Mean Warfarin Dose Research Articles

Impact of Initial Warfarin Dosing on Time in Therapeutic Range for Postoperative Left Ventricular Assist Device Patients.

Initial warfarin dosing and time in therapeutic range (TTR) are poorly characterized for early post-operative left ventricular assist device (LVAD) patients. This study evaluated TTR after LVAD implantation compared between patients receiving low-dose (<3 mg) and high-dose (≥3 mg) warfarin. This single-center, retrospective analysis included 234 LVAD patients who received warfarin within 5 days of implantation. The primary outcome was TTR during the 5 days following first international normalized ratio (INR) ≥2 compared between low-dose and high-dose groups. Secondary outcomes were hospital and intensive care unit length of stay, time to first INR ≥2, TTR after first INR ≥2, and reinitiation of parenteral anticoagulation. No difference in TTR was detected between warfarin groups (57.2% vs. 62.7%, P = 0.13). Multivariable analysis did not detect any factors predictive of TTR during the primary outcome timeframe, but age and body mass index were associated with the warfarin dose. The low-dose group received a mean warfarin dose of 1.9 mg (±0.64 mg), and the high dose group received 4.34 mg (±1.38 mg). Cohort TTR during the primary outcome timeframe was 60.5% and 56.5% for hospitalization. The low-dose group had longer intensive care unit length of stay, shorter time to therapeutic INR, and more frequently reinitiated parenteral anticoagulation. Patients with recent LVAD implantation are complex and have diverse warfarin sensitivity factors, which did not allow for optimal warfarin dose detection, although half of all patients received doses between 2.04 mg and 4.33 mg. Individualized dosing should be used, adjusting for patient-specific factors such as age, body mass index, and drug interactions.

A Multicentre Study on Average Warfarin Dose to Maintain Therapeutic International Normalised Ratio with Time in Therapeutic Range of More than 75% in Atrial Fibrillation Patients

Large interindividual variability and over-anticoagulation resulting bleeding complications due to narrow therapeutic index of warfarin has causes its pharmacodynamic activity to be highly variable. Studies shown that ethnicity, age and gender contribute to warfarin response variability. Good coagulation control of time in therapeutic range (TTR) &gt; 75% was chosen to determine the average warfarin dose in atrial fibrillation (AF) among ethnicity, age and gender. Data from Warfarin Medication Therapy Adherence Clinic of selected Pulau Pinang hospitals were used for the analysis of average warfarin dose in AF among ethnicity, age and gender. Patients who fulfilled the inclusion criteria from 2015–2016 were followed up for a year. Five hundred and seventy-six patients were included. Two hundred and ten patients had good coagulation control of TTR &gt; 75% with mean warfarin dose of 3.05 ± 1.25 mg. Only Chinese and Indian have significant difference in average warfarin dose with 2.86 ± 1.10 mg and 4.11 ± 1.40 mg, respectively (p = 0.008). Average warfarin dose was found not significantly different among gender and age. As for TTR achievement, 210 (36.4%) were able to achieve TTR &gt; 75%, 134 patients achieved TTR 60%–75% and 232 patients has TTR &lt; 60%. The median day to achieve three consecutive targeted international normalised ratio (INR) is 186.5 days for atrial fibrillation patient newly started on warfarin therapy in 2015 until 2016. Indian patients required a higher warfarin dose than Chinese patients. This study found that mean warfarin doses were not affected by age and sex.

Evaluation of Safety and Efficacy of Combined Low Dose Aspirin and Warfarin Following Mechanical Heart Valve Replacement for Mitral Valve Disease

