Activated partial thromboplastin time (aPTT)


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Detailed description of the study

APTT - activated partial thromboplastin time - a test to assess the state of the blood coagulation system. The study is carried out by adding substances to citrated platelet-poor plasma that help directly assess the functioning of plasma factors. They are proteins that play a key role in the formation of a blood clot.

The hemostatic system is a set of various mechanisms aimed at maintaining a balance between coagulation and anticoagulation factors in the blood. This avoids the pathological formation of blood clots (thrombi) or the tendency to bleed.

The formation of a blood clot (thrombus) occurs in several stages. A primary thrombus is formed by gluing blood platelets - platelets - to each other. Next, special proteins - coagulation factors - are included in the process. These proteins are produced in the liver. The result of their action is the conversion of prothrombin into thrombin under the influence of factor III (thromboplastin) and the formation of a secondary thrombus.

Activated partial thromboplastin time is the period during which a clot is formed in a test tube along with special substances that imitate the action of coagulation factors. The purpose of the test is to assess the state of the so-called intrinsic coagulation pathway (involving factors VIII, IX, XII, XI).

Prolongation of APTT in adults and children indicates hypocoagulation - a decrease in the ability to form blood clots. This increases the risk of bleeding. This can occur with hereditary and acquired defects in coagulation factors. Hereditary - hemophilia A and B, von Willebrand disease, hereditary factor XI deficiency. Acquired ones are caused by disruption of the liver, where coagulation factors are formed, exposure to anticoagulants, severe infectious diseases, and oncological processes.

The shortening of activated partial thromboplastin time reflects the predominance of hypercoagulation - increased blood clotting. A similar situation can be observed with thrombosis, including disseminated intravascular coagulation (DIC) syndrome in the hypercoagulation stage. Early diagnosis of coagulation disorders allows you to avoid serious consequences.

There are also physiological conditions under which a shortening of the APTT is observed—pregnancy.

The APTT indicator is used for monitoring during treatment with heparin in order to track the moment of excessive blood thinning. During myocardial infarction, the duration of clot formation determines the effectiveness of anticoagulant treatment, which indirectly reflects vascular patency.

Thus, determining the APTT helps to quickly assess the state of hemostasis, together with other data, suspect severe congenital and acquired diseases, and prescribe timely treatment.

APTT

Activated partial thromboplastin time (aPTT)

APTT reflects the activity of the internal and general pathways of blood coagulation. The division of the coagulation cascade into internal, external and general pathways is conditional and does not fully reflect the true mechanism of hemostasis (see Theories and models of blood coagulation), but nevertheless, it still remains a useful resource for interpreting laboratory results. The intrinsic coagulation pathway is activated when circulating f.XII comes into contact with and binds to a negatively charged surface. This causes a change in its molecular configuration and, when interacting with high molecular weight kininogen and prekallikrein, it becomes an active enzyme - f.XIIa, capable of activating f.XI. In turn, f.XIa promotes the activation of f.IX with the formation of f.IXa. F.IX can also be activated by the F.VIIa/tissue factor complex via the extrinsic coagulation pathway. Then the f.IXa complex and its cofactor f.VIIIa cause the activation of f.X with the subsequent formation of thrombin. Abnormalities of the internal coagulation pathway are the cause of many coagulopathies, in particular hemophilia A and B.

Principle of the method

Incubation of plasma with the optimal amount of phospholipids in the presence of a contact activator (kaolin, silica gel, ellagic acid) activates plasma coagulation along the internal pathway. The addition of calcium ions to the system stops plasma citrate and leads to the formation of a fibrin clot. During the APTT measurement process, the time from the moment of adding calcium ions until the formation of a clot is recorded (see link to the instructions for the APTT test).

The determination of APTT is one of the most informative and common screening tests, which reflects changes in the activity of factors of the internal coagulation pathway: f.VIII, f.IX, f.XI, f.XII, prekallikrein (Fletcher factor) and high molecular weight kininogen (Fitzgerald factor) . The test is sensitive to deficiency of all coagulation factors (except f.VII and f.XIII), to heparin, to specific and nonspecific inhibitors of coagulation factors.

When determining APTT, it should be taken into account that:

  • The time from blood sample collection to analysis should be no more than 1 hour, since the half-life of unfractionated heparin (UFH) is about 1.5 hours.
  • The blood sample for analysis should be selected in such a way as to prevent platelet aggregation and activation with subsequent release of the heparin-inactivating factor PF4.
  • If possible, it is recommended to establish the patient's baseline aPTT before initiating UFH therapy.
  • APTT values ​​may vary depending on techniques, equipment, reagent lots, and heparin used, so each laboratory should adopt its own therapeutic ranges and review them if any of these factors change.

In this cascade diagram of blood coagulation, the hemostasis factors reflected in the APTT test are highlighted in white:

Reference values:

Normal aPTT test values ​​depend on the reagent used and should be established in each clinical diagnostic laboratory.

