warfarin and Arthritis--Rheumatoid

Autoimmune diseases including rheumatoid arthritis have an increased incidence of cardiovascular disease. Rheumatoid arthritis (RA) confers a prothrombotic state and is associated with venous thrombosis, but its association with arterial thrombosis and embolism is not clear. In present report, we introduce a unique case of a 42-year-old woman with RA, who was admitted to the emergency service with back pain and diagnosed as having large right and left ventricular thrombus and myocardial infarction, associated with embolization of the thrombus. We also review the literature about RA and arterial and intraventricular thrombosis.

Topics: Adult; Arthritis, Rheumatoid; Coronary Angiography; Echocardiography; Female; Heart Ventricles; Humans; Myocardial Infarction; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

In this decade, the field of pharmacogenomics (PGx), which is related to pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention because it may provide a possible explanation for individual differences in the clinical efficacy of drugs. For the development of personalized drug therapy, it is important to accumulate evidence from PK/PD/PGx analysis in clinical trials. Warfarin (WF) is one of the most widely prescribed anticoagulants for the prevention and treatment of venous and arterial thromboembolism. However, large interindividual and interethnic differences have been observed in the WF dose required to elicit the anticoagulant effect. We investigated the factors influencing the WF maintenance dose in Japanese patients. Our study confirmed a large interindividual variability in the WF maintenance dose that was due to a VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum albumin. In addition, we found that the CYP4F2 genotype affects the plasma concentration of menaquinone-4, and that this finding was correlated with the WF sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The response to low-dose MTX demonstrated wide interpatient variability; however, the contributing factors remain unclear. We found that the frequency of the RFC1 80A allele was higher in RA patients treated with MTX alone compared with patients who received biological disease-modifying antirheumatic drugs (bDMARDs). This finding may support the combined use of bDMARDs and MTX. Further large-scale prospective clinical trials are required to confirm these findings.

Topics: Anticoagulants; Antirheumatic Agents; Arthritis, Rheumatoid; Asian People; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Drug Therapy, Combination; Gene Frequency; Humans; Maintenance Chemotherapy; Methotrexate; Pharmacokinetics; Polymorphism, Genetic; Precision Medicine; Replication Protein C; Thromboembolism; Vitamin K 2; Vitamin K Epoxide Reductases; Warfarin

A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthritis, Rheumatoid; Atrial Fibrillation; Blood Coagulation; Drug Interactions; Female; Humans; International Normalized Ratio; Isoxazoles; Leflunomide; Middle Aged; Thromboembolism; Warfarin

This therapeutic protein-drug interaction study evaluated the disease-mediated effect of sirukumab (anti-interleukin 6 [anti-IL-6] monoclonal antibody) on the pharmacokinetics of the cytochrome P450 (CYP) probe substrates midazolam (CYP3A), omeprazole (CYP2C19), warfarin (CYP2C9), and caffeine (CYP1A2) in patients with active rheumatoid arthritis (RA). Twelve patients with C-reactive protein (CRP) ≥ 8.0 mg/L at screening received oral administration of a CYP probe cocktail consisting of 0.03 mg/kg midazolam, 10 mg warfarin + 10 mg vitamin K (equivalent to 5 mg S-warfarin), 20 mg omeprazole, and 100 mg caffeine 1 week before and 1, 3, and 6 weeks after a single subcutaneous dose of 300 mg sirukumab. The results showed that the pharmacokinetics of midazolam, omeprazole, and S-warfarin were nonequivalent before and after the administration of a single dose of 300 mg sirukumab. Area under the plasma concentration-time curve (AUC0- ∞ ) for midazolam, omeprazole, and S-warfarin was reduced by 30%-35%, 37%-45%, and 18%-19%, respectively, after sirukumab administration. Caffeine AUC0-∞ was increased by 20%-34% after sirukumab administration. The effect of sirukumab on CYP substrates was sustained for at least 6 weeks. No new adverse drug reactions related to the administration of sirukumab were observed in this study. These results suggest that sirukumab may reverse IL-6-mediated suppression of CYP3A, CYP2C9, and CYP2C19 activities in patients with active RA.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Caffeine; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Humans; Interleukin-6; Male; Midazolam; Middle Aged; Omeprazole; Warfarin; Young Adult

