High International Normalized Ratio Levels Research Articles

Comprehensive Management of Anticoagulants Induced Decompensated Severe Anemia in Postmitral Valve Replacement

Abstract Mechanical prosthetic valve needs consideration for anticoagulation. The objective of this case report was to know how maintenance of oral anticoagulant therapy is very important in patients, especially with mechanical heart valve replacement. It is the holistic management of mitral valve replacement (MVR) patients with high international normalized ratio (INR) (>100), which led bleeding into the peritoneal cavity and causes decompensated severe anemia. Although it is a rare presentation for a patient of MVR with high INR level but which is most commonly presented for cerebrovascular accident. Anemia is a thoughtful worldwide problem that disturbs the quality of life in persons of all ages. A 28-year-old Indian woman with follow-up case of post-MVR came to the hospital with complaints of breathing difficulty, altered sensorium, pulse rate of 150–170 bpm (beats/min) irregularly irregular, blood pressure (80/50 mmHg), palpitation, and abdominal pain. Blood test report revealed her hemoglobin (Hb) was 3.2 g%, suggestive of severe anemia, INR was >100 s. Hence, patient diagnosed as follow-up case of MVR (#27 mm mechanical bileaflet mitral valve prosthesis) with peritoneal bleeding, an oral anticoagulant with decompensated severe anemia managment should be done. Ended the progression of her hospitalization, she received four units of packed red blood cell transfusions; Vitamin K was given intravenous once daily for 2 days and no anticoagulant was given, so far, INR was high with serial monitoring of INR and Hb. Her symptoms of breathing difficulty, pain in abdomen, weakness and giddiness resolute by the finish of her hospital stay, and she recompensed to her oral anticoagulant therapy with improved Hb and hemodynamics. Disapprovingly high INR levels are classically related with bleeding disorders revealed on imperative indicators and hemodynamic variability. To our understanding, one of the lowermost noted Hb is because of bleeding due to very high INR, so monitoring of therapeutic INR level with anticoagulants is very-very important.

Effect of troponin I and coagulation parameters on mortality in COVID-19 patients

Objective: Our aim is to determine the levels of troponin-I and some coagulation markers (D-dimer, fibrinogen and International Normalized Ratio (INR)) in coronavirus disease 2019 (COVID-19) patients and to investigate the effects of these markers on mortality.
 Patients and Methods: It is planned as a descriptive, cross-sectional and analytical study. The study was conducted by retrospectively scanning the files of COVID-19 patients who applied to Inonu University Turgut Ozal Medical Center between 01.03.2020 and 31.12.2020. Levels of cardiac troponin I markers and coagulation parameters (D-dimer, fibrinogen and INR) were detected.
 Results: The results of a total of 1858 patients were obtained. One thousand, three hundred and twenty-six patients with only troponin I and D-dimer results (Group 1), 606 patients with only troponin I and fibrinogen results (Group 2), and 1308 patients with only troponin I and INR results (Group 3) were included. Troponin I levels were significantly higher in all patients who died. 96.6% of the patients with high D-dimer levels died in Group 1, 85.5% of the patients with high fibrinogen levels died in Group 2 and 77.3 % of the patients with high INR levels died in Group 3. 
 Conclusion: Measurements of troponin-I and coagulation markers such as D-dimer, fibrinogen and INR can help predict clinical severity and mortality in COVID-19 patients.

Yüksek INR Düzeylerine Rağmen Görülen İki İskemik İnme Olgusu

Warfarin is a vitamin K antagonist commonly used in the treatment and prevention of thromboembolic cases worldwide. Its therapeutic range is narrow and is followed by the international normalized ratio (INR). Ischemic conditions are observed at low INR levels whereas bleeding is seen at higher INR levels. A 45-year-old woman and a 79-year-old man using warfarin were admitted to the emergency department with a neurological deficit. Ischemic stroke was revealed via radiological imaging in both patients. However, INR levels were significantly higher in laboratory tests (11.44 and 12.37 kU / L).Ischemic stroke occurred although bleeding is normally expected at such high INR levels. Contrary to many studies published in the literature, this case report revealed interesting information in terms of its conclusions.

