International Normalized Ratio Values Research Articles

CoaguChek® XS versus standard laboratory prothrombin time for anticoagulant monitoring in patients with antiphospholipid syndrome.

The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option. To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results. This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland-Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable. The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR <2, INR 2-3, INR 3-4, and INR >4), we found that the INR >4 group presented a lower correlation (r = 0.64) compared to the other ranges (p < 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results. Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.

Indian Polyvalent Antivenom Accelerates Recovery From Venom-Induced Consumption Coagulopathy (VICC) in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.

BackgroundVenom-induced consumption coagulopathy (VICC) is an important clinical consequence of Russell’s viper (Daboia russelii) envenoming. There is limited evidence for antivenom effectiveness in resolving VICC. We aimed to compare the recovery of VICC in patients who received and did not receive antivenom following Russell’s viper envenoming.Patients and MethodsThis was a non-randomized observational study comparing patients with VICC from Russell’s viper envenoming given antivenom for systemic envenoming and those not given antivenom. Antivenom administration was decided by the treating physicians. We included 44 patients with confirmed Russell’s viper bites with one or more International Normalized Ratio (INR) value ≥ 1.5 (VICC). We compared five patients who did not receive antivenom with 39 patients who did receive antivenom. The primary outcome was the proportion of patients with an INR < 1.5 by 48 h post-bite.ResultsThe antivenom group had higher peak serum venom concentrations [median (IQR) = 272 (96–1,076) ng/mL versus 21 (8–58) ng/mL] and more severe VICC compared to the no antivenom group. Twenty seven of 39 patients (69%) in the antivenom group had an INR < 1.5 at 48 h post-bite compared to none of the five patients (0%) in the no antivenom group (absolute difference: 69%; 95%CI: 13 to 83%; p = 0.006; Fisher’s exact test). The fibrinogen recovered in 32 of 39 patients (82%) in the antivenom group compared to one of five patients (20%) in the no antivenom group (absolute difference 62%; 95% CI: 28 to 95%; p = 0.001; Fisher’s exact test). Both INR and fibrinogen were significantly improved between 24 and 48 h post-bite in the antivenom group compared to the no antivenom group.ConclusionAntivenom accelerated the recovery of VICC in patients with Russell’s viper envenoming, compared to no recovery in a smaller group of patients with milder VICC not receiving antivenom. This supports the efficacy of antivenom in patients with VICC.

Can the preoperative hematologic factors play a role in predicting adult post-tonsillectomy hemorrhage?

OBJECTIVE: This study aimed to assess the preoperative hematologic factors for predicting post-tonsillectomy hemorrhage (PTH). METHODS: In the retrospective study, the records of 44 patients (21 males, 23 females; mean age 30.5±9.4 years; range, 18 to 55 years) who underwent tonsillectomy for chronic or recurrent tonsillar infections were reviewed. Age, sex, coagulation profile [international normalized ratio (INR), activated partial thromboplastin time (aPTT)], complete blood cell count [hematocrit (HTC), neutrophil (NEU) count, lymphocyte (LYMP) count, platelet (PLT) count, mean platelet volume (MPV), red cell distribution width (RDW)] such values have been recorded. Patients were divided into two groups according to the presence of PTH. Group A (8 males, 13 females; mean age 30.5±11.1 years) included patients without PTH and Group B (13 males, 10 females; mean age 30.5±7.8 years) was comprised of patients with PTH. RESULTS: In the evaluation of the coagulation profile, aPTT values were 24.5±1.9 sec in Group A and 26.4±17 sec in Group B (p= 0.017). Median value of INR was similar between the groups (p=0.60). No difference was detected between the groups regarding the following parameters of the complete blood count: HTC (p=0.49), NEU (p=0.17), LYMP (p=0.45), PLT (p=0.71), MPV (p=0.27), and RDW (p=0.29). CONCLUSION: It is important to perform relevant blood tests should in the preoperative period, in addition to INR and aPTT tests. New studies are needed to determine the relationship of MPV and RDW with PTH.

