BACKGROUND Randomized controlled trials(RCTs)of direct oral anticoagulants(DOACs)included a low proportion of atrial fibrillation(AF)patients with chronic kidney disease(CKD),and suggested that DOACs are safe and effe...BACKGROUND Randomized controlled trials(RCTs)of direct oral anticoagulants(DOACs)included a low proportion of atrial fibrillation(AF)patients with chronic kidney disease(CKD),and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD.In a metanalysis of RCTs and observational studies,DOACs were associated with better efficacy(vs warfarin)in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD.But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD.The effectiveness and safety of DOACs in those patients are still subject to debate.AIM To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population.METHODS A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017.The primary effectiveness outcome was a composite of ischemic stroke,systemic embolism,and death,whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation.Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards.RESULTS A total of 8899 included patients filled out a new oral anticoagulation therapy claim;3335 for warfarin and 5564 for DOACs.Compared with warfarin,15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk.Apixaban 5.0 mg was associated with a lower effectiveness composite risk[Hazard ratio(HR)0.76;95%confidence interval(CI):0.65-0.88]and a similar safety risk(HR 0.94;95%CI:0.66-1.35).Apixaban 2.5 mg was associated with a similar effectiveness composite(HR 1.00;95%CI:0.79-1.26)and a lower safety risk(HR 0.65;95%CI:0.43-0.99.Although,apixaban 5.0 mg was associated with a better effectiveness(HR 0.76;95%CI:0.65-0.88),but a similar safety risk profile(HR 0.94;95%CI:0.66-1.35).The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality(HR 0.61;95%CI:0.43-0.88).CONCLUSION In comparison with warfarin,rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.展开更多
BACKGROUND Heparin is commonly recommended for warfarin-induced skin necrosis;however, there is currently no established therapy for this disease. We present a serious case of warfarin-induced skin necrosis that was s...BACKGROUND Heparin is commonly recommended for warfarin-induced skin necrosis;however, there is currently no established therapy for this disease. We present a serious case of warfarin-induced skin necrosis that was successfully treated with oral rivaroxaban, a factor Xa inhibitor.CASE SUMMARY A 48-year-old woman was admitted to the hospital for cellulitis of the right lower extremity. After antibiotic treatment, she developed pain and swelling of the left lower extremity, and deep vein thrombosis of both lower extremities was diagnosed. She was treated with a continuous heparin injection;subsequently,oral warfarin was concomitantly administered. Heparin was terminated after the therapeutic range was reached. On the following day, the patient had swelling and pain in the left lower extremity. In addition to decrease in protein S activity due to systemic lupus erythematosus, warfarin also reduced protein C activity,resulting in further hypercoagulation and skin necrosis. Warfarin was discontinued, and continuous heparin injection was resumed. Although the patient had to undergo amputation of the distal end of her left foot, continuous heparin injection was switched to oral rivaroxaban, and she was eventually discharged from the hospital in remission.CONCLUSION Administration of direct oral anticoagulants instead of warfarin is important in patients with decreased protein S and C activity.展开更多
Background Asian population are at increased risk of bleeding during the warfarin treatment,so the recommended optimal international normalized ratio(INR)level may be lower in Asians than in Westerners.The aim of this...Background Asian population are at increased risk of bleeding during the warfarin treatment,so the recommended optimal international normalized ratio(INR)level may be lower in Asians than in Westerners.The aim of this prospective multicenter study was to determine the optimal INR level in Thai patients with non-valvular atrial fibrillation(NVAF).Methods Patients with NVAF who were on warfarin for stroke prevention were recruited from 27 hospitals in the nationwide COOL-AF registry in Thailand.We collected demographic data,medical history,risk factors for stroke and bleeding,concomitant disease,electrocardiogram and laboratory data including INR and antithrombotic medications.Outcome measurements included ischemic stroke/transient ischemic attack(TIA)and major bleeding.Optimal INR level was assessed by the calculation of incidence density for six INR ranges(<1.5,1.5–1.99,2–2.49,2.5–2.99,3–3.49,and≥3.5).Results A total of 2,232 patients were included.The mean age of patients was 68.5±10.6 years.The mean follow-up duration was 25.7±10.6 months.There were 63 ischemic stroke/TIA and 112 major bleeding events.The lowest prevalence of ischemic stroke/TIA and major bleeding events occurred within the INR range of 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.Conclusions The INR range associated with the lowest risk of ischemic stroke/TIA and bleeding in the Thai population was 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.The rates of major bleeding and ischemic stroke/TIA were both higher than the rates reported in Western population.展开更多
BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countrie...BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.展开更多
Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin w...Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole;15 patients took omeprazole;30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 - 12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.展开更多
BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received stric...BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.展开更多
Purpose: This study was performed to assess the utility and safety of an In-Office INR Monitoring Device and present a safe and efficient protocol for the management of patients on oral anticoagulants and/or antithrom...Purpose: This study was performed to assess the utility and safety of an In-Office INR Monitoring Device and present a safe and efficient protocol for the management of patients on oral anticoagulants and/or antithrombolytics requiring routine office oral and maxillofacial surgery. Patients and Methods: Sixty-one patients requiring “minor” oral and maxillofacial surgery being treated chronically with oral anticoagulation (warfarin) were entered into the study and compared in 2 groups. The control group (n = 29) was managed by discontinuing warfarin and any anti-platelet medication(s) prior to surgery. In the study group (n = 30), the decision to continue or withhold warfarin was determined by a protocol in which patients are 1) stratified based on risk for thromboembolism, and 2) classified as requiring “major” or “minor” surgery. Procedures categorized as “minor” surgery included dental extraction(s), dental implants, soft tissue and bone biopsies, and preprosthetic bone surgery, and incision and drainage. Warfarin and antiplatelet medication were not withheld in these patients, and a Point-of-Care In-Office INR Monitoring Device was used to obtain INR levels on the day of consultation and surgery. Local measures including removal of granulation tissue, packing, suturing, etc. were utilized for hemostasis. Results: The 30 patients in the study group maintained on warfarin readily achieved hemostasis using intraoperative local measures. The mean INR measured by the In-Office INR Monitoring Device was 2.36 with a range from 1.3 to 3.2. Study group patients underwent a total of 131 separate procedures including 108 dental extractions (impactions), placement of dental implants, preprosthetic bony surgery, bone cyst removal, soft tissue biopsies, facial skin cancer repair, and incision and drainage. One patient (3%) required “minor” intervention with removal of a “liver clot” on postop day 2 with repacking and suturing. The 29 patients in the control group discontinued off of war farin underwent a total of 99 procedures. One patient (3%) also required a “minor” intervention (repacking of extraction site). There were no “major” complications in either group. Conclusions: This study supports previous studies that minor oral surgery procedures can be safely performed while maintaining patients on warfarin minimizing the risk of a potentially devastating thromboembolic event. When deciding whether or not to withhold warfarin, this study supports the use of the proposed protocol based on 1) risk stratification for thromboembolism, 2) the need for “minor” versus “major” surgery, 3) and utilization of an In-Office INR Monitoring Device. An In-Office Point-of-Care INR measuring device can be a very effective tool to safely simplify and make the perioperative management of the anticoagulated patient more efficient for the patient and oral and maxillo facial surgeon.展开更多
BACKGROUND The quality of warfarin therapy can be determined by the time in the therapeutic range(TTR)of international normalized ratio(INR).The estimated minimum TTR needed to achieve a benefit from warfarin therapy...BACKGROUND The quality of warfarin therapy can be determined by the time in the therapeutic range(TTR)of international normalized ratio(INR).The estimated minimum TTR needed to achieve a benefit from warfarin therapy is≥60%.AIM To determine TTR and the predictors of poor TTR among atrial fibrillation patients who receive warfarin therapy.METHODS A retrospective observational study was conducted at a cardiology referral center in Selangor,Malaysia.A total of 420 patients with atrial fibrillation and under follow-up at the pharmacist led Warfarin Medication Therapeutic Adherence Clinic between January 2014 and December 2018 were included.Patients’clinical data,information related to warfarin therapy,and INR readings were traced through electronic Hospital Information system.A data collection form was used for data collection.The percentage of days when INR was within range was calculated using the Rosendaal method.The poor INR control category was defined as a TTR<60%.Predictors for poor TTR were further determined by using logistic regression.RESULTS A total of 420 patients[54.0%male;mean age 65.7(10.9)years]were included.The calculated mean and median TTR were 60.6%±20.6%and 64%(interquartile range 48%-75%),respectively.Of the included patients,57.6%(n=242)were in the good control category and 42.4%(n=178)were in the poor control category.The annual calculated mean TTR between the year 2014 and 2018 ranged from 59.7%and 67.3%.A high HAS-BLED score of≥3 was associated with poor TTR(adjusted odds ratio,2.525;95%confidence interval:1.6-3.9,P<0.001).CONCLUSION In our population,a high HAS-BLED score was associated with poor TTR.This could provide an important insight when initiating an oral anticoagulant for these patients.Patients with a high HAS-BLED score may obtain less benefit from warfarin therapy and should be considered for other available oral anticoagulants for maximum benefit.展开更多
Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging.There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleed...Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging.There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism.Presently,the treatments available to reverse warfarin-induced bleeding are vitamin K,fresh frozen plasma,prothrombin complex concentrates and recombinant activated factor Ⅶa.Currently,vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding.The safe use of prothrombin complex concentrates and recombinant activated factor Ⅶa in patients with mechanical heart valves is controversial and needs well-designed clinical studies.With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves,the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed.In this review article,we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve.Furthermore,there is an urgent need for separate specific guidelines from major associations/professional societies with regard to mechanical heart valves and warfarin-induced bleeding.展开更多
Dental?hemorrhagic?complications,?including?postoperative?bleeding?and?traumatic?hemorrhage?as?emergency?cases,?often?occur?in?patients?undergoing?oral?anticoagulant?therapy?such?as?warfarin?therapy.?Recent?research?r...Dental?hemorrhagic?complications,?including?postoperative?bleeding?and?traumatic?hemorrhage?as?emergency?cases,?often?occur?in?patients?undergoing?oral?anticoagulant?therapy?such?as?warfarin?therapy.?Recent?research?recommends?that?warfarin?dosage?should?be?assessed?every?12?weeks.?Therefore,?most?physicians?generally?accept?international?normalized?ratio?(INR)?monitoring?at?longer?intervals.?However,?cases?are?encountered?in?which?the?INR?prolongation?is?observed?despite?of?invariable?dosage?of?warfarin.?In?this?report,?we?present?2?cases?of?patients?with?dental?hemorrhagic?complications?undergoing?oral?anticoagulant?therapy?who?exhibited?excessive?INR?prolongation.?These?patients?exhibited?decreased?appetite?and?hypoalbuminemia. We?speculate?that?long-term?appetite?loss?resulted?in?the?increase?in?the?serum?concentration?of?free?warfarin and?vitamin?K deficiency. Our?study?indicates that we?should?notice malnourishment?when?we?treat patients?who?have?undergone?warfarin?therapy with dental?surgical procedures.?It?is?recommended?that measurement?of?INR just before?a?dental?surgical?treatment.展开更多
Objective: The objective of this study was to analyse the reversibility of the anticoagulant effect of warfarin by comparing prothrombin complex concentrate (PCC) versus frozen fresh plasma (FFP) in cardiology patient...Objective: The objective of this study was to analyse the reversibility of the anticoagulant effect of warfarin by comparing prothrombin complex concentrate (PCC) versus frozen fresh plasma (FFP) in cardiology patients with serious warfarin intoxication. Methods: This was an observational and retrospective study comprising 67 patients (18 in group I [PCC] and 49 in group II [FFP]). The primary endpoint was the reversal of anticoagulant effect of warfarin after 2 and 24 hours of PCC or FFP administration. Comparisons between the groups were made using T-test and Q-square. Multivariate analyses were conducted using logistic regression, and the results were considered significant when p Results: The medium dose used was 27.6 UI/kg of PCC and 14.5 ml/kg of FFP. Significant differences were observed between groups I and II in the INR reversibility measurements after 2 hours (33.3% vs. 6.1%, p = 0.001) and 24 hours (38.9% vs. 12.2%, p = 0.009) as well as in the occurrence of pulmonary edema (5.6% vs. 42.9%, OR = 11.10, p = 0.04). The AUC for PCC was 0.891 (CI 95% [0.72 - 1.0]), and for FFP, it was 0.291 (CI 95% [0.09 - 0.49]). Conclusions: PCC is better than FFP treatment in reversing the warfarin intoxication after 2 and 24 hours of administration. Furthermore, PCC showed lower pulmonary edema in cardiology patients.展开更多
Background and Objectives: Based on the case reports of hemorrhagic complications, recommendations for the removal of lumbar plexus catheters in anticoagulated patients were created. These guidelines are controversial...Background and Objectives: Based on the case reports of hemorrhagic complications, recommendations for the removal of lumbar plexus catheters in anticoagulated patients were created. These guidelines are controversial as they limit the use of lumbar plexus blocks in postoperative anticoagulated patients. This study was designed to evaluate the incidence of hemorrhagic complications and coagulation status using International Normalized Ratio (INR) at the time of lumbar plexus catheter removal in patients receiving warfarin after total hip replacement. Methods: A retrospective study of 371 patients on warfarin thromboprophylaxis who received continuous lumbar plexus catheters for postoperative analgesia after total hip surgery was performed. The primary outcome measure was the incidence of bleeding complications after catheter removal;secondary outcome measures included warfarin dose, bridge therapy, incidence of deep vein thrombosis, pulmonary embolism (DVT/PE) and INR values upon catheter removal. Results: Almost all lumbar plexus catheters (93%;344/371) were removed at 72 hours. At the time of catheter removal, mean INR was 1.99 [1.42-2.41] (p = 0.015);67% of patients had an INR > 1.5 and half of these patients had INRs between 2.0-3.0;5% had INR’s between 3.0-4.0. There were no adverse bleeding complications or nerve injury after the removal of catheters. Conclusions: We observed no incidence of bleeding after lumbar plexus catheter removal despite 67 % of patients demonstrating INR’s > 1.5. Our retrospective analysis illustrates the relative safety of catheter removal in anticoagulated patients and suggests that the removal of lumbar plexus catheters can be safely performed with an INR > 1.5 in patients receiving warfarin.展开更多
