Transient Elevation of International Normalized Ratio During Cisplatin-Based Chemotherapy in Patients Who are Taking Warfarin

2011 ◽  
Vol 45 (10) ◽  
pp. 1308-1308 ◽  
Author(s):  
Ryoichi Yano ◽  
Tetsuji Kurokawa ◽  
Hideaki Tsuyoshi ◽  
Akiko Shinagawa ◽  
Yoko Sawamura ◽  
...  
Keyword(s):  
International Normalized Ratio ◽  
Target Range ◽  
Probability Scale ◽  
Common Drug ◽  
Case Summary ◽  
The Common ◽  
Transient Elevation ◽  
Interaction Probability ◽  
Antineoplastic Chemotherapy ◽  
Probable Interaction

Objective: To report 2 cases of a probable interaction between cisplatin and warfarin. Case Summary: Two cases of transient elevation of international normalized ratio (INR) during Irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 6, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3–5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. Discussion: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an Interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. Conclusions: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.

Nortriptyline Cardiac Toxicity Resulting from a Probable Interaction with Telithromycin

2009 ◽  
Vol 44 (5) ◽  
pp. 397-400
Author(s):  
Angela R. Thomason ◽  
Bruce A. Waldrop ◽  
Sherry O. Price
Keyword(s):  
Adverse Effects ◽  
Cardiac Toxicity ◽  
Close Monitoring ◽  
Probability Scale ◽  
Case Summary ◽  
Atrioventricular Nodal Reentry Tachycardia ◽  
Interaction Probability ◽  
Probable Interaction ◽  
Reentry Tachycardia ◽  
New Onset

Objective To report a case of probable nortriptyline toxicity associated with a combination of telithromycin and nortriptyline. Case Summary A 50-year-old white woman was admitted to the hospital with new-onset palpitations after taking 5 days of telithromycin in combination with nortriptyline. On admission her electrocardiograph showed atrioventricular nodal reentry tachycardia. The patient was also hypotensive, with a blood pressure of 90/45 mm Hg. She had been taking nortriptyline 150 mg daily at bedtime for 10 years without complications. The final day of telithromycin therapy was completed, and nortriptyline was discontinued on admission. The tachycardia subsided with a dose of diltiazem. Discussion It is suspected that the cardiovascular symptoms observed in the patient are the result of nortriptyline toxicity caused by inhibition of CYP2D6 by telithromycin. Limited evidence shows that telithromycin may be an inhibitor of CYP2D6. An assessment of causation of the adverse effects using the Drug Interaction Probability Scale suggests a probable interaction between telithromycin and nortriptyline. Conclusion It is recommended that clinicians remain aware of possible interactions between telithromycin and known CYP2D6 substrates such as nortriptyline. Should telithromycin therapy be required, close monitoring of the potential adverse effects and/or plasma drug levels of patients taking interacting drugs is warranted.

Probable Interaction Between Warfarin and Inhaled and Oral Administration of Cannabis

2019 ◽  
Vol 33 (6) ◽  
pp. 915-918 ◽  
Author(s):  
Amy Hsu ◽  
Nathan A. Painter
Keyword(s):  
Case Reports ◽  
Middle Eastern ◽  
Signs And Symptoms ◽  
International Normalized Ratio ◽  
Cannabis Use ◽  
Bleeding Complications ◽  
Close Monitoring ◽  
Interaction Probability ◽  
Probable Interaction

Objective: To report a probable interaction between warfarin and edible cannabis that resulted in an elevated international normalized ratio (INR) without bleeding complications. Case Summary: A 35-year-old Middle Eastern male on warfarin long term with an INR goal of 2.5 (accepted range: 2.0-3.0). The patient has generally been stable on warfarin 10 mg daily from 2010 to 2018, until INR suddenly increased to 7.2 following 1 month of edible cannabis ingestion and cannabis smoking. Patient denied any signs and symptoms of bleeding. No other reasonable causes of the elevation in INR were apparent. The patient was advised to hold 2 doses of warfarin and discontinue cannabis use. The INR dropped below 4 upon discontinuation of cannabis with dose adjustments to warfarin. Discussion: The elevation in INR can be explained by the inhibition of CYP2C9 by cannabis use causing decreased metabolism of warfarin. The interaction between warfarin and cannabis was determined to be probable using the Horn Drug Interaction Probability Scale. Conclusions: There are no previous reports of interactions between edible cannabis and warfarin, with very few case reports describing the interaction with other forms of cannabis. Close monitoring of INR in patients with concomitant cannabis is recommended for proper warfarin management.

scholarly journals Monitoring "mini-intensity" anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1+2 levels

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2034-2038 ◽  
Author(s):  
MM Millenson ◽  
KA Bauer ◽  
JP Kistler ◽  
S Barzegar ◽  
L Tulin ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Factor Xa ◽  
High Sensitivity ◽  
International Normalized Ratio ◽  
Target Range ◽  
Lower Sensitivity ◽  
Sensitivity Index ◽  
Plasma Samples ◽  
Prothrombin Activation

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.