Stiffness following total knee arthroplasty is a disabling complication. One of the management options of stiffness includes manipulation under anaesthesia, but no real consensus exist on appropriate timing of intervention, and the timing and results of the manipulation under anaesthesia (MUA) are under debate in the literature. Our aim was to determine the efficacy of single and multiple manipulations under anaesthesia following total knee arthroplasty and to determine the most appropriate timing for manipulation. We retrospectively reviewed 86 patients who underwent manipulation for stiffness following primary total knee replacement with at least 1-year follow-up. Range of motion before surgery, at the time of the MUA, immediately after MUA and at 6 weeks and 1 year post-MUA were recorded. At the end of 1 year post-manipulation, manipulations performed at less than 20 weeks, following primary total knee arthroplasty, showed 31° of flexion gain as compared to only 1.5° of flexion gain when manipulation was undertaken after 20 weeks. Of the 86 patients, 21 had multiple manipulations with no significant difference in flexion gain after the second manipulation. Patients on warfarin (26%) had an increased incidence of stiffness and poor flexion gain. This study showed that better results were achieved when manipulation was performed at less than 20 weeks (particularly between 12 and 14 weeks) from primary surgery with no added benefit from re-manipulations.

Topics: Aged; Aged, 80 and over; Anesthesia; Anticoagulants; Arthritis, Rheumatoid; Arthroplasty, Replacement, Knee; Elasticity; Female; Humans; Knee Joint; Male; Manipulation, Orthopedic; Middle Aged; Osteoarthritis, Knee; Range of Motion, Articular; Retrospective Studies; Time Factors; Time-to-Treatment; Warfarin

Topics: Arthritis, Rheumatoid; Bone Density Conservation Agents; Calciphylaxis; Diagnosis, Differential; Drug Therapy, Combination; Erythema Nodosum; Female; Follow-Up Studies; Humans; Middle Aged; Osteoporosis; Prednisone; Risk Assessment; Severity of Illness Index; Teriparatide; Warfarin

Performance of joint and soft tissue injections in patients receiving anticoagulation is subject to different protocols, some of which suggest continuing treatment within the therapeutic range, while others recommend stopping the treatment prior to procedures. The aim of this study was to evaluate the safety of two approaches to the management of patients prescribed warfarin requiring joint or soft tissue injection. A systematic literature review on this subject was undertaken. Our departmental protocol was changed from one where anticoagulation treatment was temporarily stopped prior to joint/soft tissue injection to one where treatment was continued in the context of a therapeutic international normalised ratio (INR) level within 24 h of the procedure. In patients in whom warfarin was withheld, 32 procedures were performed in 18 patients (13 rheumatoid arthritis, 11 osteoarthritis, 5 spondyloarthritis and 1 each of adhesive capsulitis, rotator cuff tendinopathy and trochanteric bursitis). Of these, 30 were joint injections and 2 were soft tissue injections. In patients who continued warfarin, 32 procedures were performed in 21 patients (11 rheumatoid arthritis, 7 osteoarthritis, 6 crystal arthritis, 4 rotator cuff tendinopathy, 2 spondyloarthritis and 1 each of adhesive capsulitis and carpal tunnel syndrome). Of these, 27 were joint injections and 5 were soft tissue injections. There were no clinical hemarthroses or complications in either group. Joint and soft tissue injections appear to be safe in patients receiving warfarin anticoagulation with an INR <3. Continuation of anticoagulants reduces staff workload and patient inconvenience with no evidence of increased risk of complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthritis, Rheumatoid; Bursitis; Carpal Tunnel Syndrome; Cohort Studies; Elbow Joint; Female; Humans; Injections, Intra-Articular; International Normalized Ratio; Knee Joint; Male; Osteoarthritis; Prospective Studies; Rheumatology; Shoulder Joint; Spondylarthritis; Warfarin