Effect of Rivaroxaban in Stroke Prevention in Patient with Atrial Fibrillation due to Valvular Heart Disease

Objective: To observe the effect of rivaroxaban in patients with atrial fibrillation due to valvular heart diseases for proper anticoagulation to avoid stroke. Methodology: An observational follow up study was carried out in Cardiology Department of Aziz Fatimah Hospital, Faisalabad from February to August 2021. The study included 36 patients of valvular heart disease with atrial fibrillation on warfarin, whose INR was not tested during the last 4 months due to lack of facility nearby. All patients with non valvular atrial fibrillation were excluded .All patients were given rivaroxaban to replace warfarin. These patients were followed up for 6 months in the OPD of the same hospital to observe the end points including stroke and bleeding episodes and ischemic changes on ECG. Results: Total of 36 patients of mean age and SD of 56±7.00 years were followed up. Out of which 20 were male and 16 were female subjects.Not a single incident of stroke or bleeding episode or bruises was observed during the 6 month follow up. On echocardiographic examination, none of the patients showed clot in the left atrium. Left atrium size and LV ejection fraction remained the same, during next visit. LA size 44±5 and 44±6 on 1st and second visit respectively (p value =0.059) No other ischemic changes found in the ECG of any patient. International normalization ratio (INR) mean and SD was 2.1± 0.9, 2.2± 0.8, on 1st and 2nd visit of follow up respectively and no significant difference was noted between INR values. Conclusion: Rivaroxaban can be given safely to the patients with valvular heart disease with atrial fibrillation, particularly in patients who cannot get the INR checked on regular basis.

AVK overdose in Covid-19 infected patients.

During the Covid-19 pandemic, four patients were admitted to a healthcare centre. They were treated with vitamin K antagonists (AVK). We observed a substantial increase in their International Normalised Ratio (INR). The mean age of these patients was 90 (± 8 years). All had different usual long-term therapy treatments but had fixed doses of AVK to reach a stable INR. No changes to the background regimen were implemented. One patient presented a cough whereas the three others were asymptomatic. In the context of the pandemic, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was carried out for each patient. The results of the RT-PCR rests were all positive and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 which increased to 5.93 the day after RT-PCR positivity. AVK treatment was stopped but the INR one day after was 7.89. Ms J. presented INR values between 1.96 and 4.58, 10 days later. a PCR test was conducted and AVK treatment was stopped, but the INR still increased to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24 hours after a positive PCR result. Ms F. presented a gradual increase in INR from 1.5 to 3.36, 72 hours after a positive PCR result and three days after discontinuation of AVK. This study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a haemorrhagic risk as the INR increases. There could be a risk of overdose when patients are treated with AVK and are positive for Covid-19. This raises the question of discontinuing AVK and substituting it with another anticoagulant, or performing INR checks more frequently in the context of Covid-19. Moreover, an unexpected increase in INR should indicate the need to conduct a Covid-19 RT-PCR test in the context of this pandemic context.

Efficacy and safety of app-based remote warfarin management during COVID-19-related lockdown: a retrospective cohort study.

This study aimed to explore the effectiveness, and safety of internet-based warfarin management during the pandemic. In this single-center retrospective cohort study, we compared the safety and efficacy of online warfarin management using a smartphone app (the Alfalfa app) versus conventional outpatient clinic management from January 1, 2020 to March 31, 2020. Patients in the online management group used the Alfalfa app to communicate coagulation test results and other relevant information to a doctor or clinical pharmacist, who then responded with the dose adjustment plan and the date of the next blood test. The outcomes examined were the time in therapeutic range (TTR), incidence of clinical events (i.e., bleeding events, thrombotic events, warfarin-related emergency department visits, and warfarin-related hospital admissions), and the distribution of international normalized ratio (INR) values. Data from 117 patients were analyzed in this study. TTR was significantly higher in the online group than in the offline group (61.0% vs. 39.6%, P < 0.01). Incidence of major bleeding events, thrombotic events, and warfarin-related hospital admissions were comparable between the online and offline groups. However, minor bleeds (5.3% vs. 28.3%, P < 0.01) and warfarin-related emergency department visits (1.8% vs. 23.3%, P = 0.02) were significantly fewer in the online group than in the offline group. The proportion of INR values in the therapeutic range (53.8% vs. 40.1%, P < 0.01) was significantly higher in the online group. Warfarin management using the Alfalfa app appears to be a safe and effective method for warfarin management when patients cannot physically visit hospitals for follow-up.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02630-0.