Introduction: Warfarin is recommended following mechanical valve replacement to prevent thromboembolic complications. A combination of warfarin and aspirin may further reduce thromboembolic events in these patients. This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical mitral valve replacement. Materials and Methods: Purposively selected 99 patients who underwent mechanical mitral valve replacement were divided into two groups. Patients of Group A (n=50) received combined low dose aspirin (75mg) and warfarin. Patients of Group B (n=49) received conventional dose of warfarin alone. International normalized ratio (INR) was targeted 1.8-2.4 for group A Patients and 2.5-3.5 for group B Patients. Post-operatively INR, thromboembolic events, anti-coagulation related haemorrhage and other morbidity and mortality were registered in both groups. Result: Patients were followed up postoperatively for 9 months. The mean dose of warfarin in group A and group B was 4.36 ± 0.31 mg and 5.57±0.52 mg respectively (p&lt;0.001). The overall mean INR of two groups of patients were statistically different (P&lt;0.001) with low INR in group A (2.19±0.13) patients compared to group B (3.03±0.31). The thromboembolic events in group A (0.02/patient year) were lower than those in group B (0.08/Patient year). There was no statistically significant (p=0.362) difference in bleeding episodes between two groups but data indicate proportion of minor bleeding manifestations were higher in patients treated with warfarin plus aspirin group. Conclusion: Following mechanical mitral valve replacement, a combination of aspirin (75mg) and low dose warfarin with an aim to maintain INR between 1.8 and 2.4 (lower than recommended 2.5-3.5) may provide satisfactory outcomes in term of thrombosis, embolism and bleeding without increase in mortality. Bangladesh Heart Journal 2021; 36(1): 24-31

THE EFFECTS OF GENETIC AND NON GENETIC FACTORS ON WARFARIN DOSE RESPONSE IN VENOUS THROMBOEMBOLISM

BACKGROUND Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. METHODOLOGY In this review, we included patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose. We searched PubMed, Medline, Scopus, Google scholar and reference lists of relevant reviews. CONCLUSION Genetic and non-genetic factors affects the dose of warfarin. Genetic factors and Non genetic factors plays a signicant role and that may affects the dose of warfarin

Evaluation of the algorithm of Anticlot Assistant: an anticoagulant management system based on mobile health technology.

The purpose is to evaluate the algorithm of Anticlot Assistant, a novel anticoagulant management system based on mobile health technology which was developed to facilitate patient self-management. The eligible patients managed warfarin therapy with usual care, following the prescriptions of the doctors. The actual prescriptions of doctors and the virtual recommendations by Anticlot Assistant were compared and analyzed. There were no significant differences between the next test dates recommended by Anticlot Assistant and those prescribed by doctors. The mean warfarin dosage prescribed by doctors was lower than that recommended by Anticlot Assistant (2.74 ± 1.17 vs. 2.79 ± 1.21 mg, 95% confidence interval for the difference: -0.01--0.09, P = 0.019, n = 139), resulting in the international normalized ratio a high time below the therapeutic range (TTR) (29.9 ± 17.9%), and a low time above TTR [0.0% (0.0-18.7%)]. A mixed linear model revealed that 'the variations of the dosages prescribed by doctors from those recommended by Anticlot Assistant' were positively correlated with 'variations of next international normalized ratios from TTR' after controlling for other factors (estimate of the effect = 0.231, 95% confidence interval: 0.034-0.428, P = 0.022). Anticlot Assistant can mimic the doctors' prescriptions for the next test date and the warfarin dosages recommended by Anticlot Assistant might be more reasonable than those prescribed by doctors, which indicated that the algorithm was reliable and it was possible for the patients to manage warfarin therapy themselves with the aid of Anticlot Assistant.

Impact of body mass index on 90-day warfarin requirements: a retrospective chart review.

Background:Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin.Methods:This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18–24.9 kg/m2), Overweight (25–29.9 kg/m2), Obesity Class I (30–34.9 kg/m2), Obesity Class II (35–39.9 kg/m2), Obesity Class III (⩾40 kg/m2). The primary outcome was the mean 90-day warfarin dose required to maintain “intermediate control” or “good control” of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications.Results:A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg (p = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR.Conclusion:As BMI increases, there is an increased chronic warfarin requirement to maintain “intermediate control” or “good control” of INR between 2 and 3 in an ambulatory care setting.

The Contribution of VKORC1 and CYP2C9 Genetic Polymorphisms and Patients' Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm.

