Possible Correlation between INR and Serum Calcium

On Warfarin Use in Kidney Disease: A Therapeutic Window of Opportunity?

<h3>ABSTRACT</h3> <h3>BACKGROUND:</h3> Warfarin is indicated for the prevention and treatment of venous thrombosis and thromboembolic complications associated with atrial fibrillation. The delivery of high-quality healthcare in a rural hospital requires the same, if not higher, focus on managing patients’ international normalized ratio (INR) within the therapeutic range. Options for warfarin management include anticoagulation clinics, in-home self-testing, pharmacist-led management, and physician-led management. However, rural hospitals are usually unable to afford specialized anticoagulation clinics to monitor patients receiving warfarin therapy. The purpose of this study is to optimize and examine the efficacy of warfarin therapy management in a rural hospital by utilizing the resources available within the hospital through the use of a diagnostic management team (DMT). <h3>DESIGN:</h3> In order to evaluate the efficacy of DMT for warfarin management in a rural hospital (Hamilton General Hospital, Hamilton, TX), we conducted a retrospective chart review to analyze the time in therapeutic range (TTR) for the target and expanded therapeutic ranges (±0.2 and ±0.3 INR units), average percentage of INR values in the target and expanded therapeutic ranges, and percentage of INR &lt;1.5 and INR &gt;4.5. These outcomes were compared before and after DMT implementation. <h3>RESULTS:</h3> A total of 50 patients (48% male and 52% female) underwent 205 INR measurements before DMT implementation and 247 INR measurements after DMT. The most common indication for warfarin was atrial fibrillation, followed by DVT. TTR for the target range increased from 52% pre-DMT to 64% post-DMT. TTR for the expanded therapeutic range (±0.2 INR units) increased from 64% pre-DMT to 77% post-DMT. Similarly, TTR for the expanded therapeutic range (±0.3 INR units) increased from 69% pre-DMT to 81% post-DMT. The average percentage of therapeutic INRs was 62% pre-DMT and 74% post-DMT (<i>P</i> &lt; .05) for the target range, 72% pre-DMT and 86% post-DMT (<i>P</i> &lt; .05) for the expanded therapeutic range (±0.2 INR units), and 76% pre-DMT and 86% post-DMT (<i>P</i> &lt; .05) for the expanded therapeutic range (±0.3 INR units). The percentage of INR &lt;1.5 decreased by 6.9% and INR &gt;4.5 decreased by 1.6% post-DMT. <h3>CONCLUSION:</h3> Incorporating a comprehensive approach for optimizing warfarin therapy through the use of DMT and utilizing the resources available in a rural hospital improved TTR and the percentage of INRs in the therapeutic range for both target and expanded therapeutic ranges and decreased bleeding and clotting episodes as well as warfarin-related documentation. DMT may be an economically attractive alternative platform to prevent bleeding and clotting and improve treatment monitoring for patients on warfarin therapy.

BackgroundData are scarce regarding the optimal international normalized ratio (INR) in Thai patients who require warfarin therapy after mechanical mitral valve replacement. Accordingly, the aim of this study was to identify the optimal INR level for warfarin therapy after mechanical mitral valve replacement in Thai patients.MethodsThis is a retrospective cohort study design. We retrospectively reviewed the medical records of mechanical mitral valve replacement patients who received warfarin therapy at Siriraj Hospital. INR range was classified into 6 groups (< 2, 2.0–2.4, 2.5–2.9, 3.0–3.4, 3.5–4.5, and > 4.5). The optimal INR level was defined as the level with the lowest incidence density of thromboembolic or hemorrhagic complications.ResultsTwo hundred patients were included and followed over a period of 707.81 patient-years. Mean duration of follow-up was 3.53 ± 1.27 years. Eleven patients experienced 13 thromboembolic events (3.42 per 100 patient-years), and 12 patients experienced 18 total bleeding events (5.50 per 100 patient-years). Intracranial bleeding occurred in 3 patients (2.62 per 100 patient-years). The percentage of patient time spent within INR 2.5–3.4, INR < 2.5, and INR > 3.4 was 41.96, 54.04, and 4%, respectively. The overall event rate was lowest in the 2.0 to 3.4 INR range. Statistically significant differences were observed between INR 2.3 to 4 and < 2 (p < 0.001) and between INR 2.3 to 4 and > 3.4 (p < 0.001).ConclusionsThe optimal INR level was within the range of 2.0 to 3.4 in our cohort of Thai mechanical mitral valve replacement patients.

