warfarin and Carcinoma--Renal-Cell

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

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