Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

The Relationship Between Preoperative International Normalized Ratio and Postoperative Major Bleeding in Total Shoulder Arthroplasty.

INTRODUCTION: This study aimed to assess the relationship between preoperative international normalized ratio (INR) levels and major postoperative bleeding events after total shoulder arthroplasty (TSA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for TSA from 2011 to 2020. A final cohort of 2405 patients with INR within 2 days of surgery were included. Patients were stratified into four groups: INR ≤ 1.0, 1.0 < INR ≤ 1.25, 1.25< INR ≤ 1.5, and INR > 1.5. The primary outcome was bleeding requiring transfusion within 72 hours, and secondary outcome variables included complication, revision surgery, readmission, and hospital stay duration. Multivariable logistic and linear regression analyses adjusted for relevant comorbidities were done. RESULTS: Of the 2,405 patients, 48% had INR ≤ 1.0, 44% had INR > 1.0 to 1.25, 7% had INR > 1.25 to 1.5, and 1% had INR > 1.5. In the adjusted model, 1.0 < INR ≤ 1.25 (OR 1.7, 95% CI 1.176 to 2.459), 1.25 < INR ≤ 1.5 (OR 2.508, 95% CI 1.454 to 4.325), and INR > 1.5 (OR 3.200, 95% CI 1.233 to 8.302) were associated with higher risks of bleeding compared with INR ≤ 1.0. DISCUSSION: The risks of thromboembolism and bleeding lie along a continuum, with higher preoperative INR levels conferring higher postoperative bleeding risks after TSA. Clinicians should use a patient-centered, multidisciplinary approach to balance competing risks.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation. We compared the percentage of time spent in the international normalized ratio acceptable range (%TIR) during the first 28 days following warfarin initiation, and %TIR and count of bleeding events over the entire follow-up period. Two hundred thirty-four participants were followed up to day 28 (NextDose: 116 and standard of care: 118), and 228 participants (114 per arm) were followed up to the final study visit. Median %TIR tended to be higher for participants receiving NextDose guided warfarin management during the first 28 days (63 vs. 56%, P = 0.13) and over the entire follow-up period (74 vs. 71%, P = 0.04). The hazard of clinically relevant minor bleeding events was lower for participants in the NextDose arm (hazard ratio: 0.21, P = 0.041). In NextDose, there were 89.3% of proposed doses accepted by prescribers. NextDose guided dose management in cardiac surgery patients requiring warfarin was associated with an increase in %TIR across the full follow-up period and fewer hemorrhagic events. A theory-based, pharmacologically guided approach facilitates higher quality warfarin anticoagulation. An important practical benefit is a reduced requirement for clinical experience of warfarin management.

Medical History and Preoperative Coagulation Profile as Predictors of Outcomes in Elective Spinal Surgery: A Meta-Analysis.

BACKGROUND: In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes. METHODS: Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models. RESULTS: Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI] =1.14, 1.77, P=0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P=0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P<0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P=0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95% CI=1.24, 4.73, P=0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P<0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P<0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P<0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P=<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P=< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P=<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P=<0.00001) were predictive of complications. CONCLUSIONS: Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history.

Plasma: indications, controversies, and opportunities.

Plasma is overused as a blood product worldwide; however, data supporting appropriate use of plasma is scant. Its most common utilization is for treatment of coagulopathy in actively bleeding patients; it is also used for coagulation optimization prior to procedures with specific coagulation profile targets. A baseline literature review in PUBMED and Google Scholar was done (1 January 2000 to 1 June 2023), utilizing the following search terms: plasma, fresh frozen plasma, lyophilized plasma, indications, massive transfusion protocol, liver disease, warfarin reversal, cardiothoracic surgery, INR < 2. An initial review of the titles and abstracts excluded all articles that were not focused on transfusional medicine. Additional references were obtained from citations within the retrieved articles. This narrative review discusses the main indications for appropriate plasma use, mainly coagulation factor replacement, major hemorrhage protocol, coagulopathy in liver disease, bleeding in the setting of vitamin K antagonists, among others. The correlation between concentration of coagulation factors and INR, as well as the proper plasma dosing with its volume being weight-based, is also discussed. A high value approach to plasma utilization is supported with a review of the clinical situations where plasma is overutilized or unnecessary. Finally, a discussion of novel plasma products is presented for enhanced awareness.

