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.

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.].

Frequency of prothrombin time-international normalized ratio monitoring and the long-term prognosis in patients with mechanical valve replacement.

BACKGROUND: The study aimed to assess the correlation between the monitoring frequency of PT-INR and the long-term prognosis in patients with mechanical heart valve (MHV) replacement after discharge. METHODS: This single-center, observational study enrolled patients who underwent MHV replacement and discharged from June 2015 to May 2018. Patients or their corresponding family members were followed with a telephone questionnaire survey in July-October 2020. Based on monitoring intervals, patients were divided into frequent monitoring (FM) group (≤ 1 month) and less frequent monitoring (LFM) group (> 1 month). The primary endpoint was the composite of thromboembolic event, major bleeding or all-cause death. The secondary endpoints were thromboembolic event, major bleeding or all-cause death, respectively. RESULTS: A total of 188 patients were included in the final analysis. The median follow-up duration was 3.6 years (Interquartile range: 2.6 to 4.4 years). 104 (55.3%) patients and 84 (44.7%) patients were classified into the FM group and the LFM group, respectively. The FM group had a significantly lower incidence of the primary endpoint than the LFM group (3.74 vs. 1.16 per 100 patient-years, adjusted HR: 3.31 [95% CI 1.05-10.42, P = 0.041]). Secondary analysis revealed that the risk of thromboembolic events and all-cause death were also reduced in the FM group. CONCLUSIONS: The management of warfarin treatment in patients after MHV replacement remains challenging. Patients with less frequent monitoring of PT-INR might have worse clinical prognosis than those with frequent PT-INR monitoring.

Evaluation of adjusted international normalized ratio goal in patients with HeartMate 3 left ventricular assist devices.

BACKGROUND: The HeartMate3 left ventricular assist device (HM3 LVAD) has shown a low incidence of thrombosis, but bleeding risk is as high as 43%. We aim to describe the impact of lower international normalization ratio (INR) goal on clinical outcomes. METHODS: In February 2019, our tertiary care institution lowered INR goal in HM3 patients from manufacturer recommendations to 1.8-2.2 and retrospectively analyzed the data. Two cohorts were compared: patients with lower INR goal upon implant (De novo) and those with subsequently lowered INR goal (Adjusted). The Adjusted group also served as its own historical control. Both groups continued aspirin 81 milligrams daily per manufacturer recommendations. The primary outcomes were incidences of bleed and thrombosis events within 12 months. Secondary outcomes included survival free of disabling stroke or reoperation to remove or replace the device and Rosendaal time in therapeutic range (TTR) over 12 months. RESULTS: Thirty-one patients were evaluated for inclusion with 26 meeting criteria. Within 12 months, incidence of bleeding events was 25% and 28.6% in the De novo and Adjusted groups, respectively. Incidence of thrombotic events within 12 months was 0% in the De novo group and 7.1% in the Adjusted group. Twelve-month survival free of disabling stroke or reoperation to remove or replace the device was higher over 12 months for patients in the De novo group (91.7% vs. 78.6%). Median 12-month TTR was 36%, which was primarily attributable to subtherapeutic deviations. CONCLUSIONS: A lower INR goal may be safe when initiated De novo following implantation of the HM3. This study informs the need for larger prospective studies.

Ischemic stroke in the setting of supratherapeutic International Normalized Ratio following coronavirus disease 2019 infection: a case report.

BACKGROUND: SARS-CoV-19 infection is associated with an increased risk of thrombotic events. We present a case of acute middle cerebral artery ischemic stroke in a patient with SARS-CoV-19 infection despite being on warfarin with supratherapeutic INR (International Normalized Ratio). CASE PRESENTATION: A 68-year-old Caucasian female with multiple comorbidities was admitted to the hospital with symptoms of upper respiratory tract infection. A rapid antigen test confirmed the diagnosis of COVID-19 pneumonia, and intravenous remdesivir was initiated. On the fifth day of admission, the patient experienced sudden onset confusion, slurred speech, left-sided hemiplegia, right-sided eye deviation, and left-sided facial droop. Imaging studies revealed an occlusion of the distal anterior M2 segment of the right middle cerebral artery, and an MRI of the brain confirmed an acute right MCA infarction. Notably, the patient was receiving warfarin therapy with a supratherapeutic INR of 3.2. CONCLUSIONS: This case report highlights the potential for thromboembolic events, including stroke, in patients with COVID-19 infection, even when receiving therapeutic anticoagulation therapy. Healthcare providers should be vigilant for signs of thrombosis in COVID-19 patients, particularly those with pre-existing risk factors. Further research is necessary to understand the pathophysiology and optimal management of thrombotic complications in COVID-19 patients.