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil.

BACKGROUNDHepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIMTo evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.METHODSThis is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant.RESULTSThe mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060–1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence.CONCLUSIONTreatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.

Management strategies following slightly out-of-range INRs: watchful waiting vs dose changes

AbstractPatients' international normalized ratios (INRs) often fall slightly out of range. In these cases, the American College of Chest Physicians (ACCP) guidelines suggest maintaining the current warfarin dose and retesting the INR within the following 2 weeks (watchful waiting). We sought to determine whether watchful waiting or dose changes for slightly out-of-range INRs is more effective in obtaining in-range INRs at follow-up. INRs and management strategies of warfarin-treated patients within the Michigan Anticoagulation Quality Improvement Initiative registry were analyzed. Management strategies included watchful waiting or dose changes. INRs slightly out of range (target range 2.0-3.0) and their associated management were identified. Multilevel mixed-effects logistic regression was used to estimate the probability of the next INR being in range, adjusted for clustering due to multiple out-of-range INRs per patient. A total of 45 351 slightly out-of-range INRs (ranging 1.50-1.99 and 3.01-3.49) from 8288 patients were identified. The next INR was slightly less likely to be in range with watchful waiting than with a dose change (predicted probabilities 58.9% vs 60.0%, P = 0.024). Although a significant statistical difference was detected in the probabilities of the next INR being back in range when managed by a dose change compared with watchful waiting following a slightly out-of-range INR, the magnitude of the difference was small and unlikely to represent clinical importance. Our study supports the current guideline recommendations for watchful waiting in cases of slightly out-of-range INRs values.

Clinical Outcomes of Different Warfarin Self-Care Strategies: A Systematic Review and Network Meta-Analysis.

To compare the effects of different strategies for warfarin self-care. PubMed, EMBASE, CENTRAL, CINAHL, ProQuest Dissertations & Theses, and OpenGrey were searched from inception to August 2021. Randomized controlled trials (RCTs) of warfarin self-care, either patient self-testing (PST) or patient self-management (PSM), were included. Self-care approaches were classified based on the TIP framework (theme, intensity, provider): (1) PST ≥1/week via e-Health (PST/High/e-Health); (2) PST ≥1/week by health care practitioner (PST/High/HCP); (3) PST <1/week via e-Health (PST/Low/e-Health); (4) PSM ≥1/week by e-Health (PSM/High/e-Health); (5) PSM ≥1/week by patient (PSM/High/Pt); (6) PSM <1/week by patient (PSM/Low/Pt); and (7) PSM with flexible frequency by patient (PSM/Flex/Pt). Mean differences (MDs) and risk ratios (RRs) with 95% confidence interval (CI) were estimated using frequentist network meta-analyses with a random-effects model. The certainty of evidence was evaluated using CINeMA (Confidence in Network Meta-Analysis). Sixteen RCTs involving 5,895 participants were included. When compared with usual care, time in therapeutic range was higher in PSM/High/Pt and PST/High/e-Health with MD [95% CI] of 7.67% [0.26-15.08] and 5.65% [0.04-11.26], respectively. The certainty of evidence was rated as moderate for these findings. The risk of thromboembolic events was lower in the PSM/Flex/Pt group when compared with PST/High/e-Health (RR: 0.39 [0.20-0.77]) and usual care (RR: 0.38 [0.17-0.88]) with low and very low level of evidence, respectively. There was no significant difference in the proportion of international normalized ratio (INR) values in range, major bleeding, and all-cause mortality among different self-care features. Patient self-care (either PST or PSM) by measuring INR values at least once weekly is more effective in controlling the INR level.