Introduction: Effective anticoagulation depends on demographic factors, patient education, drug knowledge and compliance. The aim of our study is to determine the factors that influence compliance to warfarin in the m...Introduction: Effective anticoagulation depends on demographic factors, patient education, drug knowledge and compliance. The aim of our study is to determine the factors that influence compliance to warfarin in the mechanical valve patient population and its relationship with thrombo-embolic and bleeding events. Patients and Methods: 113 patients underwent mechanical valve replacement (Aortic, mitral or both) at King Abdul-Aziz University Hospital, from 2006 to 2012, patients divided into two groups according to warfarin compliant. Results: 113 patients reviewed in our study, 69 (61.1%) patients found compliant, 36 (31.9%) patients found non compliant, and 8 (7.1%) patients missed. The mean age for all patients was 39.25 y: 76 (67.3%) ware male, 37 (32.7%) were female. Mean age for compliant patients was 40.19 y versus 33.3 y for noncompliant patients with p value 0.017. Male patient less complaint than female with significant 0.01, the mean frequency of follow up was less (32.32 days) in compliant vs. (67.73 days) in non complaint patient. Conclusion: younger age, female gender, Arabic race, assistance at home, education, and single drug use are factors associated with patient compliant, non compliance are associated with higher mortality and valve related complication.展开更多
Background and Aim: Mechanical prosthetic heart valves exert a lifelong thromboembolic complication requiring continuous antithrombotic therapy. Vitamin K antagonist is the recommended therapy of choice along with met...Background and Aim: Mechanical prosthetic heart valves exert a lifelong thromboembolic complication requiring continuous antithrombotic therapy. Vitamin K antagonist is the recommended therapy of choice along with meticulous INR monitoring to achieve and maintain an INR of 2.0 - 3.0. The study aimed to assess the compliance of anticoagulant therapy in pediatric patients after AVR and to highlight the challenges faced during follow-ups. Methods: A retrospective study was conducted at NICVD Hospital in Karachi, Pakistan for a time frame of 2 years from 2020-2021 where 7 patients were selected. Data were collected using hospital medical records and then validated through a phone call mediated structured questionnaire-based interview. Results: 2 out of 7 patients in the case series were compliant to regular follow-ups and had their INR in the desired range owing to their higher education status and access to INR clinic for regular follow-up in urban setting. Younger patients in the case series were non-compliant. 4 out of 7 patients who were on dual anti-coagulant regimens including warfarin and aspirin were either closer or within the range than compared to those on single drug regimen. Conclusion: Compliance was observed in patients who had favorable demographics and higher education. Multiple recent trials including PROACT and PROACT XA are underway to develop novel treatment options apart from warfarin after mechanical aortic valve replacement. Home-based INR testing kits provide easy access to regular testing in remote areas. Multi-center studies are required for in-depth analysis regarding reasons of non-compliance in pediatric population.展开更多
Dear Sir,Iam Dr Zhe Liu, from the Eye Center of Zhejiang Provincial People’s Hospital in Hangzhou, Zhejiang Province, China. I write to present a case report of massive subretinal haemorrhage in a patient with neovas...Dear Sir,Iam Dr Zhe Liu, from the Eye Center of Zhejiang Provincial People’s Hospital in Hangzhou, Zhejiang Province, China. I write to present a case report of massive subretinal haemorrhage in a patient with neovascular age-related macular degeneration (AMD) on warfarin therapy.Anticoagulants or antiplatelet agents have been commonly used to prevent thrombosis in cardiovascular diseases.展开更多
Background:Warfarin is widely regarded as the main anticoagulant in lowering the risk of thromboembolism.This study used indicators to compare pharmacist-managed anticoagulation services,using a well-prepared protocol...Background:Warfarin is widely regarded as the main anticoagulant in lowering the risk of thromboembolism.This study used indicators to compare pharmacist-managed anticoagulation services,using a well-prepared protocol,with physician-managed anticoagulation services・Methods:A retrospective prospective pilot study was conducted to compare patient outcomes before and after transitioning patients to phannacist-managed anticoagulation services,comparing the proportion of those with therapeutic international normalized ratio(INK),subtherapeutic INK,and supratherapeutic INR,as well as their bleeding occurrences as indicators of assuring quality care.Results:A significant improvement in anticoagulation management was noted in the transition to pharmacist-managed anticoagulation services.The proportion of those with subtherapeutic INR decreased from 61.8%to 11.8%(p<0.001),those with supratherapeutic INR decreased from 20.6%to 2.9%(p<0.001),those with therapeutic INR increased from 17.6%to 85.3%(p<0.001),and the occurrence of bleeding decreased from 11.8%to 0.0%,without significant difference in warfarin doses(median from 4 before the transition to 5 after);in addition,the time to reach therapeutic INR decreased from 12-24 weeks to 2-8 weeks after transitioning to pharmacist-managed anticoagulation services.Conclusion:Pharmacist-managed anticoagulation services are considered safer and more effective than physician-managed anticoagulation services alone in terms of patientsJ adherence and satisfaction,which provide an excellent opportunity for quality assurance care.展开更多
