagulation therapy with warfarin was associated with an increased incidence rate of early or delayed postoperative endoleaks or altered rates of reduction in aneurysm sac maximum diameter. Methods: Two hundred thirty-two consecutive patients underwent abdominal aortic endografting during a 32-month period. The data were recorded prospectively with a current mean follow-up period of 18 months. The patients with endoleaks identified with 30-day postoperative computed tomographic scan angiograms subsequently underwent selective arteriography to characterize the source. The patients who underwent chronic warfarin therapy that resulted in a therapeutic internationalized normalized ratio comprised the study group. The control group was defined as all the patients with healthy coagulation profiles. Results: Thirty-six patients (15%) were undergoing warfarin therapy after surgery, and their conditions were chronically maintained with a therapeutic international normalized ratio. Forty-three patients (18%) had endoleaks on 30-day computed tomographic scan angiographic results. There were 39 patients with type II endoleaks and four patients with type I endoleaks. None of the type I endoleaks occurred in patients who were undergoing warfarin therapy, and all endoleaks were repaired with either proximal or distal covered extensions. At 30 days, seven patients (19.4%) undergoing chronic warfarin therapy had type II endoleaks as compared with 36 controls (18.4%; P =.798). Four patients had delayed type II endoleaks develop, two in the control group and two in the warfarin group (P =.3). Ten control individuals (31%) had spontaneous resolution of type II endoleaks develop, whereas spontaneous endoleak thrombosis was not observed in the warfarin group (P =.33). Aneurysm sac remodeling assessed with mean percent reduction in maximum sac diameter at 12 months revealed a statistical difference between the control group (17.5%) and the warfarin group (7.6%; P =.04). Conclusion: Warfarin treatment is not associated with an increase in the incidence rate of early or delayed postoperative endoleaks. However, the rate of reduction in maximum aneurysm sac diameter after aortic endografting is slower in patients who undergo therapeutic warfarin therapy at 1-year follow-up examination, a statistically significant difference from the control group. In addition, type II endoleaks may be less likely to undergo spontaneous thrombosis in patients who undergo warfarin therapy. (J Vasc Surg 2002;35:679-85.)