Association of Lumbar Puncture With Spinal Hematoma in Patients With and Without Coagulopathy

Coagulopathy may deter physicians from performing a lumbar puncture. To determine the risk of spinal hematoma after lumbar puncture in patients with and without coagulopathy. Danish nationwide, population-based cohort study using medical registries to identify persons who underwent lumbar puncture and had cerebrospinal fluid analysis (January 1, 2008-December 31, 2018; followed up through October 30, 2019). Coagulopathy was defined as platelets lower than 150 × 109/L, international normalized ratio (INR) greater than 1.4, or activated partial thromboplastin time (APTT) longer than 39 seconds. Coagulopathy at the time of lumbar puncture. Thirty-day risk of spinal hematoma. Risks were provided as numbers and percentages with 95% CIs. Secondary analyses included risks of traumatic lumbar puncture (>300 × 106 erythrocytes/L after excluding patients diagnosed with subarachnoid hemorrhage). Adjusted hazard rate ratios (HRs) were computed using Cox regression models. A total of 83 711 individual lumbar punctures were identified among 64 730 persons (51% female; median age, 43 years [interquartile range, 22-62 years]) at the time of the procedure. Thrombocytopenia was present in 7875 patients (9%), high INR levels in 1393 (2%), and prolonged APTT in 2604 (3%). Follow-up was complete for more than 99% of the study participants. Overall, spinal hematoma occurred within 30 days for 99 of 49 526 patients (0.20%; 95% CI, 0.16%-0.24%) without coagulopathy vs 24 of 10 371 patients (0.23%; 95% CI, 0.15%-0.34%) with coagulopathy. Independent risk factors for spinal hematoma were male sex (adjusted hazard ratio [HR], 1.72; 95% CI, 1.15-2.56), those aged 41 through 60 years (adjusted HR, 1.96; 95% CI, 1.01-3.81) and those aged 61 through 80 years (adjusted HR, 2.20; 95% CI, 1.12-4.33). Risks did not increase significantly according to overall severity of coagulopathy, in subgroup analyses of severity of coagulopathy by pediatric specialty or medical indication (infection, neurological condition, and hematological malignancy), nor by cumulative number of procedures. Traumatic lumbar punctures occurred more frequently among patients with INR levels of 1.5 to 2.0 (36.8%; 95% CI, 33.3%-40.4%), 2.1 to 2.5 (43.7%; 95% CI, 35.8%-51.8%), and 2.6 to 3.0 (41.9% 95% CI 30.5-53.9) vs those with normal INR (28.2%; 95% CI, 27.7%-28.75%). Traumatic spinal tap occurred more often in patients with an APTT of 40 to 60 seconds (26.3%; 95% CI, 24.2%-28.5%) vs those with normal APTT (21.3%; 95% CI, 20.6%-21.9%) yielding a risk difference of 5.1% (95% CI, 2.9%-7.2%). In this Danish cohort study, risk of spinal hematoma following lumbar puncture was 0.20% among patients without coagulopathy and 0.23% among those with coagulopathy. Although these findings may inform decision-making about lumbar puncture by describing rates in this sample, the observed rates may reflect bias due to physicians selecting relatively low-risk patients for lumbar puncture.

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

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. 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. 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. 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.

Can we predict severity of acute cholecystitis at admission?

Background and Objective:Acute cholecystitis (AC) is an inflammation of the gallbladder. Tokyo Guidelines (TGs) for the diagnosis of AC classified this condition according to severity as mild, moderate and severe. Therapeutic intervention regulated according to the type of severity. This study aimed to determine laboratory parameters that predict the severity of AC at hospital admission.Methods:One-hundred and ten patients with AC were retrospectively reviewed. These patients were treated in our department of surgery within a one-year period (2015–2016). Three patient groups were formed depending on the severity of Acute cholecystitis.Results:The baseline mean values for white blood cell count (WBC), blood urea nitrogen (BUN), creatinine and international normalized ratio (INR) were higher in the severe patient group at a significant level compared to the mild patient group. The WBC level was also significantly higher in the moderate group than the mild group. However, none of the laboratory parameters differentiated the severe group from the moderate group.Conclusion:Acute cholecystitis patients with high WBC, BUN, creatinine and INR levels at admission should be referred to an advanced care center for management.

Can Patients Who Develop Cerebral Death in Fulminant Liver Failure Despite Liver Transplantation Be Previously Forseen?