Self-Care Training and Information Support of Patients With Mechanical Heart Valve on International Normalized Ratio and the Bleeding Complications

2020 ◽  
Author(s):  
Shirdel Zandi ◽  
Behzad Imani ◽  
GHolamreza Safarpor
Keyword(s):  
Heart Valve ◽  
Intervention Group ◽  
Mechanical Heart Valve ◽  
Self Care ◽  
International Normalized Ratio ◽  
Information Support ◽  
Bleeding Complications ◽  
Target Range ◽  
Control Group ◽  
Care Training

Abstract BackgroundPatients with mechanical heart valve due to the possibility of coagulation complications require lifelong use of anticoagulants and International Normalized Ratio (INR) control. But if not taken care of properly, anticoagulant therapy itself can put people at risk for bleeding and be life-threatening. ObjectivesThe aim of this study was to determine the effect of Self-care training and information support of patients with mechanical heart valve on INR and the bleeding complications.DesignA randomized double-blind controlled trial.Settings and MethodsParticipants were recruited via convenience sampling from Farshchian hospital in Hamadan, Iran; and were randomly divided into two groups control (n=80) and intervention (n=80). Participants in the control group received only routine training; in addition, the intervention group received 6 sessions of self-care training and 6 months of information support. Monthly the level of INR and incidence of bleeding were determined. Data were analyzed using independent t-test and chi-square in spss16 software at a significance level of 0.05.ResultsDuring 6 months of follow-up, except for the third month, the frequency of INR levels in therapeutic target range (2.5-3.5) in the intervention group was significantly higher than the control group (p<0.05). Also in the intervention group, the incidence of bleeding complications was relatively less than the control group, but this difference was not statistically significant (p>0.05).ConclusionProper self-care training and information support in patients with mechanical heart valve replacement have positive results. By doing self-care, the level of a therapeutic target range of INR maintained and the incidence of bleeding complications can be reduced.

Angioedema Associated with Aspirin and Rofecoxib

2005 ◽  
Vol 39 (5) ◽  
pp. 944-948 ◽  
Author(s):  
Leisa L Marshall
Keyword(s):  
White Woman ◽  
Skin Testing ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Aspirin Therapy ◽  
Probability Scale ◽  
Antiinflammatory Drugs ◽  
Case Summary ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Auto Injector

OBJECTIVE: To report the probable association of angioedema with aspirin therapy and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib. CASE SUMMARY: A 44-year-old white woman, previously tolerant to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs), developed angioedema of the lips after ingesting two 325-mg aspirin tablets during one day. The reaction occurred 3 hours after taking the second aspirin and resolved within 3 hours. Two weeks later, the patient took a 25-mg rofecoxib tablet for a sore throat, and she developed angioedema 51/2 hours later. Although the woman took 50 mg of diphenhydramine, the swelling did not subside. She repeated the diphenhydramine dose in the evening and, by noon the next day, 261/2 hours after the angioedema began, it was resolved. The patient's internist prescribed an epinephrine auto-injector and advised her to consult an allergist. With skin testing and oral rechallenge with aspirin, but not rofecoxib, the allergist determined the cause of the reactions to be aspirin-induced angioedema and selective COX-2 inhibitor intolerance. The Naranjo probability scale indicated that aspirin was a highly probable cause and rofecoxib was a probable cause of this patient's angioedema. DISCUSSION: Aspirin-induced angioedema and NSAID intolerance have been well documented. There are reports of both tolerance and intolerance to selective COX-2 inhibitors in patients with documented allergy-like reactions to aspirin and NSAIDs. CONCLUSIONS: Patients with aspirin and NSAID intolerance may develop intolerance to COX-2 inhibitors, especially with repeated exposure.

Analysis of Warfarin Therapy in Pediatric Patients: A Prospective Cohort Study of 319 Patients

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3007-3014 ◽  
Author(s):  
W. Streif ◽  
M. Andrew ◽  
V. Marzinotto ◽  
P. Massicotte ◽  
A.K.C. Chan ◽  
...  
Keyword(s):  
Enteral Nutrition ◽  
Warfarin Therapy ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
International Normalized Ratio ◽  
Target Range ◽  
Age Group ◽  
Older Children ◽  
Effect Of Age ◽  
Fontan Patients

Abstract This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the ≤1 year of age group required increased warfarin doses, longer overlap with heparin, longer time to achieve target INR ranges, more frequent INR testing and dose adjustments, and fewer INR values in the target range. Although significantly different than children ≤1 year, children 1 to 6 years of age showed the same findings when compared with 7- to 18-year-olds. Fontan patients required 25% decreased dosage as compared with other congenital heart disease patients. Children on corticosteroids had less INRs in the target range and children on phenobarbital/carbamazepine required increased maintenance dosages of warfarin. Also, patients receiving enteral nutrition required increased dosages of warfarin. Serious bleeding occurred in 2 children (0.5% per patient year). Recurrent thromboembolic events (TEs) occurred in 8 children. Two children had recurrences while receiving warfarin (1.3% per patient year). This study outlines the profound effect of age and relative complexity of clinical management of warfarin therapy in children.

