Rise in international normalized ratio after a catastrophic earthquake in patients treated with warfarin

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.

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Relationship Between Total Prothrombin, Native Prothrombin and the International Normalized Ratio (INR)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656342 ◽

1992 ◽

Vol 68 (02) ◽

pp. 160-164 ◽

Cited By ~ 3

Author(s):

P J Braun ◽

K M Szewczyk

Keyword(s):

Anticoagulant Therapy ◽

Oral Anticoagulant ◽

Inverse Relationship ◽

Low Dose ◽

Oral Anticoagulant Therapy ◽

International Normalized Ratio ◽

Antigen Assay ◽

Dose Oral ◽

Anticoagulated Patients ◽

Sensitive Method

SummaryPlasma levels of total prothrombin and fully-carboxylated (native) prothrombin were compared with results of prothrombin time (PT) assays for patients undergoing oral anticoagulant therapy. Mean concentrations of total and native prothrombin in non-anticoagulated patients were 119 ± 13 µg/ml and 118 ± 22 µg/ml, respectively. In anticoagulated patients, INR values ranged as high as 9, and levels of total prothrombin and native prothrombin decreased with increasing INR to minimum values of 40 µg/ml and 5 µg/ml, respectively. Des-carboxy-prothrombin increased with INR, to a maximum of 60 µg/ml. The strongest correlation was observed between native prothrombin and the reciprocal of the INR (1/INR) (r = 0.89, slope = 122 µg/ml, n = 200). These results indicated that native prothrombin varied over a wider range and was more closely related to INR values than either total or des-carboxy-prothrombin. Levels of native prothrombin were decreased 2-fold from normal levels at INR = 2, indicating that the native prothrombin antigen assay may be a sensitive method for monitoring low-dose oral anticoagulant therapy. The inverse relationship between concentration of native prothrombin and INR may help in identification of appropriate therapeutic ranges for oral anticoagulant therapy.

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Effect of Fixed Minidose Warfarin, Conventional Dose Warfarin and Aspirin on INR and Prothrombin Fragment 1 + 2 in Patients with Atrial Fibrillation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656065 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0845-0848 ◽

Cited By ~ 23

Author(s):

B G Koefoed ◽

C Feddersen ◽

A L Gulløv ◽

P Petersen

Keyword(s):

Atrial Fibrillation ◽

International Normalized Ratio ◽

Coagulation System ◽

Nonvalvular Atrial Fibrillation ◽

Treatment Groups ◽

Prothrombin Fragment ◽

Conventional Dose ◽

Dose Warfarin ◽

Significant Difference ◽

Changes Over Time

SummaryThe efficacy of conventional dose adjusted oral anticoagulation for stroke prevention in patients with non-valvular atrial fibrillation is well- documented but not considered ideal as primary antithrombotic treatment in elderly patients. The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR 2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to investigate the effect on the coagulation system of the treatments, the International Normalized Ratio of the prothrombin time (INR) and prothrombin fragment 1 + 2 (F1 +2) were monitored at baseline and after three months of treatment in 100 patients consecutively included in the trial. At baseline no differences in INR and F1+2 between the four treatment groups were present. After three months of therapy the level of INR increased significantly from baseline in patients receiving warfarin in any dose and the level of F1+2 decreased significantly by combined minidose warfarin-aspirin and by dose adjusted warfarin. When comparing the changes over time in FI +2 (three-month value minus baseline value) during therapy with fixed minidose warfarin, combined minidose warfarin-aspirin and aspirin alone no significant difference between the groups was found. In conclusion, INR was changed by all three warfarin regimens but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1+2.

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Calibration of a Lyophilized Pooled Plasma as Candidate Reference Plasma for Standardization of the Prothrombin Time Ratio

Hämostaseologie ◽

10.1055/s-0038-1655219 ◽

1993 ◽

Vol 13 (02) ◽

pp. 96-105 ◽

Cited By ~ 2

Author(s):

H. Beeser ◽

U. Becker ◽

H. J. Kolde ◽

E. Spanuth ◽

P. Witt ◽

...

