International Normalized Ratio INR Prothrombin time Taux de prothrombine

Prothrombin time

The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. The reference range for prothrombin time is usually around 12–15 seconds; the normal range for the INR is 0.8–1.2. PT measures factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time(aPTT) which measures the intrinsic pathway.


Laboratory measurement


The prothrombin time is most commonly measured using blood plasma. Blood is drawn into a test tube containing liquid citrate, which acts as an anticoagulant by binding the calcium in a sample. The blood is mixed, then centrifuged to separate blood cells from plasma. Innewborns, a capillary whole blood specimen is used[1]

The plasma is analyzed by a biomedical scientist on an automated instrument at 37°C, which takes a sample of the plasma. An excess of calcium is added (thereby reversing the effects of citrate), which enables the blood to clot again. For an accurate measurement the proportion of blood to citrate needs to be fixed; many laboratories will not perform the assay if the tube is underfilled and contains a relatively high concentration of citrate. If the tube is underfilled or overfilled with blood, the standardized dilution of 1 part anticoagulant to 9 parts whole blood is no longer valid. For the prothrombin time test the appropriate sample is the blue top tube, or sodium citrate tube, which is a liquid anticoagulant.

Tissue factor (also known as factor III) is added, and the time the sample takes to clot is measured optically. Some laboratories use a mechanical measurement, which eliminates interferences from lipemic and icteric samples.

The prothrombin ratio is the prothrombin time for a patient, divided by the result for control plasma.

International normalized ratio

The result (in seconds) for a prothrombin time performed on a normal individual will vary depending on what type of analytical system it is performed. This is due to the differences between different batches of manufacturer's tissue factor used in the reagent to perform the test. The INR was devised to standardize the results

Each manufacturer assigns an ISI value (International Sensitivity Index) for any tissue factor they manufacture. The ISI value indicates how a particular batch of tissue factor compares to an internationally standardized sample. The ISI is usually between 1.0 and 2.0.

The INR is the ratio of a patient's prothrombin time to a normal (control) sample, raised to the power of the ISI value for the analytical system used.

 \text{INR}= \left(\frac{\text{PT}_\text{test}}{\text{PT}_\text{normal}}\right)^\text{ISI}


The prothrombin time is the time it takes plasma to clot after addition of tissue factor (obtained from animals). This measures the quality of the extrinsic pathway (as well as the common pathway) of coagulation.

The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. Factor VII has a short half-life and its synthesis requires vitamin K. The prothrombin time can be prolonged as a result of deficiencies in vitamin K, which can be caused by warfarin,malabsorption, or lack of intestinal colonization by bacteria (such as in newborns). In addition, poor factor VII synthesis (due to liver disease) or increased consumption (in disseminated intravascular coagulation) may prolong the PT.

A high INR level such as INR=5 indicates that there is a high chance of bleeding, whereas if the INR=0.5 then there is a high chance of having a clot. Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve, or bridging warfarin with a low-molecular weight heparin (such as enoxaparin) perioperatively.

Factors determining accuracy

Lupus anticoagulant, a circulating inhibitor predisposing for thrombosis, may skew PT results, depending on the assay used.[2] Variations between various thromboplastin preparations have in the past led to decreased accuracy of INR readings, and a 2005 study suggested that despite international calibration efforts (by INR) there were still statistically significant differences between various kits,[3] casting doubt on the long-term tenability of PT/INR as a measure for anticoagulant therapy.[4]


An estimated 800 million PT/INR assays are performed annually worldwide.[4]

Near-patient testing

In addition to the laboratory method outlined above, near-patient testing (NPT) or home INR monitoring is becoming increasingly common in some countries. In the United Kingdom, for example, near-patient testing is used both by patients at home, and by some anticoagulation clinics (often hospital-based) as a fast and convenient alternative to the lab method. After a period of doubt about the accuracy of NPT results, a new generation of machines and reagents seems to be gaining acceptance for its ability to deliver results close in accuracy to those of the lab.[5]

A Roche CoaguChek XS.

In a typical NPT setup a small table-top device is used; for example the Roche Coaguchek S, the International Technidyne Corporation Hemochron Signature, or the more recently (2005) introduced HemoSense INRatio. A drop of capillary blood is obtained with an automated finger-prick, which is almost painless. This drop is placed on a disposable test strip with which the machine has been prepared. The resulting INR comes up on the display a few seconds later. Similar testing methods are used by diabetics on insulin, and are easily taught and practiced.