BackgroundThe outcome of medical treatment is worse in fulminant liver failure (FLF) developing on acute or chronic ground. Recently, liver transplantations with the use of living and cadaveric donors have been performed in these diseases and good results obtained. In this study, we aimed to present the factors affecting the recovery of cerebral functions after liver transplantation in hepatic encephalopathy (HE) developing in FLF, to identify irreversible patient groups and to prevent unnecessary liver transplantation. MethodsIn Inonu University's Liver Transplant Institute, 69 patients who made an emergency notice to the National Coordination Center for liver transplantation owing to FLF from January 2012 to December 2015 were included in the study. Patients were divided into 2 groups. Group 1 consisted of 52 patients who underwent liver transplantation and recovered normal brain function, and group 2 had 17 patients who underwent liver transplantation and did not recover normal brain function and had cerebral death. All patients were evaluated before surgery for clinical encephalopathy stage, light reflex, and convulsions. Groups were compared and assessed according to age (>40, 10–40 and <10 years), body mass index, etiologic factor, preoperative laboratory values, transplantation type, mortality, and encephalopathy level. Multivariate analysis was done for specific parameters. ResultsProthrombin time (PT), international normalized ratio (INR), and total bilirubin values were significantly different between the groups. There was no significant difference between the groups regarding ammonia and lactate levels. There was a statistically significant difference between the groups regarding sodium and potassium levels from serum electrolytes. However, the averages of both groups were within normal limits. pH and total bilirubin levels were meaningful for multivariate analysis. ConclusionsHE reversibility, mortality, and morbidity are important in patients with HE who undergo liver transplantation. Therefore, West Haven clinical staging and serum INR, PT, and total bilirubin level may be helpful in predicting the reversibility of FLF patients with HE before liver transplantation. It was determined that West Haven encephalopathy grading is important in determining the reversibility of HE after transplantation in FLF; especially the probability of reversibility of stage 4 HE decreases significantly. High PT and INR levels, hyperbilirubinemia, and serum sodium and potassium concentrations were risk factors for the reversibility of HE in this study.

Determining Risk Factors of Bleeding in Patients on Warfarin Treatment

Background. Warfarin is a commonly used oral anticoagulant agent. The most common adverse effects of warfarin are bleeding complications. Methods. We performed a 1-year retrospective chart review of emergency department patients using warfarin. A total of 65 patients with bleeding disorder (study group) and 63 patients without bleeding (control group) were included, making up a total of 128 subjects. Demographic data, frequency of international normalized ratio (INR) checks, and routine blood results were extracted. Logistic regression analysis was used to determine which factors were most closely associated with bleeding complications. Results. Median age was 62.0 ± 14.4 and 61.9 ± 14.5 for study group and control group, respectively. Educational status and frequency of INR checks were similar in both groups (P = 0.101 and P = 0.483, resp.). INR levels were higher in the study group (5.45 ± 3.98 versus 2.63 ± 1.71, P < 0.001). Creatinine levels were also higher in the study group (1.14 ± 0.57 mg/dL versus 0.94 ± 0.38 mg/dL, P = 0.042). Acetylsalicylic acid use was more frequent in the study group and was associated with a 9-fold increase in bleeding complications (P < 0.001). Conclusions. High INR levels, high creatinine levels, and acetylsalicylic acid use were associated with bleeding complications in ED patients using warfarin.

Clinical Significance of Coagulation Assays in Metastatic Pancreatic Adenocarcinoma

Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation tests for various clinicopathologic factors in patients with metastatic pancreatic adenocarcinoma (MPA). A total of 17 MPA patients were enrolled into the study. All the patients were treatment-naïve. Pretreatment blood coagulation tests including prothrombin time, activated partial thromboplastin time (APTT), international normalized ratio (INR), D-dimer, fibrinogen levels, and platelet counts were evaluated. Control group comprised 50 age- and sex-matched individuals without history of malignancy and coagulation disorder. Median age of diagnosis was 59years old (range, 35-72). The plasma level of all coagulation factors revealed statistically significant difference between patient and control group (p < 0.01). Anemic patients had associated with higher D-dimer levels (p = 0.001). Similarly, the ones with elevated serum CA19-9 exhibited significantly higher D-dimer values (p = 0.011). For APTT, significant differences were found in both between gender of patients (p = 0.01) and response to chemotherapy (p = 0.01). The patients with elevated erythrocyte sedimentation rates had associated with higher INR (p = 0.05). Univariate analysis of survival revealed that the patients with unresponsive to chemotherapy (p = 0.06) and higher INR (p = 0.078) had poor overall outcome. Serum D-dimer level is elevated among MPA patients with higher serum CA19-9 and higher INR levels seem to be a poor prognostic factor in MPA.