Endoscopic band ligation is safe despite low platelet count and high INR.

BACKGROUND: Prophylactic endoscopic band ligation (EBL) is used to prevent variceal bleeding in patients with liver cirrhosis. The association of thrombocytopenia, high INR (international normalized ratio) and liver dysfunction with the risk of procedure-related bleeding (PRB) remains debated and recommendations are controversial. METHODS: We analyzed real-life data of cirrhotic patients undergoing elective EBL at two large Viennese centers between Q1/2000-Q1/2018. PRB was defined as bleeding occurring within 30 days after EBL. RESULTS: We included 617 patients undergoing a total of 1178 prophylactic EBL procedures (median 2 per patient). Sixteen (2.6%) of 617 patients experienced PRB after a median of 12.5 (IQR 17.3) days with no difference in characteristics and laboratory values between the two groups. The proportion of patients with platelets (PLT) < 50 G/L or INR ≥ 1.5 was similar in patients with vs. without PRB. A higher MELD showed a non-significant association with EBL-related bleeding risk (odds ratio, OR 1.07; 95% confidence interval 95% CI 1.00-1.16, p = 0.058). While serum bilirubin was a significant predictor for PRB (OR: 1.10; 95% CI 1.03-1.18), the presence of large varices (OR 0.85 vs. small varices; 95% CI 0.20-3.84), INR (OR 0.50; 95% CI 0.10-3.14), PLT (OR 1.00; 95% CI 1.00-1.01) and the use of non-selective betablockers (OR 1.20; CI 95% 0.38-3.76) were not associated with PRB. CONCLUSION: EBL is safe and procedure-related bleedings are rare (2.6%) including in patients with thrombocytopenia < 50 G/L or high INR ≥ 1.5. Only high MELD, and especially high bilirubin seem to be linked to an increased risk of EBL-related bleeding.

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.

PROTHROMBIN COMPLEX CONCENTRATE IN EMERGENCY DEPARTMENT.

Coagulation abnormalities are common in bleeding or critically ill patient and hemostatic management remains a major challenge for the emergency physician. Management of bleeding patients consists of bleeding control, restoration of blood volume, and correction of any associated coagulopathy. Traditionally, the fresh frozen plasma (FFP) is used for correction of coagulopathy to manage and prevent bleeding, but today Prothrombin complex concentrates (PCCs) offer an attractive alternative because they offers a number of advantages over FFP, including lower infusion volume, rapid INR normalization, faster availability, lack of blood group specificity, and better safety profile. The aim of the present review is to provide an short overview about using PCC, their indication, efficacy and safety in different bleeding setting's.

Analysis of the Dose-Response Relationship Between the International Normalized Ratio and Hepatic Encephalopathy in Patients With Liver Cirrhosis Using Restricted Cubic Spline Functions.

Background: The International Normalized Ratio (INR) is significantly associated with Hepatic Encephalopathy (HE) in patients with liver cirrhosis. However, the dose-response relationship between continuous INR changes and HE risk has not been clearly defined. Thus, our goal was to explore the continuous relationship between HE and INR among patients hospitalized with liver cirrhosis and to evaluate the role of the INR as a risk factor for HE in these patients. Methods: A total of 6,266 people were extracted from the Big Data Platform of the Medical Data Research Institute of Chongqing Medical University. In this study, unconditional logistic regression and restricted cubic spline (RCS) model were used to analyze the dose-response association of INR with HE. Alcoholic liver disease, smoking status, and drinking status were classified for subgroup analysis. Results: The prevalence of HE in the study population was 8.36%. The median INR was 1.4. After adjusting for alcoholic liver disease, age, smoking status, drinking status, total bilirubin, neutrophil percentage, total hemoglobin, aspartate aminotransferase, serum sodium, albumin, lymphocyte percentage, serum creatinine, red blood cell, and white blood cell, multivariate logistic regression analysis revealed that INR ≥ 1.5 (OR = 2.606, 95% CI: 2.072-3.278) was significantly related to HE risk. The RCS model showed a non-linear relationship between the INR and HE (non-linear test, χ2 = 30.940, P < 0.001), and an increased INR was an independent and adjusted dose-dependent risk factor for HE among patients with liver cirrhosis. Conclusion: This finding could guide clinicians to develop individualized counseling programs and treatments for patients with HE based on the INR risk stratification.

