Prothrombin: norm, prothrombin index and time, increased, decreased, reasons

Thrombin is one of the main enzymes involved in the regulation of the blood coagulation system. It is responsible for stabilizing the blood clot, which is vital during bleeding. When the amount of thrombin in the blood changes, clotting problems and hemostasis may occur, because thrombin is responsible specifically for the stage of blood clot formation. The time it takes for a clot to form under real conditions is called thrombin time.

Thrombin time in the laboratory is the period during which fibrinogen is converted into fibrin in plasma mixed with sodium citrate, calcium and thrombin. There may be several indications for prescribing an analysis:

• for liver pathologies;
• to identify a lack of fibrinogen in the body;
• to monitor heparin treatment;
• before operations and surgical interventions;
• with spontaneous termination of pregnancy up to 20 weeks.

Clinical signs of insufficient fibrinogen are increased bleeding and a tendency to form blood clots. Patients usually report the following symptoms:

• slow healing of the skin surface;
• heavy bleeding (including heavy menstruation);
• frequent occurrence of hematomas;
• rash.

What is the coagulation system

The hemostasis system is very complex, involving many tissue and serum factors. Its launch is really similar to a cascade: it is a chain of reactions, each subsequent link of which is accelerated by additional enzymes.

A simplified blood coagulation scheme looks like this: thromboplastin is released from the damaged endothelium, with the participation of calcium ions and vitamin K, it activates prothrombin. Prothrombin is converted to active thrombin, which in turn triggers the formation of insoluble fibrin from soluble fibrinogen. This process is completed by the stage of retraction of the blood clot, that is, its compaction and the actual blockage of the damage.

At each stage, many more factors are involved in this scheme. In total, there are 13 plasma and 22 platelet types.

What is prothrombin

This is a glycoprotein produced in liver cells, plasma coagulation factor II.

The synthesis of prothrombin requires vitamin K, so one of the reasons for its decrease is insufficient intake of this vitamin from food or a low level of its synthesis in the intestines.

Prothrombin is an inert protein, its activation occurs under the influence of coagulation factor XII (internal system) or when the endothelium is damaged (external mechanism of hemostasis).

The normal level of prothrombin in the blood is 0.1-0.15 g/l. However, its quantitative determination is not used in routine diagnostics. This is a rather unstable protein, easily destroyed and difficult to separate into a separate fraction and count.

In practice, qualitative tests for prothrombin are used, which reflect its content in the blood only indirectly. They are based on calculating the period of time during which the blood clots when thrombokinase activators are added to it (which in turn activates prothrombin, converting it into thrombin, and thrombin catalyzes the conversion of fibrinogen into fibrin).

Therefore, when we say “test for prothrombin”, “blood for prothrombin”, this does not mean determining its concentration in the blood, as, for example, glucose, hemoglobin or bilirubin are examined. And the result is given not in quantitative units, but as a percentage. This concept characterizes the external mechanism of hemocoagulation as a whole and reflects the activity of the entire prothrombin complex (factors II, V, VII, X).

How are prothrombin tests performed?

The essence of almost all methods for studying the activity of the prothrombin complex is to calculate the time of formation of a fibrin clot immediately after adding activators to the blood, as well as comparing this time with normal values.

Blood is drawn into a test tube with an anticoagulant (sodium citrate). The test tube with citrated blood is slightly heated in a water bath. A reagent consisting of thromboplastin and calcium chloride is added to it. The time of loss of fibrin fibers is measured using a stopwatch. This is prothrombin time (PT). Its normal value is 11-15 seconds.

Having determined the patient's PT, it is compared with the normal prothrombin time (PT). It is usually indicated on the reagent bottle and depends on the activity of the thromboplastin used. Usually this figure is from 12 to 18 seconds (it may be different in each new reagent sample). The ratio of PVN to PT of the subject, expressed as a percentage, is the prothrombin index (PI). Its normal value is 80-105%. The longer the blood clotting time (PT), the lower the PI, which will indicate hypocoagulation.

Prothrombin according to Quick

The test is also based on the ratio of the patient's normal prothrombin time to the patient's PT, expressed as a percentage. But the method is considered more accurate. For the study, several dilutions of plasma are used (1:2, 1:3,1:4) and the construction of a calibration graph. For each dilution, the PT is determined and marked on the graph.

