warfarin and Urinary-Bladder-Neoplasms

To determine the impact of fibrin clot inhibitor (FCI) use on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate bacille Calmette-Guérin (BCG).. We performed an Institutional Review Board-approved review of patients with NMIBC treated with adequate intravesical BCG, at our institution between 2000 and 2018. FCI use at the time of BCG therapy was recorded for each patient. Patients were stratified according to use of FCI medication. Recurrence- and progression-free survival were analysed using Kaplan-Meier methods and Cox proportional hazard models.. Overall, 226 of 526 patients (43.0%) used a FCI: aspirin (205), clopidogrel (38), warfarin (18) and novel oral anticoagulant (NOAC; seven). The use of FCIs did not adversely affect either recurrence- or progression-free survival (P = 0.385 and P = 0.131, respectively). These results did not change when the impact of aspirin, clopidogrel or warfarin/NOAC use on recurrence and progression was evaluated separately. On multivariate analysis, FCI use was neither associated with tumour recurrence nor progression.. The use of FCIs was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for NMIBC. Based on these results, FCIs may be safely continued during BCG immunotherapy.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Anticoagulants; Aspirin; BCG Vaccine; Clopidogrel; Fibrin; Humans; Neoplasm Recurrence, Local; Thrombosis; Urinary Bladder Neoplasms; Warfarin

Hematuria is a common and important complication in atrial fibrillation (AF) patients on oral anticoagulation therapy (OAT). This study evaluated the clinical significance of hematuria and its relationship with genitourinary disease in AF patients receiving OAT.Methods and Results:Among 20,456 consecutive AF patients who visited a tertiary hospital from January 2005 to April 2015, 5,833 had hematuria. Of these 5,833 patients, 3,798 were on OAT (OAT(+) group) and 2,035 were not (OAT(-) group). A total of 1,785 patients from each group were then matched on propensity score analysis. The prevalence of cancer and other diseases in the genitourinary tract was evaluated. While there was no difference in the prevalence of genitourinary stones or urinary tract infection, genitourinary cancer was significantly more common in the OAT(+) group than in the OAT(-) group (1.6% vs. 0.7%, P=0.011). Bladder cancer was the most common genitourinary malignancy, and it was significantly more common in the OAT(+) group (1.2% vs. 0.5%, P=0.019). Subjects on warfarin were more likely to have bladder cancers of lower pathologic grade (63.6% vs. 33.3%, P=0.124).. OAT was associated with a higher prevalence and early detection of genitourinary cancer in AF patients with hematuria. Meticulous evaluation of the cause of hematuria is necessary in AF patients with hematuria receiving OAT.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hematuria; Humans; Male; Middle Aged; Urinary Bladder Neoplasms; Urogenital Neoplasms; Urologic Diseases; Warfarin

A case of supratherapeutic International Normalized Ratio (INR) values and hematomas subsequent to concomitant administration of warfarin and intravesical gemcitabine is reported.. A 90-year-old man with bladder cancer refractory to bacillius Calmette-Guérin was diagnosed with deep vein thrombosis (DVT) and started on warfarin one month before starting treatment with intravesical gemcitabine 2 g (one dose per week for six weeks). Before intravesical gemcitabine was started, the patient reached consecutive therapeutic INR values. During the first five cycles of intravesical gemcitabine, the patient began to experience critically elevated INRs, which resulted in hospitalization and led to the discovery of hematomas. At hospital discharge, the decision was made to discontinue warfarin permanently given the patient's history of critically elevated INRs. Instead, enoxaparin was initiated due to the patient's history of DVT and active malignancy. Enoxaparin was started at a therapeutic, renally adjusted dosage of 60 mg subcutaneously once daily after the patient's hematomas resolved and hemoglobin level stabilized. The patient was cleared for discharge to his home after 17 days of hospitalization. He was scheduled to follow up with both urology and hematology departments regarding any further treatment for bladder cancer. A week after discharge, the patient's family decided that he would not receive the last (sixth) cycle of intravesical gemcitabine. To our knowledge, this is the first reported case of an interaction between intravesical gemcitabine and warfarin.. A 90-year-old man on a stable dose of warfarin experienced an increase in INR values after receiving intravesical gemcitabine for the treatment of bladder cancer.