The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the objective to suggest a warfarin dosing algorithm. In this study, 185 patients with heart valve replacement from West Azerbaijan, Iran were genotyped for VKORC1 (-1639 G>A) and CYP2C9 (*2 and *3 alleles) by PCR-RFLP. Multiple linear regression was performed to create a new warfarin dosing algorithm. The frequency of variants in studied subjects was 12% for CYP2C9 *2, 25.8% for CYP2C9 *3, and 60% for -1639A. The patients who carried the A allele at position -1639 VKORC1 and the variants CYP2C9 *2 and *3 required a significantly lower daily mean warfarin dosage (P = 0.001). Statistical analysis also indicated a significant relationship between the daily maintenance dose of warfarin with age and blood pressure among the studied patients’ cohort (P < 0.001). This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warfarin dosing.

Anticoagulation Strategy in Patients with HeartMate II Undergoing Elective Surgery

Introduction Management of anticoagulation in patients with left ventricular assist devices (LVADs) undergoing elective invasive procedures or surgeries is challenging. We studied the patterns and outcomes of management of anticoagulation in patients with HeartMate II. Methods We prospectively included patients with HeartMate II, followed at our institution, who were scheduled for elective invasive procedures or surgeries, and recorded anticoagulation management. Primary outcome was bleeding or pump thrombosis within 3 months following the procedure. Chi square test was used to calculate statistical significance. Results A total of 29 patients underwent 41 elective procedures. Before procedure, all were taking warfarin. Their mean INR was 2.3±0.9, and mean dose of warfarin was 4.9±2 mg/day. Five patients had more than one procedure. Out of them, 21 had 34 elective invasive procedures or surgeries raging from endoscopy and dental extraction to ileostomy reversal. There was no significant blood loss, with hematocrit 32.1±6.4 and 32.2±6.0 before and after procedure, respectively. INR on the day of the procedure was 1.6±0.4. Bleeding or thrombotic events within three months of the procedure occurred in 5 cases (16.1%). Anticoagulation was continued without interruption in 9 (26.4%) cases, interrupted without bridging in 16 (52.8%), and interrupted with bridging with heparin/low molecular weight heparin in 9 (26.4%) cases. In those who had uninterrupted anticoagulation during the procedure, one patient (11.1%) had oral bleeding requiring hospitalization after teeth extraction. There were no thromboembolic events. In patients with interruption of warfarin but no bridging there were no bleeding complications but there was one pump thrombosis requiring the device exchange (6.3%). Patients who were bridged had 4 bleeding events and no thrombosis (44.4%), p Additionally, 10 patients had procedures in the catheterization laboratory, including right heart catheterization and cardiomems implantation. All of them continued routine anticoagulation with warfarin. Only one patient with history of recurrent gastrointestinal bleeding was admitted for GI bleeding one month after cardiomems implantation. Conclusions In patients with HeartMate II, bridging with low molecular weight heparin results in more bleeding events than continuing anticoagulation without interruption or interrupting warfarin without bridging.

Influence of CYP2C9 and VKORC1 on Warfarin Dose and Complications in Kazakhstani Patients with Left Ventricular Assist Device