SAMe-TT2R2 Score to Predict Time in Therapeutic Range of Vitamin K Antagonists in Asian and Non-Asian patients: A Systematic Review and Meta-analysis.

BACKGROUND: Sex, age, medical history, treatment, tobacco use, and race (SAMe-TT2R2) score helps detect patients at risk of suboptimal anticoagulation control. A score above two suggests poor control; however, non-Caucasian status being assigned two points might hinder the recognition of poor control in patients of other races. OBJECTIVE: To evaluate the SAMe-TT2R2 score's ability to predict poor anticoagulation control [defined as time in therapeutic range (TTR) < 60-70%] in Asian and non-Asian populations on vitamin K antagonists (VKAs). METHODS: We searched PubMed, Cochrane Library, Scopus, SpringerLink, and Web of Science using the keyword "SAMe-TT2R2." Articles published before April 2022 were screened. We gathered mean TTR and diagnostic accuracy data for different SAMe-TT2R2 thresholds and conducted meta-analyses using random-effects models. RESULTS: A total of 30 studies were included (N = 36,690). The overall mean TTR differences were - 4.88 and - 6.41 for the cutoffs of ≥ 3 and ≥ 4, respectively. For non-Asian patients, the mean TTR differences were - 3.86, - 5.12, and - 8.09 for the cutoffs ≥ 2, ≥ 3, and ≥ 4, respectively. For Asian patients, the mean TTR differences were - 3.99 and - 4.07 for the cut-offs ≥ 3 and ≥ 4, respectively. The highest positive likelihood ratio (LR+) for the Asian subgroup was 1.17 [95% confidence interval (CI): 1.06-1.28; I2 = 0%, p heterogeneity = 0.500] at cutoff ≥ 4 and for the non-Asian subgroup, at cut-off ≥ 3, the LR+ was 1.24 (95% CI 1.14-1.34; I2 = 0% p heterogeneity = 0.455). The lowest LR- was found at a lower cutoff for both races (at cutoff ≥ 3 and ≥ 2 for Asian and non-Asian subgroups, respectively). The pooled results of other accuracy parameters were modest at all cutoffs, except for the sensitivity at cutoff ≥ 3 in the Asian subgroup (83.05%). CONCLUSION: Our study results suggest that a higher SAMe-TT2R2 score resulted in a greater reduction of TTR among Asian and all races. The accuracy parameters showed the highest sensitivity for poor TTR at the SAMe-TT2R2 cutoff of ≥ 3 for Asian patients. However, the ability to identify patients likely to have poor TTR was limited. Further research is needed to enhance the risk assessment for poor anticoagulation control with VKAs. REGISTRATION: The protocol of this systematic review was registered in the International Prospective Register of Scientific Reviews: PROSPERO, registration number CRD42021291865.

The Effect of High-Normal Preoperative International Normalized Ratios on Outcomes and Complications After Anterior Cervical Spine Surgery.

Hematoma after anterior cervical spine surgery can result in neurologic and airway compromise. Current guidelines recommend an international normalized ratio (INR) <1.5 before elective spine surgery because of increased complications. The risk associated with an INR of 1.25 is not well studied. The purpose of this study was to determine the risk of complications associated with a preoperative INR >1.25 and ≤1.5 in patients undergoing elective anterior cervical spine surgery. The American College of Surgeons National Surgical Quality Improvement Program database was queried. Patients undergoing elective anterior cervical spine surgery from 2012 to 2016 who had an INR recorded within 24 hours of surgery were included. Outcomes of interest included postoperative hematoma requiring surgery, 30-day mortality, and 30-day readmissions and reoperations. A total of 2949 patients were included. The incidence of a postoperative hematoma that required surgical management was 0.2%, 0.6%, and 4.5% in the INR≤1, 11.25 and ≤1.5 before elective anterior cervical spine surgery is associated with significantly higher rates of postoperative hematoma formation as well as 30-day readmission and reoperation; there was a trend toward significance in mortality rate. [Orthopedics. 2024;47(1):e26-e32.].

Anticoagulant drug-drug interactions with cannabinoids: A systematic review.

This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.

