Psychological Status and Warfarin Therapy in Patients after Valve Replacement during the COVID-19 Pandemic:A Cross-sectional Study

Objective The standardization of warfarin anticoagulant therapy is the key to lifelong treatment for patients after heart valve replacement.The present study explored the possible risk factors for anxiety and depression during the coronavirus disease 2019(COVID-19)pandemic and analyzed the influence of psychological state on medication safety.Methods Eligible patients received a web-based questionnaire survey via the Wenjuanxing platform during outpatient visits.Depression was evaluated by the Self-Rating Depression Scale(SDS).Anxiety was evaluated by the Self-Rating Anxiety Scale(SAS).Medication adherence was evaluated by the Morisky scale.Results A total of 309 patients(aged 52.2±11.4 years)were included in the present study.The SDS score of all included patients was 36.9±9.4 points,of which 11(3.6%)patients were diagnosed as having depression.The SAS score of all included patients was 43.1±9.3 points,of which 71(23%)patients were diagnosed as having anxiety.Seven patients(2.3%)had both anxiety and depression.Logistic regression analysis revealed that only monthly income was an independent influencing factor for depression.Regarding anxiety,patients who underwent repeated operations had a 2.264-fold greater risk,and patients who received combination medication had a 2.140-fold greater risk.More bleeding events and coagulation disorders could be observed in patients with anxiety,depression or both.When anxiety occurred,patients showed worse medication adherence.However,depression had no significant effect on medication adherence.Conclusion During the COVID-19 pandemic,the detection rate of mental illnesses such as anxiety and depression was high,which seriously affected the medication safety of warfarin.Analysis of its influencing factors will provide a reference for further standardized regulation of warfarin anticoagulant therapy after valve replacement.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease

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.

CYP2C9酶与Warfarin结合模型的立体选择性理论研究

对CYP2C9酶与S-Warfarin复合物的晶体结构进行分子对接、分子动力学模拟、通道分析及结合自由能计算,发现原晶体结构中的结合模式为'亚稳态',提出了CYP2C9与S-Warfarin结合的可催化模式;比较了CYP2C9与S-和R-Warfarin结合的异同,确定了在结合过程中起重要作用的锚定氨基酸残基,尤其是位于活性位点区域的苯丙氨酸簇.在结合过程中这些残基通过芳香环的移动对稳定底物的结合模式起到至关重要的作用,阐明了该酶呈现相关底物选择性的原因.对于CYP2C9与底物对接模式及立体选择性的研究有助于在分子层面上理解特异性底物与酶的结合特点,为潜在的药物设计提供了合理可信的理论依据.

Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats

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.

Combined Low-dose Aspirin and Warfarin Anticoagulant Therapy of Postoperative Atrial Fibrillation Following Mechanical Heart Valve Replacement

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients （620 females, mean age of 36.8-4-7.7 years） admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study （warfarin plus 75-100 mg aspirin） or control （warfarin only） groups. International normalized ratio （INR） and prothrombin time were main- tained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respec- tively （P〉0.05）. The incidence of overall thromboembolic events in study group was lower than that in control group （2.16% vs. 4.35%, P=0.049）. No statistically significant differences were found in hem- orrhage events （3.53% vs. 3.95%, P=-0.722） or mortality （0.20% vs. 0.40%, P=0.559） between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

New modified multiwalled carbon nanotubes paste electrode for electrocatalytic oxidation and determination of warfarin in biological and pharmaceutical samples

A novel sensor for the determination of warfarin based on a simple and sensitive method was developed on multiwalled-carbon-nanotube modified ZnCrFeO4 carbon paste electrodes（MWCNT/ZnCrFeO4/CPEs）. Cyclic voltammetry, differential pulse voltammetry, chronoamperometry, and electrochemical impedance spectroscopy were used to investigate the electrochemical behavior of warfarin at the chemically modified electrode. According to the results, MWCNT/ZnCrFeO4/CPEs showed high electrocatalytic activity for warfarin oxidation, producing a sharp oxidation peak current at about ＋0.97 vs Ag/AgCl reference electrode at pH = 4.0. The peak current was linearly dependent on warfarin concentration over the range of 0.02–920.0 μmol/L with a detection limit of 0.003 μmol/L. In addition, chronoamperometry was also used to determine warfarin＇s catalytic rate constant and diffusion coefficient at MWCNT/ZnCrFeO4/CPEs.

