warfarin and Prostatic-Neoplasms

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case-control study using Danish demographic and health data registries and summarized existing evidence in a meta-analysis. The case-control study included all Danish men aged 40-85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age-matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long-term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95-1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97-1.10). We observed no dose-response relationship (e.g. OR for 5-10 years of use, 1.06 95% CI, 0.97-1.16). We included 8 studies in the meta-analysis reporting effect estimates from 0.51 (95% CI, 0.23-1.13) to 1.10 (95% CI, 0.94-1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70-1.05) was obtained; however, there was considerable across-study heterogeneity (I

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Denmark; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Logistic Models; Male; Middle Aged; Odds Ratio; Phenprocoumon; Prostatic Neoplasms; Registries; Vitamin K; Warfarin

Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile. Metastatic prostate cancer is a disease of older men, a population with an increased incidence of medical comorbidities warranting anticoagulation. Prostate cancer itself, along with some of its therapies, is also prothrombotic. Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians. In this review, we describe the potential interactions between enzalutamide and various anticoagulants, and suggest management paradigms based on the current body of knowledge for patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves.

Topics: Androgen Receptor Antagonists; Anticoagulants; Atrial Fibrillation; Benzamides; Dabigatran; Drug Interactions; Embolism; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Trapeziometacarpal osteoarthritis is associated with more pain and restrictions than other hand osteoarthritis due to the functional importance of the thumb. While the effectiveness of surgical and pharmacological interventions has been widely examined, there is a lack of specific evidence about conservative non-pharmacological trapeziometacarpal osteoarthritis therapies. The objective of this systematic review was to provide evidence-based knowledge on the effectiveness of physiotherapy and occupational therapy on pain, function and quality of life.. A literature search of Medline, CINAHL, PEDro, OTseeker, EMB Dare Cochrane Database of Systematic Reviews and Cochrane CENTRAL was performed. Randomized and quasi-randomized controlled trials and corresponding systematic reviews, observational studies, pragmatic studies and case-control studies were included. The risk of bias was assessed.. Physical and occupational therapy-related interventions, especially multimodal interventions, seem to be effective to treat pain in patients with trapeziometacarpal osteoarthritis. Pre-fabricated neoprene splints and custom-made thermoplastic splints may reduce pain equally. Single interventions seem not to be effective. Significant evidence for effectiveness on function and quality of life could not be found.. The sole Na. The SUV. Genetic variants of

Topics: AC133 Antigen; Acenaphthenes; Acer; Acrosome Reaction; Adult; Agaricales; Aged; Aged, 80 and over; Animals; Animals, Zoo; Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Antimanic Agents; Antioxidants; Aortic Valve; Area Under Curve; ATP Binding Cassette Transporter, Subfamily G, Member 2; Bacillus; Bacterial Toxins; Bacterial Typing Techniques; Base Composition; Beauveria; Binge Drinking; Biomarkers; Bipolar Disorder; Blood Coagulation; Blotting, Western; Brachytherapy; Calcium Channels, L-Type; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Wall; Cells, Cultured; Ceramics; Chi-Square Distribution; China; Chlorophyll; Chlorophyta; Chloroplasts; Cholesterol, HDL; Chromatography, High Pressure Liquid; Chromobacterium; Clostridium perfringens; Clozapine; Constriction, Pathologic; Coronary Artery Bypass; Corticotropin-Releasing Hormone; Cross-Sectional Studies; Cytochrome P-450 CYP2C9; Dental Porcelain; Dental Restoration Failure; Dental Stress Analysis; Designer Drugs; Diaminopimelic Acid; DNA Fingerprinting; DNA, Bacterial; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Dosage Calculations; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Elasticity Imaging Techniques; Epsilonproteobacteria; Equipment Design; Ericaceae; Excitatory Amino Acid Antagonists; False Negative Reactions; Fatty Acids; Female; Food Analysis; Fresh Water; Gene Expression Regulation, Neoplastic; Glutathione; Graft Occlusion, Vascular; Heart Valve Prosthesis Implantation; Heart Ventricles; HEK293 Cells; Hemolymph; Humans; Hyaluronan Receptors; Hydrogen Peroxide; Hydrothermal Vents; Indoles; Inflammation Mediators; Inhibitory Concentration 50; Insecta; International Normalized Ratio; Isotope Labeling; Itraconazole; Kidney; Kinetics; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lamotrigine; Lanthanoid Series Elements; Limit of Detection; Linear Models; Lipid Peroxidation; Liver; Liver Cirrhosis; Logistic Models; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Malondialdehyde; Mediastinum; Metronidazole; Mice; Mice, Nude; Mice, Transgenic; Microbial Sensitivity Tests; Microscopy, Fluorescence; Middle Aged; Monocytes; Monomeric GTP-Binding Proteins; Multivariate Analysis; Myocytes, Cardiac; Neoplasm Staging; Neoplastic Stem Cells; Neural Pathways; Nitrates; Nucleic Acid Hybridization; Octamer Transcription Factor-3; Odds Ratio; Oxidation-Reduction; Oxidative Stress; Peptidoglycan; Phantoms, Imaging; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Phospholipids; Photolysis; Photosynthesis; Phylogeny; Plant Extracts; Polychaeta; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Preoperative Care; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyrimidines; Pyrroles; Quorum Sensing; Radiology, Interventional; Radiopharmaceuticals; Radiotherapy Dosage; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Reference Values; Regression Analysis; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Rhizosphere; Risk Factors; RNA, Ribosomal, 16S; ROC Curve; Rutin; Saphenous Vein; Seawater; Selenium; Semen Preservation; Sensitivity and Specificity; Septal Nuclei; Sequence Analysis, DNA; Serum Albumin; Serum Albumin, Human; Shear Strength; Sodium Pertechnetate Tc 99m; Sodium-Hydrogen Exchangers; Soil Microbiology; SOXB1 Transcription Factors; Spain; Species Specificity; Sperm Motility; Spermatozoa; Spheroids, Cellular; Spores, Fungal; Stroke; Superoxide Dismutase; Swine; Tandem Mass Spectrometry; Technetium Compounds; Technetium Tc 99m Exametazime; Technetium Tc 99m Sestamibi; Temperature; Thiosulfates; Thrombosis; Thyroid Neoplasms; Transducers; Transfection; Transplantation, Heterologous; Treatment Outcome; Triazines; Tumor Burden; Urocortins; Uterine Cervical Neoplasms; Vacuoles; Valproic Acid; Ventral Tegmental Area; Vitamin K 2; Vitamin K Epoxide Reductases; Warfarin; Water Microbiology; Young Adult

Increased sensitivity to warfarin anticoagulation is usually attributed to liver disease, vitamin K deficiency, or drug interactions. We describe a patient with unexplained sensitivity to warfarin and mildly elevated prostate-specific antigen levels in whom subsequent developments indicated that warfarin sensitivity was the first manifestation of occult prostatic cancer. A review of all published cases of coagulopathy associated with cancer of the prostate shows that, unlike other solid tumors with secondary disseminated intravascular coagulation (DIC), in prostate cancer increased bleeding is more common than thrombotic phenomena. Chronic DIC due to occult prostate cancer should be included in the differential diagnosis of excessive prothrombin time prolongation in patients receiving anticoagulants.