scholarly journals Monitoring "mini-intensity" anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1+2 levels

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2034-2038 ◽  
Author(s):  
MM Millenson ◽  
KA Bauer ◽  
JP Kistler ◽  
S Barzegar ◽  
L Tulin ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Factor Xa ◽  
High Sensitivity ◽  
International Normalized Ratio ◽  
Target Range ◽  
Lower Sensitivity ◽  
Sensitivity Index ◽  
Plasma Samples ◽  
Prothrombin Activation

Abstract Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.

Thalidomide-Associated Thrombocytopenia

2005 ◽  
Vol 39 (11) ◽  
pp. 1936-1939 ◽  
Author(s):  
Michiel Duyvendak ◽  
Mark Naunton ◽  
Bert J Kingma ◽  
Jacobus RBJ Brouwers
Keyword(s):  
Multiple Myeloma ◽  
Laboratory Testing ◽  
Hematologic Toxicity ◽  
Antineoplastic Drugs ◽  
Clinical Use ◽  
Adverse Consequence ◽  
Shortness Of Breath ◽  
Probability Scale ◽  
Case Summary ◽  
One Year

OBJECTIVE To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. Melphalan and prednisolone were discontinued, and monotherapy with dexamethasone 40 mg for 12 days per month was started. The patient's hematologic condition deteriorated again after about one year; dexamethasone was discontinued, and treatment with oral thalidomide 200 mg/day was initiated. About 2 weeks after thalidomide administration, the woman developed disabling adverse effects (flu-like symptoms, swollen fingers, rash and hematoma on her legs, shortness of breath, dry mouth, multiple petechiae). Laboratory testing showed neutropenia (neutrophils 0.4 × 109/L) and thrombocytopenia (platelets 58 × 109/L). Thalidomide was promptly discontinued; within 3 weeks, the laboratory values returned to pretreatment levels (1.3 × 109/L and 267 × 109/L, respectively) and her symptoms disappeared. DISCUSSION Thrombocytopenia is a rarely reported hematologic adverse consequence of thalidomide therapy. A recent report identified 5 patients who developed thrombocytopenia while undergoing monotherapy with thalidomide for MM. According to the Naranjo probability scale, thalidomide was classified as the probable cause of thrombocytopenia in our patient. CONCLUSIONS Unlike other antineoplastic drugs, thalidomide is rarely reported to cause severe hematologic toxicity. We present this case to increase clinicians’ awareness for the potential of thalidomide to adversely affect platelet counts, particularly because its effectiveness in MM will likely result in expansion of its clinical use.

Successful Desensitization to Oxaliplatin

2005 ◽  
Vol 39 (5) ◽  
pp. 966-969 ◽  
Author(s):  
Lydia ◽  
Nishan H Fernando ◽  
Hurbert I Hurwitz ◽  
Michael A Morse
Keyword(s):  
White Woman ◽  
Initial Response ◽  
Response To Therapy ◽  
Controlled Environment ◽  
Metastatic Colon Cancer ◽  
Hypersensitivity Reactions ◽  
Platinum Compounds ◽  
Probability Scale ◽  
Case Summary ◽  
Life Threatening

OBJECTIVE: To report the successful desensitization of a patient to oxaliplatin utilizing an 8-hour desensitization regimen in a controlled environment. CASE SUMMARY: A 53-year-old white woman with metastatic colon cancer was receiving oxaliplatin, bevacizumab, and capecitabine every 2 weeks, with a partial response to therapy. On her fifth cycle of this regimen, she experienced diaphoresis, hypotension, nausea, abdominal cramping, and coryza. According to the Naranjo probability scale, oxaliplatin, and not bevacizumab, was the probable cause of the hypersensitivity reaction. The woman continued therapy with capecitabine and bevacizumab, resulting in stable disease. Due to her initial response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin in a controlled, inpatient environment. An 8-hour desensitization schedule was employed, and the patient successfully completed an additional 3 cycles with full-dose oxaliplatin. DISCUSSION: Hypersensitivity reactions to platinum-containing compounds are well described and potentially life threatening. With expanded use of oxaliplatin in various malignancies, an increased number of hypersensitivity reactions will likely be reported. Patients with previous hypersensitivity reactions to carboplatin are at risk for similar reactions to oxaliplatin. We achieved successful desensitization for oxaliplatin using increased concentrations of the drug over an 8-hour period concomitant with oral and intravenous corticosteroids and histamine blockers. CONCLUSIONS: Hypersensitivity reactions to platinum compounds may result in discontinuation of active therapies in patients with metastatic disease. Desensitization to oxaliplatin is possible utilizing this approach.

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