Randomized Controlled Trial of Supervised Patient Self-Testing of Warfarin Therapy Using An Internet Based Expert System

To compare the international normalized ratios (INRs) of patients positive for lupus anticoagulant and the INRs of control patients receiving warfarin therapy with equivalent therapeutic chromogenic factor X levels. Prospective case series. A 625-bed, adult, private, tertiary care teaching hospital. Sixty-eight outpatients positive for lupus anticoagulant and 57 control patients receiving long-term warfarin therapy. Concomitant INR and chromogenic factor X activity were measured in all patients. In 44 control patients (77%) and 46 patients with lupus anticoagulant (68%), chromogenic factor X activity was 22-40% of normal, which is therapeutic. Of the 44 control patients, 4 (9%) had an INR above 3.0, and none had an INR above 4.0. In contrast, 18 (39%) of the 46 patients with lupus anticoagulant had an INR above 3.0, and 5 (11%) had an INR above 4.0. At least 10% of patients with lupus anticoagulant receiving long-term warfarin therapy may have falsely high INR values, which could lead to inappropriate warfarin dosage reduction. Monitoring warfarin therapy by chromogenic factor X activity in patients with lupus anticoagulant avoids this INR artifact.

BackgroundMaintaining stable levels of anticoagulation using warfarin therapy is challenging. Few studies have examined the stability of the international normalized ratio (INR) in patients with nonvalvular atrial fibrillation (NVAF) who have had ≥6 months’ exposure to warfarin anticoagulation for stroke prevention.ObjectiveOur objective was to describe INR control in NVAF patients who had been receiving warfarin for at least 6 months.MethodsUsing retrospective patient data from the CoagClinic™ database, we analyzed data from NVAF patients treated with warfarin to assess the quality of INR control and possible predictors of poor INR control. Time within, above, and below the recommended INR range (2.0–3.0) was calculated for patients who had received warfarin for ≥6 months and had three or more INR values. The analysis also assessed INR patterns and resource utilization of patients with an INR >4.0. Logistic regression models were used to determine factors associated with poor INR control.ResultsPatients (n = 9433) had an average of 1.6 measurements per 30 days. Mean follow-up time was 544 days. Approximately 39 % of INR values were out of range, with 23 % of INR values being <2.0 and 16 % being >3.0. Mean percent time with INR in therapeutic range was 67 %; INR <2.0 was 19 % and INR >3.0 was 14 %. Patients with more than one reading of INR >4.0 (~39 %) required an average of one more visit and took 3 weeks to return to an in-range INR. Male sex and age >75 years were predictive of better INR control, whereas a history of heart failure or diabetes were predictive of out-of-range INR values. However, patient characteristics did not predict the likelihood of INR >4.0.ConclusionsOut-of-range INR values remain frequent in patients with NVAF treated with warfarin. Exposure to high INR values was common, resulting in increased resource utilization.

Chronic kidney disease (CKD) patients are belonging to high risk patients to atherosclerosis with vascular calcification. These patients are well recognized advanced arteriosclerosis with vascular medial calcification, with high risk of cardiovascular death. With basic investigated results, the mechanism of vascular calcification is making clear. A lot of various factors which participate in calcification have been specified. Especially, in long term dialysis patients, the very high grade vascular calcification with advanced atherosclerosis is common with calcium/phosphate/PTH and skeletal problem. This CKD related metabolic bone disorder (CKD-MBD) highly induced and progressed vascular calcification. Participates in vascular calcification. It is extremely important in order to prevent vascular calcification to manage serum phosphorus, serum calcium and parathyroid function within the suitable range. In addition, hyperphosphatemia is becoming the powerful risk factor for patients' survival. The new powerful phosphate binder is developing. The beneficial effect of the new agent on patients' survival is now focused.

