Prothrombin time

Reference values (norm) of prothrombin time: adults - 11-15 s, newborns - 13-18 s.

Prothrombin time characterizes phases I and II of plasma hemostasis and reflects the activity of the prothrombin complex (factors VII, V, X and prothrombin itself - factor II).

Determination of prothrombin time plays a key role in monitoring anticoagulant therapy, but in such monitoring prothrombin time depends on the sensitivity of the thromboplastin used for these purposes. Therefore, comparison of the results of studies using different thromboplastins is an important task in practical medicine. Different thromboplastins are distinguished by ISI [International Sensitivity Index - International Sensitivity Index (ISI)], which is included in the description of each kit. In 1983, WHO together with the International Society of Thrombosis and Haemostasis adopted human brain thromboplastin as a reference and established that the ISI of this thromboplastin is 1 (International Reference Preparation of the World Health Organization). All other commercial thromboplastins are calibrated against it, and their own sensitivity (ISI) is determined for each. To compare the results of prothrombin time studies in patients receiving anticoagulant therapy, it is necessary to calculate the INR [International Normalized Ratio (INR)].

INR (INR) = (Prothrombin ratio) ^ISI; Prothrombin ratio (PTR) = patient's prothrombin time (s) / control's prothrombin time (s).

INR is an attempt to mathematically correct the difference in study results associated with the different sensitivity of thromboplastins, that is, bringing the result to the data obtained with the reference thromboplastin.

Normalization of prothrombin time using four different thromboplastins for INR calculation

Thromboplastin ISI	Prothrombin time, s		Calculated values
	Patient	Control	PTR	MNO
1,2	24	11	2,2	2.6
3.2	16	12	1.3	2.6
2.0	21	13	1.6	2.6
1.0	38	14.5	2.6	2.6

Laboratories are advised to use thromboplastins with an MIC of less than 1.5. Rabbit thromboplastins have an MIC of 2-3. In the US, all laboratories have switched to placental human thromboplastin, which has an MIC of 1.

The main task of monitoring the intake of oral anticoagulants is to prevent bleeding. Until recently, it was recommended to maintain prothrombin time during treatment with indirect anticoagulants 2-2.5 times longer than normal (rabbit thromboplastin). However, this time turned out to be too long, which often led to bleeding. Currently, WHO has developed recommendations for monitoring anticoagulant therapy, expressed in INR.

INR values recommended for anticoagulant therapy

Clinical condition	Recommended INR
Prevention of deep vein thrombosis	2-3
Treatment of deep vein thrombosis and pulmonary embolism	2-3
Recurrent deep vein thrombosis, pulmonary embolism	2-3
Heart valve prostheses made from autologous tissue	2-3
Mechanical prosthetic heart valves	2.5-3.5
Recurrent deep vein thrombosis and pulmonary embolism	3-4.5
Vascular diseases, including myocardial infarction	3-4.5
Recurrent systemic embolism	3-4.5

For ease of calculation of INR, we provide a scale showing the dependence of INR on MIC and PTR. The vertical scale on the left shows the PTR values (the ratio of the patient's prothrombin time to the prothrombin time of the control plasma), and the horizontal scale at the top shows the MIC values (for different thromboplastins). The INR for a given patient is located at the intersection of the lines of these two parameters.

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