Keyword(s):

Prothrombin Time ◽

International Study ◽

International Normalized Ratio ◽

Measurement Methods ◽

Factor V ◽

Diagnostic Instruments ◽

Plasma Pool ◽

Normal Plasma ◽

German Association ◽

Prothrombin Time Ratio

SummaryThe prothrombin time (PT), obtained from a fresh normal plasma pool (FPP), is the basis both for the establishment of the 100% activity (normal plasma) and for the ratio calculation used in the International Normalized Ratio (INR) according to the recommendations of the ICSH/ICTH (6). Today the PT of lyophilized normal plasma pools are successfully used as reference for the assessment of samples in proficiency studies. However, a lack of comparability is to be recognized. Therefore the Committee of Hematology of the German Association of Diagnostics’ and Diagnostic Instruments’ Manufacturers (VDGH) decided to produce a candidate reference plasma (VDGH Reference Plasma) which was calibrated against fresh normal plasma pools in an international study.The basic calibration was performed by using the same certified BCR thromboplastin (BCT/099) by all participants. The endpoint was determined manually and by using the coagulometer Schnitger-Gross. In additional testings each participant used his own routine thromboplastins and methods. Calculating the ratio [PT VDGH Reference Plasma (sec)/PT fresh normal plasma pool (sec)] the VDGH Reference Plasma showed a deviation from the average fresh normal plasma pool of 1.05 both with the BCT/099 and with all thromboplastins. There were obtained some statistical differences between “plain” and “combined’’ (added factor V and fibrinogen) thromboplastins. No statistical difference was found between the different endpoint measurement methods (manual, mechanical, optical).In spite of these statistical deviations the VDGH Reference Plasma can be used for the standardization of the PT-normal (100%) value with different ratios for plain (1.06) and combined (1.02) thromboplastins. The manufacturers will use this VDGH Reference Plasma for the calibration of their commercially available calibration plasmas, which allows the user of such a material to calculate a calibrated 100% PT value.

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Comparison of Fibrinolytic versus Surgical Therapy in the Treatment of Obstructive Prosthetic Valve Thrombosis: A Single-Center Experience

The Heart Surgery Forum ◽

10.1532/hsf98.20101062 ◽

2011 ◽

Vol 14 (2) ◽

pp. 87 ◽

Cited By ~ 6

Author(s):

Necip Ermis ◽

Hakan Atalay ◽

Hakan Altay ◽

Muhammet Bilgi ◽

Suleyman Binici ◽

...

Keyword(s):

New York ◽

Prosthetic Heart Valve ◽

Heart Association ◽

International Normalized Ratio ◽

Fibrinolytic Therapy ◽

Surgical Approaches ◽

Specific Patient ◽

Single Center Experience ◽

Surgery Group ◽

Valve Thrombosis

Objective: Prosthetic heart valve thrombosis (PVT) is a rare but severe cardiac condition. There are only a few data regarding comparison of the fibrinolytic and surgical approaches for the treatment of PVT. In this study, we compared the results of fibrinolytic therapy versus surgery in patients who presented to our institution with a diagnosis of obstructive-type PVT.Methods: From January 2001 to August 2008 in our institution, 33 patients who met clinical and echocardiographic criteria for obstructive-type PVT were included in the study. Fifteen of these patients underwent fibrinolytic treatment with streptokinase, which consisted of an initial bolus of 250,000 U followed by 100,000 U/h. Eighteen patients were treated with surgery.Results: The 2 groups had similar baseline characteristics, including New York Heart Association functional status, types and positions of prosthetic valves, international normalized ratio values, and presentation symptoms. Full hemodynamic success was achieved in 12 patients who underwent fibrinolytic therapy and in 15 patients in the surgery group. The mean (SD) streptokinase infusion time was 17.8 11.1 hours. Two major hemorrhages and 2 cases of systemic embolism were observed in the fibrinolytic group. The 2 groups did not differ with respect to mortality rate (P = .79). The duration of hospitalization was longer in the fibrinolytic group than in the surgery group (10.7 6.6 days versus 6.9 6.7 days, P = .045).Conclusions: Although fibrinolytic therapy is generally recommended for the treatment of PVT for specific patient groups, our results suggest that it may be as efficacious and safe as surgery, depending on patient selection.