Objective To study perioperative management in treatment of traumatic intracranial hemorrhage in patients with pretraumatic anticoagulation therapy of oral warfarin.Methods 10 patients of traumatic intracranial hemorr...Objective To study perioperative management in treatment of traumatic intracranial hemorrhage in patients with pretraumatic anticoagulation therapy of oral warfarin.Methods 10 patients of traumatic intracranial hemorrhage with pretraumatic anticoagulation therapy of oral warfarin received vitamin K,FFP and PCC展开更多
Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warf...Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin (range 0.8‐1 μg per 1 cm 2 ) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA + ) cells indicated reparative processes in injured skin. Infiltration of CD3 + cells (T lymphocytes) along with the increased production of tumor necrosis factor‐α (TNF‐α) by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.展开更多
文摘BACKGROUND Randomized controlled trials(RCTs)of direct oral anticoagulants(DOACs)included a low proportion of atrial fibrillation(AF)patients with chronic kidney disease(CKD),and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD.In a metanalysis of RCTs and observational studies,DOACs were associated with better efficacy(vs warfarin)in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD.But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD.The effectiveness and safety of DOACs in those patients are still subject to debate.AIM To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population.METHODS A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017.The primary effectiveness outcome was a composite of ischemic stroke,systemic embolism,and death,whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation.Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards.RESULTS A total of 8899 included patients filled out a new oral anticoagulation therapy claim;3335 for warfarin and 5564 for DOACs.Compared with warfarin,15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk.Apixaban 5.0 mg was associated with a lower effectiveness composite risk[Hazard ratio(HR)0.76;95%confidence interval(CI):0.65-0.88]and a similar safety risk(HR 0.94;95%CI:0.66-1.35).Apixaban 2.5 mg was associated with a similar effectiveness composite(HR 1.00;95%CI:0.79-1.26)and a lower safety risk(HR 0.65;95%CI:0.43-0.99.Although,apixaban 5.0 mg was associated with a better effectiveness(HR 0.76;95%CI:0.65-0.88),but a similar safety risk profile(HR 0.94;95%CI:0.66-1.35).The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality(HR 0.61;95%CI:0.43-0.88).CONCLUSION In comparison with warfarin,rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.
文摘BACKGROUND Heparin is commonly recommended for warfarin-induced skin necrosis;however, there is currently no established therapy for this disease. We present a serious case of warfarin-induced skin necrosis that was successfully treated with oral rivaroxaban, a factor Xa inhibitor.CASE SUMMARY A 48-year-old woman was admitted to the hospital for cellulitis of the right lower extremity. After antibiotic treatment, she developed pain and swelling of the left lower extremity, and deep vein thrombosis of both lower extremities was diagnosed. She was treated with a continuous heparin injection;subsequently,oral warfarin was concomitantly administered. Heparin was terminated after the therapeutic range was reached. On the following day, the patient had swelling and pain in the left lower extremity. In addition to decrease in protein S activity due to systemic lupus erythematosus, warfarin also reduced protein C activity,resulting in further hypercoagulation and skin necrosis. Warfarin was discontinued, and continuous heparin injection was resumed. Although the patient had to undergo amputation of the distal end of her left foot, continuous heparin injection was switched to oral rivaroxaban, and she was eventually discharged from the hospital in remission.CONCLUSION Administration of direct oral anticoagulants instead of warfarin is important in patients with decreased protein S and C activity.
基金the Health System Research Institute(59-053)the Heart Association of Thailand under the Royal Patronage of H.M.the King.All authors had no conflicts of interest to disclose.The authors gratefully acknowledge Pontawee Kaewcomdee and Olaree Chaiphet for data management,and all investigators and nurse coordinators of the COOL-AF registry.
文摘Background Asian population are at increased risk of bleeding during the warfarin treatment,so the recommended optimal international normalized ratio(INR)level may be lower in Asians than in Westerners.The aim of this prospective multicenter study was to determine the optimal INR level in Thai patients with non-valvular atrial fibrillation(NVAF).Methods Patients with NVAF who were on warfarin for stroke prevention were recruited from 27 hospitals in the nationwide COOL-AF registry in Thailand.We collected demographic data,medical history,risk factors for stroke and bleeding,concomitant disease,electrocardiogram and laboratory data including INR and antithrombotic medications.Outcome measurements included ischemic stroke/transient ischemic attack(TIA)and major bleeding.Optimal INR level was assessed by the calculation of incidence density for six INR ranges(<1.5,1.5–1.99,2–2.49,2.5–2.99,3–3.49,and≥3.5).Results A total of 2,232 patients were included.The mean age of patients was 68.5±10.6 years.The mean follow-up duration was 25.7±10.6 months.There were 63 ischemic stroke/TIA and 112 major bleeding events.The lowest prevalence of ischemic stroke/TIA and major bleeding events occurred within the INR range of 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.Conclusions The INR range associated with the lowest risk of ischemic stroke/TIA and bleeding in the Thai population was 2.0–2.99 for patients<70 years and 1.5–2.99 for patients≥70 years.The rates of major bleeding and ischemic stroke/TIA were both higher than the rates reported in Western population.