Topics: Administration, Intravesical; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; BCG Vaccine; Carcinoma, Transitional Cell; Deoxycytidine; Drug Interactions; Enoxaparin; Gemcitabine; Humans; International Normalized Ratio; Male; Urinary Bladder Neoplasms; Venous Thrombosis; Warfarin

We determined the rate, timing and predictors of venous thromboembolism after open radical cystectomy for urothelial bladder cancer. We also compared the use of warfarin (1971 to 2008) and unfractionated heparin (2008 to 2012) as prophylaxis.. We retrospectively reviewed the records of 2,316 patients who underwent open radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer with intent to cure at our institution between 1971 and 2012. The rate and timing of symptomatic venous thromboembolism that developed within 3 months of surgery was calculated in the cohort. Multivariate stepwise logistic regression was used to find significant predictors of symptomatic venous thromboembolism and compare the warfarin based and heparin based prophylaxis protocols.. A total of 109 symptomatic venous thromboembolism cases developed for a rate of 4.7%, including 2.1% for deep vein thrombosis and 2.6% for pulmonary embolism. Of these cases 57.8% developed after discharge home at a median of 20 days postoperatively (range 2 to 91). Four significant predictors of venous thromboembolism were identified, including body mass index (p = 0.0015), surgical margins (p = 0.025), diversion type (p = 0.023) and hospitalization duration (p <0.0001). Use of prophylactic heparin vs warfarin was not a significant predictor (p = 0.31).. Venous thromboembolism remains a significant complication of open radical cystectomy. Using an in-house, heparin based anticoagulation protocol consistent with current AUA (American Urological Association) guidelines has not decreased the rate of venous thromboembolism compared to historical warfarin use. On closer evaluation most venous thromboembolism cases in our population occurred after discharge home. Future studies are needed to establish the benefits of extended duration venous thromboembolism prophylaxis regimens that cover the critical post-hospitalization period.

Topics: Aged; Anticoagulants; Cystectomy; Female; Heparin; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Time Factors; Urinary Bladder Neoplasms; Venous Thromboembolism; Warfarin

We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Aspirin; Cystectomy; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Postoperative Complications; Retrospective Studies; Urethra; Urinary Bladder Neoplasms; Warfarin

To determine if there is a difference in clinical outcomes among non-muscle-invasive bladder cancer patients taking fibrin clot-inhibiting (FCI) medications (aspirin, clopidogrel, or warfarin) while receiving Bacillus Calmette-Guérin (BCG) therapy compared with their counterparts not taking anticoagulation.. Our Investigational Review Board-approved database was queried for patients who received an induction course of BCG from 2001 to 2011. The analysis included 224 patients with a minimum of 3 months of follow-up. Recurrence-free survival (RFS), cystectomy-free survival, overall survival, and disease-specific survival were analyzed using the Kaplan-Meier method stratified by FCI status. Logistic regression was used to predict the initial response rate to BCG and progression by FCI status.. Of the 224 patients analyzed, 68, 19, and 23 patients were taking aspirin, clopidogrel and warfarin, respectively, at BCG induction. No specific FCI was associated with differences in cystectomy-free survival, overall survival, disease-specific survival, or the likelihood of progression at recurrence. Neither warfarin nor clopidogrel affected RFS. Patients taking aspirin trended toward increased RFS, although this was not statistically significant (P = .058). Multivariate analysis showed aspirin use was associated with an increased initial response to BCG (odds ratio, 2.41; P = .031). Contrary to the postulated inhibitory molecular effect of FCI on BCG-binding activity, this study did not substantiate a significant impact on BCG efficacy of the concomitant use of these medications during BCG induction. The observation that aspirin use potentiates an increased initial response to BCG may warrant further analysis.