Anticoagulation Control in Older Atrial Fibrillation Patients Receiving Vitamin K Antagonist Therapy for Stroke Prevention.

Introduction: Efficacy and safety of vitamin K antagonists (VKAs) among atrial fibrillation (AF) patients are enhanced when the International Normalised Ratio (INR) is 2.0-3.0. Anticoagulation control among older patients is perceived to be lower and contributes to poorer initiation and uptake. Objective: To examine the quality of INR control, adverse clinical outcomes, and factors associated with bleeding in older AF patients (≥80 years). Methods: Anticoagulation control assessed by time in therapeutic range (TTR) (Rosendaal method) and percentage INRs in range (PINRR). Among the 205 patients aged ≥80 years, 58.5% were female, with mean (SD) CHA2DS2-VASc 4.4 (1.3) and HAS-BLED 1.8 (0.8) scores. Results: Mean (SD) TTR and PINRR were similar for those aged ≥80 vs. <80 years (66.7 (13.8) vs. 66.7 (13.1)) despite significantly lower INR monitoring intensity (51.2 (22.7) vs. 60.7 (25.8)) and shorter follow-up (4.4 (2.6-6.2) vs. 5.7 years (3.3-7.1)) in those ≥80 years of age. Good anticoagulation control (TTR and PINRR ≥70%) of 44% was seen in both age groups. No significant differences in composite major adverse clinical events were evident for those aged ≥80 vs. <80 years (p = 0.55). Cox regression analysis confirmed that age ≥80 years was associated with higher risk of bleeding (HR 1.90 (1.01-3.56); p = 0.047). Conclusions: Suboptimal (TTR and PINRR <70%) anticoagulation control was evident in all patients. Risk of bleeding increased, but there was no difference in thromboembolic events and all-cause mortality in those aged ≥80 years. Improving TTR to ≥70% and enhancing anticoagulation monitoring of VKA use remain a clinical priority to prevent bleeding complications, particularly among those aged 80 years and above.

Quality of Oral Anticoagulation in Atrial Fibrillation Patients at a Tertiary Hospital in Brazil. / Qualidade da Anticoagulação Oral em Pacientes com Fibrilação Atrial em um Hospital Terciário no Brasil.

BACKGROUND: Atrial fibrillation (AF) affects 0.5% to 2.0% of the general population and is usually associated with cardiac structural diseases, hemodynamic damage, and thromboembolic complications. Oral anticoagulation prevents thromboembolic events and is monitored by the international normalized ratio (INR). OBJECTIVES: To evaluate INR stability in nonvalvular AF patients treated with warfarin anticoagulation, to evaluate thromboembolic or hemorrhagic complications, and to identify the group at higher risk for thromboembolic or hemorrhagic events. METHODS: Data from the medical records of 203 patients who received medical care at a tertiary hospital in Brazil were reviewed, and the time in therapeutic range (TTR) was calculated using the Rosendaal method. The possible TTR influencing factors were then analyzed, and the relationship between the TTR and thromboembolic or hemorrhagic events was calculated. The level of significance was 5%. RESULTS: The mean TTR was 52.2%. Patients with INR instability in the adaptation phase had a lower mean TTR (46.8%) than those without instability (53.9%). Among the studied patients, 6.9% suffered hemorrhagic events, and 8.4% had a stroke. The higher risk group for stroke and bleeding consisted of patients with INR instability in the adaptation phase. CONCLUSIONS: The quality of anticoagulation in this tertiary hospital in Brazil is similar to that in centers in developing countries. Patients with greater INR instability in the adaptation phase evolved to a lower mean TTR during follow-up, had a 4.94-fold greater chance of stroke, and had a 3.35-fold greater chance of bleeding. Thus, for this patient group, individualizing the choice of anticoagulation therapy would be advised, considering the cost-benefit ratio.