Abstract 10: Intracranial Hemorrhage Risks among Warfarin Treated Acute Ischemic Stroke Patients Receiving Thrombolytic Therapy

Background While intravenous thrombolytic therapy (tPA) improves the outcomes of ischemic stroke, treatment of those receiving warfarin raises concerns regarding symptomatic intracranial hemorrhage (ICH). While guidelines suggest excluding patients with an international normalized ratio (INR) &gt;1.7, little is known about the use and safety of tPA in warfarin-treated patients in clinical practice. Methods Data from 23,437 ischemic stroke patients treated with tPA with an INR ≤1.7 in 1,203 Get With The Guidelines-Stroke hospitals between April 2009 and June 2011. Multivariable logistic regression analysis was performed to evaluate the association of preadmission warfarin use on ICH risk while adjusting for potential confounders. Results Overall 1,802 (7.7%) were taking warfarin prior to admission. Warfarin treated patients were older (median 77 vs. 71 years, p&lt;0.001) and had more comorbid illness and greater stroke severity (median National Institutes of Health Stroke Scale 14 vs. 11, p&lt;0.001). Crude rates of ICH were higher in those taking warfarin 5.7% vs. 4.7% (unadjusted OR 1.22, 95% CI 0.99-1.51). However, after risk adjustment, ICH risks were similar (adjusted OR 1.01, 95% CI 0.82-1.25). These findings were consistent across several sensitivity analyses (Table). There were no significant differences between warfarin and non-warfarin users for serious systemic hemorrhage (0.9% vs. 0.9%; adjusted OR 0.78; 95% CI 0.48-1.24), any tPA complications (10.6% vs. 8.4%; adjusted OR 1.09; 95% CI 0.93-1.29), and in-hospital mortality (11.4% vs. 7.9%; adjusted OR 0.94; 95% CI 0.79-1.13). Among those receiving warfarin, a trend toward higher crude ICH rates was observed among those with higher baseline INR levels (Cochran-Mantel-Haenszel trend test, p=0.03). After adjustment for risk factors, higher INR levels had a marginally significant association with ICH risk (adjusted OR 1.10, 95% CI 1.00-1.20, p=0.06 for each 0.1 units increase in INR). Conclusion This represents the largest clinical experience of the safety of thrombolysis in warfarin treated patients who meets clinical guideline eligibility criteria. Use of intravenous tPA among warfarin-treated stroke patients (INR ≤1.7) was not associated with increased ICH risk compared to non-warfarin treated patients in routine clinical practice. These data provide empirical support of current AHA/ASA guideline recommendations.

Warfarin: Implementing Its Safe Use in Hospitalized Patients from Nursing Homes and Community Through a Performance Improvement Initiative

Warfarin is increasingly used to prevent thromboembolism but adverse drug events (ADEs) are common. The National Safety Goals (3E) 2008 recommend that institutions develop processes to monitor the safe use of warfarin. Despite these guidelines, adverse events (bleeding) are common. This initiative, in an academic hospital, tracked warfarin use before and after using a PI process aimed at improving safe use of warfarin in hospitalized adults. Retrospective (PRE-initiative, September-December 2007) and prospective (POST-initiative, January-December 2008) data were collected on in-hospital and prior warfarin use, demographics, medical history, initial and in-hospital warfarin maintenance dosing, hematocrit, International Normalized Ratio (INR), hepatic and renal function and adverse events related to warfarin use. Education on the appropriate use of warfarin was provided through formal and informal sessions and during daily hand-off sessions. A total of 308 patients receiving oral warfarin were examined (mean age 70 ± 17(SD) years, 47% males, 36% from nursing homes). Age, sex ratios, and place of residence were similar PRE- versus POST-initiative. Overall initial and maintenance warfarin doses were significantly lower POST-initiative (P = .0129 and P = .0319, respectively) and these decreases occurred exclusively in patients with supratherapeutic INR levels (>3.0). During the POST-period, the prevalence of high INR levels and bleeding events during hospitalization also decreased significantly (P = .015 and P < .0005, respectively). Finally, concomitant use of anticoagulant and/or antiplatelet drugs was significantly decreased POST-initiative (P = .028). Most hospitalized patients (PRE- and POST-) presented with INRs in the sub- or supratherapeutic ranges (<2 and >3, respectively), requiring warfarin dose adjustments. Education through this initiative resulted in significantly lower average maintenance doses of warfarin, less use of concomitant anticoagulant or antiplatelet drugs, fewer supratherapeutic range INRs, and fewer adverse events during warfarin therapy. Education through a PI initiative is a simple and effective means to implement safer use of warfarin in the in-hospital setting.