Purpose The use of anti-platelet and anti-thrombotic therapy is a main stay in left ventricular assist devises (LVAD) to mitigate complicationssuch as pump thrombosis or systemic thromboembolism. Although multiple reports have documented the influence of CYP2C9 and VKORC1 variants on warfarin dose, risk of over-anticoagulation and hemorrhage, their influence on anticoagulation maintenance is limited. The purpose of this study is to evaluate the influence of CYP2C9 and VKORC1 polymorphisms on warfarin response and dosing algorithms in LVAD patients. Methods 100 patients implanted the HW, HM2, HM3 LVAD, irrespective of intended goal of therapy (either bridge to transplantation or destination therapy) after December 2011 at a single clinic - National Research Center for Cardiac Surgery, Astana, Kazakhstan with genotype data available for CYP2C9 (*1, *2, and *3 [rs1799853 and rs1057910]) and VKORC1 (-1639 G>A [rs9923231]) variants were included into study after institutional ethics committee approved the protocol. Postoperative warfarin dose, international normalized ratio (INR), and bleeding events were measured until discharge, 6 months, or composite end point (in-hospital MCS recovery, heart transplant, or death). Results 32.0% of patients with implanted LVADs had at least one polymorphism: VKORC1 (14.0%), CYP2C9*2 (15.0%), CYP2C9*2 and VKORC1 (3.0%). At discharge or before composite end point, patients with any polymorphism received a lower mean warfarin dosage than patients having no polymorphism (3.2±1.5 vs. 5.5±3.7 mg, p = 0.015) and achieved a similar mean INR (2.20±0.67 vs. 2.19±0.69, p = 0.96). There was no significant difference in bleeding rates within 6 months or before composite end point (6.13 vs. 8.02 events/patient-year, p = 0.13). Neither CYP2C9 nor VKORC1 influenced the risk of minor hemorrhage. CYP2C9 and VKORC1 explained 6.3% of the variance in dose change over the first days of therapy demonstrating that the usefulness of genotype-guided dosing may extend beyond first days of therapy. Conclusion This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in LVAD patients and demonstrates an impact of genetic factors on clinical outcomes and proof of concept that genotype data could be incorporated into Warfarin dosing algorithm in LVAD patients.

The effect of oral progesterone for the treatment of abnormal uterine bleeding in women taking warfarin following prosthetic valve replacement.

Objectives:To evaluate the effect of oral progesterone for the treatment of abnormal uterine bleeding in patients taking warfarin after prosthetic valve replacement.Methods:A total of 85 women of reproductive age, who were on warfarin due to prosthetic valve replacement were enrolled in the study. After detailed evaluation, their menstrual bleeding was quantified using Pictorial Bleeding Evaluation Chart. The patients were then prescribed an oral progesterone (Norethisterone) 5mg three times daily. The first follow up was done after one-month then at 3-months and at six months. The improvement in PBAC score was recorded at each visit. Data was entered and analyzed using SPSS (version 23.0). The mean ± Standard Deviation were calculated for quantitative variables while qualitative variables were presented in frequency table. The normality of data was checked using Kolmogorov-Smirnov test. Due lack of normal distribution of data in various groups, the Wilcoxon Sign Rank test was used to test the significance before and after treatment. The p-value of <0.05 was taken as statistically significant.Results:The mean age of the patients was 30.13±7.69 years. The mean PBAC score was 162.8 ± 24.86 before initiation of treatment while at the end of the treatment it was 105.48 ± 8.38. Forty-six (54.1%) patients had continuous per vaginal bleeding, 33 (38.8%) had menorrhagia, 4 (4.7%) had inter-menstrual bleeding and 2 (2.4%) had menorrhagia along with polymenorrhea. The mean dose of warfarin taken by the patients was 5.85 ± 2.69 mg. The median parity of the patients was 2. The Wilcoxon Sign Rank test showed p-value of <0.00001 for comparison of the pre-treatment PCBA values with those of one, three and six-months after the treatment. The Friedman’s test also had a p-value of <0.00001. This confirmed that the post treatment bleeding was significantly less than pretreatment bleeding.Conclusion:The warfarin induced abnormal uterine bleeding can be controlled effectively and safely with low dose of oral progesterone.

Warfarin Dose and CYP2C Gene Cluster: An African Ancestral-Specific Variant Is a Strong Predictor of Dose in Black South African Patients.