Virtual Education for Patient Self-Testing for Warfarin Therapy Is Effective During the COVID-19 Pandemic.

BackgroundPrior to the COVID-19 pandemic, warfarin users were required to complete in-person training in order to participate in approved international normalized ratio (INR) patient self-testing (PST) programs. To minimize in-person contact during the pandemic, a federal waiver of the in-person training requirement allowed new patients to begin PST after completing virtual training. However, it was uncertain whether such patients achieved comparable levels of INR control to patients receiving in-person training.MethodsINR results for patients receiving virtual training upon PST commencement between April 1, 2020, and December 31, 2020, were compared to those of patients initiating PST with in-person training between April 1, 2019, and December 31, 2019. The primary outcome was the difference in warfarin time in therapeutic range (TTR) between the groups, with secondary outcomes including differences in the percentages of INR values within individually prescribed INR range and of critical INR values.ResultsThe records of 33,683 patients were included in the analysis (13,568 in the “In-Person” sample; 20,115 in the “Virtual” sample). Patients in the Virtual sample achieved a TTR of 66.78%, compared to the In-Person sample (64.19%; absolute difference 2.59; 95% confidence interval [CI] = 2.50–2.68, p < 0.001). The TTR values were also statistically significantly higher in all subgroups evaluated across categories of patient age, gender, geography, and indication. Similarly favorable results were achieved for INR values in range and critical values.ConclusionVirtual education for PST for warfarin therapy is effective and should continue to be an option for patients and providers throughout the pandemic, and possibly beyond.

Assessment of Stability of Prothrombin Time, International Normalized Ratio, and Activated Partial Thromboplastin Time Under Different Storage Conditions in Human Plasma.

BackgroundIn this study, we aimed to determine the effects of storage time and temperature on commonly performed coagulation tests such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) in human plasma.MethodologyWhole blood samples from 100 patients were collected in a 3.2% sodium citrate vacutainer. The blood was centrifuged within two hours of collection at 2,000 g for 10 minutes, and the platelet-poor plasma (PPP) obtained was analyzed for PT, INR, and APTT tests at zero hours (baseline) and repeated at 12 hours, 24 hours, and 36 hours on a fully automated coagulation analyzer at various storage conditions (room temperature, refrigerator, and freezer). The results were categorized into two groups: group 1 comprised results with normal coagulation profile and group 2 comprised results with abnormal coagulation profile. The percentage change of the results from baseline (zero hours) for PT, INR, and APTT tests was also studied. A percentage change of more than ±10% from baseline was considered as a clinically significant change.ResultsIn this study, a total of 95 PPP samples were evaluated. The median age of all patients was 44 years (range: 19-65 years). The male-to-female ratio was 0.9:1. The baseline PT, INR, and APTT values were 12.1 seconds, 1.06, and 26.5 seconds, respectively, in group 1, whereas the baseline PT, INR, and APTT values were 19.1 seconds, 1.80, and 36.0 seconds, respectively, in group 2. In the freezer, the samples were stable for PT, INR, and APTT tests at 12 hours, 24 hours, and 36 hours showing a change of <10% from baseline at all three time-points. In the refrigerator, the samples were stable for PT and INR tests for up to 24 hours showing a change of <10% from baseline. In comparison, the samples for the APTT test were not stable at 12 hours, 24 hours, and 36 hours showing a change of 12.1%, 15.5%, and 17.9%, respectively, from the baseline (zero hours). Finally, at room temperature, the samples deteriorated at 12 hours for all coagulation parameters (PT, INR, and APTT).ConclusionsThe patient plasma samples for PT, INR, and APTT tests could be safely stored for up to 36 hours in the freezer. In the refrigerator, samples for PT and INR tests could be safely stored for up to 24 hours while the samples for APTT deteriorated at 12 hours. All patient samples for PT, INR, and APTT tests deteriorated at 12 hours at room temperature.