Local policy determines whether the patient or a coagulation specialist (nurse, general practitioner or hospital doctor) interprets the result and determines the dose of medication. In Germany, patients may adjust the medication dose themselves,[citation needed] while in the UK and the USA this remains in the hands of a health care professional. For example, patients using services such as Philips INR@Home [1]will phone in their INR results on a weekly basis and this information is transmitted to their doctor, who is also alerted if out-of-range levels should require an immediate intervention or adjustment to medications.

A significant advantage of home testing is the evidence that patient self-testing with medical support and patient self-management (where patients adjust their own anticoagulant dose) improves anticoagulant control. A meta analysis which reviewed 14 trials showed that home testing led to a reduced incidence of complications (bleeding and thrombosis) and improved the time in the therapeutic range, which is an indirect measure of anticoagulant control.[6]

Other advantages of the NPT approach are that it is fast and convenient, usually less painful, and offers, in home use, the ability for patients to measure their own INRs when required. Among its problems are that quite a steady hand is needed to deliver the blood to the exact spot, that some patients find the finger-pricking difficult, and that the cost of the test strips must also be taken into account. In the UK these are available on prescription so that elderly and unwaged people will not pay for them and others will pay only a standard prescription charge, which at the moment represents only about 20% of the retail price of the strips. In the USA, NPT in the home is currently reimbursed by Medicare for patients with mechanical heart valves, while private insurers may cover for other indications.Medicare is now covering home testing for patients with chronic atrial fibrillation. Requires a doctor's prescription.

There is some evidence to suggest that NPT may be less accurate for certain patients, for example those who have the lupus anticoagulant.[citation needed]


International guidelines were published in 2005 to govern home monitoring of oral anticoagulation by the International Self-Monitoring Association for Oral Anticoagulation.[7] The international guidelines study stated, “The consensus agrees that patient self-testing and patient self-management are effective methods of monitoring oral anticoagulation therapy, providing outcomes at least as good as, and possibly better than, those achieved with an anticoagulation clinic. All patients must be appropriately selected and trained. Currently available self-testing/self-management devices give INR results which are comparable with those obtained in laboratory testing.”

Medicare coverage for home testing of INR has been expanded in order to allow more people access to home testing of INR in the USA. The release on the 19th March 2008 said, “[t]he Centers for Medicare & Medicaid Services (CMS) expanded Medicare coverage for home blood testing of prothrombin time (PT) International Normalized Ratio (INR) to include beneficiaries who are using the drug warfarin, an anticoagulant (blood thinner) medication, for chronic atrial fibrillation or venous thromboembolism.” In addition, “[t]hose Medicare beneficiaries and their physicians managing conditions related to chronic atrial fibrillation or venous thromboembolism will benefit greatly through the use of the home test.”[8]


The prothrombin time was discovered by Dr Armand Quick and colleagues in 1935[9], and a second method was published by Dr Paul Owren[10], also called the "p and p" or "prothrombin and proconvertin" method. It aided in the identification of the anticoagulants dicumaroland warfarin,[11] and was used subsequently as a measure of activity for warfarin when used therapeutically.

The INR was introduced in the early 1980s when it turned out that there was a large degree of variation between the various prothrombin time assays, a discrepancy mainly due to problems with the purity of the thromboplastin (tissue factor) concentrate.[12] The INR became widely accepted worldwide, especially after endorsement by the World Health Organisation.[13]

Taux de prothrombine

Le taux de prothrombine (TP, PR ou Prothrombine Ratio en anglais) est un test de laboratoire utilisé pour mesurer la coagulation sanguine. Il en explore la voie extrinsèque impliquant les facteurs de coagulation suivants (appelés complexe prothrombinique) : facteur I(fibrinogène), facteur IIfacteur Vfacteur VII et facteur X.

Il s'agit d'une expression en pourcentage du temps de Quick d'un groupe de patients normaux utilisés comme groupe témoin, ce qui permet de minimiser les biais liés aux modes de mesure des laboratoires.

Dans la pratique médicale, l'INR (International Normalized Ratio), dérivé du taux de prothrombine, est souvent utilisé, en particulier pour adapter les doses d'antivitamine K.