Topics: Diagnosis, Differential; Disseminated Intravascular Coagulation; Hemorrhage; Humans; Male; Middle Aged; Neoplasms, Unknown Primary; Prostatic Neoplasms; Prothrombin Time; Sensitivity and Specificity; Warfarin

Anticoagulants may reduce mortality of cancer patients, though the evidence remains controversial. We studied the association between different anticoagulants and cancer death.. All anticoagulant use during 1995-2015 was analyzed among 75,336 men in the Finnish Randomized Study of Screening for Prostate Cancer. Men with prevalent cancer were excluded. Multivariable Cox regression was performed to compare risk of death from any cancer and disease-specific death from 9 specific cancer types between (1) anticoagulant users overall and (2) warfarin users compared to anticoagulant non-users and (3) warfarin or (4) low-molecular-weight heparins (LMWH) compared to users of other anticoagulants. Medication use was analyzed as time-dependent variable to minimize immortal time bias. 1-, 2- and 3-year lag-time analyses were performed.. During a median follow-up of 17.2 years, a total of 27,233 men died of whom 8033 with cancer as the primary cause of death. In total, 32,628 men (43%) used anticoagulants. Any anticoagulant use was associated with an increased risk of cancer death (HR = 2.50, 95% CI 2.37-2.64) compared to non-users. Risk was similar independent of the amount, duration, or intensity of use. The risk increase was observed both among warfarin and LMWH users, although not as strong in warfarin users. Additionally, cancer-specific risks of death were similar to overall cancer mortality in all anticoagulant categories.. Our study does not support reduced cancer mortality among anticoagulant users. Future studies on drug use and cancer mortality should be adjusted for anticoagulants as they are associated with significantly higher risk of cancer death.

Topics: Aged; Anticoagulants; Early Detection of Cancer; Finland; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Warfarin

Anticoagulants, especially vitamin K antagonists (VKAs) such as warfarin, have been hypothesized to have antitumor properties, and use of VKAs has been associated with a lower prostate cancer (PCa) risk. This study estimated PCa risk among users of warfarin and other anticoagulants.. All anticoagulant use among 78,615 men during 1995-2009 was analyzed. Cox regression, adjusted for age, screening trial arm and use of other medications, with medication use as a time-dependent variable, was used to estimate PCa risk overall, and by tumor grade and stage.. In total, 6537 men were diagnosed with PCa during 1995-2009 (1210 among warfarin users). Compared to non-users, warfarin use was associated with an increased risk of PCa [multivariable-adjusted hazard ratio (HR) = 1.11, 95% confidence interval (CI) 1.01-1.22]. This was limited to short-term, low-dose use, and was not observed in long-term use. A similar overall risk increase was observed for Gleason grade 7-10 PCa. Low-dose, short-term use of warfarin was associated with an increased risk of metastatic PCa. However, the increase in risk vanished with continued use. Compared to other anticoagulants, low-dose use of warfarin was associated with a slightly elevated overall PCa risk (HR = 1.19, 95% CI 1.00-1.43). The increase in risk disappeared in long-term, high-dose use.. This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users. A similar risk of PCa was found among warfarin users and the general population, and no difference in risk was found between warfarin and other anticoagulants.

Topics: Aged; Anticoagulants; Early Detection of Cancer; Finland; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Prostatic Neoplasms; Risk Factors; Time Factors; Warfarin

In the present study we aimed to demonstrate the efficacy of short-term pretreatment with finasteride in patients undergoing transurethral resection of the prostate (TUR-P). For this purpose 40 patients with BPH, who were candidates for TUR-P, were randomized into two groups. The first group (n=20) received 5 mg finasteride/day for 4 weeks prior to surgery and the second group (n=20) remained as the control. Patients who underwent prior prostate or urethral surgery and had a diagnosis of prostate cancer or chronic renal failure, patients who received finasteride, aspirin, coumadin or similar anticoagulant drugs prior to surgery and patients who had capsule perforations or open sinuses during the surgery were excluded from the study. All patients had a normal digital rectal examination and PSA values less than 4 ng/ml. As we look at the results there was no statistically significant difference between the finasteride group and control group regarding age, IPSS, PSA, prostate volumes, preoperative serum hemoglobin, hematocrit values and mean operating times and used irrigating fluids. The total amount of bleeding and bleeding per gram resected tissue were significantly lower in the finasteride group regardless of prostate volume. Furthermore the decrease in the hemoglobin and hematocrit values was higher in the control group. As a conclusion four weeks of finasteride pretreatment provided a significant decrease in peroperative bleeding regardless of prostate volume without any major side effects.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Finasteride; Hemoglobins; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Renal Insufficiency; Risk; Time Factors; Transurethral Resection of Prostate; Urethra; Warfarin

To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC).. A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered. At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES.. Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines > or = 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots.. PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgens; Anticoagulants; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Complementary Therapies; Cross-Over Studies; Diethylstilbestrol; Disease Progression; Drug Contamination; Drugs, Chinese Herbal; Estradiol Congeners; Ethinyl Estradiol; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Reproducibility of Results; Treatment Outcome; Warfarin

The purpose of The Cancer and Leukemia Group B (CALGB) 90203 trial is to determine which of 2 treatment strategies is superior in treating men with high-risk, clinically localized adenocarcinoma of the prostate (stage T1 to T3a NX M0), defined as a predicted probability < or =60% of remaining free from disease recurrence for 5 years after surgery. Patients with a > or =10-year life expectancy will be randomized to either radical prostatectomy (RP) alone versus estramustine and docetaxel before RP. Participants will be excluded if they have received prior therapy for prostate cancer (except transurethral resection of the prostate) or are judged not to be appropriate candidates for RP. Eligible patients will be stratified according to their predicted probability of remaining free from disease recurrence at 5 years after surgery (0% to 20%, 21% to 40%, and 41% to 60%) and randomized. Neoadjuvant chemotherapy will be 6 cycles (1 cycle = 21 days) of estramustine (280 mg tid, days 1 to 5) and docetaxel (70 mg/m2 on day 2). Warfarin (2 mg/day orally) will be given for prophylaxis against deep venous thrombosis. Bilateral pelvic lymph node dissection and RP will be performed within 60 days of registration/randomization for men randomized to the surgery-alone arm. For men randomized to receive preoperative chemotherapy, the surgical procedure will be performed within 60 days of completion of chemotherapy. Patients will be monitored with history review, physical examination, and serum prostate-specific antigen (PSA) levels every 3 months for the first 3 years after surgery, every 6 months for the next 3 years, and annually thereafter. Biochemical disease recurrence will be defined as a serum PSA level >0.4 ng/mL on 2 consecutive occasions > or =3 months apart after RP. The time of biochemical failure is measured from the date of randomization to the time of the first PSA level <0.4 ng/mL that is confirmed on the second serial PSA. The primary study end point is to determine if early systemic treatment with neoadjuvant estramustine and docetaxel before RP in patients with high-risk prostate cancer will decrease 5-year recurrence rates when compared with RP alone. Secondary outcomes will include (1) the safety and tolerability of neoadjuvant estramustine and docetaxel before RP; (2) the impact of this neoadjuvant strategy on pathologic tumor stage, including lymph node and surgical margin status; (3) time to clinically apparent disease recurrence; and (4) overall sur