The Effect of Serum Magnesium Level on Stable Anticoagulation in Patients Using Warfarin for Various Cardiac Indications.

Warfarin is a vitamin K antagonist agent that inhibits clotting factors used for long-term anticoagulation. Time in therapeutic range (TTR) in patients using warfarin is one of the primary treatment effectiveness requirements. We aim to investigate the relationship between serum magnesium levels, the international normalized ratio (INR) values, and TTR values in people using warfarin for various indications. Our study is a single-center, cross-sectional, and retrospective study that included 169 patients between 18 and 70 who used warfarin for various indications. Demographic data, biochemical analysis, and coagulation parameters, including TTR calculation, were evaluated for all patients. Those with a TTR value below 60 were defined as labile INR, and those with 60 and above as stable INR group and compared. The mean INR value was higher in the labile INR group than the stable INR group (3.7 ± 2.9, 3.2 ± 0.3, respectively; p = 0.030). The Mg values are significantly lower in the labile INR group than the stable group (1.8 ± 0.2mg/dL, 2.0 ± 0.1mg/dL, respectively; p < 0.001). In binary multivariate logistic regression analysis, magnesium value was the most influential INR stabilization factor (p < 0.001). As a result of our study, it was concluded that magnesium levels are an influential factor in stabilizing INR. We can state that we have contributed to the literature and can be a reference for future studies.

Control-Relevant Adaptive Personalized Modeling From Limited Clinical Data for Precise Warfarin Management.

Warfarin is a challenging drug to administer due to the narrow therapeutic index of the International Normalized Ratio (INR), the inter- and intra-variability of patients, limited clinical data, genetics, and the effects of other medications. Goal: To predict the optimal warfarin dosage in the presence of the aforementioned challenges, we present an adaptive individualized modeling framework based on model (In)validation and semi-blind robust system identification. The model (In)validation technique adapts the identified individualized patient model according to the change in the patient's status to ensure the model's suitability for prediction and controller design. Results: To implement the proposed adaptive modeling framework, the clinical data of warfarin-INR of forty-four patients has been collected at the Robley Rex Veterans Administration Medical Center, Louisville. The proposed algorithm is compared with recursive ARX and ARMAX model identification methods. The results of identified models using one-step-ahead prediction and minimum mean squared analysis (MMSE) show that the proposed framework effectively predicts the warfarin dosage to keep the INR values within the desired range and adapt the individualized patient model to exhibit the true status of the patient throughout treatment. Conclusion: This paper proposes an adaptive personalized patient modeling framework from limited patientspecific clinical data. It is shown by rigorous simulations that the proposed framework can accurately predict a patient's doseresponse characteristics and it can alert the clinician whenever identified models are no longer suitable for prediction and adapt the model to the current status of the patient to reduce the prediction error.

Bleeding Complications in Relation to the International Normalized Ratio for Dental Extractions in Patients under Chronic Anticoagulant Therapy - An Evaluative Study.

Recent simple dental extraction protocols suggest that therapeutic levels of the anticoagulant drug should be maintained because bleeding complications could be managed with local haemostasis manoeuvres. The aim of the present study was to evaluate the association between bleeding complications and the international normalized ratio (INR) values in patients after dental extractions completed with a plug of bismuth subgallate, without interrupting anticoagulant administration. Patients undergoing oral Vitamin K antagonist chronic anticoagulant therapy requiring simple dental extractions were included in the study. INRs were recorded on the day of the surgery, and dental extractions were performed applying bismuth subgallate as a haemostatic agent. Patients took their anticoagulation drug normally. Bleeding complications were recorded. The study included 694 patients, of whom 11 (1.58%) presented mediate post-operative bleeding that was effectively controlled through local manoeuvres. No episode of thromboembolism or infectious endocarditis was observed. The incidence of bleeding complications was not related to the INR values (P > 0.05). INR values were not related to bleeding complications when simple dental extractions were performed applying bismuth subgallate as a haemostatic agent.