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Anticoagulants; Aspirin; BCG Vaccine; Clopidogrel; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunomodulation; Induction Chemotherapy; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Odds Ratio; Proportional Hazards Models; Retrospective Studies; Ticlopidine; Urinary Bladder Neoplasms; Warfarin

A 74-year-old female patient with bladder cancer presented with edema in the right lower limb in a follow-up at the outpatient department.She was diagnosed with deep vein thrombosis in the right lower limb, and warfarin treatment was started.Subsequent gemcitabine and cisplatin combination(GC)therapy for prevention of bladder cancer recurrence prolonged the PT-INR to an immeasurable level on day 6 of therapy.Thus, warfarin was immediately discontinued and a single dose of menatetrenone was administered.Subsequently, the PT-INR recovered to 1.36 one day after discontinuation of warfarin.In the second course of GC therapy, warfarin was discontinued before administration of the anticancer drugs, and there was no change in the PT-INR.The abnormally high PT-INR observed in the early stage after GC therapy in this case shows that it is important to monitor blood coagulation from immediately after administration of GC therapy in a patient under treatment with warfarin.

Topics: Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Edema; Female; Gemcitabine; Humans; International Normalized Ratio; Leg; Prothrombin; Thrombophlebitis; Urinary Bladder Neoplasms; Warfarin

Topics: Aged; Angiography, Digital Subtraction; Angioplasty; Brachial Artery; Embolectomy; Embolism; Forearm; Hand; Heparin; Heparin, Low-Molecular-Weight; Humans; Ischemia; Male; Postoperative Care; Postoperative Complications; Radial Artery; Suction; Ulnar Artery; Ultrasonography, Doppler, Color; Urinary Bladder Neoplasms; Warfarin

The case of a patient receiving long-term anticoagulation with warfarin who had supratherapeutic International Normalized Ratios (INRs) after receiving concomitant acetaminophen and moxifloxacin as prophylaxis with bacille Calmette-Guérin (BCG) therapy for bladder cancer is reported.. An 89-year-old man receiving long-term anticoagulation with warfarin sodium (total weekly dosage of 19 mg) arrived at the anticoagulation clinic for his monthly visit. On the day before this visit, he had received the third of six serial weekly BCG bladder instillations for the treatment of bladder cancer. He did not report that acetaminophen 1000 mg four times daily and one dose of moxifloxacin 400 mg had been prescribed before these instillations. An INR check revealed a value of 6.7. He was instructed to take 2.5 mg of oral phytonadione and to withhold his warfarin dose that night. On the next day, his INR was 3.2. Each time he arrived at the anticoagulation clinic after his BCG therapy, his INR was supratherapeutic, except after his fourth treatment (INR of 2.5), which can be explained by residual effects from the phytonadione he received a week earlier. After completion of his BCG therapy, he was instructed to resume his usual warfarin sodium dosage of 19 mg weekly, and his INR remained in the desired therapeutic range. According to the Drug Interaction Probability Scale, the development of supratherapeutic INRs was probably associated with concomitant acetaminophen and moxifloxacin use.. An 89-year-old man receiving long-term anticoagulation with warfarin had supratherapeutic INRs after receiving acetaminophen and moxifloxacin as prophylaxis during BCG therapy for bladder cancer.

Topics: Acetaminophen; Adjuvants, Immunologic; Aged, 80 and over; Analgesics, Non-Narcotic; Anti-Infective Agents; Anticoagulants; Antifibrinolytic Agents; Aza Compounds; BCG Vaccine; Drug Interactions; Fluoroquinolones; Humans; International Normalized Ratio; Male; Moxifloxacin; Quinolines; Urinary Bladder Neoplasms; Vitamin K 1; Warfarin

Topics: Aged; Anticoagulants; Atherosclerosis; Cystitis; Diagnosis, Differential; Embolism, Cholesterol; Female; Foreign-Body Reaction; Gastrointestinal Hemorrhage; Granuloma; Hematuria; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Ischemic Attack, Transient; Risk Factors; Syndrome; Tuberculosis, Urogenital; Urinary Bladder Neoplasms; Warfarin