文摘BACKGROUND Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation(AF)originated from western countries.AIM To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran,rivaroxaban,and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODS Medline,Cochrane,and ClinicalTrial.gov databases were reviewed.A randomeffect model meta-analysis was used and I-square was utilized to assess the heterogeneity.The primary outcome was ischemic stroke.The secondary outcomes were all-cause mortality,major bleeding,intracranial hemorrhage,and gastrointestinal bleeding.RESULTS Twelve studies from East Asia or Southeast Asia and 441450 patients were included.Dabigatran,rivaroxaban,and apixaban were associated with a significant reduction in the incidence of ischemic stroke[hazard ratio(HR)=0.78,95%confidence interval(CI):0.65-0.94;HR=0.79,95%CI:0.74-0.85,HR=0.70,95%CI:0.62-0.78;respectively],all-cause mortality(HR=0.68,95%CI:0.56-0.83;HR=0.66,95%CI:0.52-0.84;HR=0.66,95%CI:0.49-0.90;respectively),and major bleeding(HR=0.61,95%CI:0.54-0.69;HR=0.70,95%CI:0.54-0.90;HR=0.58,95%CI:0.43-0.78;respectively)compared to warfarin.CONCLUSION Dabigatran,rivaroxaban,and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.
文摘Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole;15 patients took omeprazole;30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 - 12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.
文摘BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.
文摘Purpose: This study was performed to assess the utility and safety of an In-Office INR Monitoring Device and present a safe and efficient protocol for the management of patients on oral anticoagulants and/or antithrombolytics requiring routine office oral and maxillofacial surgery. Patients and Methods: Sixty-one patients requiring “minor” oral and maxillofacial surgery being treated chronically with oral anticoagulation (warfarin) were entered into the study and compared in 2 groups. The control group (n = 29) was managed by discontinuing warfarin and any anti-platelet medication(s) prior to surgery. In the study group (n = 30), the decision to continue or withhold warfarin was determined by a protocol in which patients are 1) stratified based on risk for thromboembolism, and 2) classified as requiring “major” or “minor” surgery. Procedures categorized as “minor” surgery included dental extraction(s), dental implants, soft tissue and bone biopsies, and preprosthetic bone surgery, and incision and drainage. Warfarin and antiplatelet medication were not withheld in these patients, and a Point-of-Care In-Office INR Monitoring Device was used to obtain INR levels on the day of consultation and surgery. Local measures including removal of granulation tissue, packing, suturing, etc. were utilized for hemostasis. Results: The 30 patients in the study group maintained on warfarin readily achieved hemostasis using intraoperative local measures. The mean INR measured by the In-Office INR Monitoring Device was 2.36 with a range from 1.3 to 3.2. Study group patients underwent a total of 131 separate procedures including 108 dental extractions (impactions), placement of dental implants, preprosthetic bony surgery, bone cyst removal, soft tissue biopsies, facial skin cancer repair, and incision and drainage. One patient (3%) required “minor” intervention with removal of a “liver clot” on postop day 2 with repacking and suturing. The 29 patients in the control group discontinued off of war farin underwent a total of 99 procedures. One patient (3%) also required a “minor” intervention (repacking of extraction site). There were no “major” complications in either group. Conclusions: This study supports previous studies that minor oral surgery procedures can be safely performed while maintaining patients on warfarin minimizing the risk of a potentially devastating thromboembolic event. When deciding whether or not to withhold warfarin, this study supports the use of the proposed protocol based on 1) risk stratification for thromboembolism, 2) the need for “minor” versus “major” surgery, 3) and utilization of an In-Office INR Monitoring Device. An In-Office Point-of-Care INR measuring device can be a very effective tool to safely simplify and make the perioperative management of the anticoagulated patient more efficient for the patient and oral and maxillo facial surgeon.
文摘BACKGROUND The quality of warfarin therapy can be determined by the time in the therapeutic range(TTR)of international normalized ratio(INR).The estimated minimum TTR needed to achieve a benefit from warfarin therapy is≥60%.AIM To determine TTR and the predictors of poor TTR among atrial fibrillation patients who receive warfarin therapy.METHODS A retrospective observational study was conducted at a cardiology referral center in Selangor,Malaysia.A total of 420 patients with atrial fibrillation and under follow-up at the pharmacist led Warfarin Medication Therapeutic Adherence Clinic between January 2014 and December 2018 were included.Patients’clinical data,information related to warfarin therapy,and INR readings were traced through electronic Hospital Information system.A data collection form was used for data collection.The percentage of days when INR was within range was calculated using the Rosendaal method.The poor INR control category was defined as a TTR<60%.Predictors for poor TTR were further determined by using logistic regression.RESULTS A total of 420 patients[54.0%male;mean age 65.7(10.9)years]were included.The calculated mean and median TTR were 60.6%±20.6%and 64%(interquartile range 48%-75%),respectively.Of the included patients,57.6%(n=242)were in the good control category and 42.4%(n=178)were in the poor control category.The annual calculated mean TTR between the year 2014 and 2018 ranged from 59.7%and 67.3%.A high HAS-BLED score of≥3 was associated with poor TTR(adjusted odds ratio,2.525;95%confidence interval:1.6-3.9,P<0.001).CONCLUSION In our population,a high HAS-BLED score was associated with poor TTR.This could provide an important insight when initiating an oral anticoagulant for these patients.Patients with a high HAS-BLED score may obtain less benefit from warfarin therapy and should be considered for other available oral anticoagulants for maximum benefit.
