warfarin and Bone-Neoplasms

A thromboembolic complication such as pulmonary embolism in patients who had cancer and mobile thrombi in the heart is a rare but fatal complication. Surgical thromboembolectomy is considered as the classical treatment of choice. In case of inoperable patient, catheter-directed therapy may be an alternative treatment. We report an interesting case of metastatic breast cancer with a large and mobile right atrial thrombus complicated by a massive and subsequently recurring pulmonary embolism, followed by thrombocytopenia developed after heparin and warfarin treatment.

Topics: Adult; Bone Neoplasms; Breast Neoplasms; Fatal Outcome; Female; Fibrinolytic Agents; Heart Atria; Heparin; Humans; Pulmonary Embolism; Recurrence; Thrombocytopenia; Thrombolytic Therapy; Thrombosis; Ultrasonography; Warfarin

Herein we report the clinical presentation and radiographic findings of a patient with a known history of multiple nonossifying fibromas, also known as the Jaffe-Campanacci syndrome, who presented with persistent pleuritic chest pain after a fall and was found to have a small pulmonary embolus. The presentation, pathophysiology and management of the syndrome are briefly discussed.

Topics: Angiography; Bone Neoplasms; Cafe-au-Lait Spots; Chest Pain; Female; Fibroma; Heparin; Humans; Pleurisy; Pulmonary Embolism; Syndrome; Treatment Outcome; Warfarin; Young Adult

As both cancer and major orthopaedic surgery are risk factors for venous thromboembolism, patients undergoing lower-extremity oncologic endoprosthetic arthroplasty for neoplastic processes are at substantial risk of the development of symptomatic venous thromboembolism. Therefore, the primary purpose of this study was to determine the incidence of symptomatic venous thromboembolism in patients undergoing lower-extremity oncologic endoprosthetic arthroplasty. Secondary purposes were to assess whether chemoprophylaxis influenced the incidence of venous thromboembolism, surgical complications, or the incidence of local sarcoma recurrence. We also sought to determine whether any known risk factors for venous thromboembolism could be identified in this patient population.. We performed a retrospective comparative review of 423 patients who had undergone mega-endoprosthetic reconstruction following cancer resection. Univariate analysis was used to assess the association between chemoprophylaxis and the incidence of venous thromboembolism, to postulate the surgical complications associated with chemoprophylaxis, and to assess the rate of recurrence of local sarcoma as well the association between risk factors and venous thromboembolism.. Seventeen patients (4.0%) (95% confidence interval: 2.5% to 6.3%) had a venous thromboembolic event, ten with deep venous thrombosis and seven with nonfatal pulmonary embolism. Risk factors and chemoprophylactic regimens were not statistically associated with the occurrence of venous thromboembolism.. The incidence of symptomatic venous thromboembolism in our group of cancer patients who underwent lower-extremity endoprosthetic arthroplasty was lower than anticipated. A significant difference was not identified between the use of any or no chemoprophylactic agent and the incidence of venous thromboembolism or complication rates. No risk factors were associated with the incidence of symptomatic venous thromboembolism.

Topics: Adolescent; Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Bone Neoplasms; Femoral Neoplasms; Heparin, Low-Molecular-Weight; Humans; Limb Salvage; Neoplasm Recurrence, Local; Pulmonary Embolism; Tibia; Venous Thromboembolism; Venous Thrombosis; Warfarin