Studies suggest that the antitumor effect of bacillus Calmette-Guerin depends on bacillus Calmette-Guerin attachment to fibronectin at fibrin clot formation sites and medications that impact fibrin clot formation may modify bacillus activity. We evaluated the impact of fibrin clot inhibitors on the clinical efficacy of bacillus Calmette-Guerin.. We reviewed the records of 907 consecutive patients treated with bacillus Calmette-Guerin between 1990 and 2006. Time to disease recurrence and progression to surgery were compared in patients who did and did not receive fibrin clot inhibitors by Kaplan-Meier methods and multivariate Cox regression models.. Overall 221 patients (24%) received at least 1 fibrin clot inhibitor, including 170, 34 and 52 on aspirin, clopidogrel and warfarin, respectively. Patients on warfarin had shorter time to progression than patients not on warfarin (median 2.1 vs 9.0 years, p <0.005). Patients on aspirin had a significantly improved 5-year probability of freedom from surgery (66% vs 56%, p = 0.029). On multivariate analysis warfarin was associated with an increased risk of progression to surgery (HR 1.89, 95% CI 1.31, 2.74, p = 0.0007), while aspirin was associated with a decreased risk (HR 0.71, 95% CI 0.52, 0.96, p = 0.024). Warfarin alone was associated with an increased risk of tumor recurrence (HR 1.39, 95% CI 1.00, 1.94, p = 0.047).. These data suggest that the risks of recurrence and progression to surgery after bacillus Calmette-Guerin are higher in patients on warfarin, while the risk of progression is lower in patients on aspirin. These findings may have important treatment implications in patients in whom bacillus Calmette-Guerin is contemplated.

Topics: Adjuvants, Immunologic; Aged; Anticoagulants; Aspirin; BCG Vaccine; Carcinoma, Transitional Cell; Clopidogrel; Drug Interactions; Female; Fibrinolytic Agents; Humans; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Ticlopidine; Urinary Bladder Neoplasms; Warfarin

Topics: Adjuvants, Immunologic; Anticoagulants; Aspirin; BCG Vaccine; Carcinoma, Transitional Cell; Clopidogrel; Drug Interactions; Female; Fibrinolytic Agents; Humans; Male; Platelet Aggregation Inhibitors; Ticlopidine; Urinary Bladder Neoplasms; Warfarin

There has been growing interest in studying the biological effects of certain drugs and their potential to reduce the risk of various cancers. One study reported a decrease in the incidence of urogenital cancers in a trial with patients who received warfarin for treatment of venous thromboembolism, but a limitation to this study of urogenital cancers was the very small number of bladder cancer cases that developed following warfarin therapy. The objective of the present study is to measure the association between warfarin use and bladder cancer. A total of 330 cases with bladder cancer were identified at the James A. Haley Veterans' Administration (VA) Hospital in Tampa, Florida, using a combination of computerized pathology records and inpatient and outpatient diagnoses. Controls were randomly selected from the VA computerized administrative database and 1293 controls were included for analysis. Unconditional logistic regression analysis was performed to assess the risk of bladder cancer after adjusting for age, gender, and cigarette smoking. Among warfarin users, although there was a 27% elevation in risk, it did not differ significantly from nonusers (OR = 1.27, 95% CI = 0.85, 1.89). No duration-response relationship was observed between anticoagulant use and risk of bladder cancer. The results suggest that warfarin does not protect against bladder cancer, at least in male smokers, the highest risk population for bladder cancer.

Topics: Age Factors; Aged; Aged, 80 and over; Analgesia; Anticoagulants; Case-Control Studies; Female; Humans; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk; Sex Factors; Smoking; Urinary Bladder Neoplasms; Warfarin

A 63-year-old Caucasian man had a painless episode of dark-colored urine while taking warfarin 62.5 mg/week for lone atrial fibrillation in the presence of documented stable anticoagulation. Urinalysis revealed microscopic hematuria. Three weeks later, he had an episode of gross, painless hematuria. Thorough evaluation of the upper and lower urinary tract with renal ultrasound, intravenous pyelography, and cystoscopy revealed poorly differentiated, early-stage, transitional cell carcinoma of the bladder. The patient was not aware of any exposure to carcinogens known to predispose to bladder cancer, nor was he a tobacco user. Early identification of the malignancy allowed for aggressive surgical intervention. Although this patient was considered low risk for the development of bladder cancer and was taking anticoagulants, the presence of hematuria was indicative of underlying pathology. Timely and thorough evaluation of hematuria in patients taking anticoagulants is necessary to identify and treat clinically important pathology.

