Method of diagnosing resistance to acetylsalicylic acid

FIELD: medicine.

SUBSTANCE: in patients with IHD before therapy with acetylsalisylic acid (ASA) ADP-induced and ASA-dependent platelet aggregation are examined and by their difference value of coefficient of aggregation inhibition (CAI) is calculated. CAI value <24% testifies to resistance to ASA, if CAI ≥24% - about sensitivity to ASA.

EFFECT: method ensures high prediction accuracy and makes it possible to prevent development of undesirable coronary events in IHD patients.

1 tbl, 4 ex, 4 dwg

 

The invention relates to medicine, namely cardiology, may be used in the treatment of patients with coronary heart disease (CHD).

There is a method of defining resistance to acetylsalicylic acid (ASA) through aggregatometry platelets, in which resistance to aspirin identify 2-3 days and 5 days after the beginning of reception of the ACK [2]. In the case of aspirin resistance, the patient should receive another antiplatelet drug. Diagnostic value of this method is limited, as such, does not allow you to diagnose resistance to aspirin before drug treatment.

Known another method for diagnosis of aspirin resistance in patients with ischemic heart disease, which is the definition of prior therapy activity levels of NAD - and NADP-dependent dehydrogenases in platelets peripheral blood and the ratio calculation cofactoring exchange platelets (CCOT) [4]. When the value CCOT above 0.3 predict resistance to the ASC, and a value of KCAT equal to or less than 0.3, - sensitivity to aspirin. This method allows to predict the resistance to the ASC before the start of therapy, however, is very time-consuming in execution and is not suitable for rapid diagnosis.

It is known that platelets are an important part of hemostasis and their functional status along with the vascular endothelium is on determines thrombogenic the situation. To prevent unwanted vascular events in patients with CHD are used antiplatelet drugs, the most popular of which is the ASC. However, in recent years there are reports of the presence of aspirin resistance[1, 2, 3, 5], that can lead to the development of adverse coronary events (myocardial infarction, stroke, cardiovascular death) in patients with CHD. Therefore, the development of a simple, reliable method for diagnosis of aspirin resistance before therapy is highly relevant for clinical practice.

The objective of the invention is the elimination of adverse coronary events in patients with CHD, simplicity and reliability of the diagnosis.

Task due to the fact that before therapy ASA in patients with CHD explore ADP-induced and ASC-dependent platelet aggregation and the difference determines the value of the coefficient of inhibition of aggregation (KIA), the value of KIA<24% indicates resistance to the ASC, when KIA≥24% - sensitivity to aspirin.

A value of 24% obtained empirically based on the mapping results of ADP-induced and ASC-dependent platelet aggregation and subsequent clinical and laboratory examination of patients with CHD in the dynamics of treatment ASC.

The method is performed as follows. 9 ml of stabilized sodium citrate blood through the heart is pulirovaniya at 140 g for 5 minutes to obtain platelet-rich plasma [2] (platelet rich plasma 300×109/l). Carefully select the supernatant and transferred to a plastic tube. Platelet aggregation research on aggregometry "Biola" with 5 μm adenosine diphosphate (ADP). Additionally incubated platelet-rich plasma from 10 ál to 3.36 mm ASA for 3 minutes at 37°C, and re-examine platelet aggregation with ADP.

Then, the level difference ADF-at and ask-find at value KIA. Value KIA for less than 24% indicates resistance of the patient to the ASC, and equal to 24% and over - sensitivity to aspirin.

The table presents the survey results 12 patients with coronary artery disease, carried out in the cardiac Department of the Krasnoyarsk regional clinical hospital. Before treatment the ASC, in the proposed method, determined the size of KIA. Further patients taking ASA at a dose of 75 mg/day, and 10-14 days again determined ADP-at. According to a study in the ADP-at in 5 patients diagnosed laboratory resistance to the ASC. The remaining 7 patients classified as ASA-sensitive patients.

The results of the comparison of the method of prediction with laboratory data evaluation of resistance/sensitivity to aspirin
№ p/pThe forecast for the proposed method Value KIAMatch prediction
1ARthe 10.1Yes
2AR6,2Yes
3ACH35,3Yes
4ACH27,7Yes
5AR81Yes
6ACH26,1Yes
7ACH24,3Yes
8AR5,5Yes
9ACH38,2Yes
10ACH29,4Yes
11ARthe 9.7Yes
12ACHof 31.8Yes
Note: AR - resistance to ASC, AH - sensitivity to aspirin.

Clinical example 1. Patient R., 62 years history No. 4848 (data No. 1 in the table). Was hospitalized in cardiac surgical Department of the Regional clinical hospital with 26.02.09, 31.03.2009, with a diagnosis of ischemic heart disease, stable angina of 4 functional class, postinfarction cardiosclerosis. At the time of admission to the hospital conducted a study of the magnitude KIA: the level of ADP-at was 65.6%, the level of ASC-at was 55.5%, KIA equal to 10.1%, which reflects the resistance to the ASC. After 14 days of treatment ask again carried out the determination of ADP-at, the value of which amounted to 49.9%. I.e. the reduction of ADP-induced aggregation during treatment ASC 15.7%, on the basis of what the patient diagnosed with resistance to aspirin and patient recommended treatment thienopyridine.

Figure 1 shows the ASC-dependent platelet aggregation (a) and ADP-induced platelet aggregation of a patient before () and after 14 days of therapy ASC ().