Point‐of‐care reversal treatment in phenprocoumon‐related intracerebral hemorrhage

Rapid reversal of the anticoagulatory effect of vitamin K antagonists represents the primary emergency treatment for oral anticoagulant-related intracerebral hemorrhage (OAC-ICH). Predicting the amount of prothrombin complex concentrate (PCC) needed to reverse OAC in individual patients is difficult, and repeated international normalized ratio (INR) measurements in central laboratories (CLs) are time-consuming. Accuracy and effectiveness of point-of-care INR coagulometers (POCs) for INR reversal in OAC-ICH have not been evaluated. In phase 1, the agreement of emergency POC and CL INR measurements was determined. In phase 2, stepwise OAC reversal was performed with PCC using a predetermined dosing schedule. Concordance of POC and CL INR measurements during reversal and time gain due to POC were determined. In phase 1 (n = 165), Bland-Altman analysis showed close agreement between POCs and CLs (mean INR deviation 0.04). In phase 2 (n = 26), POCs caused a median initial net time gain of 24 minutes for the start of treatment with PCC. Median time for POC-documented complete OAC reversal was 28 minutes, compared with 120 minutes for CLs. Bland-Altman analysis between POCs and CLs revealed a mean INR deviation of 0.13 during stepwise PCC administration. POCs tended to slightly overestimate the INR, especially at higher INR levels. Remarkably, POC-guided reversal led to a median reduction of 30.5% of PCC dose compared with the a priori dose calculation. Hematomas enlarged in 20% of patients. POC INR monitoring is a fast, effective, and economic means of PCC dose-titration in OAC-ICH. Larger studies examining the clinical efficacy of this procedure are warranted.

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A re-appraisal of warfarin control in the treatment of deep vein thrombosis and / or pulmonary embolism.

Warfarin is commonly used for management of deep vein thrombosis (DVT) and pulmonary embolism (PE), controlling therapy by means of the International Normalized Ratio (INR). To identify differences in INR results between patients with thromboembolic and haemorrhagic complications and controls. Two nested case-control studies from within a controlled trial of the duration of warfarin therapy (47 thrombotic and 16 haemorrhagic complications). Patients whose thromboembolism failed to resolve during treatment or recurred during or after treatment had non-significantly lower INR levels than matched controls (geometric mean 2.2 versus 2.3, p = 0.12). Patients with haemorrhage also had not statistically significant lower INR levels than their matched controls (2.1 versus 2.3, p = 0.22). The variability of INR levels was similar in both case groups and controls. The mean percentage of INR levels in the therapeutic range 2 - 3 was almost identical in thrombotic cases and controls (56.5% versus 56.1%). Compared to the haemorrhagic group, better control was achieved in controls (61.5% versus 43.0%, p=0.01), but controls had slightly more INR values above the therapeutic range (12.1% versus 10.5%, p = 0.74) whilst haemorrhagic cases had more INR values below the therapeutic range (46.6% versus 26.4%, p = 0.03). In this study, higher INR levels were not associated with haemorrhage suggesting that, for patients being treated for DVT/PE, a modest increase in the target therapeutic range could be considered.

Consensus Guidelines for Periprocedural Management of Coagulation Status and Hemostasis Risk in Percutaneous Image-guided Interventions

From the Division of Vascular and Interventional Radiology, Jefferson Radiology, Hartford Hospital, 85 Seymour St, Ste 200, Hartford, CT 06106 (P.C.M.); Department of Radiology, Boston Healthcare System, VAMC Boston, Massachusetts (C.J.G.); Department of Medical Imaging, Scarborough General Hospital, Richmond Hill, Ontario, Canada (S.K.); Department of Radiology, GI/GU Division, Massachusetts General Hospital, Boston, Massachusetts (D.A.G.); Department of Radiology and Radiologic Sciences, Uniformed Services University of the Health Sciences and Department of Radiology, National Naval Medical Center, Bethesda, Maryland (D.L.M.); RADIA, Everett, Washington (R.B.O.); Department of Radiology, University of Florida, Gainesville, Florida (D.W.P.); Department of Medical Imaging, Division of Vascular and Interventional Radiology, University of Toronto, University Health Network, Toronto, Ontario, Canada (D.K.R.); Department of Interventional Radiology, The Reading Hospital and Medical Center, West Reading, Pennsylvania (D.S.); Radiology Associates of Central Florida, Mt Dora, Florida (M.S.S.); Mallinckrodt Institute of Radiology, St Louis, Missouri (D.A.Z.); and Geisinger System Radiology, Geisinger Health System, Danville, Pennsylvania (J.F.C.). Received November 18, 2008; accepted November 24, 2008. Address correspondence to P.C.M.; E-mail: pmalloy@ jeffersonradiology.com