Warfarin is a widely prescribed anticoagulant with a narrow therapeutic index. The rs12777823G>A single-nucleotide polymorphism (SNP) in the CYP2C gene cluster has been shown to influence optimal warfarin doses in African Americans. We report here effects of rs12777823G>A SNP on warfarin dose requirements in two South African population groups, black Africans (BA) and mixed ancestry (MA). A total of 425 participants on warfarin treatment were enrolled in the study. The age group of the studied population ranged between 44 and 66 years, with 69% females enrolled. Genetic characterization of the rs12777823G>A was done using the TaqMan SNP genotyping assay. To further compare effects of rs12777823G>A to those of other SNPs, VKORC1 g.-1639G>A and 4 SNPs in CYP2C9 gene (i.e., CYP2C9 c.430C>T, c.1075A>C, c.449G>A, and c.1003C>T) were analyzed. The rs12777823A variant allele frequencies were 0.28 and 0.25 in the BA and MA, respectively. The rs12777823A/A genotype was associated with significantly (p = 0.002) reduced mean warfarin dosage (27 ± 5.3 mg/week) compared with the G/G genotype (45 ± 16.1 mg/week) among BA, but not among the MA. The rs12777823G>A is located in a nongenomic region, suggesting that this SNP might be in linkage disequilibrium with another, likely causal SNP that is present in BA only. Given ongoing worldwide efforts to identify clinically relevant human genetic variation impacting on optimal warfarin dose selection, the African ancestry-specific genetic variant in the CYP2C cluster and others warrant further research and consideration in development of future warfarin dosing algorithms for precision medicine guidelines.

Efficacy of Feracrylum as Topical Hemostatic Agent in Therapeutically Anticoagulated Patients Undergoing Dental Extraction: A Comparative Study.

To compare the efficacy of feracrylum with tranexamic acid (TXA), following dental extraction in patients who are therapeutically anticoagulated with warfarin. Sixty patients on warfarin were randomly divided into three groups. Groups 1 and 2 patients were given feracrylum (1%), and TXA (5%) solution pressure pack and a control group (Group 3) was given normal saline (NS) pressure pack after extraction. Postoperative bleeding was assessed and graded numerically and periodically (0, 1, 2, 5 and 7days). The values were statistically analyzed. Sixty patients (M:F::37:23) with a mean age of 56years who were therapeutically anticoagulated for different medical conditions were included. The mean warfarin dosage was 3.5mg, and the mean INR was 2.83. Out of 27 patients who showed bleeding on day of extraction, eight, ten and nine patients belonged to groups I, II and III, respectively, and the difference was nonsignificant. Out of 15 patients who showed bleeding on post-extraction day 1, one, five and nine patients belonged to groups I, II and III, respectively. The difference was statistically significant on day 1 and nonsignificant in the next follow-ups. Local hemostatic agents like TXA and feracrylum arrest bleeding without having any systemic action and without the necessity of altering the anticoagulant regimen. Feracrylum has an added advantage of a single application, formation of a mechanical barrier and an additional antimicrobial effect. These agents should be incorporated in the protocol for managing patients on oral anticoagulants.

The Influence of CYP4F2 Polymorphisms on Warfarin Doses in Korean Patients with a Variety of Diseases

Purpose We sought to determine if the CYP4F2 gene could affect warfarin maintenance dosage in Korean patients with a variety of diseases. CYP4F2 was reported to affect warfarin dose, but it was controversial. Some papers showed that CYP4F2 genotype could affect warfarin stable dose to some extent. But other papers reported that CYP4F2 genotype did not affect warfarin dose. Methods We enrolled 101 patients treated with warfarin in our registry. Non-genetic factors (clinical characteristics, stable warfarin dose, INR, medication information) and CYP4F2 polymorphisms were assessed. The definition of warfarin stable dose was the amount of medication given to maintain the patient’s INR within the target range throughout at least 3 consecutive laboratory measurements separated by at least 1 week. Each patient’s target therapeutic INR range was determined by the clinicians according to the indication for warfarin treatment. Results In our study, average patient age was 64.0± 11.9 years. Females accounted for 52% of the sample. The average warfarin maintenance dose was 3.26± 1.38 (1-9) mg/day. Compared with CYP4F2 wild type patients (GG), the patients carrying a CYP4F2 heterozygous variant (GA) or a CYP4F2 homozygous variant (AA) required higher warfarin dose. The mean warfarin dose in the patients with the CYP4F2 AA genotype was 4.1± 1.9 mg/day, while that for the patients with the CYP4F2 GA genotype was 3.3± 1.3 mg/day, and that for the patients with the CYP4F2 GG genotype was 3.0± 1.2 mg/day. The difference among them was significant (P= 0.038). Conclusion CYP4F2 polymorphisms statistically influenced the stability of warfarin maintenance dosage in Korean patients with a variety of diseases. Keywords: CYP4F2 polymorphisms, Warfarin dose, Korean

The influence of fibrate initiation on INR and warfarin dose in patients receiving chronic warfarin therapy.