Increased age, bilirubin, international normalized ratio, and creatinine score to triglyceride ratio are associated with alcohol-associated primary liver carcinoma: a single-centered retrospective study.

BACKGROUND: This study analyzed the clinical features and biomarkers of alcohol-associated liver disease (ALD) to investigate the diagnostic value of age, bilirubin, international normalized ratio (INR), and creatinine (ABIC) score to triglyceride (TG) ratio (ABIC/TG) in ALD-associated primary liver carcinoma (PLC). MATERIALS AND METHODS: Data were collected from 410 participants with ALD, and the epidemiological and clinical records of 266 participants were analyzed. Participants were divided into ALD-without-PLC and ALD-associated-PLC groups. Relationships between clinical characteristics, biomarkers and ALD-associated PLC were estimated. Serum lipid levels and liver function were compared between ALD patients without PLC and patients with ALD-associated PLC. Scoring systems were calculated to investigate ALD severity. The robustness of the relationship was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Age and dyslipidemia were more strongly associated with ALD-associated PLC than with ALD-without PLC, with AORs of 2.39 and 0.25, respectively, with P less than 0.05. Drinking time and average daily intake, ABIC score, and ABIC/TG ratio were significantly higher in the ALD-associated-PLC group than in the ALD-without-PLC group. The AUC for the ABIC/TG ratio predicting the incidence of PLC was 0.80 (P < 0.01), which was higher than that of the ABIC and TG scores alone; additionally, the specificity and Youden index for the ABIC/TG ratio were also higher, and the cutoff value was 6.99. CONCLUSIONS: In ALD patients, age, drinking time, and average daily intake were risk factors for PLC. Drinking time, average daily intake, TG and ABIC score have diagnostic value for ALD-associated PLC. The ABIC/TG ratio had a higher AUC value and Youden index than the ABIC score and TG level.

Use of four-factor prothrombin complex concentrate (4F-PCC) for management of bleeding not associated with therapeutic anticoagulant use.

INTRODUCTION: Four-factor prothrombin complex concentrate (4F-PCC) may be an option for patients with bleeding unrelated to therapeutic anticoagulation to help with bleeding cessation and reduce blood component requirements. MATERIALS AND METHODS: Retrospective, observational study of adult patients who received 4F-PCC for bleeding not associated with therapeutic anticoagulation between June 2019 and July 2021. Primary outcome was to describe off-label 4F-PCC use in patients not on therapeutic anticoagulation for bleeding management in surgical and non-surgical patients. Additional outcomes evaluated were blood product use, chest tube and drainage output, and coagulation studies before and after 4F-PCC administration as well as other hemostatic agent use and thromboembolic events. RESULTS: Seventy-six patients were included; median age 64 years (IQR 50-69), 66% of bleeding events were associated with surgery, and the majority of 4F-PCC doses ordered by cardiac surgery (68.4%). A total of 110 4F-PCC doses were administered; median 1 dose/patient (IQR 1-2), median total dose 1000 units (IQR 500-1484). Other hemostatic agents commonly administered were protamine (59%), desmopressin (43%), and tranexamic acid (42%). Packed red blood cells, fresh frozen plasma, platelet, and cell saver blood administration and prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (aPTT) were significantly reduced following 4F-PCC administration. Eight patients (11%) experienced thromboembolic complications. CONCLUSION: Relatively low doses of 4F-PCC (median total dose 1000 units) were associated with decreased blood component requirements and improved PT, INR, and aPTT values in patients with bleeding unrelated to therapeutic anticoagulation. Other hemostatic agent use was common and thromboembolic complications occurred.

Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese.

PURPOSE: The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes. METHODS: We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0. FINDINGS: A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P = 0.016). IMPLICATIONS: Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing.

Prothrombin Time and International Normalized Ratio as Predictors of Factor VII Coagulation Activity in Pediatric Patients.

