International Normalized Ratio (INR) is the test of choice for patients taking vitamin K antagonists. It is used to determine the risk of bleeding or a clotting condition. Currently, special devices are used around the world to determine the international normalized ratio.
Prothrombin time
The oral anticoagulant Warfarin (also called Coumadin) is a vitamin K antagonist that is widely used to prevent venous thrombosis. It inhibits post-translational carboxylation of coagulation factors II, IX, VII, and X, which reduces their ability to interact with phospholipid membranes. The degree of anticoagulation achieved by Warfarin is monitored by a general coagulation test known as the prothrombin time (PTT). It is carried out on citrate plasma. PTV is initiatedby adding tissue factor along with phospholipids and calcium chloride. This combination is called thromboplastin.
Concept and meaning
The international normalized ratio was introduced in an attempt to standardize PTV. In its original manifestation, prothrombin time was highly variable because different thromboplastins were non-standardized and obtained from many different sources. INR has no units of measurement (this is a ratio) and is determined with an accuracy of one decimal place. The first step in its calculation is the "normalization" of PTT by comparing it with the geometric mean of the prothrombin time of a he althy adult population. At the second stage, this ratio is raised to the degree indicated by the IHR, or International Sensitivity Index. It is a function of the thromboplastin reagent. Two sets of data are used to obtain the MIC of normal he althy individuals and patients stabilized with Warfarin.
The definition of the international sensitivity index does not include patients whose prothrombin time is prolonged, for example, due to severe liver disease. The relationship between normal and warfarin patients does not make any predictions about the relationship between the working thromboplastin reagent and the INR standard in liver disease. Its increased value in the latter case does not protect patients from deep venous thrombosis.
Formula
Patients taking oralanticoagulants should control INR. The World He alth Organization uses the following formula for the international normalized ratio:
INR=PTT (prothrombotic time) of the patient ÷ PTT control.
PTV is measured in plasma. It determines the number of seconds it takes to form a clot in the presence of sufficient calcium and tissue thromboplastin, activating coagulation via the extrinsic pathway. The international normalized ratio ranges from 2 to 3. It may depend on the characteristics of the patient, concomitant diseases, nutrition and other drugs. Observations are made every 3-4 weeks at thrombosis centres, he alth care centers or at home.
Possible samples
A routine clotting test can be done in a medical laboratory. This requires high deadlines, including the collection, transport and processing of blood samples. Therefore, the International Normalized Ratio test, also known as the “bedside” or “near pathology” test, was developed. It can be performed on patients with the advantage of a shorter turnaround time and improved clinical outcome. Apparatus for express determination of the international normalized ratio is used in the offices of doctors, long-term care, pharmacies and for self-monitoring of the patient. Potential benefits of these devices include convenience, better handling, frequent measurement, and less risk of bleeding. However, they tend to overestimate low values and underestimatehigh INR values.
Test order
It is recommended by the Standard Clinical and Laboratory Institutes (2017) that samples for international normalized ratio analysis be collected from venous blood. It should be received in a tube with a light blue top containing an anticoagulant. Basically, it is a concentrate of sodium citrate 3.2%. The tube must be filled to 90% of its volume. It is then inverted several times to properly mix the blood with the anticoagulant. The total time between sampling and testing should not exceed 24 hours.
Express method. Features
In addition to laboratory research, it is allowed to use the express definition of the international normalized ratio. To do this, capillary blood from a finger is applied to a test strip or cartridge. The value is considered acceptable if it does not exceed plus or minus 0.5 units compared to the laboratory result.
What is the test for
The patient may need this test if they are taking medications that change the way the blood clot. Anti-clotting drugs are useful if the patient is at risk of stroke. The treating physician uses the INR to find out if anti-clotting drugs are being targeted or if the dosage needs to be changed. It also helps diagnose and manage liver disease and bleeding.
Related tests
If the attending physician is concerned about liver function or the risk of bleeding inpatient, he may order additional tests:
- Platelet count.
- Prothrombin time.
- Research on partially activated thromboplastin time.
- Fibrin D-dimer.
- Fibrinogen level.
- Thrombin time.
