International Normalized Ratios (INR): the first 20 years

Poller, L.

doi:10.1111/j.1538-7836.2004.00775.x

Cited by 135 publications

(100 citation statements)

References 93 publications

(95 reference statements)

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“…The recommended scale of reporting PT results is the International Normalized Ratio (INR), calculated as follows: INR ϭ (patient PT/mean normal PT) ISI . 7,8 This standardization allows safe and effective dosing of vitamin K antagonists, independently of the sensitivity of the thromboplastin used. 1 Thromboplastin responsiveness also varies widely with respect to the coagulation defects induced by liver failure.…”

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A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology

et al. 2007

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International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms. Our aim was to determine whether, in the calibration model for thromboplastins proposed by the World Health Organization, the use of plasmas from patients with liver diseases instead of plasmas from patients on oral anticoagulation could lead to a new INR specific for liver diseases (INR "LD"), achieving a real standardization of PT. First, 5 thromboplastins were calibrated against an international reference using 60 plasmas of patients with liver failure and, in a second step, the variation of PT reported as seconds, the ratio of patient PT to normal PT, See Editorial on Page 295 P rothrombin time (PT) is the usual test for monitoring oral anticoagulation by vitamin K antagonists 1 and is widely adopted to assess the severity of acute and chronic liver injury. 2 PT is the recalcification time of citrated plasma in the presence of a thromboplastin reagent. 3 The term thromboplastin refers to a complex mixture of tissue factor and phospholipids prepared from tissue extracts of animal or human origin. Recent thromboplastins contain recombinant tissue factor. PT is influenced by the levels of the following coagulation factors: I (fibrinogen), II, V, VII, and X, all factors being synthesized by the liver and, among them, 3 (II, VII, and X) being vitamin K dependent. Thromboplastins can vary markedly in their responsiveness to the defects induced by vitamin K antagonist therapy. As a result, the poor agreement between PT in different laboratories whatever the methods of reporting results 4 has led to important differences in oral anticoagulant dosing. 5,6 Standardization of PT reporting in patients on oral anticoagulation has been improved by the calibration model for thromboplastins proposed by the World Health Organization (WHO). 7 This system defines, for a specific thromboplastin reagent, the International Sensitivity Index (ISI) obtained by a calibration using plasmas of patients on stable oral anticoagulant doses, against a WHO international reference thromboplastin. 7 The ISI is a numerical value that reflects the responsiveness of a given thromboplastin to reduction of the vitamin K-dependent coagulation factors; the lower the ISI value, the greater the sensitivity of the reagent. The recommended scale of reporting PT results is

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confidence: 99%

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology

et al. 2007

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“…The INR is a calculated value derived by the following formula: (patient PT/mean normal PT) ISI , where ISI is a value assigned to the PT reagent when compared with a WHO reference standard with an ISI of 1.0. 31,43,44 The INR was standardized on plasmas from patients on chronic warfarin therapy that affects only VKD factors II, VII, IX, and X. Use of the INR is therefore inappropriate in other medical conditions in which clotting factors other than VKD factors are affected.…”

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Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy

Matevosyan¹,

Madden²,

Barnett³

et al. 2011

JNS

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H emostasis is a complex interaction among 1) the fluid phase of procoagulants that generate thrombin, 2) the natural anticoagulants that regulate thrombin, 3) the fibrinolytic system that controls the size of thrombus and maintains vascular patency, and 4) the cellular phase that includes platelets and endothelium. To date, no single global test exists to assess these 4 components of hemostasis. The in vitro coagulation tests, the PT and PTT, were developed to identify the cause of bleeding in a symptomatic bleeding patient; they have never been shown to assess the risk of bleeding in a nonbleeding patient. 16,20,35 Because different sensitivities of tissue thromboplastin reagents account for the variability of PT, the INR was introduced to monitor warfarin therapy. The INR is a calculated value derived by the following formula: (patient PT/mean normal PT) ISI , where ISI is a value assigned to the PT reagent when compared with a WHO reference standard with an ISI of 1.0. 31,43,44 The INR was standardized on plasmas from patients on chronic warfarin therapy that affects only VKD factors II, VII, IX, and X. Use of the INR is therefore inappropriate in other medical conditions in which clotting factors other than VKD factors are affected.10 However, the INR is often (mis)used in clinical practice to assess hemostasis in patients not receiving warfarin therapy; thus, patients with mildly elevated INRs are reflexively transfused with FFP, usually perioperatively.In the past, less-sensitive thromboplastin reagents (ISI > 2.0) caused a prolonged PT only when factor VII Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy Object. Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study.Methods. The authors tested 30 plasma specimens from 25 patients with an INR of 1.3-1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results.Results. At the time of plasma orders the median INR was 1.35 (range 1.3-1.7, normal reference range 0.9-1.2) with a corresponding median PT of 13.6 seconds (range 12.8-17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3-33.7 seconds). The median factor VII level was 57% (range 25%-124%), whereas the hemostatic levels recommended for major surgery are 15%-25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were mod...

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“…Важным шагом в адаптации лечения АВК к реальной практике стало использованием оценки коагуляции посредством измерения протромбино-вого времени и в последующем стандартизирован-ного показателя -так называемого международного нормализованного отношения (МНО) [1,2]. Тради-ционно лечение АВК начинается с фиксированной, одинаковой для большинства больных, дозы препа-рата.…”

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Randomized Comparison of Two Approaches to Warfarin Dosage in Cardiovascular Hospital Section

Мищенко¹,

Averkov²,

Gordeev³

et al. 2015

Ross. kardiol. ž.

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Цель. Сравнение двух подходов к дозированию варфарина: стандартного и с использованием клинического алгоритма. Материал и методы. В качестве изучаемого подхода к дозированию варфа-рина использовалась методика, учитывающая клинические особенности боль-ных. В группу изучаемого подхода (группу вмешательства) рандомизирован 31 человек, в группу с использованием стандартного подхода (группу конт-роля) -29 человек с различными показаниями к лечению антагонистом вита-мина К. Целевой диапазон международного нормализиванного отношения (МНО) для всех больных составлял от 2,0 до 3,0. Результаты. Стабильного целевого МНО в обеих группах в период госпитали-зации удалось добиться лишь у небольшой части больных: 19,4% в группе вмешательства и 17,2% в группе контроля. Больные группы вмешательства достигали стабильного МНО в среднем к 6,8 дню, что почти в два раза быстрее больных группы контроля, которые достигали первого из последовательных целевых МНО в среднем к 12,4 дню (p<0,05). Доля значений МНО выше 4,0 в группе вмешательства составила 3,6%, в группе контроля -18,2% (p<0,05). Тромбоэмболических событий (инсультов, рецидивов тромбоэмболии ветвей лёгочной артерии) не было в обеих группах. В каждой группе было зарегистри-ровано по одному эпизоду кровотечения. Заключение. Возможности по достижению целевого МНО, независимо от режима дозирования, в условиях стационара очень ограничены. У больных, достигших стабильного МНО в целевом диапазоне, использование клиниче-ского алгоритма для подбора дозы варфарина, позволило добиться этих зна-чений значительно раньше, чем при использовании стандартного подхода. Частота развития избыточной гипокоагуляции при использовании клиниче-ского алгоритма меньше таковой в группе стандартного дозирования.

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International Normalized Ratios (INR): the first 20 years

Cited by 135 publications

References 93 publications

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology

Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy

Randomized Comparison of Two Approaches to Warfarin Dosage in Cardiovascular Hospital Section

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