Causes of prolongation and shortening of activated partial thromboplastin time (APTT)

Causes leading to prolongation of activated partial thromboplastin time (APTT)

• Violation of the activated partial thromboplastin time (APTT) with normal prothrombin and thrombin time is observed only in case of deficiency or inhibition of factors VIII, IX, XI, XII, as well as prekallikrein and high-molecular kininogen. Of these forms of pathology, the most frequently observed are deficiency and/or inhibition of factors VIII and IX, which is typical for hemophilia A and B, as well as deficiency of von Willebrand factor. More rarely, immune inhibitors of factor VIII appear in the blood of previously healthy individuals.
• Slowing of coagulation when determining both activated partial thromboplastin time (APTT) and prothrombin time with normal thrombin time and fibrinogen concentration is observed with a deficiency of factors X, V, II, as well as under the influence of indirect anticoagulants.
• Prolongation of prothrombin time with normal values of activated partial thromboplastin time (APTT) and thrombin time is characteristic only of factor VII deficiency.
• Prolongation of activated partial thromboplastin time (APTT), prothrombin and thrombin time is observed in deep hypofibrinogenemia, treatment with fibrinolysis activators. Prolongation of clotting time only in the thrombin test is characteristic of dysfibrinogenemia and disturbances in the polymerization of fibrin monomers.
• Afibrinogenemia and hypofibrinogenemia, both congenital and associated with severe liver damage, are accompanied by prolongation of activated partial thromboplastin time (APTT).
• During heparin therapy, activated partial thromboplastin time (APTT), prothrombin time and thrombin time are prolonged. Determination of activated partial thromboplastin time (APTT) is of great importance. It is known that patients may have increased or decreased sensitivity to heparin. The issue of tolerance to heparin can be finally clarified by repeated determination of activated partial thromboplastin time (APTT) 1 hour before the next administration of heparin. If the activated partial thromboplastin time (APTT) at this time is prolonged by more than 2.5 times compared to the norm, then increased sensitivity to heparin is stated and its dose is reduced or the interval between administrations is increased.

Prolongation of activated partial thromboplastin time (APTT) may indicate the presence of lupus anticoagulant (LA) in the patient, in the absence of violations of other coagulogram parameters.

Shortening of the activated partial thromboplastin time (APTT) indicates the prevalence of hypercoagulation and is observed in the first (hypercoagulation) phase of acute DIC syndrome.

Detection of hypercoagulation signs (shortening of blood clotting time, prothrombin time, APTT) is considered an indication for prescribing medium-molecular (15,000-25,000 Da) or low-molecular (4200-6100) heparin. To monitor the adequacy of the therapy, it is necessary to determine the blood clotting time or activated partial thromboplastin time (APTT) 2 times a day. When studying the blood clotting time, heparin infusion (using infusion pumps) should be selected in such a way as to maintain this indicator within 15-23 minutes, and APTT 2-3 times higher than normal. In addition, when prescribing high doses of heparin, daily monitoring of the ATIII content is necessary, since its level decreases sharply as a result of consumption.

Low-molecular (fractionated) heparins cause lower consumption of ATIII, practically do not activate platelets and do not cause immune reactions. They are not capable of binding thrombin and ATIII simultaneously, therefore they do not accelerate the inactivation of ATIII, but retain the ability to catalyze the inhibition of factor Xa by ATIII. Acceleration of factor Xa inactivation does not require the formation of a ternary complex and can be achieved only through the binding of heparin to ATIII (depending on the low-molecular heparin preparation, the anti-Xa/anti IIa ratio ranges from 2:1 to 4:1).

To monitor treatment with low-molecular heparin, a more sensitive test than APTT is used - anti-Xa activity of plasma is determined (quantitative determination of heparin, where factor Xa is used as a reagent). When determining anti-Xa activity of plasma, dextran sulfate is used to displace heparin from the complex with proteins, which ensures the accuracy of measuring the amount of Xa complexes with ATIII. A reaction with a chromogenic substrate for factor Xa is used as an indicator.

Monitoring scheme for treatment with medium molecular weight heparin

Heparin dose	Route of administration	Ratio of APTT patient/APTT control and number of determinations
Less than 20,000 IU/day	Subcutaneously (2-3 injections)	No monitoring needed
20,000-30,000 IU/day	Subcutaneously (2-3 injections)	1.2-1.5, determination before the next administration and after 4-6 hours
More than 30,000 IU/day	Intravenously (intermittent administration of 5000-7500 IU every 4 hours or 7500-10,000 IU every 6 hours)	1.5-4, determination before the next introduction
500-1000 U/h	Intravenous (infusion)	2.0-2.5

Low Molecular Weight Heparin Treatment Monitoring Scheme

Heparin dose	Route of administration	Anti-Xa, U/ml
2000-2500 U	Subcutaneously (once a day)	No monitoring needed
4000-5000 U	Subcutaneously (1-2 times a day)	Before the next administration - 0.2-0.4 U/ml
100-120 IU/kg	Subcutaneously (2 times a day)	Before injection - over 0.3 U/ml, after 3-4 hours - less than 1.5 U/ml
30-40 IU/kg once, then 10-15 IU (kg/h)	Continuous intravenous infusion	0.5-1.0 U/ml, rate adjustment every 3-6 hours

In myocardial infarction, the effectiveness of anticoagulant therapy (heparin) is judged by the degree of prolongation of APTT, which also reflects the patency of the coronary arteries.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]