When applicable
Indications for obtaining the INR value are:
- Bleeding diathesis in patients with deficiency of clotting factors in the extrinsic pathway.
- Disseminated intravascular coagulation.
- Basic sampling before starting anticoagulation.
- Monitoring the effectiveness and safety of the patient under the influence of "Warfarin". To eliminate the risk of heart clots, atrial fibrillation and venous thromboembolism.
- Test for synthetic liver function and calculation of the model for assessing the end stage of its disease.
Potential diagnosis
International Normalized Ratio is commonly used as a surrogate for prothrombin time. It increases in the following cases:
- Use of anticoagulants. "Warfarin" inhibits gamma-carboxylation of factors dependent on vitamin K. The full anticoagulant effect is expressed within one week after taking "Warfarin". Use of other anticoagulants (heparin, rivaroxaban, apixaban,edoxaban, dabigatran, argatroban) may lead to PTV prolongation.
- Liver dysfunction. The liver synthesizes both vitamin K-dependent and vitamin-K-independent clotting factors. "Warfarin" is metabolized in it. Liver disease is associated with prolongation of PTT. With its increased value, patients are not "auto-anticoagulants" because they reflect homeostatic abnormalities in coagulation factors and increase thrombotic risk.
- Vitamin K deficiency. Malnutrition, long-term use of multi-spectrum antibiotics, and fat malabsorption syndrome can prolong PTT.
- Intravascular disseminated coagulation increases prothrombotic time.
- Deficiency of clotting factors in the external tract, acquired fibrinogen inhibitors, or a combined deficiency can lead to PTP prolongation.
- Antiphospholipid antibodies. Lupus anticoagulants may prolong prothrombotic time.
Normal and critical results
For normal patients who are not on anticoagulation, the international normalized ratio is usually 1.0. For patients who are on anticoagulation, the INR ranges from 2 to 3. Levels above 4.9 are considered critical and increase risk bleeding. The therapeutic INR range differs in patients with a prosthetic valve:
- With a mechanical bicuspid aortic valve without other risk factors for thromboembolism International Normalized Ratiois 2-3 during the first trimester after valve surgery. In three months - from 1.5 to 2.
- With new generation butterfly valve INR is 2.5.
- With a mechanical prosthetic aortic valve and an additional risk factor for thromboembolic events (atrial fibrillation, previous thromboembolism, left ventricular systolic dysfunction, hypercoagulable state) or an older generation mechanical prosthetic aortic valve, the international normalized ratio is 3.
- With a mechanical mitral or tricuspid prosthetic valve, the target INR is 3.
Interfering factors
Several factors that can affect the value of the international normalized ratio are listed below:
- Rules for the use of anticoagulants. Dose control and adjustment along with food and drug interactions make treatment difficult in clinical practice.
- Drug interactions. Drugs that cause an increase in INR: antibiotics, antifungals, chemotherapy drugs, third-generation antidepressants, amiodarone, alopurinol. Several medications can decrease the INR value. For example, dicloxacillin, nafcillin, azathioprine, antiepileptics, vitamin K, St. John's wort extract.
- Chronic liver disease can interfere with Warfarin dosage, INR value, and coagulation homeostasis.
- Acute infections and gastrointestinalillnesses can impact INR management.
Possible risks
INR levels below the target range are associated with an increased risk of thrombosis. Studies have shown that more than three times the risk of recurrent venous thromboembolism is associated with the subtherapeutic level of the international normalized ratio.
INR higher than the therapeutic range is associated with an increased risk of bleeding, among which the most alarming condition is intracranial hemorrhage. It could also be hematuria or gastrointestinal bleeding.
Patient safety and education
To reduce adverse events associated with anticoagulants, intensive patient education through leaflet distribution has been proposed. Clinical guidelines recommend testing patients for knowledge of the basics of the international normalized ratio. Portable devices for its measurement are becoming available to most patients.
Clinical significance
Timely monitoring of INR and patient-centered education on its management is considered essential in patient care. The international normalized ratio in therapeutic nomenclature holds the promise of optimal patient outcomes through clinical practice guidelines.
