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

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

• Violation of the indices of activated partial thromboplastin time (APTT) in normal prothrombin and thrombin time is observed only with the deficiency or inhibition of factors VIII, IX, XI, XII, as well as prekallikrein and high-molecular kininogen. Of these forms of pathology, deficiency and / or inhibition of factors VIII and IX are most often observed, which is characteristic of haemophilia A and B, as well as deficiency of von Willebrand factor. More rarely in the blood of previously healthy individuals, there appear immune factor VIII inhibitors.
• Deceleration of coagulation in the determination of both activated partial thromboplastin time (APTT) and prothrombin time at normal thrombin time and fibrinogen concentration is observed with deficiency of factors X, V, II, as well as under the influence of indirect anticoagulants.
• Elongation of prothrombin time with normal indications of activated partial thromboplastin time (APTT) and thrombin time is characteristic only for factor VII deficiency.
• Elongation of activated partial thromboplastin time (APTT), prothrombin and thrombin time is observed with deep hypofibrinogenemia, treatment with activators of fibrinolysis. The prolongation of the clotting time only in the thrombin test is characteristic for dysfibrinogenemia and violations of the polymerization of fibrin monomers.
• Afibrinogenemia and hypofibrinogenemia, both congenital and associated with severe liver damage, are accompanied by lengthening of activated partial thromboplastin time (APTTV).
• During heparin therapy, activated partial thromboplastin time (APTT), prothrombin and thrombin time are prolonged. Importance is attached to the definition of activated partial thromboplastin time (APTT). It is known that patients may have increased and decreased sensitivity to heparin. Finally, the question of tolerance to heparin can be refined by re-determining the activated partial thromboplastin time (APTT) 1 hour before the next administration of heparin. If activated partial thromboplastin time (APTT) at this time will be elongated by more than 2.5 times compared with the norm, then they detect increased sensitivity to heparin and reduce its dose or increase the interval between administrations.

Elongation of activated partial thromboplastin time (APTT) may indicate the presence of lupus anticoagulant (VA) in the patient, in the absence of violations of other indicators of the coagulogram.

The shortening of activated partial thromboplastin time (APTT) indicates a predominance of hypercoagulability and is noted in the first (hypercoagulable) phase of acute DIC syndrome.

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

Low molecular weight (fractionated) heparins cause less consumption of ATIII, practically do not activate platelets and cause no immune reactions. They are not able to bind simultaneously thrombin and ATIII, so do not accelerate the inactivation of ATIII, but retain the ability to catalyze the inhibition of factor Xa ATIII. Acceleration of the inactivation of factor Xa does not require the formation of a ternary complex and can be achieved only through the binding of heparin with ATIII (depending on the preparation of low molecular weight heparin, the anti-Xa / anti IIa ratio is 2: 1 to 4: 1).

To monitor the treatment with low molecular weight heparin, a more sensitive test is used than APTT - determine the anti-Xa activity of the plasma (quantification of heparin, where Xa is used as a reagent). In determining the anti-Xa activity of plasma, dextran sulfate is used to drive out heparin from the complex with proteins, which provides an accurate measurement of the amount of Xa complexes with ATIII. As an indicator, the reaction with the chromogenic substrate on the factor Xa is used.

Control scheme for treatment with medium molecular weight heparin

The dose of heparin	Method of administration	The ratio of the patient's APTT / APTT control and the number of determinations
Less than 20 000 units / day	Subcutaneously (2-3 administrations)	Monitoring is not needed
20 000-30 000 U / day	Subcutaneously (2-3 administrations)	1,2-1,5, determination before the next administration and after 4-6 hours
More than 30 000 units / day	Intravenous (intermittent administration of 5000-7500 units in 4 hours or 7500-10 000 units after 6 hours)	1.5-4, determination before the next administration
500-1000 U / h	Intravenous (infusion)	2.0-2.5

The scheme for monitoring the treatment of low molecular weight heparin

The dose of heparin	Method of administration	Anti-Xa, U / ml
2000-2500 IU	Subcutaneously (1 time per day)	Monitoring is not needed
4000-5000 IU	Subcutaneously (1-2 times per day)	Before the next introduction - 0,2-0,4 U / ml
100-120 IU / kg	Subcutaneously (2 times per day)	Before injection - more than 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, correction of speed every 3-6 h

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

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