Diagnostic Value of D-Dimer and INR in Patients Suspected to Have Prosthetic Valve Dysfunction.

Prosthetic valve dysfunction is a potentially critical complication of heart valve replacement. An easy and quickly applicable diagnostic procedure is required for recognizing the prosthetic valve dysfunction. The purpose of this study was to prospectively define the diagnostic value of D-dimer and INR level in predicting prosthetic valve dysfunction. This cross-sectional study was performed in 70 patients suspected to have prosthetic valve dysfunction admitted to Imam Ali Hospital, affiliated with Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. Cinefluoroscopy, as the gold standard diagnostic test, was used for the diagnosis of prosthetic valve dysfunction in enrolled patients. Two milliliters of blood from each patient were taken into a tube containing sodium citrate anticoagulant. To evaluate D-dimer, the cutoff value was set at 500 ng/ml. Also, to evaluate international normalized ratio (INR), the cutoff value was set at 2. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of the serum markers were used to describe predictive properties. Of 70 patients, 27 (38.6%) were male and 43 (61.4%) were female, and the mean age was 54.67±15.11 years (range, 18 to 80 years). Of 70 patients, 27 (38.6%) had prosthetic heart valve malfunction demonstrable by fluoroscopy, and 19 patients (27.1%) had D-dimer levels &gt;500 ng/ml. Elevated D-dimer levels (&gt;500 ng/ml) have been indicated to have sensitivity of 70.4%, and hence an NPV of 84.3%, specificity of 100%, PPV of 100%, NLR of 0.3, and the infinity value of PLR for predicting prosthetic valve dysfunction. There was a significant relationship between fluoroscopy and D-dimer test (P=0.001). A kappa coefficient value of 0.745 indicated a substantial agreement between D-dimer and fluoroscopy testing. Mixing test (combination of D-dimer and INR) showed to have 100% sensitivity, and hence a NPV of 69.8%, specificity of 69.8%, PPV of 51.8%, NLR of 1.41, and PLR of 1.44 for predicting prosthetic valve dysfunction. D-dimer with moderate sensitivity and high specificity is an ideal marker for the diagnosis of prosthetic valve dysfunction in suspected patients. Enhanced plasma D-dimer level is not by itself diagnostic of a prosthetic valve dysfunction but may alert physicians to refer the patient for more detailed examination, preferably by fluoroscopy. Mixing test with 100% sensitivity can apply as a rule-out test.

Coagulation profile and D-dimer level in hospitalized COVID-19 patients: A cross-sectional study in a tertiary care hospital

Background: Most of the patients of Coronavirus Disease-19 (COVID-19) presented with mild symptoms and recovered, but a considerable number of cases deteriorated and succumbed to death. They often present with hemostatic abnormalities mimicking disseminated intravascular coagulation with increased risk of thrombosis rather than bleeding. Hence, early prediction of disease severity by some easily available hematological parameters might be helpful to reduce mortality in COVID-19 cases. Aim and Objectives: The aim of the study was to determine whether values of Prothrombin Time (PT), International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT) and D-Dimer (DD) correlate with disease severity in COVID-19 and also to find out cutoff value of these parameters to predict disease severity. Materials and Methods: This observational cross-sectional study was done on total 400 hospitalized COVID-19 adult patients where patients were categorized into moderate and severe cases as per guideline of Government of India. Patients with pre-existing coagulation disorder or receiving anticoagulant drugs were excluded from the study. PT, INR, APTT, and DD values of these two groups were evaluated and compared statistically to determine their significance and the cut-off value to predict severity. Results: Among the measured blood parameters means of PT (P < 0.001), INR (P < 0.001) and DD (P < 0.001) found to be significantly higher in the severe group of patients compared to moderate ones and DD value ≥1.365 mg/L indicates severe disease. APTT showed no statistically significant association with severity. Conclusion: PT and INR can be used as severity marker in COVID-19 patients; however, DD is the most reliable marker correlating with disease severity.