Prothrombin rates according to Quick are from 75% to 140%.

Within the normal protein content, the Kwik and PTI results may be identical. At low contents, these indicators sometimes diverge.

Another indicator is the INR (international normalized ratio). It is mainly used to assess the effectiveness of anticoagulants. This indicator is calculated using the formula:

INR = (patient's PT/normal PT)*value of the international thromboplastin sensitivity index (ISI).

This index is indicated on each package of the reagent. INR allows standardization of the results of PT and IPT performed in different laboratories. The INR value in healthy individuals is 0.8-1.2.

The numbers of prothrombin according to Quick and INR are inversely proportional to each other: if prothrombin according to Quick is increased, then the INR is reduced and vice versa.

When is prothrombin tested?

A coagulation test (coagulogram) is not a routine examination; it is not prescribed to all patients in a row. The test is carried out in the following situations:

• The presence of symptoms indicating problems with clotting: frequent nosebleeds and other bleeding, bruising for no apparent reason, bleeding gums when brushing teeth, hemorrhagic rash on the skin.
• Thrombophlebitis of the veins of the lower extremities.
• Examination of the patient before any surgical interventions.
• Pregnant women must be examined.
• Control during treatment with anticoagulants. They are prescribed to patients with arrhythmias, after valve replacement, and for thrombophlebitis. The purpose of these drugs is to increase blood clotting time, but keep it within a safe range. In this case, PT will be increased by 1.5-2 times, PTI and prothrombin according to Quick will be reduced, INR will be increased (safely up to 2-3).
• For liver diseases to clarify its functional insufficiency.
• Before prescribing estrogen-containing hormones, as well as during their use.

Indications for prescribing prothrombin time analysis

• detailed examination of the whole body;
• pre- and postoperative examination;
• suspicion of impaired hemostasis;
• suspicion of hidden bleeding;
• suspicion or presence of thrombosis;
• control of hemostasis functions during treatment with direct and indirect anticoagulants;
• diagnosis of liver diseases;
• a history of cardiovascular diseases and their complications, as well as thromboembolism of various organs;
• diagnosis of nosebleeds and hemorrhages in various organs and tissues;
• diagnosis of chronic anemia.

Preparing for a blood test for prothrombin time:

• do not eat 12 hours before taking a blood test;
• do not smoke 30-60 minutes before the test;
• limit physical and psycho-emotional stress;
• if possible, discontinue medications that affect coagulation or prescribe a study before starting therapy;
• follow a diet excluding fried and very fatty foods.

Prothrombin norms in different groups of patients

The levels of this glycoprotein in the blood vary somewhat among different age groups. In children under 18 years of age, its normal content ranges from 80 to 110%, in adults – from 78 to 145%.

The norms for adult men and women are no different. A moderate increase in prothrombin may occur in women before childbirth.

Prothrombin index

This indicator is determined in all coagulograms. What does prothrombin index mean?

The normal prothrombin index is 80-105%. The greater the patient’s PV compared to normal, the lower his PI will be and vice versa. Accordingly, a low index indicates poor coagulability, and a high index indicates hypercoagulation (propensity for thrombosis).

The prothrombin index test is prescribed in the same situations as the Quick prothrombin test. Basically, both of these values ​​are in direct correlation and in the range of normal content can be the same.

The norm of the prothrombin index during pregnancy differs slightly by trimester:

• I trimester – 80-119%
• II – 85-120%
• III – 90-130%.

Complexes with this research

Miscarriage Identification of the main causes of miscarriage RUB 40,070 Composition
Examination during pregnancy. 1st trimester 16,690 RUR Composition

Examination during pregnancy. 3 trimester 9 620 RUR Composition

IN OTHER COMPLEXES

• Entry into IVF RUB 23,020
• Extended coagulogram RUB 4,150
• Female infertility RUB 16,210
• Pregnancy planning. Clinical indicators 6,630 R
• Coagulogram RUR 2,020

How to decipher a coagulogram

This analysis is carried out in order to obtain answers to the questions:

• does the blood clot normally?
• is there a risk of postoperative or postpartum hemorrhage;
• what is the cause of frequent bleeding and bruising;
• what dose of anticoagulants is safe if their use is necessary.

Blood hypocoagulation and tendency to bleeding will be indicated by:

• reduced prothrombin according to Quick (less than 75);
• decreased prothrombin index (less than 80);
• increased prothrombin time (more than 18 seconds);
• increased INR (more than 1.3).

