Which indicator should be used to measure coagulation function?

Many people don’t know much about the coagulation function. It is mainly a function of the human body itself. It mainly means that after bleeding occurs in the human body, the blood will coagulate in a short period of time to ensure that the blood does not flow out. However, some people have poor coagulation function and cannot stop bleeding. At this time, doctors will recommend a coagulation function test. So which indicator should be used to measure coagulation function?

Coagulation function test indicators include prothrombin time (PT), activated partial thromboplatin time (APTT), thrombin time (TT), fibrinogen (FIB), clotting time (CT) and international normalized ratio (INR), etc. Several of them can be selected to make a package, which is called coagulation X items. Since different hospitals use different testing methods, their reference ranges are also different.

➤ PT-prothrombin time

PT refers to adding tissue factor (TF or tissue thromboplastin) and Ca2+ to plasma to activate the exogenous coagulation system and observe the coagulation time of plasma. PT is one of the most commonly used screening tests in clinical practice and is used to evaluate the function of the extrinsic coagulation pathway. The normal reference value is 10 to 14 seconds.

➤ APTT - activated partial thromboplastin time

APTT is a test in which factor XII activator, Ca2+, and phospholipids are added to plasma to initiate the intrinsic coagulation pathway of plasma and observe the plasma coagulation time. APTT is also one of the most commonly used screening tests in clinical practice and is used to evaluate the function of the intrinsic coagulation pathway. The normal reference value is 32 to 43 seconds.

➤ INR - International Normalized Ratio

INR is the ratio of the PT of the tested patient to the PT of the normal control raised to the ISI power (ISI is the international sensitivity index, which is calibrated by the manufacturer when the reagent leaves the factory). The same plasma tested in different laboratories using different ISI reagents will produce very different PT values, but the measured INR values ​​are the same, making the results comparable. The normal reference value is 0.9~1.1.

➤ TT - thrombin time

TT is a test that adds standard thrombin to plasma to detect the third stage of the coagulation process, reflecting the level of fibrinogen in plasma and the amount of heparin-like substances in plasma. The normal reference value is 16 to 18 seconds.

➤ FIB-fibrinogen

FIB is achieved by adding a certain amount of thrombin to the plasma being tested to convert the fibrinogen in the plasma into fibrin, and then calculating the fibrinogen content by the turbidimetric principle. The normal reference value is 2-4 g/L.

➤ FDP-plasma fibrin degradation products

FDP is a general term for degradation products produced by the breakdown of fibrin or fibrinogen under the action of plasmin produced during hyperfibrinolysis. The normal reference value is 1 to 5 mg/L.

➤ CT-clotting time

CT refers to the time it takes for blood to leave the blood vessels and coagulate outside the body. It is mainly used to determine whether various coagulation factors in the intrinsic coagulation pathway are deficient, whether their functions are normal, or whether there is an increase in anticoagulants.

Key point: Which indicator should be considered in different clinical situations?

Although all indicators can reflect the patient's coagulation function, the emphasis is different in different situations and the required indicator control targets are also different.

Thrombolytic therapy for acute myocardial infarction

The most common emergency in cardiology is acute myocardial infarction. As a thrombotic disease, anticoagulation testing is essential. When an acute myocardial infarction patient is admitted to the emergency department, the first blood sample should be tested for coagulation function (before heparin or thrombolytic therapy), and at least the APTT should be checked as a basic control indicator.

Currently, specific plasminogen activators are the first choice for intravenous thrombolytic therapy of acute ST-segment elevation myocardial infarction (STEMI), and guidelines require immediate heparin treatment after diagnosis. Intravenous injection of unfractionated heparin 5000 U (60-80 U/kg), followed by intravenous drip of 12 U/(kg·h). During and after thrombolysis, the APTT or ACT should be monitored to 1.5-2.0 times the control value (APTT is 50-70 seconds), usually for 48 hours. After 48 hours, the dose can be gradually reduced according to the situation and replaced with subcutaneous injection of low molecular weight heparin. Subcutaneous injection of low molecular weight heparin does not require routine monitoring of APTT. If necessary and conditions permit, anti-activated factor X activity can be monitored for evaluation.