BACKGROUND: Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by determining protein level and coagulation activity (FVII:C). FVII:C measurements are expensive and time consuming. OBJECTIVES: To analyze correlations between PT, international normalized ratio (INR), and FVII:C in pediatric patients before otolaryngology surgery and to establish alternative methods for identifying FVII deficiency. METHODS: FVII:C data were collected from 96 patients with normal aPTT and prolonged PT values during preoperative otolaryngology surgery coagulation workup between 2016 and 2020. We compared demographic and clinical parameters using Spearman correlation coefficient and receiver operating characteristic (ROC) curve analysis to determine the accuracy of PT and INR values to predict FVII deficiency. RESULTS: The median values of PT, INR and FVII:C were 13.5 seconds, 1.14, and 67.5%, respectively. In total, 65 participants (67.7%) displayed normal FVII:C compared to 31 (32.3%) with decreased FVII:C. A statistically significant negative correlation was observed between FVII:C and PT values and between FVII:C and INR. Despite statistically significant ROC of 0.653 for PT (P-value = 0.017, 95% confidence interval [95%CI] 0.529-0.776) and 0.669 for INR (P-value = 0.08, 95%CI 0.551-0.788), we were unable to determine an optimal cutoff point to predict FVII:C deficiency with high sensitivity and high specificity. CONCLUSIONS: We could not identify a PT or INR threshold to best predict clinically relevant FVII:C levels. When PT is abnormal, determining FVII:C protein levels is needed for diagnosing FVII deficiency and considering surgical prophylactic treatment.

Integrated analysis of clinical and genetic factors on the interindividual variation of warfarin anticoagulation efficacy in clinical practice.

AIM: The anticoagulation effect of warfarin is usually evaluated by percentage of time in therapeutic range (PTTR), which is negatively correlated with the risk of warfarin adverse reactions. This study aimed to explore the effects of genetic and nongenetic factors on anticoagulation efficacy of warfarin during different therapeutic range. METHODS: We conducted an observational retrospective study aiming at evaluating the impact of clinical and genetic factors on PTTR from initial to more than six months treatment. This analysis included patients with heart valve replace (HVR) surgery who underwent long-term or life-long time treatment with standard-dose warfarin for anticoagulation control in Second Xiangya Hospital. All patients were followed for at least 6 months. We genotyped single nucleotide polymorphisms in VKORC1 and CYP2C9 associated with altered warfarin dose requirements and tested their associations with PTTR. RESULTS: A total of 629 patients with intact clinical data and available genotype data were enrolled in this study, and only 38.63% patients achieved good anticoagulation control (PTTR > 0.6). Clinical factors, including male gender, older age, overweight, AVR surgery and stroke history, were associated with higher PTTR. Patients with VKORC1 -1639AA genotype had significantly higher PTTR level compared with GA/GG genotype carriers only in the first month of treatment. Patients with CYP2C9*3 allele had higher PTTR compared with CYP2C9*1*1 carriers. Moreover, compared with VKORC1 -1639 AG/GG carriers, INR > 4 was more likely to be present in patients with AA genotype. The frequency of CYP2C9*1*3 in patients with INR > 4 was significantly higher than these without INR > 4. CONCLUSION: We confirmed the relevant factors of warfarin anticoagulation control, including genetic factors (VKORC1 -1639G > A and CYP2C9*3 polymorphisms) and clinical factors (male gender, older age, overweight, AVR surgery and stroke history), which could be helpful to individualize warfarin dosage and improve warfarin anticoagulation control during different treatment period.

Patient on Hemodialysis with Elevated International Normalized Ratio Presents for Removal of Residual Roots in the Mandible.

Dentists should consult the patient's nephrologist to obtain the most recent medical records for patients with chronic kidney disease (CKD) including the stage and level of control. Patients on hemodialysis are ideally seen the day after dialysis with consideration to arteriovenous shunt placement for blood pressure measurement and avoiding or changing the dose of certain drugs based on the patient's glomerular filtration rate. Drugs cleared during hemodialysis may require a supplemental dose. Patients taking oral anticoagulants and requiring oral surgery should have the international normalized ratio (INR) measured the day of the procedure.

Association between PT, PT-INR, and in-hospital mortality in critically ill patients with tumors: A retrospective cohort study.