Topics: Adenocarcinoma; Anticoagulants; Clinical Trials, Phase III as Topic; Disease-Free Survival; Docetaxel; Estramustine; Feasibility Studies; Humans; Lymph Node Excision; Male; Multicenter Studies as Topic; Neoadjuvant Therapy; Patient Selection; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk; Taxoids; Thromboembolism; Treatment Outcome; Warfarin

Potential interaction between suramin and warfarin was evaluated when coadministered to patients with cancer. Thirteen men with advanced hormone-refractory prostate cancer were initially stabilized with warfarin to a prothrombin time (PT) of 2 +/- 0.2 International Normalized Ratio (INR) during a lead-in period of 4 weeks. A baseline daily warfarin dose was established, and treatment with suramin plus hydrocortisone was then started. The effect of suramin on the anticoagulant activity of warfarin was assessed in each patient by comparing his baseline warfarin dose with average daily doses required to maintain the same INR level over each of the initial 6 weeks of a 12-week course of suramin treatment. The average daily dose of warfarin required to maintain PT at 2 +/- 0.2 INR decreased from a baseline value of 4.2 to between 3.4 and 4.0 during the 6 weeks of suramin plus warfarin treatment. Despite failing to demonstrate equivalence applying a 90% confidence interval approach, required reductions in warfarin dose were clinically minor and the combination was well tolerated. Based on these results, the eligibility criteria for a large ongoing randomized study were amended to allow entry of men receiving warfarin therapy. This interaction study, together with experience gained in a larger trial setting, has confirmed that warfarin and suramin can be safely coadministered, provided that coagulation status is appropriately monitored.

Topics: Anti-Inflammatory Agents; Anticoagulants; Antineoplastic Agents; Blood Coagulation; Drug Interactions; Humans; Hydrocortisone; International Normalized Ratio; Male; Prostatic Neoplasms; Prothrombin Time; Suramin; Warfarin

This prospective study was designed to determine the safety and efficacy of low dose warfarin in the prophylaxis of thromboembolic disease in patients receiving diethylstilbestrol therapy for advanced prostatic carcinoma.. Patients were stratified to receive 1 mg. warfarin and 3 mg. diethyl-stilbestrol daily (younger than 65 years) or 1 mg. warfarin and 2 mg. diethylstilbestrol daily (older than 65 years). Efficacy of therapy was determined by measuring serum prostate specific antigen (PSA), testosterone and international normalized ratio. Patients were monitored for signs and symptoms of hypercoagulability, bleeding and fluid retention.. Of the 32 patients enrolled in the study 6 were lost to followup and 4 died of advanced prostatic disease (2), pneumonia (1) and myocardial infarction (1). Patients were followed for a total of 272 months. Median patient age was 73.5 years. Median pretreatment serum PSA was 95.4 microg./l. with a median pretreatment serum testosterone value of 12.9 nmol./l. After 3 months of therapy the median serum PSA was 1.5 microg./l. with a median serum testosterone value of 0.1 nmol./l. Adverse events were common. In 10 patients (31%) clinically significant proximal deep venous thrombosis developed, 2 (7%) had a myocardial infarction, 2 (7%) had transient ischemic attacks, 1 had new prolonged chest pain and 1 had marked dyspnea due to congestive heart failure. Clotting factor assays performed in a subset of 7 patients demonstrated that factor VII failed to normalize.. The significant thromboembolic toxicity associated with the hypercoagulable state induced by diethylstilbestrol is not reduced by fixed low dose warfarin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Thromboembolism; Warfarin

VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.

Topics: Adenocarcinoma; Blood Coagulation; Carcinoma, Small Cell; Clinical Trials as Topic; Colonic Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Prostatic Neoplasms; Random Allocation; Warfarin

To assess the impact of continued perioperative anticoagulant drug administration on bleeding and complications in patients undergoing robot-assisted radical prostatectomy.. Between January 2014 and January 2020, 620 patients with prostate cancer underwent robot-assisted radical prostatectomies and were retrospectively reviewed. Fourteen patients who discontinued antithrombotic therapy were excluded. Among the 606 included patients, 31 continued anticoagulant therapy during the perioperative phase (anticoagulant group). The anticoagulant group outcomes were compared with those of patients who continued clopidogrel and prasugrel (thienopyridine group = 13), aspirin monotherapy (aspirin group = 61), and no chronic antithrombotic agent (control group = 501). The primary outcome was the incidence of bleeding complications requiring transfusion, additional intervention, or readmission. Secondary outcomes were the incidence of thrombotic complications, estimated blood loss, and overall complication rates.. Among the 31 patients in the anticoagulant group, 20 (65%) used directed oral anticoagulants, 11 (35%) used warfarin, and 5 used combined aspirin. Only 1 (3%) patient in the anticoagulant group required postoperative transfusion, and none required additional interventions or readmission. No significant differences were detected between the anticoagulant and other groups (anticoagulant vs thienopyridine, aspirin, and control groups) regarding bleeding complications (3% vs 8%, P = .51; 0%, P = .34; 0.4%, P = .17, respectively), thrombotic complications (3% vs 0%, P = .70; 2%, P = .56; 0.2%, P = .11, respectively), estimated blood loss (200 vs 100 mL, P = .63; 175 mL, P = .64; 165 mL, P = .74, respectively), or other high-grade complications (6% vs 0%, P = .49; 2%, P = .26; 3%, P = .24, respectively).. Perioperative continuation of anticoagulant use is feasible for patients undergoing robot-assisted radical prostatectomy.

Topics: Aged; Anticoagulants; Antithrombins; Aspirin; Blood Transfusion; Clopidogrel; Continuity of Patient Care; Humans; Incidence; Male; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Prasugrel Hydrochloride; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Robotic Surgical Procedures; Thrombosis; Warfarin

Warfarin treatment has been associated with lower risks of prostate cancer, without a specified biological mechanism. Our study tested the hypothesis that reluctance to perform prostate biopsies in men who are anticoagulated results in lower rates of diagnosed prostate cancer, leading to an apparent protective effect. Rates of prostate biopsies have decreased from 2000 to 2015, allowing calendar time to be used as the intervention. In a national population-based sample of elderly men, our study compared trends in prostate cancer incidence between 17,815 men treated with chronic oral anticoagulation for prosthetic heart valve thromboprophylaxis and a general population comparison group of 356,300 men. Cancer events were based on administrative claims. Among men enrolled in 2000-2001 and followed through 2015, prostate cancer incidence was substantially lower in the anticoagulation group (adjusted incidence rate ratio [IRR] 0.70; 95% confidence interval [CI] 0.62-0.80). Incidence decreased over time in the general population group to approach that of the anticoagulation group among men enrolled in 2008-2010 (IRR 0.86; 95% CI 0.71-1.04). Rates of prostate biopsies also decreased over time in the general population group to match the rate in the anticoagulation group. These results indicate that the apparent protective effect of warfarin treatment on the risk of prostate cancer is likely the result of detection bias from lower rates of biopsies among men who are anticoagulated.