Monitoring of oral anticoagulants

There are many diseases in the cardiology department that require the use of oral anticoagulants, such as non-valvular atrial fibrillation, pulmonary embolism, deep vein thrombosis, symptomatic hereditary thrombophilia, antiphospholipid syndrome, rheumatic heart disease, congenital heart disease and atrial fibrillation caused by thyrotoxicosis, cardioversion, mural thrombosis and heart valve repair.

Warfarin

Warfarin is a classic anticoagulant drug. Although new anticoagulant drugs continue to emerge, warfarin, as a classic old drug, is cheap and still widely used in clinical practice. The most common clinical practice is preventive anticoagulation treatment for patients with atrial fibrillation. The guidelines require that the INR be controlled at 2.0~3.0.

Because warfarin interacts with many drugs and foods, and individual medication differences are also large, close monitoring is required in the initial stage of medication. Even if the indicators are satisfactory after dosage adjustment, regular monitoring is required. Generally, the initial dose of warfarin in clinical practice is 3 mg. The INR should be checked every 1 to 3 days, usually at least 3 times in the first week of medication. If the indicators are well controlled after one week, change to once a week until the fourth week. After the INR reaches the target value and stabilizes (two consecutive times within the target range for treatment), check the INR every 4 weeks.

If the INR is found to be too high or too low, the cause of the change in INR should be carefully investigated and the warfarin dose should be adjusted if necessary. The dose adjustment should be based on the INR value, and the amount of increase or decrease each time should be 0.5~1 mg/d. If the INR has been very stable in the past and occasionally increases, as long as the INR does not exceed 3.5-4.0, you can temporarily not adjust the dosage and check the INR again in 3-7 days.

In addition to being used to treat atrial fibrillation, the INR should also be controlled at 2.0~3.0 when treating venous thrombosis, pulmonary embolism, and valvular heart disease. When used to prevent deep vein thrombosis, the INR is 1.5~2.5. It is also required to be controlled within this range before non-hip surgery. In the treatment of arterial embolism, mechanical heart valve replacement, and recurrent systemic embolism, the INR can be controlled at 3.0~4.0.

New anticoagulant drugs

Routine coagulation function monitoring is not currently recommended for new anticoagulants. However, in some cases, it is necessary to evaluate the anticoagulant effect of anticoagulants, which can provide early indications of high bleeding risk.

➤ Dabigatran

APTT is sensitive to changes in the blood concentration of dabigatran and is dose-dependent, and can be used to evaluate the qualitative anticoagulant effect of dabigatran. A normal APTT indicates a lack of pharmacological anticoagulation effect, and a prolongation of about 1.5 times is considered to have reached the expected anticoagulation level. TT is highly sensitive to dabigatran in the blood, but due to its high sensitivity, the correlation between TT and dabigatran levels in plasma is poor. If the APTT trough value exceeds twice the basal control value, it indicates a high risk of bleeding.

➤ Rivaroxaban

PT is sensitive to changes in rivaroxaban blood concentrations, but different monitoring methods have large differences in sensitivity. It is recommended to use the NeoplastinPlus method to measure PT to evaluate the anticoagulant effect of rivaroxaban. The test reagent used in this method has a relatively high international sensitivity index (ISI), has a good correlation with the plasma concentration of rivaroxaban, and is dose-dependent. Take rivaroxaban orally for 4 hours and monitor. If the value is prolonged by more than 2 times the baseline value, high bleeding risk should be observed.

Some literature recommends the use of APTT monitoring for bivalirudin and argatroban, with a control range of 1.5~2.5.

Which patients require special attention to coagulation monitoring?

Although some literature has given recommendations and opinions on coagulation function monitoring, and there are also recommendations that routine monitoring is not necessary, safety still comes first in clinical practice. In the treatment of critically ill patients and the detection of anticoagulant therapy, it is necessary to focus on the following patients and recheck the coagulation function in time if necessary:

➤ Children, elderly patients or pregnant women

➤ Underweight or overweight patients

Patients with gastrointestinal malnutrition

Patients with organ dysfunction

Patients at risk of life-threatening bleeding

Patients receiving epidural block anesthesia or requiring emergency surgery

➤ Patients with acute stroke who may require thrombolytic therapy

Patients who are taking other drugs that may affect the metabolism of anticoagulants

Patients who have failed anticoagulation therapy