Successful treatment of warfarin-induced skin necrosis using oral rivaroxaban: A case report

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.

Establishment of Occupational Exposure Limit for Warfarin in China

This study aims to establish the occupational exposure limit （OEL） in the air for workplace of warfarin based on the available toxicological studies and field investigations by using questionnaire and air monitoring. The clinical therapeutic dose was used as lowest observed effect level （LOEL）, and no observed effect level （NOEL） was achieved by using a safety factor. The highest concentration of warfarin monitored in the worksite of centrifuge washing, drying and packing were 0.029 mg/m3, 0.052 mg/m3 respectively, which did not exceed the OEL 0.2 mg/m3 recommended by NIOSH and ACGIH. Considering its feasibility for enforcement and protection for workers, we recommend OEL 0.2 mg/m3 of warfarin in China.

CYP4F2 polymorphism as a genetic risk factor for major hemorrhagic complications in Chinese patients on warfarin therapy

Warfarin is a commonly used anticoagulant with a narrow therapeutic range and risk of hemorrhagic complications. After CYP2C9 and VKORC1, CYP4F2 was confirmed as the third principle genetic determinant of warfarin dose variability.

Dabigatran,rivaroxaban,and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation:An updated metaanalysis

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.

基于Warfarindosing网站预测汉族人群华法林给药剂量与实际剂量的相关性研究

目的考察基于Warfarindosing网站预测汉族人群华法林剂量与实际剂量的相关性。方法选取某院2017年7月至2018年11月住院期间行华法林基因检测的108例汉族患者,记录其基本信息和华法林等用药情况,利用原位杂交荧光染色DNA测序的方法检测CYP2C9*3和VKORC1(-1639G>A)的基因型,并应用Warfarindosing网站预测患者华法林剂量,比较预测剂量与实际剂量差异。结果行基因检测的108例汉族患者中,以CYP2C9*1/*1 VKORC1AA基因型为主(71.30%),其次为CYP2C9*1/*1 VKORC1GA基因型(19.44%)。47例患者服用华法林,其中CYP2C9*1/*1 VKORC1 AA型患者实际剂量在预测剂量范围内的比例为82.85%(29/35),高于CYP2C9*1/*1 VKORC1 GA型患者实际初始剂量在预测剂量范围内的比例70.00%(7/10)。在院INR达标的23例患者中,CYP2C9*1/*1 VKORC1 AA型和CYP2C9*1/*1 VKORC1 GA型预测周剂量分别为(21.37±5.15)、(31.73±8.85)mg,实际维持周剂量分别为(21.29±6.26)、(27.00±6.00)mg,CYP2C9*1/*1 VKORC1 AA型预测的维持周剂量与实际维持周剂量差异无统计学意义,而CYP2C9*1/*1 VKORC1 GA型预测的维持周剂量显著大于实际维持周剂量。结论基于Warfarindosing网站预测汉族人华法林用药剂量具有一定的参考价值,可适用于汉族人群,尤其对CYP2C9*1/*1 VKORC1 AA型汉族患者华法林的周剂量预测准确性较高,具有较大的临床参考意义;但对于汉族CYP2C9*1/*1 VKORC1 GA基因型患者华法林的剂量预测亦存在局限性,有待于进一步临床研究。

Optimal INR level in elderly and non-elderly patients with atrial fibrillation receiving warfarin: a report from the COOL-AF nationwide registry in Thailand

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.

Interaction between Warfarin and Proton Pump Inhibitors

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.

Patients’time in therapeutic range on warfarin among atrial fibrillation patients in Warfarin Medication Therapy Adherence Clinic

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.

Management dilemmas in patients with mechanical heart valves and warfarin-induced major bleeding

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.

Effect of rifampicin on anticoagulation of warfarin:A case report

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.

Protocol for the management of oral surgery patients on warfarin utilizing a Point-of-Care In-Office international normalized ratio monitoring device

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.

Patients with dental hemorrhagic complicationsundergoing warfarin therapy exhibit excessiveinternational normalized ratio prolongation: A report of 2 cases

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.

Superiority of Prothrombin Complex Concentrate versus Frozen Fresh Plasma in Cardiology Patients with Warfarin Intoxication–Observational Study

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.

Continuous Lumbar Plexus Catheter Removal in Postoperative Total Hip Replacement Patients Receiving Warfarin Thromboprophylaxis: A Retrospective Analysis

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.