warfarin and Kidney-Neoplasms

We are presenting a rare case of a spontaneous extensive perirenal hematoma caused by ruptured renal adenocarcinoma in a patient who was on warfarin therapy because she had atrial fibrillation and three myocardial infarctions. A 77-year-old woman was admitted to our department with acute right flank pain and hemorrhagic shock. The anamnestic data revealed no trauma and hematuria. Abdominal ultrasonography and computed tomography scan showed large retroperitoneal hematoma. The patient underwent urgent surgery and radical nephrectomy was performed. A large retroperitoneal hematoma was found originating from a ruptured renal neoplasm in the upper pole of the right kidney. The pathohistological diagnosis was chromophobe renal cell carcinoma. The clinical, diagnostic and therapeutic peculiarities of this rare condition are presented, along with the literature review on the topic.

Topics: Adenocarcinoma; Aged; Anticoagulants; Atrial Fibrillation; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Hematoma; Humans; Kidney Neoplasms; Warfarin

In patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC.. In this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated.. Between 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]).. This real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.

Topics: Administration, Oral; Anticoagulants; Carcinoma, Renal Cell; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Kidney Neoplasms; Neoplasms; Venous Thromboembolism; Warfarin

Pazopanib is an orally available multi-tyrosine kinase inhibitor and has been used to treat renal cell carcinoma (RCC). Here, we report the case of a patient with RCC with an increased prothrombin time- international normalized ratio (PT-INR) due to pazopanib therapy. In addition, we have reported the change in the blood levels of pazopanib. A 75-year-old man underwent a left nephrectomy for RCC. Four years later, his cancer recurred and pazopanib therapy was initiated. He was also taking warfarin for atrial fibrillation and his PT-INR was constant at approximately 2. His warfarin dose was reduced from 3.5 mg/day to 3.0 mg/day on day 10 because his PT-INR increased from 2.19 to 3.07 compared to that before starting pazopanib. On day 28, his PT-INR further increased to 4.34, and his aspartate aminotransferase, alanine transaminase, and alkaline phosphatase levels increased. The target concentration of pazopanib was 20.5 to 50.3 µg/mL, but his blood concentrations were 92.1 µg/mL on day 6 and 93.7 µg/mL on day 13. Therefore, both pazopanib and warfarin were discontinued. One week later, his laboratory tests recovered, and hence, warfarin treatment was resumed. However, pazopanib therapy was terminated due to concerns about liver dysfunction. His hepatic dysfunction and increased PT-INR were considered to be due to pazopanib treatment. Pazopanib has been reported to have no effect on the pharmacokinetics of warfarin in clinical patients. In this case, blood levels of pazopanib were abnormally high, possibly causing liver dysfunction and drug interactions, leading to his PT-INR prolongation. TDM monitoring, in addition to the recommended monitoring for pazopanib hepatotoxicity, may help identify patients at risk for drug interactions. For patients receiving concomitant pazopanib and warfarin, close monitoring of PT-INR is warranted.

Topics: Administration, Oral; Aged; Carcinoma, Renal Cell; Drug Interactions; Drug Monitoring; Humans; Indazoles; Kidney Neoplasms; Male; Pyrimidines; Sulfonamides; Warfarin

Topics: Anilides; Anticoagulants; Antineoplastic Agents; Carcinoma, Renal Cell; Combined Modality Therapy; Drug Incompatibility; Humans; International Normalized Ratio; Kidney Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Pulmonary Embolism; Pyridines; Treatment Outcome; Warfarin

Topics: Adult; Anticoagulants; Carcinoma, Renal Cell; Echocardiography; Fibrinolytic Agents; Follow-Up Studies; Heart Atria; Heparin; Humans; Kidney Neoplasms; Male; Nephrectomy; Risk Factors; Tachycardia; Thrombosis; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome; Vena Cava, Inferior; Vena Cava, Superior; Warfarin

New approaches targeting metastatic neovasculature are needed. Payload capacity, cellular transduction efficiency, and first-pass cellular uptake following systemic vector administration, motivates persistent interest in tumor vascular endothelial cell (EC) adenoviral (Ad) vector targeting. While EC transductional and transcriptional targeting has been accomplished, vector administration approaches of limited clinical utility, lack of tumor-wide EC expression quantification, and failure to address avid liver sequestration, challenged prior work. Here, we intravenously injected an Ad vector containing 3 kb of the human roundabout4 (ROBO4) enhancer/promoter transcriptionally regulating an enhanced green fluorescent protein (EGFP) reporter into immunodeficient mice bearing 786-O renal cell carcinoma subcutaneous (SC) xenografts and kidney orthotopic (KO) tumors. Initial experiments performed in human coxsackie virus and adenovirus receptor (hCAR) transgenic:Rag2 knockout mice revealed multiple ECs with high-level Ad5ROBO4-EGFP expression throughout KO and SC tumors. In contrast, Ad5CMV-EGFP was sporadically expressed in a few tumor vascular ECs and stromal cells. As the hCAR transgene also facilitated Ad5ROBO4 and control Ad5CMV vector EC expression in multiple host organs, follow-on experiments engaged warfarin-mediated liver vector detargeting in hCAR non-transgenic mice. Ad5ROBO4-mediated EC expression was undetectable in most host organs, while the frequencies of vector expressing intratumoral vessels and whole tumor EGFP protein levels remained elevated. In contrast, AdCMV vector expression was only detectable in one or two stromal cells throughout the whole tumor. The Ad5ROBO4 vector, in conjunction with liver detargeting, provides tractable genetic access for in-vivo EC genetic engineering in malignancies.