Objectives: Prothrombin time (PT) and PT-INR are independent predictors of mortality in patients with cancer. The PT and PT-INR of cancer patients are independent predictive variables of mortality. However, whether the PT or PT-INR is related to in-hospital mortality in severely ill patients with tumors remains unknown. Design: This was a case-control study based on a multicenter public database. Settings: This study is a secondary analysis of data extracted from 2014 to 2015 from the Electronic Intensive Care Unit Collaborative Research Database. Participants: The data relevant to seriously ill patients with tumors were obtained from 208 hospitals spread throughout the USA. This research included a total of 200,859 participants. After the samples were screened for patients with combination malignancies and prolonged PT-INR or PT, the remaining 1745 and 1764 participants, respectively, were included in the final data analysis. Primary and secondary outcome measures: The key evaluation methodology was the PT count and PT-INR, and the main outcome was the in-hospital mortality rate. Results: After controlling for confounding variables, we found a curvilinear connection between PT-INR and in-hospital mortality (p < 0.001), and the inflection point was 2.5. When PT-INR was less than 2.5, an increase in PT-INR was positively associated with in-hospital mortality (OR 1.62, 95% CI 1.24 to 2.13), whereas when PT-INR was greater than 2.5, in-hospital mortality was relatively stable and higher than the baseline before the inflection point. Similarly, our study indicated that the PT exhibited a curvilinear connection with in-hospital mortality. On the left side of the inflection point (PT <22), a rise in the PT was positively linked with in-hospital mortality (OR 1.08, 95% CI 1.04 to 1.13, p < 0.001). On the right side of the inflection point, the baseline PT was above 22, and the in-hospital mortality was stable and higher than the PT count in the prior range (OR 1.01, 95% CI 0.97 to 1.04, 0.7056). Conclusion: Our findings revealed that there is a curved rather than a linear link between the PT or PT-INR and in-hospital mortality in critically ill cancer patients. When these two laboratory results are below the inflection point, comprehensive therapy should be employed to reduce the count; when these two laboratory results are above the inflection point, every effort should be made to reduce the numerical value to a value below the inflection point.

Blasting the myth of predictive INR changes related to plasma transfusion: an academic institution's experience

Abstract Introduction Plasma transfusion is a common therapeutic strategy used to lower international normalized ratio (INR) values in the non-emergent setting. However, due to lack of evidence of its efficacy, standardized guidelines for this practice have not been well established. Methods This retrospective observational cohort study analyzed 276 inpatient encounters that involved plasma transfusions focusing on change in INR values from pre- to post-transfusion, with respect to the following predictor variables: vitamin K co-administration, number of plasma units transfused, order indication and body mass index (BMI). Results The overall average change in the INR was 1.35. Patients who received vitamin K showed an average change of 2.51, while patients that did not receive vitamin K demonstrated an average change of 0.70. Increased numbers of plasma units transfused showed benefit up to three-unit orders. Greater decreases in the INR were observed for patients requiring plasma for anticoagulation reversal or active bleeding. There was no significant difference in the change in INR based on the BMI. By multivariate and regression analyses, the stepwise addition of each successive predictor variable demonstrated an increase in the shared variance in the outcome of the post-transfusion INR: the pre-transfusion INR and vitamin K co-administration alone was not significant (p= 0.45); the additional number of plasma units transfused was significant (R² = 0.13, p < 0.001), and; the subsequent additional plasma order indications (R² = 0.19, p < 0.001) and BMI (R² = 0.18, p < 0.001) were increasingly significant. Conclusion Taking into consideration the combination of multiple predictive factors may aid in a more efficient use of plasma products.

Comparison of the International Normalized Ratio Between a Point-of-Care Test and a Conventional Laboratory Test: the Latter Performs Better in Assessing Warfarin-induced Changes in Coagulation Factors.

Background: Point-of-care testing (POCT) coagulometers are increasingly used for monitoring warfarin therapy. However, in high international normalized ratio (INR) ranges, significant discrepancy in the INR between POCT and conventional laboratory tests occurs. We compared the INR of POCT (CoaguChek XS Plus; Roche Diagnostics, Mannheim, Germany) with that of a conventional laboratory test (ACL TOP 750; Instrumentation Laboratory SpA, Milan, Italy) and explored possible reasons for discrepancy. Methods: Paired POCT and conventional laboratory test INRs were analyzed in 400 samples from 126 patients undergoing warfarin therapy after cardiac surgery. Coagulation factor and thrombin generation tests were compared using the Mann-Whitney U test. Correlations between coagulation factors and INRs were determined using Pearson correlation coefficients. Results: The mean difference in the INR between the tests increased at high INR ranges. Endogenous thrombin potential levels were decreased at INR <2.0 for CoaguChek XS Plus and 2.0< INR <3.0 for ACL TOP 750 compared with those at INR <2.0 for both tests, indicating a better performance of ACL TOP 750 in assessing thrombin changes. The correlation coefficients of coagulation factors were stronger for ACL TOP 750 INR than for CoaguChek XS Plus INR. Vitamin K-dependent coagulation factors were found to contribute to the INR discrepancy. Conclusions: Decreases in vitamin K-dependent coagulation and anticoagulation factors can explain the significant discrepancy between the two tests in high INR ranges. Since conventional laboratory test INR values are more reliable than POCT INR values, a confirmatory conventional laboratory test is required for high INR ranges.