Hypercoagulability and tendency to form blood clots is characterized by:

• increased prothrombin index (more than 110);
• increased prothrombin (above 145);
• shortening of PT (less than 10 s);
• decrease in INR value less than 0.8.

References

1. Clinical guidelines for the diagnosis and treatment of rare blood clotting disorders: hereditary deficiency of factors X, II, VII, 2021.
2. Volkova, P.O., Zolotavina M.L., Didenko S.N. and others. Dependence of polymorphism of blood coagulation genes and blood group and rhesus affiliations in women. — Scientific almanac, 2021. — No. 1-2(15). — P.455-458.
3. Sturov, V.G., Plyushkin, V.A., Anmut, S.Ya. and others. The final stage of blood coagulation: modern clinical and laboratory diagnosis of dysfibrinogenemia syndrome. - Thrombosis, hemostasis and rheology, 2008. - No. 2 (34). — P.8-15.
4. Undas, A. Determination of fibrinogen and thrombin time (TT). — Methods in molecular biology, 2021.

The main reasons for the decrease in prothrombin

We remember that prothrombin is a protein that is formed in liver cells with the participation of vitamin K. It becomes active with the help of several tissue and plasma clotting factors. The gene responsible for normal prothrombin synthesis is recessive and is located on chromosome 11.

In addition, there are also anticoagulant factors in the blood, the increased activity of which can inhibit the components of the prothrombin complex.

The main causes of low prothrombin and IPT (PT and INR are increased) follow from this physiological mechanism:

• Congenital pathology - changes in the genes responsible for the synthesis of prothrombin (quite rare).
• Liver diseases accompanied by decreased function or death of hepatocytes: chronic hepatitis, cirrhosis. The insufficiency of structural units for synthesis leads to the fact that prothrombin in the blood is reduced.
• Vitamin K deficiency. This happens both when there is insufficient intake from food, and when its absorption and synthesis in the intestines is impaired. Therefore, gastrointestinal diseases accompanied by dysbiosis and impaired fat absorption can also lead to its deficiency.
• Reduced levels of blood clotting factors V, VIII, X.
• Autoimmune diseases, including the production of antibodies to prothrombin (more precisely, to the phosphatidylserine-prothrombin complex).
• Low fibrinogen levels.
• 2nd phase of DIC syndrome (exhaustion phase).
• Increased activity of the anticoagulant factor antithrombin III.
• Treatment with anticoagulants (heparin, fraxiparin, warfarin, neodicoumarin).

Increased thrombin time

This indicates a tendency to hypocoagulation. Thrombin time is increased when:

• treatment with fibrinolytics, heparin;
• a significant decrease in fibrinogen in the blood plasma (with functional disorders in the liver);
• excess physiological anticoagulants;
• some blood diseases;
• the second stage of the syndrome-DIC (impaired blood coagulation processes in critical conditions: severe injuries, shock, burns, massive thrombosis).

A shortening of thrombin time indicates a risk of thrombosis, and also occurs in conditions accompanied by an increase in fibrinogen content in the blood and in the first stage of DIC syndrome.

Reasons for increased prothrombin and PTI

An increase in PTI indicates hypercoagulation and is dangerous for the development of thrombosis (heart attacks, strokes, thrombosis of the veins in the legs, pulmonary embolism). This condition is especially unfavorable after operations and after childbirth.

• Last weeks of pregnancy.
• DIC – syndrome (1st stage).
• The use of estrogen-containing hormones by women (and sometimes men).
• Congenital thrombophilia.
• Excess vitamin K.
• Mutation of the prothrombin gene G20210A (carriers of the defective gene are 2-3% of the population).
• The period after severe operations, burn disease.
• Postpartum stage.
• Malignant tumors.
• Antithrombin III deficiency.
• Antiphospholipid syndrome.

What to do with indicators that do not fit into the norm?

Prothrombin is increased or decreased, what to do?

First, you need to see a doctor. Many people think that the answers to all questions can now be found on the Internet. In fact, this is far from the case. This is especially true for the coagulation system. The information presented on the Internet about this matter is very confusing and 50% of it is completely wrong. This indicates the high complexity of this issue.

Which doctor should I contact?

To the one who ordered the analysis. If you took a coagulogram on your own, first we go to a therapist.