Topics: Aged; Anticoagulants; Bias; Biopsy; Coronary Thrombosis; Heart Valve Prosthesis; Humans; Male; Prostatic Neoplasms; Retrospective Studies; Venous Thromboembolism; Warfarin

Flutamide, a chemotherapeutic agent for prostate cancer, is known to enhance warfarin anticoagulation. However, not much is known about its pharmaceutical interaction. We herein report the case of a patient with an implanted pacemaker for atrial fibrillation with bradycardia who was on warfarin. This patient presented with deterioration of hematuria, gingival, ear, and subcutaneous bleeding. The prothrombin time-international normalized ratio was extremely elevated after starting flutamide to treat progression of prostate cancer. Fatal bleeding complications were able to be prevented by the immediate administration of prothrombin complex concentrate, but the effect of flutamide on warfarin was prolonged for about two more weeks after the withdrawal of flutamide.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Factors; Drug Synergism; Flutamide; Hemorrhage; Humans; International Normalized Ratio; Male; Pacemaker, Artificial; Prostatic Neoplasms; Prothrombin Time; Warfarin

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230-771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78-3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07-2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83-1.42). Relative outcomes with higher-dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31-1.15] for malignancy versus HR , 0.89 [95% CI, 0.76-1.05] for no malignancy; interaction P=0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69-1.40] for malignancy versus HR , 0.79 [95% CI, 0.69-1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher-dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31-0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88-1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Embolism; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Hemorrhage; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Prostatic Neoplasms; Pyridines; Stroke; Thiazoles; Warfarin

Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease.. The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias.. In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death.. We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

Topics: Aged; Anticoagulants; Finland; Humans; Insurance, Health, Reimbursement; Male; Prostatic Neoplasms; Registries; Risk Factors; Venous Thromboembolism; Warfarin

Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed in other cancers. We sought to determine if the target of warfarin, vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene is associated with prostate cancer risk.. The expression of VKOR was quantified by immunohistochemistry in an institutional series of 54 radical prostatectomy samples and metastatic biopsies, as well as in 40 other cancers and matched benign tissues on a tissue microarray. Genotyping of SNP rs2359612 was performed in a prospective series of 57 patients.. VKOR is highly expressed in benign human prostate epithelial cells but is not expressed or expressed at very low levels in cancerous cells. This expression pattern is unique to prostate cancer. Additionally, the proportion of the carrier C allele of rs2359612 in the patients with prostate cancer was significantly higher than in the population, suggesting an association between this allele and the risk of having a diagnosis of prostate cancer.. The expression of VKOR in benign prostate epithelial cells, along with the association between a functional VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating the effect of warfarin on prostate cancer risk. Larger multi-institutional cohort studies are warranted, as are molecular studies on the role of VKOR in prostate cancer development.

Topics: Aged; Alleles; Anticoagulants; Biopsy; Genotyping Techniques; Humans; Immunohistochemistry; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; Prostate; Prostatectomy; Prostatic Neoplasms; Tissue Array Analysis; Vitamin K Epoxide Reductases; Warfarin

Long-term use of warfarin has been shown to be associated with a reduced risk of prostate cancer. Warfarin belongs to the vitamin K antagonist class of anticoagulants, which inhibit vitamin K epoxide reductase (VKOR). The vitamin K cycle is primarily known for its role in γ-carboxylation, a rare post-translational modification important in blood coagulation. Here we show that warfarin inhibits the transcriptional activity of the androgen receptor (AR), an important driver of prostate cancer development and progression. Warfarin treatment or knockdown of its target VKOR inhibits the activity of AR both in cell lines and in mouse prostate tissue. We demonstrate that AR can be γ-carboxylated, and mapped the γ-carboxylation to glutamate residue 2 (E2) using mass spectrometry. However, mutation of E2 and other glutamates on AR failed to suppress the effects of warfarin on AR suggesting that inhibition of AR is γ-carboxylation independent. To identify pathways upstream of AR signaling that are affected by warfarin, we performed RNA-seq on prostates of warfarin-treated mice. We found that warfarin inhibited peroxisome proliferator-activated receptor gamma (PPARγ) signaling, which in turn, inhibited AR signaling. Although warfarin is unfit for use as a chemopreventative due to its anticoagulatory effects, our data suggest that its ability to reduce prostate cancer risk is independent of its anticoagulation properties. Furthermore, our data show that warfarin inhibits PPARγ and AR signaling, which suggests that inhibition of these pathways could be used to reduce the risk of developing prostate cancer.

Topics: Animals; Anticoagulants; Antineoplastic Agents; Cell Line, Tumor; Humans; Immunohistochemistry; Immunoprecipitation; Male; Mass Spectrometry; Mice; Mice, Nude; Mutagenesis, Site-Directed; Polymerase Chain Reaction; PPAR gamma; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction; Vitamin K Epoxide Reductases; Warfarin

Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.. Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.. Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.. There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Breast Neoplasms; Cohort Studies; Colorectal Neoplasms; Databases, Factual; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Proportional Hazards Models; Prostatic Neoplasms; Warfarin

Topics: Anticoagulants; Humans; Male; Prostatic Neoplasms; Pulmonary Embolism; Venous Thromboembolism; Warfarin; Watchful Waiting

Topics: Anticoagulants; Humans; Male; Prostatic Neoplasms; Pulmonary Embolism; Venous Thromboembolism; Warfarin; Watchful Waiting

High-risk prostate cancer (PC) has poor outcomes due to therapeutic resistance to conventional treatments, which include prostatectomy, radiation, and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in PC patients. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit when administered with radiotherapy in patients with high-risk PC.. Analysis was performed on 74 high-risk PC patients who were treated with radiotherapy from 2005 to 2008 at UT Southwestern. Of these patients, 43 were on AC including aspirin (95.6%), clopidogrel (17.8%), warfarin (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS, distant metastasis, and toxicity were analyzed.. Median follow-up was 56.6 mo for all patients. For patients taking any AC compared with no AC, there was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF was 84% vs. 65% (P = 0.008). Aspirin use was also associated with reduced rates of distant metastases at 5 years (12.2% vs. 26.7%, P = 0.039). On subset analysis of patients with Gleason score (GS) 9-10 histology, aspirin resulted in improved 5-year OS (88% vs. 37%, P = 0.032), which remained significant on multivariable analysis (P<0.05).. AC use was associated with a FFBF benefit in high-risk PC which translated into an OS benefit in the highest risk PC patients with GS 9-10, who are most likely to experience mortality from PC. This hypothesis-generating result suggests AC use may represent an opportunity to augment current therapy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Chemoradiotherapy; Clopidogrel; Drug Screening Assays, Antitumor; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Retrospective Studies; Risk; Ticlopidine; Treatment Outcome; Warfarin