Avec le temps de céphaline activé et la numération de plaquettes, le taux de prothrombine est l'un des trois examens sanguins de dépistage d'une anomalie de la coagulation sanguine. Il est en particulier fait avant toute chirurgie ou acte comportant un risque d'hémorragie.


Mesure du taux de prothrombine

Il se fait par une simple prise de sang, le patient n'ayant pas besoin d'être à jeun. Le résultat peut être disponible en moins d'une heure. Le taux de prothrombine est la transformation d'un temps de coagulation (temps de Quick) en pourcentage. Le temps de Quick est réalisé en mettant en présence un plasma citraté (donc décoagulé) avec un réactif : la thromboplastine calcique, qui joue le rôle d'activateur tissulaire de la coagulation. Le plasma coagule et le temps obtenu s'appelle le temps de Quick.

Pour transformer le temps de Quick en taux de prothrombine (conversion très spécifique à la France), on se réfère à une droite de conversion construite par chaque laboratoire avec ses réactifs. On réalise les temps de Quick pour des plasmas témoins que l'on dit avoir un taux de prothrombine (TP) à 100 % et les temps de Quick pour des plasmas dilués (TP à 50 % et 25 %). On obtient ainsi une droite qui permet ensuite de transformer chaque TQ en TP.

Mesure du temps de Quick

Le temps de Quick est le temps de coagulation d'un plasma sanguin citraté en présence de thromboplastine calcique (contenant du facteur tissulaire et des phospholipides en large excès). Ce temps est exprimé en secondes par rapport au temps obtenu pour un plasma témoin (moyenne d'une cinquantaine de patients normaux).

Détermination du taux de prothrombine

Ce résultat en pourcentage est obtenu en reportant le temps de Quick obtenu pour le plasma à tester sur la droite de Thivolle (obtenue en testant des dilutions successives d'un plasma témoin normal). L'activité du plasma normal étant par définition de 100 %, celle du plasma normal dilué au demi de 50 %, etc. Ce taux de prothrombine a le principal défaut de varier suivant le réactif utilisé, c'est pourquoi on préfère se baser sur l'INR pour pouvoir comparer des mesures répétées chez un même patient.

Calcul de l'INR

L'INR (International Normalized Ratio, parfois dénommé « rapport international normalisé » en français) est réservé à la surveillance des traitements anticoagulants oraux par antivitamines K (AVK). Il est calculé comme suit :

 INR = \left( \frac{TQ_{patient}}{TQ_{T\acute emoin}} \right)^{ISI} Avec :

  • TQpatient : le temps de Quick mesuré pour le plasma du patient à tester ;
  • TQTemoin : le temps de Quick témoins (TP = 100 %) ;
  • ISI : l'indice de sensibilité international spécifique du réactif thromboplastine utilisé.

L'INR n'a pas d'unité. Il est, par définition, indépendant du réactif utilisé, et plusieurs mesures successives, faites dans des laboratoires différents, peuvent être comparées entre elles sans problème.

Valeurs cibles

Du temps de Quick

Le temps de Quick normal se situe entre 12 et 15 secondes.

Du taux de prothrombine

Le TP est normalement compris entre 70 à 100 %.

Le foie est l'organe producteur des protéines « facteurs de coagulation sanguine ». Celui d'un nouveau-né ne produit que 30 % du taux optimal. Il n'optimalise son fonctionnement que le 7e jour après la naissance où ce taux atteint 100 %, le 9e jour, ce taux est aussi à 100 % et il décroît très lentement tout au cours de la vie. Seul le 8e jour, le taux de fabrication de ces protéines atteint 110 % ou même parfois 115 %. C'est ainsi que, de tous les jours de la vie d'un être humain, le jour où l'organisme est le plus propice à une opération chirurgicale est le 8ejour.

Une diminution du TP (un allongement du temps de Quick) peut être observé lors de :

De l'INR

Chez les personnes saines, l'INR a des valeurs se situant entre 0,8 et 1,2. Chez les personnes traitées par anticoagulants oraux, la valeur cible d'INR (celle souhaitée pour obtenir l’efficacité thérapeutique) est le plus souvent de 2,5 ; l'intervalle toléré est compris entre 2 et 3, mais il s'étend parfois jusqu'à 4 voire 4,5 en cas de prothèse cardiaque ou de prévention des thromboses artérielles.

Liens externes