Topics: Adenoviridae; Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Endothelial Cells; Genetic Therapy; Genetic Vectors; Humans; Kidney Neoplasms; Liver; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Receptors, Cell Surface; Transcription, Genetic; Transgenes; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Carcinoma, Renal Cell; Female; Hemorrhage; Heparin; Humans; Incidental Findings; Kidney Neoplasms; Risk Factors; Tomography, X-Ray Computed; Warfarin

To determine whether treatment guidelines for patients with lower-extremity venous thrombosis (DVT) could be applied to patients with renal vein thrombosis (RVT). The rates of recurrent venous thrombosis and survival for patients with these 2 diseases were compared.. Inception cohort of individuals was identified with their first lifetime incident of RVT. Recurrent thrombosis and survival were compared with those for patients with DVT in a case-control fashion.. All patients with a diagnosis of RVT at Mayo Clinic from 1980 to 2000.. Survival and recurrent venous thrombosis rates were compared with those for patients with DVT. Survival rates were also compared with those for US white residents.. 218 patients (mean age, 55 +/- 19 years) were included (35% women). Malignancy (66%) and nephrotic syndrome (20%) were the most common underlying causes. Warfarin was prescribed for 74 patients (46% with lifelong therapy). During a mean follow-up of 42 +/- 57 months (768 patient-years), there were 8 recurrent venous thrombotic events (1.0/100 patient-years). This recurrence rate was less than that for patients with DVT (P < 0.001). Survival was lower compared with patients with DVT or age- and sex-matched US white residents (P < 0.001). Active malignancy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7) and infection (HR, 2.4; 95% CI, 1.4 to 4.0) were associated with poor survival. Survival was influenced positively by warfarin therapy (HR, 0.53; 95% CI, 0.31 to 0.90).. Retrospective nonrandomized study.. RVT represents a distinct clinical entity with unique recurrence and survival rates. The finding of RVT should prompt a thorough evaluation for an underlying renal malignancy. Oral anticoagulation therapy may be associated with a survival advantage.

Topics: Adult; Aged; Anticoagulants; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Kidney Neoplasms; Male; Middle Aged; Multivariate Analysis; Nephrotic Syndrome; Odds Ratio; Recurrence; Renal Veins; Retrospective Studies; Survival Analysis; Survival Rate; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin; White People

Topics: Anticoagulants; Diagnosis, Differential; Female; Hematuria; Hemorrhage; Humans; Kidney Diseases; Kidney Neoplasms; Kidney Pelvis; Middle Aged; Mucous Membrane; Radiography; Warfarin

The authors describe the case history of a 54-year-old female patient, who presented with breathlessness, deteriorating general health and a 12 kg weight loss due to extensive metastatic renal cancer. Pulmonary emboli complicated the presentation. The patient entered a remarkable complete radiological remission by 18 weeks following the introduction of interleukin-2/alpha-interferon immunotherapy. The possibility of immediate nephrectomy or warfarin contributing to the augmentation of the effects of the immunotherapy is discussed.

Topics: Anticoagulants; Antineoplastic Agents; Carcinoma, Renal Cell; Female; Humans; Immunotherapy; Interferon-alpha; Interleukin-2; Kidney Neoplasms; Middle Aged; Nephrectomy; Radiography; Remission Induction; Warfarin

The excretory urogram of patients with acute renal vein thrombosis typically demonstrates symmetric enlargement of the involved kidney. We report a case of renal vein thrombosis that presented as a discrete renal mass on excretory urography and abdominal computerized tomography. The entity of renal vein thrombosis is briefly reviewed along with the computerized tomography findings seen in this setting.

Topics: Diagnosis, Differential; Heparin; Humans; Kidney Neoplasms; Male; Middle Aged; Renal Veins; Thrombosis; Tomography, X-Ray Computed; Warfarin

Topics: Aged; Anticoagulants; Diagnosis, Differential; Female; Hematoma; Humans; Kidney Diseases; Kidney Neoplasms; Tomography, X-Ray Computed; 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: Aged; Diagnosis, Differential; Female; Hematuria; Hemorrhage; Humans; Kidney; Kidney Neoplasms; Nephrectomy; Thrombophlebitis; Urography; Warfarin

Topics: Diagnosis, Differential; Female; Hematoma; Hematuria; Hemorrhage; Humans; Kidney Diseases; Kidney Neoplasms; Male; Middle Aged; Urography; Warfarin