文摘Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging.There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism.Presently,the treatments available to reverse warfarin-induced bleeding are vitamin K,fresh frozen plasma,prothrombin complex concentrates and recombinant activated factor Ⅶa.Currently,vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding.The safe use of prothrombin complex concentrates and recombinant activated factor Ⅶa in patients with mechanical heart valves is controversial and needs well-designed clinical studies.With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves,the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed.In this review article,we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve.Furthermore,there is an urgent need for separate specific guidelines from major associations/professional societies with regard to mechanical heart valves and warfarin-induced bleeding.
文摘Dental?hemorrhagic?complications,?including?postoperative?bleeding?and?traumatic?hemorrhage?as?emergency?cases,?often?occur?in?patients?undergoing?oral?anticoagulant?therapy?such?as?warfarin?therapy.?Recent?research?recommends?that?warfarin?dosage?should?be?assessed?every?12?weeks.?Therefore,?most?physicians?generally?accept?international?normalized?ratio?(INR)?monitoring?at?longer?intervals.?However,?cases?are?encountered?in?which?the?INR?prolongation?is?observed?despite?of?invariable?dosage?of?warfarin.?In?this?report,?we?present?2?cases?of?patients?with?dental?hemorrhagic?complications?undergoing?oral?anticoagulant?therapy?who?exhibited?excessive?INR?prolongation.?These?patients?exhibited?decreased?appetite?and?hypoalbuminemia. We?speculate?that?long-term?appetite?loss?resulted?in?the?increase?in?the?serum?concentration?of?free?warfarin and?vitamin?K deficiency. Our?study?indicates that we?should?notice malnourishment?when?we?treat patients?who?have?undergone?warfarin?therapy with dental?surgical procedures.?It?is?recommended?that measurement?of?INR just before?a?dental?surgical?treatment.
文摘Objective: The objective of this study was to analyse the reversibility of the anticoagulant effect of warfarin by comparing prothrombin complex concentrate (PCC) versus frozen fresh plasma (FFP) in cardiology patients with serious warfarin intoxication. Methods: This was an observational and retrospective study comprising 67 patients (18 in group I [PCC] and 49 in group II [FFP]). The primary endpoint was the reversal of anticoagulant effect of warfarin after 2 and 24 hours of PCC or FFP administration. Comparisons between the groups were made using T-test and Q-square. Multivariate analyses were conducted using logistic regression, and the results were considered significant when p Results: The medium dose used was 27.6 UI/kg of PCC and 14.5 ml/kg of FFP. Significant differences were observed between groups I and II in the INR reversibility measurements after 2 hours (33.3% vs. 6.1%, p = 0.001) and 24 hours (38.9% vs. 12.2%, p = 0.009) as well as in the occurrence of pulmonary edema (5.6% vs. 42.9%, OR = 11.10, p = 0.04). The AUC for PCC was 0.891 (CI 95% [0.72 - 1.0]), and for FFP, it was 0.291 (CI 95% [0.09 - 0.49]). Conclusions: PCC is better than FFP treatment in reversing the warfarin intoxication after 2 and 24 hours of administration. Furthermore, PCC showed lower pulmonary edema in cardiology patients.
文摘Background and Objectives: Based on the case reports of hemorrhagic complications, recommendations for the removal of lumbar plexus catheters in anticoagulated patients were created. These guidelines are controversial as they limit the use of lumbar plexus blocks in postoperative anticoagulated patients. This study was designed to evaluate the incidence of hemorrhagic complications and coagulation status using International Normalized Ratio (INR) at the time of lumbar plexus catheter removal in patients receiving warfarin after total hip replacement. Methods: A retrospective study of 371 patients on warfarin thromboprophylaxis who received continuous lumbar plexus catheters for postoperative analgesia after total hip surgery was performed. The primary outcome measure was the incidence of bleeding complications after catheter removal;secondary outcome measures included warfarin dose, bridge therapy, incidence of deep vein thrombosis, pulmonary embolism (DVT/PE) and INR values upon catheter removal. Results: Almost all lumbar plexus catheters (93%;344/371) were removed at 72 hours. At the time of catheter removal, mean INR was 1.99 [1.42-2.41] (p = 0.015);67% of patients had an INR > 1.5 and half of these patients had INRs between 2.0-3.0;5% had INR’s between 3.0-4.0. There were no adverse bleeding complications or nerve injury after the removal of catheters. Conclusions: We observed no incidence of bleeding after lumbar plexus catheter removal despite 67 % of patients demonstrating INR’s > 1.5. Our retrospective analysis illustrates the relative safety of catheter removal in anticoagulated patients and suggests that the removal of lumbar plexus catheters can be safely performed with an INR > 1.5 in patients receiving warfarin.