To evaluate the risk of late rectal bleeding and its association with the timing and type of anticoagulation use in patients receiving dose-escalated radiation therapy (RT) (≥ 7,560 cGy) for prostate cancer.. Between 2003-2010, 465 patients were treated at our Institution with dose-escalated RT and included in this analysis. Patients were placed into the following categories: no anticoagulation use, aspirin during RT, clopidogrel/warfarin during RT, aspirin after completion of RT, clopidogrel/warfarin after completion of RT.. The overall bleeding rate was 7.5%. For those on aspirin during RT, the 4-year freedom from rectal bleeding (FFBS) rate was 91%, compared to 94.7% for patients who were never on anticoagulation (p=0.16). For those on warfarin/clopidogrel during RT the 4-year FFBS rate was 78.2%, compared to 94.7% in those never on anticoagulation (p<0.001). On multivariate analysis, use of warfarin/clopidogrel during radiation treatment were strongly associated with an increased risk of rectal bleeding (multivariate HR=4.84, 95% CI=1.84-12.68, p=0.001). However, initiation of anticoagulation after completion of radiation treatment did not significantly increase the risk of rectal bleeding (multivariate HR=0.78, 95% CI=0.21-2.91, p=0.71).. The use of clopidogrel or warfarin during radiation is associated with significantly increased risk of rectal bleeding. However, initiation of these medications after completion of radiation does not appear to impact such risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiation Injuries; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Rectum; Retrospective Studies; Risk; Telangiectasis; Ticlopidine; Warfarin

Recent evidence suggests that warfarin use may be associated with a reduced risk of prostate cancer. We aimed to determine whether exposure to warfarin is also associated with a reduced risk of prostate cancer death.. A nested case-control study was conducted within a population-based cohort of 10,012 men aged ≥50 years with newly diagnosed prostate cancer between 1985 and 2002 and with no history of cancer since 1970 using the linked records of Saskatchewan Health and Saskatchewan Cancer Agency registry. We identified 2,309 cases who died of prostate cancer during follow-up. For each case, one control alive at the time of the case's death and matched for length of follow-up (±6 months) was randomly selected. Prescription counts were used to define warfarin exposure. Multivariate conditional logistic regression analysis was used to calculate the adjusted incidence rates of prostate cancer death in relation to warfarin use while adjusting for confounding by age, year of prostate cancer diagnosis, clinical stage and grade of cancer at diagnosis, Chronic Disease Score, and use of warfarin before diagnosis.. Ever use of warfarin following a diagnosis of prostate cancer was associated with an adjusted rate ratio of 1.44 (95 % confidence interval (CI) 1.33-1.84) for prostate cancer death. The adjusted rate ratio with one-year use of warfarin was 1.77 (95 % CI 1.25-2.50) compared to never use. The unadjusted rate ratio with five-year use of warfarin was 0.64 (95 % CI 0.40-1.00) and remained unchanged in the adjusted analysis (0.65, 95 % CI 0.37-1.13), although no longer statistically significant.. Our study does not provide conclusive evidence for a protective effect of long-term warfarin on prostate cancer-specific mortality. Moreover, short-term warfarin use may be associated with an increased risk of prostate cancer death.

Topics: Aged; Case-Control Studies; Cohort Studies; Humans; Male; Middle Aged; Pharmacoepidemiology; Prostatic Neoplasms; Risk Factors; Saskatchewan; Warfarin

Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed.. Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain.. In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified.. Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.

Topics: Aged; Anticoagulants; Biomarkers, Tumor; Combined Modality Therapy; Feasibility Studies; Fiducial Markers; Gastrointestinal Hemorrhage; Gold; Humans; Male; Middle Aged; Pain Measurement; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Rectal Diseases; Salvage Therapy; Ultrasonography, Interventional; Warfarin

Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer.. This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer-specific mortality (PCSM) was compared between the AC and non-AC groups.. After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02).. AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Chemoprevention; Clopidogrel; Enoxaparin; Humans; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Risk; Ticlopidine; Warfarin

To determine whether patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with increased sampling numbers are more likely to experience bleeding complications and whether warfarin or low-dose aspirin are independent risk factors.. 930 consecutive patients with suspected prostatic cancer were followed up after biopsy. Warfarin/low-dose aspirin was not stopped prior to the procedure. An eight to 10 sample regime TRUS-guided prostate biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications.. 902 patients returned completed questionnaires. 579 (64.2%) underwent eight core biopsies, 47 (5.2%) underwent nine, and 276 (30.6%) underwent 10. 68 were taking warfarin [mean international normalized ratio (INR) = 2.5], 216 were taking low-dose aspirin, one was taking both, and 617 were taking neither. 27.9% of those on warfarin and 33.8% of those on aspirin experienced haematuria. 37% of those on no blood-thinning medication experienced haematuria. 13.2% of those on warfarin and 14.4% of those on aspirin experienced rectal bleeding. 11.5% of those on no blood-thinning medication experienced rectal bleeding. 7.4% of those on warfarin and 12% of those on aspirin experienced haematospermia. 13.8% of those on neither experienced haematospermia. Regression analysis showed a significant association between increasing sampling number and occurrence of all bleeding complication types. There was no significant association between minor bleeding complications and warfarin use; however, there was a significant association between minor bleeding complications and low-dose aspirin use. There was no severe bleeding complication.. There is an increased risk of bleeding complications following TRUS-guided prostate biopsy with increased sampling numbers but these are minor. There is also an increased risk with low-dose aspirin use; however, there is no increased risk of bleeding complications with warfarin use. These results suggest that up to 10 cores during prostate biopsy remains acceptable safe practice and cessation of warfarin and low-dose aspirin is usually not necessary.

Topics: Aged; Anticoagulants; Aspirin; Biopsy; Hemorrhage; Humans; Male; Prospective Studies; Prostatic Neoplasms; Regression Analysis; Risk Factors; Surveys and Questionnaires; Ultrasonography, Interventional; Ultrasound, High-Intensity Focused, Transrectal; Warfarin

What's known on the subject? and What does the study add? There is controversy over the use of anti-platelet and anti-coagulant drugs in men undergoing TURP with contradictory evidence on the effect of the drugs on bleeding following the operation, particularly for aspirin. If anti-platelet or anti-coagulant drugs are not stopped for TURP, there is an unacceptable burden of bleeding. If the drugs are stopped there is an unacceptable rate of cardiovascular events.. • To determine the morbidity associated with perioperative management of antiplatelet (AP) or anticoagulant (AC) medication and transurethral prostatectomy.. • A retrospective review was performed on 163 consecutive patients undergoing transurethural prostatectomy. • Patients were grouped according to the perioperative management of AP and AC medications: control patients not prescribed any AP/AC drugs (group 1), those on AP/AC who had ceased them perioperatively (group 2) and those whose AP/AC were continued (group 3). • Warfarin was withheld perioperatively for all patients. • Morbidity associated with increased blood loss and cardiovascular or cerebrovascular events was recorded and differences were analysed with SPSS version 16 software.. • There was a statistically significant increase in bleeding-associated morbidity in group 2 (13/65) and group 3 (6/7) compared with the controls (9/91) (P < 0.01). • Cardiovascular and cerebrovascular events were only seen in group 2 (6/65), statistically significantly higher than the event rate in the other groups (P ≤ 0.01). • All cardiovascular or cerebrovascular events occurred in patients prescribed these medications for secondary prevention.. • Patients taking AP or AC medications have a higher rate of perioperative bleeding compared with those who are not taking any. • However, for patients prescribed AP or AC medication for secondary prevention, withholding these medications results in an increased rate of cardiovascular and cerebrovascular complications. • Careful consideration of the risks and other management options should be undertaken before performing transurethural prostatectomy in this high risk group of patients.