To report 4 cases of hypoprothrombotic response resulting from addition of levofloxacin therapy to chronic warfarin therapy and to review related literature to support or refute a warfarin-levofloxacin interaction. Four patients, 34-81 years old, were prescribed levofloxacin concomitantly with stable warfarin therapy. Three patients had a target international normalized ratio (INR) range of 2.0-3.0 and experienced an increase in INR to 3.5, 8.12, and 11.5 on days 11, 5, and 4 of a 10-day course of levofloxacin, respectively. The fourth patient experienced minor bleeding, with a slightly elevated INR on the second day of levofloxacin therapy that required up to a 19% warfarin dose reduction during levofloxacin treatment. An initial premarketing clinical trial concluded that levofloxacin had no effect on warfarin's pharmacokinetics and pharmacodynamic response. Two case reports have since documented an increase in INR in patients taking long-term warfarin on completion of levofloxacin therapy. Our case reports provide further evidence of a significant increase in INR observed during concomitant levofloxacin therapy. The proposed mechanism of this interaction is displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism. Prolonged prothrombin response in patients undergoing chronic warfarin therapy has been well documented with many antibiotics, including fluoroquinolones. Recognition of newer antibiotics' effects on warfarin therapy is important to guide safe use and monitoring of anticoagulation therapy. Our case studies demonstrate significant elevations in INR values during and up to 1 day after levofloxacin therapy in patients undergoing stable warfarin therapy.

Thromboembolic Consequences of Subtherapeutic Anticoagulation in Patients Stabilized on Warfarin Therapy: The Low INR Study

Objective To evaluate the impact of pharmacist interventions on international normalized ratio (INR) control during the warfarin initiation phase after mechanical valve replacement. Methods This was a retrospective cohort study conducted in a cardiovascular surgery ward in a tertiary hospital from August 1, 2015, to July 31, 2019. Patients aged ≥20 years who were admitted for mechanical valve replacement were enrolled in this study and further classified into conventional and pharmacist-managed warfarin therapy (PMWT) groups. All participants were prospectively followed up until the first outpatient appointment after valve replacement. The effectiveness outcomes were time in therapeutic range (TTR), time to therapeutic INR, number of patients with therapeutic INR at discharge and at first outpatient appointment, and length of hospital stay. The safety outcome was the number of patients with any supratherapeutic INR during the hospital stay. Multivariate logistic regression analyses were also used to determine the predictors of a therapeutic INR at discharge or with any supratherapeutic INR during admission. Results A total of 39 and 33 patients were enrolled in the conventional and PMWT groups, respectively. At discharge, 18 patients (46.2%) in the conventional group and 24 patients (72.7%) in the PMWT group had achieved the therapeutic INR (P=0.023). Compared to the conventional group, fewer patients in the PMWT group had supratherapeutic INR during hospital stay (35.9% vs. 9.0%, P=0.008). No significant differences were found in TTR, time to therapeutic INR, number of patients with therapeutic INR at return appointment, and length of stay between the study groups. In the multivariate regression analyses, PMWT predicted achieving therapeutic INR at discharge (odds ratio (OR) and 95% confidence interval (CI), 3.14 [1.08–9.14]) and was inversely associated with supratherapeutic INRs during admission (OR = 0.21 [0.05–0.82]). Conclusions Among patients admitted for mechanical valve replacement, the implementation of PMWT was associated with optimal therapeutic INR at discharge and no supratherapeutic INR during admission. Therefore, pharmacist participation is essential for improving the quality of warfarin therapy.

Effects of Oral Paricalcitol on Secondary Hyperparathyroidism and Proteinuria of Kidney Transplant Patients