Clinical example 2. Patient L., 72 years, the history of the disease No. 29146. Was hospitalized in cardiac surgical Department of the Regional clinical hospital with 10.12.08, 13.01.2009, with a diagnosis of ischemic heart disease, stable angina III functional class, postinfarction cardiosclerosis. At the time of admission to the hospital conducted a study of the magnitude KIA: the level of ADP-ATA amounted to 67.9%level ASC-at was 58.7%, KIA equal to 9.2%, which reflects the resistance to the ASC. After 12 days of treatment ask again carried out the determination of ADP-at, the value of which amounted to 55%. I.e. the reduction of ADP-induced aggregation during treatment ASA amounted to 12.9%, on the basis of what the patient diagnosed with resistance to aspirin and patient recommended treatment thienopyridine.

Figure 2 shows the ASC-dependent platelet aggregation (a) and ADP-induced platelet aggregation of a patient before () and after 12 days of therapy ASC ().

Clinical example 3. Patient H., 62 years history No. 4396. Was hospitalized in cardiac surgical Department of the Regional clinical hospital with 10.03.09, 31.03.2009, with a diagnosis of coronary artery disease, progressive angina, postinfarction cardiosclerosis. At the time of admission to the hospital conducted a study of the magnitude KIA: the level of ADP-at was 76.7%, the level of ASC-at made up 41.1%, KIA equal to 35.6%, reflecting a sensitivity to aspirin. 13 suto the treatment ask again carried out the determination of ADP-at, the value of which amounted to 32.6 per cent. I.e. the reduction of ADP-induced aggregation during treatment ASA amounted to 44.1%, based on which a patient to be diagnosed with a sensitivity to aspirin and patient treatment recommendations ASC.

Figure 3 shows the ASC-dependent platelet aggregation (a) and ADP-induced platelet aggregation of a patient before () and after 13 days of therapy ASC ().

Clinical example 4. Patient P., 49, case history No. 4601. Was hospitalized in cardiac surgical Department of the Regional clinical hospital with 10.12.08, 13.01.2009, with a diagnosis of ischemic heart disease, stable angina III functional class. At the time of admission to the hospital conducted a study of the magnitude KIA: the level of ADP-at was 65.6%, the level of ASC-ATA amounted to 37.9%, KIA equal to 27.7%, reflecting a sensitivity to aspirin. After 12 days of treatment ask again carried out the determination of ADP-at, the value of which amounted to 32.8 per cent. I.e. the reduction of ADP-induced aggregation during treatment ASC accounted for 32.8%, based on which a patient to be diagnosed with a sensitivity to aspirin and patient treatment recommendations ASC.

Figure 4 shows the ASC-dependent platelet aggregation (a) and ADP-induced platelet aggregation of a patient before () and after 12 days of therapy ASC ().

The technical result from implementation of the proposed method:

in moznosti rapid diagnosis of aspirin resistance before treatment with aspirin;

- high level of coincidence of the forecast - 100%;

- helps prevent the development of undesirable coronary complications in patients with coronary artery disease.

Thus, the proposed method allows in a hospital at any level quickly and inexpensively make the diagnosis of aspirin resistance before treatment. Timely diagnosis of aspirin resistance will prevent adverse coronary events in patients with coronary artery disease, resistant to the drug. The method can be recommended for use in clinical practice.

Sources of information

1. Grinstein SCI, Savchenko A.A., Grinstein YOU, Savchenko E.A. Features of hemostasis, the metabolic activity of platelets and frequency of resistance to aspirin in patients with chronic heart failure after coronary artery bypass surgery // Cardiology. - 2008. - T, No. 6. - P.51-56.

2. Momot A.P. Pathology of hemostasis. Principles and algorithms of clinical laboratory diagnostics. - SPb.: Format, 2006. - c.95.

3. Nasonov EL Nonsteroidal anti-inflammatory drugs (prospects of application in medicine). - Moscow: Publishing house "Anko", 2000. - 143 S.

4. RF patent №2348041 C1, G01N 33/68 (2006.01). Published 27.02.2009. Bull. No. 6.

5. Pamukcu Century, Oflaz H., Onur I., et al. Relationship between the serum sCD40L level and aspirin-resistant platelet aggregation in patients with stable coronary artery disease // Circ. J. - 2008. - Vol.72, No. 1. - P.61-66.

The way diagnostician is Ki resistance to acetylsalicylic acid (ASA), including the sampling of venous blood, characterized in that before the start of therapy ASA in patients with CHD explore ADP-induced and ASC-dependent platelet aggregation and the difference determines the value of the coefficient of inhibition of aggregation (KIA), the value of KIA<24% indicates resistance to the ASC, when KIA≥24% - sensitivity to aspirin.



 

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7 ex

FIELD: medicine.

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7 ex

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1 dwg, 4 ex

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9 ex

FIELD: medicine.

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4 dwg, 4 tbl, 4 ex

FIELD: medicine.

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3 dwg, 3 tbl, 4 ex

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2 ex

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2 ex

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1 tbl, 2 ex

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3 dwg, 3 ex, 2 tbl

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1 ex, 4 tbl

FIELD: medicine.

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1 tbl

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4 ex, 2 tbl

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2 ex

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2 tbl

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2 ex

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2 ex, 1 tbl

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