Topics: Aged; Anticoagulants; Aspirin; Blood Loss, Surgical; Cardiovascular Diseases; Case-Control Studies; Cerebrovascular Disorders; Humans; Male; Perioperative Care; Platelet Aggregation Inhibitors; Prostatic Hyperplasia; Prostatic Neoplasms; Retrospective Studies; Transurethral Resection of Prostate; Warfarin

To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy.. The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits.. With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >or=70 Gy was <10% or the rectum receiving >or=50 Gy was <50%.. Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anticoagulants; Clopidogrel; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Rectum; Severity of Illness Index; Ticlopidine; Transurethral Resection of Prostate; Urologic Diseases; Warfarin

Prolonged warfarin use may decrease the risk of prostate cancer. We aimed to assess the effect of warfarin on histological grade and clinical stage of prostate cancer at diagnosis.. We carried out a retrospective population-based cohort study of men older than 50 years of age diagnosed with prostate cancer between 1985 and 2002 and registered with the Saskatchewan Cancer Registry. We compared a composite score of histological grade and clinical stage of prostate cancer at diagnosis according to warfarin use in the 5 years preceding the diagnosis of prostate cancer.. Compared with non-users, men with at least 2 years of cumulative warfarin use in the 5 year period preceding the diagnosis of prostate cancer were at a lower risk of a poor prognosis composite score at the time of their prostate cancer diagnosis (OR 0.40, 95%CI (0.19-0.83)), and when intermediate and poor prognosis scores were combined, a similar estimate of association was observed (OR 0.55, 95%CI (0.33-0.91)), adjusted for age at diagnosis and year of diagnosis. However, an increased risk of poor prognosis disease was observed with 4 years of cumulative warfarin use compared to never use (OR 2.2, 95%CI (1.03-4.81)).. There is a suggestion that at least 2 years of warfarin use is associated with a more favourable prognosis but that extended duration of use beyond 2 years may be associated with poor prognosis disease. Further investigation with a more complete assessment of confounders and that addresses potential detection biases is warranted.

Topics: Anticoagulants; Cohort Studies; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Humans; Male; Pharmacoepidemiology; Prognosis; Prostatic Neoplasms; Registries; Retrospective Studies; Risk; Saskatchewan; Time Factors; Warfarin

An important limitation of Saskatchewan Drug Plan is the incomplete prescription data during an 18-month period (1987-1988), referred to here as the "black-hole".. To assess the impact of assuming drug non-exposure during the "black-hole" on measures of effect.. We used data from a matched case-control study carried out to assess the association between warfarin use and risk of prostate cancer. All subjects diagnosed with prostate cancer between 1981 and 2002 were matched to six controls. In order to avoid the "black-hole", we included subjects whose cancer was diagnosed after 1994. Conditional logistic regression was used to calculate adjusted incidence rates and 95% confidence intervals (CIs) of prostate cancer in relation to warfarin. Two analyses were carried out: (a) without a "black-hole" and (b) with a random "black-hole" of 18 months imposed in the drug history, during which time subjects were assumed to be unexposed.. Compared to non-use, the OR of prostate cancer for ever-use of warfarin in the preceding 5 years was 0.91 (95%CI: 0.81-1.02) (without "black-hole") and 0.89 (95%CI: 0.79-1.01) (with "black-hole"). Compared to non-use, cumulative use of 1, 2, 3, and 4 years were associated with ORs of 1.02, 0.94, 0.77, and 0.76, respectively in the analyses without a "black-hole", and 1.02, 0.88, 0.75, and 0.76, respectively in the analyses with a "black-hole" imposed.. When using Saskatchewan Drug Plan data, assuming non-exposure to warfarin during the "black-hole" has a minor effect on the measures of association.

Topics: Case-Control Studies; Databases, Factual; Drug Prescriptions; Humans; Insurance, Pharmaceutical Services; Logistic Models; Male; Pharmacoepidemiology; Prostatic Neoplasms; Saskatchewan; Validation Studies as Topic; Warfarin

To create physician awareness of complementary and alternative medicine therapy use in patients with prostate cancer so that physicians can monitor for adverse events. Approximately one fourth to one third of patients diagnosed with prostate cancer reported complementary and alternative medicine use, and many of these patients are taking a supplement called "Dr. Donsbach's Prostasol.". We discuss the cases of 2 patients with prostate cancer who were taking Dr. Donsbach's Prostasol and developed venous thromboembolic events while taking this supplement, in the absence of other obvious risk factors. We review these 2 cases and the time-line for the development of the venous thromboembolic events and use of Dr. Donsbach's Prostasol. We compared Prostasol with PC-SPES, a similar supplement that was associated with thrombosis and was ultimately taken off the market because of patient safety concerns.. Prostasol contains phytoestrogens that could result in both the suppression of testosterone and the predisposition to thrombosis. Both patients had suppression of their testosterone to castrate levels with an associated decrease in prostate-specific antigen at the time of their thrombotic event.. These cases are suggestive of an association between Prostasol use and venous thromboembolic events. Physicians should be aware of the use of this agent in their patients, although it is not known whether it would be appropriate to prescribe prophylactic low-dose warfarin therapy. If possible, additional study of complementary and alternative medicine therapies for safety and efficacy are indicated.