Several drug interaction compendia report a risk of warfarin potentiation after initiation of a fibrate; however, the evidence of this interaction is limited. The objective of this study was to evaluate warfarin dose and international normalized ratio (INR) response among a large sample of patients receiving chronic warfarin who initiated a fibrate. This was a retrospective, one-sample, pre-to-post study. Adult patients who were receiving chronic warfarin therapy at the time of gemfibrozil or fenofibrate dispensing between 1/1/2000 and 3/31/2016 were included. Patients had at least one and two therapeutic INRs during the 90 days prior to (baseline) and after (follow-up), respectively, fibrate initiation. Comparison of stable warfarin dose:INR ratio between the baseline and follow-up periods and assessment of safety outcomes during follow-up were performed. There were 321 patients included. Patients were predominantly male (62.6%) with an indication of atrial fibrillation (44.2%). The mean warfarin dose:INR ratio was equivalent between the baseline and follow-up periods (13.4mg/INR [± 6.9] vs. 13.5mg/INR [± 7.5], respectively, p = 0.711). Rates of thromboembolism, bleeding, and all-cause mortality in the 90-day follow up were 0, 0.6, and 1.2%, respectively. Although individual patients may have labile INRs after fibrate initiation, no significant interaction between fibrate and warfarin in a large sample of real world patients was identified. The utility of additional INR monitoring after fibrate initiation in otherwise stable patients receiving chronic warfarin therapy is unclear.

Clinical profile, management and outcome of pulmonary embolism in Shahid Gangalal National Heart Centre, Kathmandu, Nepal.

Background and aimsPulmonary embolism (PE) is associated with a significant mortality and morbidity. We aim to study clinical profile, management and outcome of PE at Shahid Gangalal National heart Centre, Kathmandu, Nepal.MethodsIt was a retrprospective, single centre study, conducted from January 2015 to December 2016. Haemodynamics was used for risk Simplified, PESI score, predisposing factors, symptoms, clinical features at the time of admission, ECG features, echocardiogram, treatment received and the outcome were reviewed.ResultsDuring the study period 23 cases of PE were admitted. Nine were males and 14 were females. Eleven patients were diagnosed as provoked PE. High risk PE was diagnosed in four patients, Non-high risk in 19 patients. The most common clinical presentation was shortness of breath. The most common finding in ECG is sinus tachycardia followed by ST-T changes in V1-V3. Eight patient had SPO2 less than 90%. Most of the patients had a normal chest radiograph. Echocardiography revealed dilated RA and RV in 20 patients.All high risk PE patients were thrombolyzed with streptokinase. All patients who were diagnosed as Non-high risk PE were treated with LMWH. All the patients were treated with oral anticoagulants. Mean hospital stay was 9.7 ± 4.9 days. Two patients died during hospital stay. S-PESI score was 1.4 ± 0.9 respectively. Mean warfarin dose at the time of discharge was 5.9 ± 1.6 mg.ConclusionPE is an under diagnosed clinical problem world over. Suspicion is the most important part to come to the diagnosis of PE.