Clinical Impact of the Time in Therapeutic Range on Early Hospital Readmission in Patients with Acute Heart Failure Treated with Oral Anticoagulation in Internal Medicine

Patients with heart failure (HF) often present with non-valvular atrial fibrillation and require oral anticoagulation with coumarin anticoagulants such as acenocoumarol. The objective of this study was to evaluate the relationship between time in therapeutic range (TTR) and the risk of early readmission. A retrospective descriptive study was carried out on hospitalized patients with a diagnosis of HF between 2014 and 2018 who had adverse effects due to oral anticoagulation with acenocoumarol (underdosing, overdosing, or hemorrhage). Clinical, analytical, therapeutic, and prognostic variables were collected. TTR is defined as the duration of time in which the patient's International Normalized Ratio (INR) values were within a desired range. Early readmission was defined as readmission within 30 days after hospital discharge. Patients were divided into two groups depending on whether or not they had a TTR less than 60% (TTR < 60%) over the 6 months prior to the adverse event. In the cohort of 304 patients, the mean age was 82 years, 59.9% of the patients were female, and 54.6% had a TTR < 60%. Patients with TTR < 60% had a higher HAS-BLED score (4.04 vs. 2.59; P < 0.001) and INR (6 vs. 5.31; P < 0.05) but lower hemoglobin (11.67 vs. 12.22 g/dL; P < 0.05). TTR < 60% was associated with early readmission after multivariate analysis (OR: 2.05 (CI 95%: 1.16-3.61)). They also had a higher percentage of hemorrhagic events and in-hospital mortality but without reaching statistical significance. Patients with HF and adverse events due to acenocoumarol often have poor INR control, which is independently associated with a higher risk of early readmission.

Varfarin Kullanan Hastalarda Kanama ile İlişkili Faktörler

Objective: The most serious side effect of warfarin, an oral anticoagulant widely prescribed by many different disciplines, is bleeding. In this study, the factors affecting the bleeding complications resulting from the use of warfarin were investigated.Material and Methods: In this study, 111 patients using warfarin and admitted to the emergency department with bleeding complaints were evaluated. All patients were divided into two groups as Group I (international normalized ratio &amp;gt;3.5) and Group II (international normalized ratio ≤3.5) according to the "international normalized ratio" value at the time of admission. The groups were compared in terms of demographic characteristics, admission complaint, indications for warfarin use, concomitant diseases, other drugs used, duration of warfarin use, international normalized ratio value, bleeding localization, treatment and interventions.Results: Of the 115 patients, 85 were in Group I and 26 were in Group II. Fifty-six (50.5%) of the patients were women. In our study, the most common reason for warfarin use was heart valve replacement (46.8%). The most common complaint was bloody stool (41.5%). Of the patients, 79 of had at least one concomitant disease. The most common comorbid disease of our patients was hypertension (n=50, 45%). Seventy-six patients were found to have major bleeding and major bleeding was higher in Group I.Conclusion: It was determined that major bleeding and need for hospitalization were higher in patients with an international normalized ratio value &amp;gt;3.5, and the follow-up period in the emergency department was longer. Although the international normalized ratio value is an important factor for warfarin-induced bleeding, the international normalized ratio value is not the only cause of bleeding and additional factors may be responsible for bleeding.

The usage and outcomes of dextran in the treatment of acute deep venous thrombosis.