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Endogenous Heparinoids Detected by anti-Xa Activity are Present in Blood during Acute Variceal Bleeding in Cirrhosis. A Prospective Study

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.232.cht1 ◽

2014 ◽

Vol 23 (2) ◽

pp. 187-194 ◽

Cited By ~ 4

Author(s):

Christos Triantos ◽

Emmanuel Louvros ◽

Maria Kalafateli ◽

Anne Riddell ◽

Ulrich Thalheimer ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Variceal Bleeding ◽

Blood Cells ◽

Venous Pressure ◽

White Blood Cells ◽

International Normalized Ratio ◽

Ulcer Bleeding ◽

Factor X ◽

Packed Red Blood Cells ◽

Bacterial Peritonitis

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleedingbut was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)].Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti-Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.List of abbreviations: AFP, alpha-fetoprotein; aPTT, activated partial thromboplastin time; CP, Child-Pugh; FXa, activated factor X; GAGS, glycosaminoglycans; Hb, hemoglobin; HCC, hepatocellular carcinoma; HVPG, hepatic venous pressure gradient; INR, International normalized ratio; LMWHs, low molecular weight heparins; MELD, Model for End-stage Liver Disease; PPP, platelet-poor plasma; PRBC, packed red blood cells; PT, prothrombin time; SBP, sponataneous bacterial peritonitis; TEG, thromboelastography; WBC, white blood cells.

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Severe Alveolar Hemorrhage – What’s in it for the Gastroenterologist?

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.254.cut ◽

2016 ◽

Vol 25 (4) ◽

pp. 555-558

Author(s):

Alina Popp

Keyword(s):

Celiac Disease ◽

International Normalized Ratio ◽

Gluten Free Diet ◽

Alveolar Hemorrhage ◽

Severe Anemia ◽

Gluten Free ◽

Pulmonary Infiltrates ◽

Pulmonary Hemosiderosis ◽

Threatening Condition ◽

Life Threatening

Background: Alveolar hemorrhage is a potentially life-threatening condition which is usually managed by the pulmonologist. When considering its etiology, there is a rare association that sets the disease into the hands of the gastroenterologist. Case presentation: We report the case of a 48 year-old female who was admitted to the intensive care unit for severe anemia and hemoptysis. On imaging, diffuse pulmonary infiltrates suggestive of alveolar hemorrhage were detected and a diagnosis of pulmonary hemosiderosis was made. She received cortisone therapy and hematologic correction of anemia, with slow recovery. In search of an etiology for the pulmonary hemosiderosis, an extensive workup was done, and celiac disease specific serology was found positive. After confirmation of celiac disease by biopsy, a diagnosis of Lane-Hamilton syndrome was established. The patient was recommended a gluten-free diet and at 6 months follow-up, resolution of anemia and pulmonary infiltrates were observed. Conclusion: Although the association is rare, celiac disease should be considered in a patient with idiopathic pulmonary hemosiderosis. In our case, severe anemia and alveolar infiltrates markedly improved with glucocorticoids and gluten-free diet. Abbreviations: APTT: activated partial thromboplastin time; BAL: bronchoalveolar lavage; CD: celiac disease; Cd: crypt depth; GFD: gluten-free diet; GI: gastrointestinal; IEL: intraepithelial lymphocyte; INR: international normalized ratio; IPH: idiopathic pu

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Laboratory predictors of death from coronavirus disease 2019 (COVID-19) in the area of Valcamonica, Italy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-0459 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1100-1105 ◽

Cited By ~ 16

Author(s):

Graziella Bonetti ◽

Filippo Manelli ◽

Andrea Patroni ◽

Alessandra Bettinardi ◽

Gianluca Borrelli ◽

...

Keyword(s):

Hospital Stay ◽

Clinical Decision Making ◽

Troponin I ◽

Laboratory Data ◽

High Sensitivity ◽

Clinical Decision ◽

International Normalized Ratio ◽

Serum Glucose ◽

Hospital Death ◽

Laboratory Findings

AbstractBackgroundComprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity.MethodsThe final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge).ResultsCompared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death.ConclusionsThe most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.

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