Clinical features and microsurgical treatment of warfarin-associated intracerebral hemorrhage (a report of 65 cases)

Objective To discuss the clinical features and surgical outcome of warfarin-associated intracerebral hemorrhage (WICH). Methods Sixty-five consecutive patients with WICH were admitted to Department of Neurosurgery, Beijing Anzhen Hospital, Capital Medical University, from January 2005 to May 2016. Their clinical presentation, therapies and outcomes were retrospectively analyzed and discussed with reference to the relevant literatures. Among these patients, 7 cases underwent drilling and drainage, intracranial hematomas were removed by small craniotomy in 50 cases, and both hematoma and bone were removed in the remaining 8 cases. Results The average volume of hematomas in 65 patients was (46.8±13.7) ml.The mean dose of warfarin was 1.5-6.0 mg/d and the average dose was(3.5±1.5) mg/d. The medication time was 3-72 with a mean of 27.8±3.4 months. When the intracerebral hemorrhage occurred, the international normalized ratio (INR) was 1.2-5.6 (mean, 2.7±1.2). WICH occurred in 48 (73.8%) patients within the recommended range of anticoagulation (INR: 2.0-3.0). There were no operative complications in the 65 patients. Based on the Glasgow coma scale (GOS), 28 cases (43.1%) were in grade Ⅴ, 15 cases (23.1%) in grade Ⅳ, 8 cases (12.3%) in grade Ⅲ, 5 cases (7.7%) in grade Ⅱ, and 9 cases (13.8%) in grade Ⅰ (13.8%). Nine cases (13.8%) died, among which 4 cases died due to rebleeding and multiple systemic organ failure occurred in the remaining 5 cases. Conclusion Appropriate surgical timing and surgical treatment of WICH could help prevent the enlargement of hemotomas, improve the prognosis and reduce its mortality. Key words: Intracerebral hemorrhage; Warfarin; Neurosurgical procedures; Anticoagulants

Predictors of warfarin dose requirements in South African patients attending an anticoagulation clinic

Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital. The most common indication for anticoagulation was atrial fibrillation (n=55, 37.4%). The mean warfarin dose was significantly higher in black patients as compared to white patients (5.4±2.9mg/day and 3.8±2.1mg/day, respectively; P<0.001). Older age was significantly associated with a lower maintenance warfarin dose (P<0.001). Drugs which decreased the international normalized ratio (INR) were significantly associated with a higher maintenance warfarin dose of 6.4±3.4mg/day (P<0.034). In contrast, there was no significant difference in warfarin dosage requirements in the presence of CYP2C9 and VKORC1 variant alleles (P>0.05). Patients, however, homozygous for CYP2C9 *1,*3, and VKORC1 required less than 5mg/day of warfarin to maintain the INR within the therapeutic range. In conclusion, this study indicates that clinical characteristics including; age, ethnic group, and drugs which decrease the INR might help to predict better dose requirements in this population group and thereby reduce the risk of bleeding and thrombotic complications.

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice

BackgroundPeople infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims...

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review.

BackgroundWarfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.ObjectiveTo explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.MethodsIn this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.ResultsWe identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.ConclusionVariants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.

The effects of Ramadan fasting on patients with prosthetic heart valve taking warfarin for anticoagulation

IntroductionOral anticoagulation with warfarin is indicated for patients with prosthetic heart valves. The effects of religious fasting during Ramadan month (in the Islamic calendar) on anticoagulation aren’t clear. ObjectivesTo study the impact of Ramadan fasting on international normalized ratio (INR), quality of anticoagulation, dose of warfarin used and blood osmolarity. Methods18 patients were followed-up prospectively for 3months (pre- Ramadan, Ramadan and post-Ramadan months). Patients presented for weekly visits in which blood samples were obtained. ResultsNo significant difference in INR and warfarin dose was found between Ramadan month, and months before and after it. The post-Ramadan INR was significantly larger than pre-Ramadan (p=0.004). Blood osmolarity was significantly lower during Ramadan compared to pre- and post-Ramadan months. A significantly better quality of anticoagulation was noticed during Ramadan (p<0.001). A significantly larger ratio of supratherapeutic INR values occurred in the post-Ramadan month (p<0.05). A significantly larger ratio of infra-therapeutic INR values was noticed in the pre-Ramadan month (p<0.05). ConclusionNo significant difference in mean INR or warfarin dose was found and a better quality of anticoagulation was achieved during Ramadan. A tendency toward supra-therapeutic anticoagulation occurred after Ramadan, thus a closer follow up during this period may be reasonable.