To evaluate the effect of levofloxacin coadministration on the international normalized ratio (INR) in patients receiving warfarin therapy. Prospective analysis. Outpatient clinic at a Veterans Affairs medical center. Eighteen adult patients receiving warfarin. On the basis of clinical diagnosis and judgment, levofloxacin was prescribed to the 18 patients for treatment of various types of infection. The INR was measured before and at 2-8-day intervals after the coadministration of levofloxacin therapy, and once after completing therapy. Warfarin dosages were adjusted when necessary. Warfarin dosages were changed in seven patients as a result of the first nontherapeutic INR values obtained after start of levofloxacin therapy. Owing to a concern regarding noncompliance and the adverse effect of bleeding, warfarin dosage was adjusted in one patient even though his first INR value was in the high end of the therapeutic range (2.98, therapeutic range 2-3). One patient withdrew from the study after the first INR measurement after levofloxacin coadministration. Because of a concern about the possible bleeding complication, warfarin dosage was also adjusted in this patient after obtaining his first INR value. Therefore, only the INR values obtained before and the first INR values obtained after levofloxacin administration were compared to evaluate the effect of levofloxacin on INR determination of warfarin therapy. The INR values obtained before levofloxacin administration did not differ significantly from the first INR values obtained after levofloxacin coadministration (mean +/- SD 2.61 +/- 0.44 vs 2.74 +/- 0.83, 95% confidence interval -0.449-0.196, p=0.419). The INR values measured before and after concomitant levofloxacin therapy were not significantly different. However, the ability to detect a significant difference may be affected by the small number of patients studied. Further studies with a larger sample are required to better determine the effect of levofloxacin coadministration on INR monitoring during warfarin therapy

Management and dosing of warfarin therapy

To compare the international normalized ratio (INR) measured by a point-of-care testing device with that measured by a reference laboratory method for patients receiving either warfarin only or warfarin plus low-molecular-weight heparin (LMWH). Retrospective study. Outpatient anticoagulation clinic. Ninety-one patients receiving warfarin for various indications; 59 of them receiving only warfarin and 32 receiving warfarin plus LMWH. Capillary blood was obtained for INR determination by a point-of-care device, and venous blood was obtained for INR determination in a standard reference laboratory. Ninety-one patients had INR pairs run on a point-of-care device and by the laboratory. In both the patients receiving only warfarin and in those receiving warfarin plus LMWH, the mean INR as determined by the point-of-care testing device was statistically significantly higher than the mean INR determined by the laboratory. Although the differences were statistically significant in both groups, the clinical significance of this difference was accentuated in the patients receiving warfarin plus LMWH. The measure of divergence between the point-of-care and laboratory methods was greater in the group receiving warfarin plus LMWH than in the warfarin-only group, with a mean +/- SD percent change between the INR values of 24.19 +/- 27.54% in the warfarin plus LMWH group and 7.21 +/- 17.73% in the warfarin-only group. In assessing the clinical impact of such variability, a greater degree of discordance in dosing adjustment decisions was noted for patients receiving warfarin plus LMWH. In this group, a 25% rate of discordance was noted compared with 8% in the warfarin-only group. Such discrepancy in dosing decisions based on the point-of-care INR would have resulted in discontinuation of LMWH therapy before the patient acquired a true therapeutic INR, with use of the laboratory measurement. The INR measured with the point-of-care device in patients receiving concurrent LMWH and warfarin therapy may be inaccurate. Patients receiving LMWH in addition to warfarin should have INRs checked by means of the standard reference laboratory method.

The use of an off-label dose of four-factor prothrombin complex concentrate (PCC) for International Normalized Ratio (INR) reversal in a patient before a diagnostic lumbar puncture is reported. A 57-year-old, 122-kg man arrived at the hospital with a possible diagnosis of meningitis and had an INR of >3 while on warfarin therapy. The patient initiated warfarin therapy in 2009 due to recurrent deep vein thrombosis. The patient required reversal of his elevated INR in order for a lumbar puncture to be safely performed (INR must be no higher than 1.4). Multiple units of fresh frozen plasma (FFP) were administered, with a subsequent INR decrease to 1.9. Additional units of FFP were given. The patient developed respiratory decompensation due to volume overload, partially caused by the administration of multiple units of FFP. As the INR remained above 1.4 but was less than 2, an alternative dosing strategy was used. A dose of 1020 units of factor IX, equaling about 10 mg/kg based on a maximum dosing weight of 100 kg, was administered. The two vials of PCC administered each contained 510 units of factor IX. No vitamin K was given. The patient's INR, checked 30 minutes after PCC administration, was 1.3, and the lumbar puncture was performed. The lumbar puncture was completed without complication, and the patient was restarted on therapeutic anticoagulation the following day. A 57-year-old patient was successfully treated with low-dose PCC to reverse an INR from 1.7 to 1.3 in order to perform a diagnostic lumbar puncture.