Topics: Anticoagulants; Carcinoma, Transitional Cell; Hematuria; Humans; Male; Middle Aged; Urinary Bladder Neoplasms; Warfarin

Bacillus Calmette-Guérin (BCG) is currently thought to act as a biological immune modifier in effecting antitumour activity. Recent evidence suggests that BCG binding to fibronectin (FN), a tissue glycoprotein, may be a prerequisite step in initiating this response. Drugs inhibiting the availability of exposed FN in the bladder after urothelial disruption may adversely affect the efficacy of BCG. Data are presented of 45 patients with tumour limited to mucosa (pTa) or carcinoma in situ (CIS) given intravesical BCG therapy, with (group 1) or without (group 2) fibrin clot-inhibiting drugs concurrently during treatment. The success rate of 11.1% for group 1 (1/9) patients was significantly less than that of 69.4% for group 2 (25/36), (chi 2 = 7.79, P < 0.01 Fisher's exact test) supporting the suggestion that the concurrent administration of fibrin-clot inhibiting drugs may adversely affect the outcome of BCG therapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; BCG Vaccine; Blood Coagulation; Carcinoma in Situ; Female; Fibronectins; Humans; Male; Middle Aged; Urinary Bladder Neoplasms; Warfarin

After transurethral resection (TUR) of superficial bladder tumors, intravesical instillations with BCG are successfully used to lower the recurrence rate. The mechanism of the antitumor activity of BCG is not completely understood. After TUR, a fibrin clot is formed on the damaged urothelium. Fibronectin (FN) is part of the clot. It has been demonstrated that binding of BCG to the bladder wall is mediated by FN, and therefore FN seems necessary for the antitumor activity of BCG. This binding can be inhibited by fibrin clot inhibitors, like aspirin and coumarin. A reduced efficacy of BCG in patients with superficial bladder cancer using these drugs has been described. We studied 183 patients with superficial bladder cancer, treated with one or two 6-week courses of intravesical BCG instillations. Of the 42 patients that used fibrin clot inhibitors, 13 (31%) experienced a recurrent tumor, as compared to 56 (40%) of 141 patients who did not use these drugs (p = 0.28). The mean time to recurrence was the same in both groups. These results did not depend on the BCG strain used (Tice or RIVM, p = 0.92) and were not influenced by the use of antibiotics against urinary tract infections. We conclude that in our study fibrin clot inhibitors have no adverse effect on the efficacy of BCG therapy for superficial bladder cancer.

Topics: Administration, Intravesical; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; BCG Vaccine; Carcinoma in Situ; Carcinoma, Transitional Cell; Coumarins; Dipyridamole; Fibrin; Humans; Male; Random Allocation; Urinary Bladder Neoplasms; Warfarin

Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.

Topics: Administration, Intravesical; BCG Vaccine; Carcinoma in Situ; Carcinoma, Transitional Cell; Fibrin; Fibronectins; Humans; Neoplasm Recurrence, Local; Platelet Aggregation Inhibitors; Retrospective Studies; Urinary Bladder Neoplasms; Warfarin

Twelve resections of prostate and 1 extensive bladder tumour were performed in patients on long-term anticoagulation without withdrawal of warfarin therapy. The mean preoperative prothrombin index was 2.3. Four patients required blood transfusion. There were no major complications. The effects of surgery and infusion of fresh frozen plasma (FFP) on the level of anticoagulation were monitored. FFP reduced the prothrombin index by 0.25/unit. Transurethral resection can be carried out safely by an experienced urologist on patients anticoagulated with warfarin, reducing the risk of serious thromboembolic complications associated with withdrawal of anticoagulation.

Topics: Aged; Blood Transfusion; Hemoglobins; Humans; Male; Middle Aged; Plasma; Postoperative Complications; Prostatectomy; Prothrombin; Urinary Bladder Neoplasms; Warfarin