FUNDAMENTO: A fibrilação atrial (FA) afeta de 0,5% a 2,0% da população geral e geralmente está associada a doenças estruturais cardíacas, comprometimento hemodinâmico e complicações tromboembólicas. A anticoagulação oral previne eventos tromboembólicos e é monitorada pela razão normalizada internacional (RNI). OBJETIVOS: Avaliar a estabilidade do RNI em pacientes com FA não valvar tratados com anticoagulante varfarina, avaliar complicações tromboembólicas ou hemorrágicas e identificar o grupo com risco mais alto de eventos tromboembólicos ou hemorrágicos. MÉTODOS: Dados de prontuários médicos de 203 pacientes atendidos em um hospital terciário no Brasil foram analisados e o tempo de intervalo terapêutico (TTR) foi calculado usando-se o método Rosendaal. Em seguida possíveis fatores que influenciam o TTR foram analisados e a relação entre TTR e eventos tromboembólicos ou hemorrágicos foi calculada. O nível de significância foi 5%. RESULTADOS: O TTR médio foi 52,2%. Pacientes com instabilidade de RNI na fase de adaptação tinham um TTR médio mais baixo (46,8%) do que aqueles sem instabilidade (53,9%). Entre os pacientes estudados, 6,9% sofreram eventos hemorrágicos e 8,4% tiveram um acidente vascular cerebral. O grupo com risco mais alto de acidente vascular cerebral e sangramento era composto de pacientes com instabilidade de RNI na fase de adaptação. CONCLUSÕES: A qualidade da anticoagulação nesse hospital terciário no Brasil é semelhante à de centros de países em desenvolvimento. Pacientes com instabilidade de RNI maior na fase de adaptação evoluíram para um TTR médio mais baixo durante o acompanhamento, tinham uma chance de acidente vascular cerebral 4,94 vezes maior e uma chance de sangramento 3,35 vezes maior. Portanto, para esse grupo de pacientes, individualizar a escolha de tratamento anticoagulante seria recomendado, considerando-se a relação custo-benefício.

Characteristics and management of patients with stroke and major hemorrhagic episodes with atrial fibrillation under vitamin K antagonist therapy. EVENTHO study.

INTRODUCTION AND OBJECTIVE: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes. MATERIALS AND METHODS: EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months. RESULTS: The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2-4.4] and HAS-BLED: 2.2 [2.1-2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death. CONCLUSIONS: In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.

Procedural bleeding risk, rather than conventional coagulation tests, predicts procedure related bleeding in cirrhosis.

BACKGROUND: Standard coagulation parameters are used to guide prophylactic blood product transfusion prior to invasive procedures in cirrhotic patients despite limited high-quality evidence. AIMS: We aimed to describe coagulation parameters and prophylactic blood product use in cirrhotic patients having invasive procedures, and the influence of both on periprocedural bleeding. METHODS: We conducted a cohort study of cirrhotic patients undergoing invasive procedures at a referral hospital. Procedures were classified into low or moderate-high bleeding risk. Prophylactic blood component was defined as fresh frozen plasma, cryoprecipitate or platelet transfusion prior to procedures. Univariate and multivariate logistic regression was performed to identify factors associated with procedure-related bleeding. RESULTS: We identified 566 procedures in 233 cirrhotic patients. Prophylactic blood product was given before 16% of high-risk and 11% of low-risk procedures (P = 0.18). Eight (8.3%) high-risk procedures were complicated by postprocedural bleeding, six of which occurred in patients without significant coagulopathy. The bleeding rate for low-risk procedures was 0.4%. For patients with international normalized ratio >1.5, platelet count <50 x 109/L, or both, the rate of bleeding was comparable between those given and not given prophylactic blood products (3.1 vs. 1.9%; P = 0.63). After adjusting for age, sex, platelet count, international normalized ratio, acute kidney injury, sepsis and model of end-stage liver disease, the only factor significantly predicting procedure-related bleeding was the procedural bleeding risk category (P < 0.01). CONCLUSIONS: Procedure-related bleeding in cirrhotic patients cannot be accurately predicted by INR or platelet count, nor prevented by blood component prophylaxis using these parameters. Procedure-related bleeding is best predicted by the bleeding risk status of procedures.