Topics: Arthritis, Rheumatoid; Aspirin; Drug Interactions; Gastrointestinal Diseases; Humans; Hypersensitivity; Migraine Disorders; Oral Ulcer; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Tanacetum parthenium; Warfarin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthritis, Rheumatoid; Drug Synergism; Hematuria; Humans; International Normalized Ratio; Isoxazoles; Leflunomide; Male; Middle Aged; Warfarin

It is possible that platelet activation may play a pathogenic role in the increased risk of thrombosis associated with antiphospholipid antibodies (APA). In this study, levels of in vivo platelet activation were measured in 20 patients with primary antiphospholipid syndrome (PAPS) and 30 systemic lupus erythematosus (SLE) patients (14 of whom had secondary APS) using sensitive flow cytometry. Soluble P-selectin levels were also assayed. Platelet CD63 expression was significantly higher in PAPS than normal controls (P = 0.007), as well as SLE patients with and without secondary APS (P = 0.03 and P = 0.002 respectively). PAC-1 binding was significantly higher in PAPS than the control group (P = 0.007) and SLE patients without APS (P = 0.015). Platelet-leucocyte complexes were significantly higher in SLE patients than both PAPS and the control group, and platelet-monocyte complexes were significantly increased in PAPS compared with the control group. (Platelet-leucocyte complexes were also significantly higher than controls in 10 rheumatoid arthritis (RA) patients without APA). Soluble P-selectin levels were significantly higher in PAPS and SLE patients than the control group. Platelet CD62p expression, annexin V binding and platelet microparticle numbers were not increased in PAPS or SLE patients. We conclude that there is evidence of increased platelet activation in PAPS and SLE, and this is important to note as it may have potential therapeutic implications with respect to use of antiplatelet agents in these patients.

Topics: Adult; Aged; Annexin A5; Antiphospholipid Syndrome; Arthritis, Rheumatoid; Aspirin; Blood Platelets; Cell Aggregation; Cell Degranulation; Dual Specificity Phosphatase 2; Female; Humans; Leukocytes; Lupus Erythematosus, Systemic; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Count; Protein Phosphatase 2; Protein Tyrosine Phosphatases; Thrombosis; Warfarin

A female patient with a history of migraines and chorea developed polyarthralgia at age 24 and was diagnosed with rheumatoid arthritis. In 1991 she was hospitalized because of impaired renal function and hypertension. Examination revealed thrombocytopenia and the presence of lupus anticoagulant. Antinuclear antibody was weakly positive, but anti-DNA antibody was negative, and no decrease in leukocyte count or complement level was observed. Rheumatoid arthritis with antiphospholipid syndrome was diagnosed. Renal biopsy showed renal thrombotic microangiopathy. This renal lesion was considered to be associated with antiphospholipid syndrome. Cyclophosphamide pulse therapy and anticoagulation therapy decreased proteinuria and improved renal function.

Topics: Adult; Antiphospholipid Syndrome; Arthritis, Rheumatoid; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Kidney; Kidney Diseases; Radiography; Thrombosis; Warfarin

Topics: Aged; Arthritis, Rheumatoid; Female; Hemarthrosis; Humans; Radiography; Thrombophlebitis; Warfarin

Rheumatoid arthritis is not considered to be associated with recurrent thrombosis. We report a patient, who while receiving anticoagulants had repeated life-threatening episodes of thrombosis. She later developed severe rheumatoid arthritis. After receiving successful antiarthritic therapy and withdrawal of anticoagulants, she had no further episodes of thrombosis.