Interpretation of results

Diagnostic significance of the method. Currently, in addition to testing the activity of intrinsic coagulation factors (including for the diagnosis and monitoring of hemophilia A and B), the APTT method is also recommended for determining lupus anticoagulant and monitoring anticoagulant therapy with unfractionated heparin. When interpreting the results of the APTT test, it must be borne in mind that increased activity of one of the coagulation factors (for example, f.VIII) may mask the existing functional deficiency of other factors (for example, f.IX or f.XI). Therefore, in the presence of clinical symptoms of bleeding and normal aPTT values, further research is necessary to determine the causes of coagulopathy.

The shortening of clotting time obtained in the APTT test may indicate activation of the internal blood coagulation pathway, disseminated intravascular coagulation syndrome (at the stage of hypercoagulation - more often in combination with a shortening of PT, TV, high levels of fibrinogen, etc.); f.V resistance to activated protein C in patients with thrombophilia; violations of the APTT test at the preanalytical stage.

Prolongation of APTT may indicate a congenital or acquired deficiency of the internal pathway of blood coagulation (including in hemophilia A and B) with normal PT results; deficiency of factors of the common blood coagulation pathway with prolongation of PT; DIC syndrome (in the hypocoagulation stage - more often in combination with prolongation of PT, TV, reduced fibrinogen levels, etc.); deficiency of von Willebrand factor or f.VIII in von Willebrand disease; the presence of lupus anticoagulant, heparin, hirudin, fibrin/fibrinogen degradation products; liver dysfunction.

If the aPTT is prolonged, a test should be performed mixing the patient's plasma with normal donor plasma in a 1:1 ratio. If the aPTT remains prolonged, this means that the sample contains heparin or antiphospholipid antibodies (lupus anticoagulant) or clotting factor specific inhibitors. If the plasma mixing test shows normal results, then a deficiency of clotting factors VIII, IX, XI or XII is likely. Additional studies should be carried out to identify the true cause of the prolongation of the APTT test.

(See table Interpretation of basic test indicators)

What you need to know about APTT:

  1. An aPTT activator, such as kaolin, should be selected so that the aPTT is sensitive to moderate deficiency of factors VIII, IX and XI. To date, there is no activator that is fully sensitive to very small deficiencies of coagulation factors, so a normal APTT level does not exclude the presence of small deficiencies of factors VIII, IX and XI.
  2. The term “partial thromboplastin” refers to the phospholipid component of complete thromboplastin, devoid of apoproteins (tissue factor). The presence of a contact activator (kaolin, ellagic acid, silica gel, etc.) in the test system accelerates the clotting time and increases the accuracy and reproducibility of the APTT method by preventing uncontrolled contact activation of coagulation.
  3. If the optical density method is used to monitor clot formation, a falsely normal APTT may be recorded if the plasma is turbid (eg, hyperbilirubinemia, hyperlipidemia).
  4. Factor XIII deficiency does not prolong APTT or PT.
  5. APTT can be used to detect antiphospholipid antibodies (i.e., lupus anticoagulant), but in these cases reagents with low phospholipid concentrations sensitive to lupus anticoagulant should be used.
  6. When choosing phospholipids for APTT, it is important to choose the right reagent that is sensitive to deficiencies in coagulation factors.
  7. APTT may be made more or less sensitive to certain clotting factors by shortening the incubation time. It should be noted that the degree of APTT prolongation can give an idea of ​​the nature of hemostasiological disorders. For example, if the aPTT is very prolonged, for example, >120 sec, then most likely the cause of the prolongation lies in a deficiency of contact factors, and not in a deficiency of factors VIII or IX (hemophilia A and B). Conversely, an aPTT of 70–80 seconds is associated with a diagnosis of severe hemophilia A or B rather than with contact phase factor deficiency.
  8. APTT is often used to monitor the effects of unfractionated heparin (UFH). However, APTT is also very sensitive to the level of f.VIII, which is an acute phase protein. If f.VIII levels rise, the aPTT may be misleadingly short and may not reliably reflect the degree of anticoagulation. In these cases, monitoring of UFH should be carried out by measuring anti-Xa activity.
  9. The APTT forms the basis for analyzing the levels of factors VIII, IX, XI and XI. Factors II, V and X can also be analyzed by APTT, although they are more often analyzed by PT.
  10. APTT is used to detect the presence of FVIII clotting inhibitors.
  11. In patients receiving very high doses of UFH, for example during cardiopulmonary bypass, the aPTT will not be recorded (as a clot will not form at all). In these cases, monitoring the degree of heparinization is usually carried out using activated clotting time (ACT).
  12. When receiving UFH, when aPTT is used to monitor the degree of heparinization, it is important to separate the plasma within 1 hour after drawing blood from the patient. This recommendation is due to the fact that 1 hour after blood collection, platelet factor 4 is released from platelets and neutralizes heparin. Neutralization of heparin may lead to insufficient prolongation of aPTT and underestimation of the degree of heparinization, which ultimately can lead to an overdose of prescribed heparin with possible hemorrhagic complications.

When preparing this section, data from the scientific website www.practical-hemostasis.com was used.

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