文摘Introduction: Effective anticoagulation depends on demographic factors, patient education, drug knowledge and compliance. The aim of our study is to determine the factors that influence compliance to warfarin in the mechanical valve patient population and its relationship with thrombo-embolic and bleeding events. Patients and Methods: 113 patients underwent mechanical valve replacement (Aortic, mitral or both) at King Abdul-Aziz University Hospital, from 2006 to 2012, patients divided into two groups according to warfarin compliant. Results: 113 patients reviewed in our study, 69 (61.1%) patients found compliant, 36 (31.9%) patients found non compliant, and 8 (7.1%) patients missed. The mean age for all patients was 39.25 y: 76 (67.3%) ware male, 37 (32.7%) were female. Mean age for compliant patients was 40.19 y versus 33.3 y for noncompliant patients with p value 0.017. Male patient less complaint than female with significant 0.01, the mean frequency of follow up was less (32.32 days) in compliant vs. (67.73 days) in non complaint patient. Conclusion: younger age, female gender, Arabic race, assistance at home, education, and single drug use are factors associated with patient compliant, non compliance are associated with higher mortality and valve related complication.
文摘Background and Aim: Mechanical prosthetic heart valves exert a lifelong thromboembolic complication requiring continuous antithrombotic therapy. Vitamin K antagonist is the recommended therapy of choice along with meticulous INR monitoring to achieve and maintain an INR of 2.0 - 3.0. The study aimed to assess the compliance of anticoagulant therapy in pediatric patients after AVR and to highlight the challenges faced during follow-ups. Methods: A retrospective study was conducted at NICVD Hospital in Karachi, Pakistan for a time frame of 2 years from 2020-2021 where 7 patients were selected. Data were collected using hospital medical records and then validated through a phone call mediated structured questionnaire-based interview. Results: 2 out of 7 patients in the case series were compliant to regular follow-ups and had their INR in the desired range owing to their higher education status and access to INR clinic for regular follow-up in urban setting. Younger patients in the case series were non-compliant. 4 out of 7 patients who were on dual anti-coagulant regimens including warfarin and aspirin were either closer or within the range than compared to those on single drug regimen. Conclusion: Compliance was observed in patients who had favorable demographics and higher education. Multiple recent trials including PROACT and PROACT XA are underway to develop novel treatment options apart from warfarin after mechanical aortic valve replacement. Home-based INR testing kits provide easy access to regular testing in remote areas. Multi-center studies are required for in-depth analysis regarding reasons of non-compliance in pediatric population.
基金Supported by Zhejiang Innovation Program for Graduates, China(No.YK2010015)
文摘Dear Sir,Iam Dr Zhe Liu, from the Eye Center of Zhejiang Provincial People’s Hospital in Hangzhou, Zhejiang Province, China. I write to present a case report of massive subretinal haemorrhage in a patient with neovascular age-related macular degeneration (AMD) on warfarin therapy.Anticoagulants or antiplatelet agents have been commonly used to prevent thrombosis in cardiovascular diseases.
文摘Background:Warfarin is widely regarded as the main anticoagulant in lowering the risk of thromboembolism.This study used indicators to compare pharmacist-managed anticoagulation services,using a well-prepared protocol,with physician-managed anticoagulation services・Methods:A retrospective prospective pilot study was conducted to compare patient outcomes before and after transitioning patients to phannacist-managed anticoagulation services,comparing the proportion of those with therapeutic international normalized ratio(INK),subtherapeutic INK,and supratherapeutic INR,as well as their bleeding occurrences as indicators of assuring quality care.Results:A significant improvement in anticoagulation management was noted in the transition to pharmacist-managed anticoagulation services.The proportion of those with subtherapeutic INR decreased from 61.8%to 11.8%(p<0.001),those with supratherapeutic INR decreased from 20.6%to 2.9%(p<0.001),those with therapeutic INR increased from 17.6%to 85.3%(p<0.001),and the occurrence of bleeding decreased from 11.8%to 0.0%,without significant difference in warfarin doses(median from 4 before the transition to 5 after);in addition,the time to reach therapeutic INR decreased from 12-24 weeks to 2-8 weeks after transitioning to pharmacist-managed anticoagulation services.Conclusion:Pharmacist-managed anticoagulation services are considered safer and more effective than physician-managed anticoagulation services alone in terms of patientsJ adherence and satisfaction,which provide an excellent opportunity for quality assurance care.
文摘Objective To study perioperative management in treatment of traumatic intracranial hemorrhage in patients with pretraumatic anticoagulation therapy of oral warfarin.Methods 10 patients of traumatic intracranial hemorrhage with pretraumatic anticoagulation therapy of oral warfarin received vitamin K,FFP and PCC
基金supported by the Ministry of Science and Technological Development of the Republic of Serbia, Grant # 143038
文摘Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin (range 0.8‐1 μg per 1 cm 2 ) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA + ) cells indicated reparative processes in injured skin. Infiltration of CD3 + cells (T lymphocytes) along with the increased production of tumor necrosis factor‐α (TNF‐α) by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.