Topics: Arthritis, Rheumatoid; Drug Therapy, Combination; Female; Follow-Up Studies; Gold; Heparin; Humans; Middle Aged; Naproxen; Prednisone; Thrombophlebitis; Warfarin

A patient with severe rheumatoid arthritis (RA) receiving chronic anticoagulation therapy developed acute life threatening airway obstruction. The source of obstruction was a retropharyngeal hematoma compressing the upper airway rather than acute laryngeal dysfunction from the patient's RA. Our case illustrates a new cause of acute stridor and airway obstruction in RA. Publications on upper airway obstruction in RA and airway obstruction secondary to retropharyngeal hematoma are discussed.

Topics: Airway Obstruction; Arthritis, Rheumatoid; Drug Interactions; Female; Hematoma; Humans; Middle Aged; Pharynx; Pressure; Sulindac; Warfarin

The clinical pharmacology of ibuprofen (Motrin, Upjohn) in relation to the pathophysiologic aspects of various diseases is explained. An understanding of prostaglandin's numerous effects can help the clinician to expand the use of ibuprofen (as in Barttern's syndrome) and to exercise caution as warranted, as when treating patients with renal disease. Knowledge of ibuprofen's clinical pharmacology may also enable practitioners to prescribe the drug rationally in situations not well represented in the literature, as in the elderly or in individuals with bleeding diatheses or severe liver disease. The use of ibuprofen in multiple-drug therapy with aspirin, warfarin, phenytoin, digoxin, or lithium is explored. Perusal of the literature enables the clinician to gain an awareness of patient subpopulations warranting careful use of medication, including the elderly or individuals with systemic lupus erythematosus, mixed connective tissue disease, or aspirin-induced asthma.

Topics: Arthritis, Rheumatoid; Aspirin; Bartter Syndrome; Cyclooxygenase Inhibitors; Digoxin; Drug Hypersensitivity; Drug Interactions; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Kidney; Kinetics; Lithium; Liver; Lupus Erythematosus, Systemic; Mixed Connective Tissue Disease; Phenytoin; Platelet Aggregation; Prostaglandins E; Warfarin

Topics: Aged; Anticoagulants; Arthritis, Rheumatoid; Arthroplasty; Aspirin; Blood Coagulation; Blood Platelets; Dextrans; Follow-Up Studies; Heparin; Hip Joint; Humans; Joint Prosthesis; Osteoarthritis; Postoperative Complications; Spondylitis, Ankylosing; Vitamin K; Warfarin

Topics: Adult; Aged; Arthritis, Rheumatoid; Cloxacillin; Female; Hematoma; Hip; Hip Dislocation; Hip Joint; Humans; Joint Prosthesis; Male; Middle Aged; Ossification, Heterotopic; Osteoarthritis; Postoperative Complications; Pulmonary Embolism; Staphylococcal Infections; Streptomycin; Surgical Wound Infection; Thromboembolism; Warfarin

Topics: Adolescent; Adult; Aged; Anticoagulants; Arthritis, Rheumatoid; Female; Femoral Fractures; Follow-Up Studies; Gastrointestinal Hormones; Hematoma; Hip; Hip Dislocation; Hip Joint; Humans; Iatrogenic Disease; Joint Prosthesis; Male; Middle Aged; Ossification, Heterotopic; Osteoarthritis; Postoperative Complications; Thromboembolism; Warfarin

Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Arthroplasty; Female; Follow-Up Studies; Hematoma; Heparin; Hip; Hip Joint; Humans; Joint Prosthesis; Male; New York City; Osteoarthritis; Paralysis; Peroneal Nerve; Postoperative Care; Postoperative Complications; Pulmonary Embolism; Splints; Surgical Wound Infection; Thromboembolism; Warfarin; Wound Healing

Topics: Acetates; Adenosine Diphosphate; Animals; Anti-Inflammatory Agents; Arteriosclerosis; Arthritis, Rheumatoid; Blood Coagulation; Collagen; Coumarins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ethyl Biscoumacetate; Fibrinolysis; Humans; In Vitro Techniques; Methods; Phenylbutazone; Platelet Adhesiveness; Pyrazoles; Rats; Thrombophlebitis; Warfarin