Topics: Aged; Aged, 80 and over; Complementary Therapies; Dietary Supplements; Drugs, Chinese Herbal; Enoxaparin; Humans; Male; Medical Oncology; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Venous Thromboembolism; Venous Thrombosis; Warfarin

Patients requiring chronic anticoagulation therapy (CAT) with warfarin require special attention perioperatively. We retrospectively reviewed our experience of treating patients requiring CAT who underwent robotic-assisted radical prostatectomy (RARP) to evaluate the role of perioperative bridging therapy.. A total of 60 patients receiving cat with warfarin who underwent rarp were identified as having been treated using 1 of 2 protocols: protocol 1, the cessation of CAT 7 days before surgery and its resumption the evening of catheter removal (postoperative day 4-21); or protocol 2, warfarin substituted with perioperative subcutaneous low-molecular-weight heparin, with oral anticoagulation restarted after catheter removal. The decision to use perioperative bridging was made in conjunction with the patient's primary care physician. The peri- and postoperative parameters and complications were compared with a matched control group of 181 contemporary patients who underwent RARP but did not require CAT.. The most common indications for CAT were atrial fibrillation (58%) and recurrent deep vein thrombosis (22%). Compared with the control cohort, the patients with CAT had an increased operative time (189 vs 170 minutes, P = .005) and hospital stay (1.4 vs 1.1 days, P = .004). The estimated blood loss (123.9 vs 146.6 mL, P = .07) and 24-hour change in hemoglobin (2.2 vs 2.3 g/dL, P = .44) were similar. When comparing the 2 protocols, a significantly greater transfusion rate (23% vs 2%, P = .042) occurred with protocol 2, but no increase was seen in the complication or readmission rate. One nonfatal thromboembolic event occurred in 1 patient treated using protocol 1.. The results of our study have shown that RARP can be performed safely in patients requiring CAT, with and without bridging therapy. Patients in protocol 2 had greater transfusion rates, but this did not translate into increased complications or readmissions.

Topics: Administration, Oral; Aged; Anticoagulants; Disease-Free Survival; Humans; Intraoperative Care; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Recurrence; Retrospective Studies; Robotics; Treatment Outcome; Warfarin

Topics: Anticoagulants; Humans; Male; Prostatic Neoplasms; Warfarin

Topics: Anticoagulants; Biopsy, Needle; Hemorrhage; Humans; Male; Prostate; Prostatic Neoplasms; Ultrasonography, Interventional; Ultrasound, High-Intensity Focused, Transrectal; Warfarin

To determine the relation between warfarin use and the frequency of bleeding complications after biopsy of the prostate guided by transrectal ultrasound (TRUS).. Overall, 1022 consecutive patients with suspected prostatic disease were followed after biopsy. Warfarin and aspirin use was determined on the day of the procedure. A TRUS-guided biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Follow-up telephone calls were made to those who had not replied within the stipulated period.. Of the 1000 patients who replied, 49 were receiving warfarin, 220 were receiving aspirin and 731 were not receiving any anticoagulant drugs. Of the 49 subjects reporting current use of warfarin, 18 (36.7%) experienced haematuria, compared with 440 (60.2%) of the patients receiving no anti-coagulant drugs who reported haematuria. This was statistically significant (p = 0.001). Of the group receiving warfarin, 4 (8.2%) experienced haematospermia whereas 153 (21%) of the group receiving no anticoagulant medication reported haematospermia. This difference also was statistically significant (p = 0.030). Rectal bleeding was experienced by 7 (14.3%) of the group receiving warfarin compared with 95 (13%) in the group without anticoagulant medication, but this was not statistically significant (p = 0.80). We also demonstrated that there was no statistically significant association between the severity of the bleeding complications and medication with warfarin.. None of the group receiving warfarin experienced clinically important bleeding complications. Our results suggest that the frequency and severity of bleeding complications were no worse in the warfarin group than in the control group and that discontinuing anticoagulation medication before prostate biopsy may be unnecessary.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Biopsy; Blood; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Middle Aged; Postoperative Hemorrhage; Prostate; Prostatic Neoplasms; Rectum; Semen; Severity of Illness Index; Ultrasonography, Interventional; Warfarin

Topics: Anticoagulants; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Complementary Therapies; Diethylstilbestrol; Drug Contamination; Drugs, Chinese Herbal; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Warfarin

Topics: Anticoagulants; Antineoplastic Agents, Phytogenic; Disseminated Intravascular Coagulation; Drug Interactions; Drugs, Chinese Herbal; Humans; Male; Plant Extracts; Prostate-Specific Antigen; Prostatic Neoplasms; Warfarin

Topics: Animals; Antineoplastic Agents, Phytogenic; Dietary Supplements; Diethylstilbestrol; Drug Contamination; Drugs, Chinese Herbal; Humans; Male; Phytotherapy; Plant Extracts; Prostatic Neoplasms; Rats; Warfarin

The herbal mixture PC-SPES, used to manage advanced prostate cancer, has proven thrombogenic and highly estrogenic in clinical trials. However, attempts to identify the active compounds in PC-SPES have yielded incongruous results. Moreover, warfarin was identified in the serum of a patient taking PC-SPES who experienced a bleeding disorder. To determine the active components in PC-SPES potentially responsible for these effects, we analyzed PC-SPES lots manufactured from l996 through mid-2001.. Antineoplastic activity of PC-SPES and its individual component extracts was determined by colony-forming assays with several prostate cancer cell lines, and estrogenicity was determined by analyzing expression of an estrogen-responsive reporter gene in breast cancer cells. High-pressure liquid chromatography was used to isolate, identify, and quantify components of PC-SPES. Components were also identified by proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis.. PC-SPES lots manufactured from 1996 through mid-1999 contained the synthetic compounds indomethacin (range = 1.07-13.19 mg/g) and diethylstilbestrol (range = 107.28-159.27 micro g/g) and were two to six times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In lots manufactured after mid-1999, gradual declines in the concentrations of indomethacin (from 1.56 to 0.70 mg/g), diethylstilbestrol (from 46.36 to 0.00 micro g/g), and total phytosterols (from 0.586 to 0.085 mg/g) were observed. Warfarin was identified for the first time in lots manufactured after July 1998 (range = 341-560 micro g/g). In the August 2001 lot, increases were found in concentrations of the natural products licochalcone A (from 27.6 to 289.2 micro g/g) and baicalin (from 12.5 to 38.8 mg/g).. The phytochemical composition of PC-SPES varied by lot, and chemical analyses detected various amounts of the synthetic drugs diethylstilbestrol, indomethacin, and warfarin and several natural products. To qualify for clinical pharmacologic exploration, nutritional supplements including herbal mixtures should meet standards of quality control under the Good Manufacturing Practice system, and the manufacturers of such supplements should provide reliable analytical quality assurance.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Chromatography, High Pressure Liquid; Colony-Forming Units Assay; Diethylstilbestrol; Drugs, Chinese Herbal; Estrogen Receptor alpha; Gas Chromatography-Mass Spectrometry; Humans; Indomethacin; Male; Neoplasms, Hormone-Dependent; Phytosterols; Plant Extracts; Prostatic Neoplasms; Receptors, Estrogen; Tumor Cells, Cultured; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antineoplastic Agents, Phytogenic; Drug and Narcotic Control; Drugs, Chinese Herbal; Estrogens; Humans; Indomethacin; Male; Plant Extracts; Prostatic Neoplasms; Warfarin

Topics: Aged; Anticoagulants; Antineoplastic Agents, Phytogenic; Drug Interactions; Drugs, Chinese Herbal; Humans; Male; Plant Extracts; Prostatic Neoplasms; Warfarin

Topics: Aged; Aged, 80 and over; Anticoagulants; Humans; Male; Prostatic Neoplasms; Thromboembolism; Time Factors; Warfarin