The international normalised ratio predicts perioperative complications in revision total hip arthroplasty.

BACKGROUND: Standard preoperative protocols in total joint arthroplasty utilise the international normalised ratio (INR) to determine patient coagulation profiles. However, the relevance of preoperative INR values in joint arthroplasty remains controversial. Therefore, we examined (1) the relationship between preoperative INR values and various outcome measures, including, but not limited to: surgical site complications, medical complications, bleeding, number of readmissions, and mortality. Additionally, we sought to determine (2) specific INR values associated with these complications and (3) cutoff INR levels which correlated with specific outcomes. We additionally applied these analyses to (4) examine the relationship between INR and length-of-stay (LOS). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP) was queried for rTHA procedures performed between 2006 and 2017. INR ranges were used to stratify cohorts: ⩽1.0, 1.0-⩽1.25, 1.25-⩽1.5, >1.5. INR values were determined using receiver operating characteristics (ROC) curves for each outcome of interest. Optimal cutoff INR values for each outcome were then obtained using univariate/multivariate models. 2012 patients who underwent rTHA met inclusion criteria. RESULTS: Patients with progressively higher INR values had a significantly different risk of mortality within 30 days (p = 0.005), bleeding requiring transfusion (p < 0.001), sepsis (p = 0.002), stroke (p < 0.001), failure to wean from ventilator within 48 hours (p = 0.001), readmission (p = 0.01), and hospital length of stay (p < 0.001). Similar results were obtained when utilising optimal INR cutoff values. When correcting for other factors, the following poor outcomes were significantly associated with the respective INR cutoff values (Estimate, 95% CI, p-value): LOS >4 days (1.67, 1.34-2.08, p < 0.001), bleeding requiring transfusion (1.65, 1.30-2.09, p < 0.001), sepsis (2.15, 1.11-4.17, p = 0.022), and any infection (1.82, 1.01-3.29, p = 0.044). CONCLUSIONS: Our analysis illustrates a direct relationship between specific preoperative INR levels and poor outcomes following rTHA, including increased LOS, transfusion requirements and infection. Therefore, current INR guideline targets may need to be re-examined when optimising patients for revision arthroplasty.

Safety of thrombolytic therapy in patients with prosthetic heart valve thrombosis who have high international normalized ratio levels.

BACKGROUND AND AIM: Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication of heart valve replacement. Based on the current guidelines, the treatment of a large number of these patients could be performed through the administration of thrombolytic agents. In the present study, we aim to assess the safety of thrombolytic therapy in patients with PVT who have high international normalized ratio (INR) levels. METHODS: In this study, we retrospectively analyzed outcomes of thrombolytic therapy in 65 PVT patients with different levels of INR at the time of fibrinolysis at a tertiary cardiac center. RESULTS: Mean age of patients was 51.6 ± 12.47 years. The tricuspid valve was the most common site of prosthetic valve thrombosis (64.6%). The Median (range) of INR was 2.1 (0.9-4.9). The majority of patients (50.8%) achieved a complete response following thrombolytic treatment. There were no cases of intracranial hemorrhage. Other major and minor bleedings occurred in 3 (4.6%) and 10 (15.4%) patients, respectively. No embolic stroke and systemic embolism were observed. We found no significant difference in the frequency of major (P-value = .809) and minor (P-value = .483) bleeding as well as response to thrombolytic therapy (P-value = .658) between patients with different levels of INR. Total administered dose of Streptokinase was also similar in PVT patients with or without major (P-value = .467) and minor (P-value = .221) bleeding complications. CONCLUSIONS: We concluded that there was no significant difference between PVT patients presenting with subtherapeutic and high INR levels who received thrombolytic treatments regarding both minor and major bleeding complications as well as response to thrombolysis.

Point-of-care testing INR: an overview.