In this study, we retrospectively compared the outcomes of patients with acute deep vein thrombosis treated with dextran 40 infusion and unfractionated heparin with those of patients treated with unfractionated heparin alone. We evaluated 104 patients with the diagnosis of acute deep vein thrombosis. The pain complaints of the patients at the time of admission and the pain complaints in the calf with dorsiflexion of the foot were evaluated with the visual analogue pain scale, and the calf diameter of affected limbs was measured. Fifty five patients had dextran 40 infusion and unfractionated heparin treatment concomitantly (Group HD), while 49 patients had unfractionated heparin treatment (Group H). Heparin dose was adjusted to obtain 1.5- to 2.5-fold of normal activated partial thromboplastin time in both groups. Oral anticoagulant, warfarin sodium, was administered in the first day and resumed. Unfractionated heparin infusion therapy was resumed until international normalized ratio values of 2-2.5 were obtained. Dextran 40 infusion therapy was administered for 3 days. Calf diameters, current pain, and calf pain at foot dorsiflexion were recorded at 48 h and 72 h. 65 patients were distal, and 39 patients were proximal and popliteal acute DVT. None of the patients had phlegmasia. All were acute DVT. At 48 and 72 h of therapy, it was determined that the decrease of the calf diameter and the pain were more significant both at 48th and 72nd hours in the Group HD. The calf circumference change, especially at 72 h, was 2.58 ± 0.39cm in the group receiving heparin + dextran, while it was 1.76 ± 0.56cm in the group receiving only heparin. (p = 0.000). While there were only 1.24 ± 1.02 people in the group that received dextran at 72 h, leg pain persisted in 3.35 ± 1.11 people in the other group. (p = 0.000). Evaluation was made only with calf vein diameter measurement. When patients with Homan's sign were evaluated for their calf pain at foot dorsiflexion; both groups had decreased pain at 48th and 72nd hours. In this study, we observed that the use of dextran 40 infusion therapy concomitantly with unfractionated heparin accelerates recovery substantially and decreases patient complaints significantly in early stages. In particular, reduction in leg pain and calf circumference reduction were more adequate in the dextran group. The early decrease in the calf circumference will have clinical consequences such as less heparin intake, earlier return to normal life, and a decrease in the total cost of treatment. Since the antithrombotic and anticoagulant effects of dextran are well known, we think that its use in this treatment as well as venous thromboembolism prophylaxis should be discussed.

VKA overdose in Covid-19 infected patients

During the Covid-19 pandemic, four patients were admitted in a healthcare center. They were treated by vitamin K antagonists (VKA). We observed a substantially increased of their International Normalized Ratio (INR) The mean age of patients was 90 (± 8). All had different usual long-term therapy treatments but had fixed doses of VKA to reach a stable INR. No change of background treatment were realized. One patient presented cough whereas the three others were asymptomatic. In the pandemic context, a reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 was realized for each patients. RT-PCR were all positives and were associated with a substantially increased INR. Mr H. was admitted with an INR of 2.25 and it increased to 5.93 the day after RT-PCR positivity. The VKA treatment was stopped but the INR one day after was 7.89. Mrs J. presented INR value from 1.96 to 4.58, 10 days later. PCR have been realized and VKA treatment was stopped: INR still increased up to 5.85. The INR of Mr R. increased from 1.82 to 8.05, 24h after positive PCR results. Mrs F. presented a gradually increase of INR from 1.5 to 3.36, 72h after PCR results three days after VKA discontinuation. Finally, this study suggest a link between the Covid-19 infection and an increased INR. It has been established that SARS-CoV-2 infection induces hypercoagulability in severe forms. Inversely, these four cases show a hemorrhagic risk with the elevation of the INR. It could have a risk of overdose when patients treated with VKA and positive to Covid-19. This raises the question of discontinuing VKA and substituting them with another anticoagulant, or performing INR controls more frequently in the context of Covid-19. Moreover, an unexpected increase of INR could lead to realize a Covid-19 RT-PCR in this pandemic context.