To assess the safety of transurethral prostatectomy (TURP) in patients on long-term full anticoagulation.. Twelve TURPs were performed on 11 patients with urinary retention or severe symptoms from prostatic obstruction who also required anticoagulation for a history of life-threatening thromboembolic disease (seven) or prosthetic heart valves (four). Patients stopped taking warfarin 3 days before surgery; on admission a day later, full intravenous heparinization was commenced. Heparin was stopped 4 h before TURP and re-commenced with an initial bolus in the recovery room, and warfarin re-started that evening.. The mean weight of prostate resected was 23 g and the mean peri-operative decrease in haemoglobin was 1.6 g/dL. Only one patient required a transfusion of 3 units, but the activated partial thromboplastin time (APTT) had risen to >4. The mean pre- and post-operative APTT were 1.7 and 2.64, respectively, and the mean total length of hospital stay 6.7 days. Three patients were re-admitted for secondary haemorrhage at 8, 9 and 28 days after TURP, but all resolved with catheterization for 24 h only. There were no other major complications or thrombo-embolic phenomena.. TURP can be conducted safely in this high-risk group of patients with a regimen that allows a brief but controlled interruption to their full anticoagulation. This protects from the risks of thromboembolic incidents with no major increase in haemorrhage or hospital stay.

Topics: Aged; Anticoagulants; Humans; Length of Stay; Male; Neoplasm Recurrence, Local; Postoperative Hemorrhage; Prostatectomy; Prostatic Neoplasms; Reoperation; Retrospective Studies; Thromboembolism; Urinary Retention; Warfarin

To explore mechanisms of coagulation activation in adenocarcinoma of the prostate, the occurrence and distribution of components of coagulation and fibrinolysis pathways in situ were studied by means of immunohistochemical techniques applied to frozen sections of fresh malignant and benign hyperplastic prostatic tissue obtained at transurethral resection. Fibrinogen was distributed throughout the perivascular and tumor connective tissue in both malignant and benign disease but was not present in adjacent areas of normal prostate. Antibodies specific for fibrin and D-dimer crosslink sites stained vascular endothelium focally in both malignant and benign tissues. Both neoplastic cells and benign hyperplastic glandular epithelial cells stained weakly and in a patchy distribution for tissue factor and focally for low-molecular-weight urokinase-type plasminogen activator. Focal staining of vascular endothelium was also observed for tissue plasminogen activator and plasmin-antiplasmin complex neoantigen. By contrast, no tissue staining was observed for factor VII, factor X, factor XIII "a" subunit, high-molecular-weight urokinase-type plasminogen activator, plasminogen activator inhibitors 1 to 3, protein C, and protein S. Thus, the similarity in findings between benign hyperplastic and neoplastic prostate tissue, the lack of either an intact tumor cell-associated coagulation pathway or fibrin formation, and the presence of fibrin on vascular endothelium are consistent with the concept that coagulation activation in prostatic cancer may not be due to a direct effect of the tumor cells on the clotting mechanism. Rather, such activation may be induced by a soluble tumor product that activates procoagulant activity on certain host (for example, vascular endothelial) cells. These findings, together with the lack of effect of warfarin anticoagulation on the clinical course of patients with prostatic cancer, contrast with findings in certain other tumor types and suggest that coagulation activation may not contribute to progression of adenocarcinoma of the prostate.

Topics: Antibodies, Monoclonal; Endothelium, Vascular; Fibrin; Fibrinogen; Humans; Male; Molecular Weight; Plasminogen Activators; Prostatic Hyperplasia; Prostatic Neoplasms; Survival Rate; Thromboplastin; Warfarin

The PAIII rodent metastatic prostatic adenocarcinoma model was employed to evaluate the effects of dietary warfarin, a prototypic antagonist of thrombin generation on the lymphatic and pulmonary metastases of the tumor from the tail site of subcutaneous transplantation in male Lobund Wistar (LW) rats. In addition, the anticoagulant effects of warfarin were determined in the same animals. Warfarin, administered in the diet at concentrations equivalent to 0.063, 0.125 or 0.250 mg./kg. b.w. for 30 days had no effect on final body weight, gluteal or iliac lymph node weights. Significant (p less than 0.05) dose-dependent extensions of whole blood prothrombin (WBPT), activated partial thromboplastin (WBAPTT) and clotting times (WBCT) over control values were observed with warfarin treatment. Preliminary studies demonstrated that the 0.500 mg./kg. dose produced 50 per cent mortality at +14 days. Warfarin produced significant (p less than 0.05) dose-dependent decreases in the number of PAIII pulmonary metastases as indicated by reductions in dry lung weights and lung colony numbers when compared to untreated tumor-bearing controls. While the therapeutic index of warfarin is a limiting factor in clinical use as an antimetastatic agent, these results suggest that compounds capable of altering hemostatic mechanisms may be potential inhibitors of tumor metastasis. The PAIII prostatic adenocarcinoma model may be a useful system to quantitatively evaluate potential antimetastatic and cytotoxic agents.

Topics: Adenocarcinoma; Animals; Blood Coagulation; Blood Coagulation Tests; Diet; Dose-Response Relationship, Drug; Male; Neoplasm Metastasis; Prostatic Neoplasms; Rats; Warfarin

Analysis of 182 patients with chronic disseminated intravascular coagulopathy and malignancy shows common features. Migratory thrombophlebitis occurred in 96 patients while at least a single episode of thrombophlebitis was noted in 113. Seventy-five of the patients bled and 45 had arterial emboli in various organs. Twelve patients had the triad of thrombophlebitis, hemorrhage, and arterial emboli, often sequentially. Hematologic data showed derangements associated with intravascular coagulation, the most prominent of which were hypofibrinogenemia and thrombocytopenia. Other abnormalities included prolonged prothrombin time, increased fibrinogen-fibrin degradation products, decreased levels of factors V and VIII, cryofibrinogenemia, and microangiopathic hemolytic anemia. Forty-one patients had lesions of non-bacterial thrombotic endocarditis at autopsy; 31 of these had arterial emboli during life. None of the lesions were infected. Mitral and aortic valves were most frequently involved. No single mechanism that causes the disseminated intravascular coagulopathy has been identified. However, cell products--secretions and enzymes--and the cells themselves have been proposed as the procoagulant(s) responsible for the syndrome. In addition to treatment of the underlying neoplasm, symptomatic disseminated intravascular coagulopathy should be controlled. Heparin is the drug of choice for treatment of this problem, very little benefit having been observed with warfarin therapy. Long-term use of anticoagulants is potentially feasible for control of chronic disseminated intravascular coagulopathy, but without effective control of the underlying tumor ultimately will be unsuccessful.

Topics: Adult; Aged; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Brain Neoplasms; Breast Neoplasms; Chronic Disease; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Prothrombin Time; Pulmonary Embolism; Solitary Pulmonary Nodule; Thrombophlebitis; Warfarin

Topics: Acid Phosphatase; Afibrinogenemia; Blood Coagulation Disorders; Blood Proteins; Bone Marrow Examination; Diethylstilbestrol; Factor V; Factor VIII; Fibrinogen; Humans; Male; Middle Aged; Prostatic Neoplasms; Warfarin