What should you definitely tell your doctor?

• You must list all medications that you are taking or have taken recently, including dietary supplements. Many medications tend to affect coagulogram parameters, and this applies not only to anticoagulants. Thus, Nevigramon, Streptomycin, Tetracycline, Levomycetin, L-thyroxine, vitamin A, and Aspirin in high doses can reduce prothrombin.

The following can increase PTI: contraceptive hormonal drugs, caffeine, antihistamines, high doses of vitamins C, K, corticosteroid hormones.

• Long-term alcohol abuse can also reduce PTI.
• An excess of foods rich in vitamin K in the diet can lead to an increase in prothrombin, and insufficient consumption of them can, on the contrary, lead to a decrease. These are foods such as greens, green vegetables and fruits, liver.
• Women must be informed about their pregnancy.

What additional examinations can be prescribed?

• Liver function test (advanced biochemical analysis with determination of bilirubin, liver transaminases, total protein, albumin).
• Ultrasound of the liver and biliary tract.
• Fibroelastography of the liver for suspected cirrhosis.
• Determination of antibodies to viral hepatitis.
• Extended examination of the coagulation system (APTT, fibrinogen, thrombin time, D-dimers, plasminogen, antithrombin III, plasma fibrinolytic activity, lupus anticoagulant, etc.)
• Intestinal examination (stool analysis for dysbacteriosis, colonoscopy).

How to lower or increase the prothrombin index?

If the readings are only slightly outside the normal range, there is no need to panic. It is possible that some time after stopping some medications, a repeat analysis will not reveal any abnormalities. Many women are concerned about the question - what to do with taking contraceptives? If cardiovascular diseases are diagnosed, definitely stop taking it, but if the woman is generally healthy, the pills can be taken, but the analysis should be periodically monitored.

You can also try to correct PTI with a diet if you are sure that your diet is clearly lacking foods such as greens (parsley, dill, spinach), vegetables (cabbage, broccoli), beef or pork liver. Green tea improves PTI quite well.

If prothrombin levels are elevated and there is a risk of thrombosis, doctors usually prescribe anticoagulants. At the same time, only warfarin will clearly reduce this indicator. New generation anticoagulants (Pradaxa, Xarelto, Eliquis and others) act on other coagulation factors, but the level of prothrombin may not change.

Aspirin also does not change this indicator, but taking it in small doses makes sense to reduce the risk of blood clots.

In what cases should you not waste time on a diet?

• If the coagulogram values ​​are significantly higher or lower than normal.
• There are symptoms of impaired homeostasis: recurrent bleeding or thrombosis.
• Presence of pregnancy.
• Abnormal coagulogram in a child.
• There are other symptoms (yellow skin, dark urine, swelling, rash, itchy skin, etc.)

In these cases, you need to undergo a full examination and find out the cause of the pathology of the coagulation system.

Author:

Akimova Valentina Konstantinova general practitioner

Changes in indicator during pregnancy

Monitoring this indicator of blood clotting is extremely important during pregnancy, especially when pregnant women are taking medications that affect the blood clotting process. Normally, thrombin time during pregnancy is increased and ranges from 18 to 25 seconds. Imbalance of the coagulation and anticoagulation systems can lead to serious complications during pregnancy. The most dangerous is disseminated intravascular coagulation (DIC), which develops as a result of activation of the coagulation system on the one hand and the fibrinolysis system on the other. In pregnant women, DIC syndrome can be caused by various reasons:

• premature placental abruption with bleeding, which is caused by a decrease in the concentration of coagulation factors in the plasma.
• amniotic fluid embolism – leads to shock and acute respiratory failure and the development of disseminated intravascular coagulation syndrome due to the entry into the bloodstream of a large amount of tissue thromboplastin, which triggers the blood clotting process;
• endometritis, as a complication after childbirth, can lead to the development of a fulminant form of DIC syndrome.

A common cause of miscarriage is antiphospholipid syndrome, which is characterized by arterial and venous thrombosis, leading to disturbances in intrauterine development of the fetus. Pregnant women with APS are at high risk of spontaneous abortion and miscarriage. In the clinic, determination of thrombin time is used for monitoring during heparin therapy and fibrinolytic therapy, for diagnosing activation of fibrinolysis, as well as indirect diagnosis of dysfibrinogenemia.

time, blood clot