Estimating the measurement uncertainties of the international sensitivity index of 12 thromboplastins through Monte Carlo simulation.

BACKGROUND: Measurement uncertainty (MU) estimation has become an important process in clinical laboratories; however, calculating the MUs of the international sensitivity index (ISI) of thromboplastins is difficult because of the complex mathematical calculations required in calibration. Therefore, this study quantifies the MUs of ISIs through the Monte Carlo simulation (MCS), which involves random sampling of numerical values to solve a complex mathematical calculation. METHODS: Eighty blood plasmas and commercially available certified plasmas (ISI Calibrate) were used to assign the ISIs of each thromboplastin. Prothrombin times were measured using reference thromboplastin and 12 commercially available thromboplastins (Coagpia PT-N, PT Rec, ReadiPlasTin, RecombiPlasTin 2G, PT-Fibrinogen, PT-Fibrinogen HS PLUS, Prothrombin Time Assay, Thromboplastin D, Thromborel S, STA-Neoplastine CI Plus, STA-Neoplastine R 15, and STA-NeoPTimal) with two automated coagulation instruments: ACL TOP 750 CTS (ACL TOP; Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). Then, the MUs of each ISI were simulated through MCS. RESULTS: The MUs of ISIs ranged from 9.7 % to 12.1 % and 11.6 % to 12.0 % when blood plasma and ISI Calibrate were used, respectively. For some thromboplastins, the ISI claimed by manufacturers significantly differed from the estimated results. CONCLUSIONS: MCS is adequate to estimate the MUs of ISI. These results would be clinically useful for estimating the MUs of the international normalized ratio in clinical laboratories. However, the claimed ISI significantly differed from the estimated ISI of some thromboplastins. Therefore, manufacturers should provide more accurate information about the ISI value of thromboplastins.

Determining a preoperative international normalised ratio threshold safe for hip fracture surgery.

INTRODUCTION: The purpose of this study was first, to assess the relationship between preoperative INR (international normalised ratio) and postoperative complication rates in patients with a hip fracture, and second, to establish a threshold for INR below which the risk of complications is comparable to those in patients with a normal INR. METHODS: We retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program and found 35,910 cases who had undergone surgery for a hip fracture between 2012 and 2018. Cases were stratified into 4 groups based on their preoperative INR levels: <1.4; ⩾1.4 and <1.6; ⩾1.6 and <1.8 and ⩾1.8. These cohorts were assessed for differences in preoperative factors, intraoperative factors, and postoperative course. Multivariate logistic regression was used to assess the risk of transfusion, 30-day mortality, cardiac complications, and wound complications adjusting for all preoperative and intraoperative factors. RESULTS: Of the 35,910 cases, 33,484 (93.2%) had a preoperative INR < 1.4; 867 (2.4%) an INR ⩾1.4 and <1.6; 865 (2.4%) an INR ⩾ 1.6 and <1.8 and 692 (1.9%) an INR ⩾ 1.8. A preoperative INR ⩾ 1.8 was independently associated with an increased risk of bleeding requiring transfusion. A preoperative INR ⩾ 1.6 was associated with an increased risk of mortality. CONCLUSIONS: We found that an INR of <1.6 is a safe value for patients who are to undergo surgery for a hip fracture. Below this value, patients avoid an increased risk of both transfusion and 30-day mortality seen with higher INR values. These findings may allow adjustment of preoperative protocols and improve the outcome of hip fracture surgery in this group of patients.