The effect of the proinflammatory cytokine interleukin (IL)-1beta on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1beta stimulated the proliferation of SaM-1 and MG-63 cells, but had no effect on that of SaOS-2 or HOS cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, the mRNA expression of IL-1 receptor type I (IL-1R1) was detected in SaM-1 and MG-63 cells consistently, but not in SaOS-2 or HOS cells in the proliferative stage. Neither the decoy inhibitory IL-1 receptor type II (IL-1R2) nor IL-1R antagonist mRNA was detected in any of the cell lines, suggesting that IL-1beta stimulated proliferation via IL-1R1. The IL-1beta -stimulated proliferation was inhibited by the MAPK kinase (MEK) inhibitor PD98059 but not by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or the cyclooxygenase-2 specific inhibitor NS-398, suggesting that IL-1beta stimulated proliferation via MEK, without affecting prostaglandin E(2) synthesis. IL-1beta stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K(2) (VK(2)), which is a cofactor for gamma-carboxylase. Furthermore, the inhibitory effect of VK(2) on IL-1beta -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-beta, suggesting that IL-1beta is involved in VK(2) dependent gamma-calboxylation but not SXR-activation. These results suggest that IL-1beta stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK(2) via gamma-carboxylation.

Topics: Adult; Anticoagulants; Bone Neoplasms; Cell Line; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprostone; Enzyme Inhibitors; Flavonoids; Glutamic Acid; Humans; Imidazoles; Interleukin-1; Interleukin-1beta; Male; Mitogen-Activated Protein Kinase Kinases; Nitrobenzenes; Osteoblasts; Osteocalcin; Osteosarcoma; p38 Mitogen-Activated Protein Kinases; Pregnane X Receptor; Protein Kinase Inhibitors; Pyridines; Receptors, Steroid; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Messenger; Sulfonamides; Vitamin K; Vitamins; Warfarin; Young Adult

One of the standard treatments for cancer-associated thrombosis has been initial therapy with unfractionated heparin (UFH) followed by long-term therapy with an oral anticoagulant (i.e., warfarin). However, characteristics associated with these two agents may make them suboptimal for many cancer patients. This article will explore some of the considerations and limitations when using UFH and warfarin in the cancer population and will also utilize case studies to emphasize the importance of individualized care.. UFH is an effective anticoagulant when doses are adjusted to maintain the activated partial thromboplastin time (aPTT) within a specified therapeutic range. However, due to the complex pharmacokinetics of this agent, patients must undergo frequent monitoring to maintain a therapeutic aPTT. In addition, UFH can be associated with serious adverse events including osteoporosis, heparin-induced thrombocytopenia, and bleeding. Similar to UFH, warfarin requires frequent monitoring and dose adjustments to maintain the International Normalized Ratio (INR) within the therapeutic range of 2.0 to 3.0. Warfarin also has numerous drug-herbal, drug-food, and drug-drug interactions, including interactions with many commonly used anti-tumor therapies. Complications related to UFH and warfarin in the treatment of cancer-associated thrombosis have gradually been minimized with the increased use of low molecular weight heparins (LMWHs), which are associated with reduced incidence of bleeding, heparin-induced thrombocytopenia, and drug interactions. In addition, LMWHs allow for convenient daily dosing without requiring routine monitoring and the option of home therapy.. When deciding on the optimal anticoagulant strategy, pharmacists must take into account the unique characteristics and needs of each individual patient as well as the specifics of the various anticoagulant therapies. Future strategies for the initial and long-term treatment of cancer-associated thrombosis may increasingly incorporate LMWHs because of factors related to safety and convenience.

Topics: Anticoagulants; Bone Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Fatigue; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Thrombosis; Warfarin

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyclophosphamide; Drug Interactions; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Mitral Valve Stenosis; Prothrombin Time; Time Factors; Warfarin

A study of warfarin anticoagulation as an adjunct to amputation of osteosarcomas was undertaken after finding dramatic results in experimental systems. Anticoagulation was started 7 days preoperatively, continued during the operation, and for up to six months postoperatively. Three of 21 (14%) non-anticoagulated control patients are alive at 5-11 years. Five of 9 (56%) of the anticoagulated patients remain alive 5-8 years. The presumed mechanism of increased survival is an inhibition of fibrin deposition around circulating tumor cells, thereby preventing their adherence to capillary endothelium to initiate metastasis formation.

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Osteosarcoma; Prothrombin Time; Remission, Spontaneous; Time Factors; Warfarin