Oral anticoagulant therapies with the anti-vitamin K drugs (AVK), warfarin, acenocoumarol and phenprocoumon, are employed in primary and secondary anti-thrombotic prophylaxis in patients with venous thromboembolism, atrial fibrillation and cardiac mechanical valves. However, a monitoring test such as the International Normalized Ratio (INR) is required. The periodic monitoring of this therapy entails discomfort for the patients. Telemedicine and telecare can provide significant aid in the management of this therapy allowing patients to perform the test at home or anywhere else with a portable device, i.e. point-of-care testing (POCT), and to send the result to a thrombosis (TC) via web. Patients can receive dose adjustment sent back by the TC. The effectiveness of this type of management is equal or superior to the traditional AVK monitoring in terms of hemorrhagic and thrombotic events. Analysis of the costs with a horizon of 10 years reveals that both self-testing and self-management are cost-effective. The aim of this overview is to describe the pros and cons of the use of POCT as an alternative in the monitoring of AVK. In particular, description of the POCT, decentralization, quality of the therapy, safety and costs will be examined.

[INR telemonitoring: efficacy and safety of a telemonitoring program in 453 patients]. / telemonitorização de INR: eficácia e segurança de um sistema de avaliação em 453 doentes.

INTRODUCTION: The INR analyses of patients taking oral anticoagulants brings great burden to healthcare professionals, overspending founds from the National Health Service (NHS) and loss of quality of life of patients who are forced to frequent hospital visits. It should not be surprising that the technology is at the forefront of health care nowadays and some projects have been developed in the area of anticoagulation for INR self-monitoring by telephone, mobile phone or internet. The aim of this study was to assess the efficacy and safety of an INR telemonitoring system that was implemented in our hospital in 2006. METHODS: A prospective, observational study of 453 patients who were included in this telemonitoring system from 2006 until late November 2010. The communication between patients and health professionals was done via mobile phone messages in a standardized and codified system that included information about maintenance or modification of therapy and the date of the next evaluation. When necessary the patient could send a request for help through a code for that purpose. In the studied population the following parameters were evaluated: withdrawal of the telemonitoring project, need for change of anticoagulant dose, requests for clarification by the patient, hospitalization for bleeding complications and INR > 10. RESULTS: In our study population 53% were female, mean age = 57 +/- 16 years. The percentage of INR values within the therapeutic range was 83%. There were no dropouts of the telemonitoring project. The percentage of patients with major and minor bleeding complications during follow-up was 0.4% and 0.2% respectively. CONCLUSIONS: The telemonitoring system proves safe and effective remote monitoring of INR analysis, allowing efficient monitoring of INR with low prevalence of major or minor bleeding.

Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial.

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined. METHODS: Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily). RESULTS: During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001). CONCLUSIONS: The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis.

BACKGROUND: It is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset. METHODS: The authors performed a systematic review of the literature and included studies that assessed the relation between prior warfarin use with subtherapeutic INR and outcome after intravenous or intra-arterial thrombolytic therapy in acute ischaemic stroke. Outcome measures were symptomatic intracranial haemorrhage (SICH), modified Rankin scale score 0-2 and mortality. Second, the authors performed a meta-analysis of the included studies. RESULTS: Seven studies with 3631 patients were included. 240 (6.6%) patients used warfarin before stroke onset. The risk of SICH was increased in the warfarin group (OR 2.6; 95% CI 1.1 to 5.9. p=0.02). There was no significant difference, however, in functional outcome (OR 0.9; 95% CI 0.6 to 1.2, p=0.32) or death from all causes (OR 1.2; 95% CI 0.9 to 1.8). DISCUSSION: The risk of SICH after thrombolytic therapy is increased in patients using warfarin with subtherapeutic INR levels. The authors found no evidence of an increase in death from all causes or worsening of functional outcome in warfarin treated patients.

Predicting the risk of venous thromboembolism recurrence.

Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence rate. The highest incidence of recurrence is in the first 6 months. Active cancer significantly increases the hazard of early recurrence, and the proportions of time on standard heparin with an APTT ≥ 0.2 anti-X(a) U/mL, and on warfarin with an INR ≥ 2.0, significantly reduce the hazard. The acute treatment duration does not affect recurrence risk after treatment is stopped. Independent predictors of late recurrence include increasing patient age and body mass index, leg paresis, active cancer and other persistent VTE risk factors, idiopathic VTE, antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D-dimer. A recommendation for secondary prophylaxis should be individualized based on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding. The appropriateness of secondary prophylaxis should be continuously reevaluated, and the prophylaxis stopped if the benefit no longer exceeds the risk.