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UDC 616.24-002.31-07:616.15-07
D-DIMERS AND C-REACTIVE PROTEIN IN PATIENTS WITH PURULENT-DESTRUCTIVE PULMONARY DISEASES
Altai State Medical University, Barnaul
A.P. Momot, S.Yu. Kapitulin, S.D. Fokeyev, A.A. Medvedev,Yu.G. Belokrylova, M.A. Zhelkombayeva, Ya.N. Shoikhet
This article presents the results of a comprehensive examination of 35 patients aged 48.2+4.8 years with purulent-destructive pulmonary disease. Determination of D-dimers in the blood plasma of patients was performed, the level of C-reactive protein was determined in the serum by the immunometric method. To determine the control values, the results obtained from 25 practically healthy people were used. As a result of the study, it was determined that plasma D-dimer levels and C-reactive protein in serum can serve as laboratory criteria for assessing the prognosis of the course of the disease.
Key words: d-dimers, c-reactive proteins, lung diseases, hemostasis.
The increase in the level of C-reactive protein as an integral marker of the inflammatory reaction is inextricably linked by many threads with hemostasis reactions [1, 2].
The C-reactive protein (CRP) was discovered by Tilet and Francis (1930) in the plasma of patients with pneumonia and was so named because of its ability to bind and precipitate pneumococ-cal C-polysaccharide. It is synthesized in hepato-cytes and is an important participant in two types of inflammatory reactions: A) an acute inflammatory process associated with systemic infections or tissue necrosis (for example, burns, malignant tumors, myocardial infarction). In such situations, the level of CRP in the serum increases in the acute phase inflammatory range from 10 mg/l and higher (up to 1000 mg/l) and reflects the severity and dynamics of the systemic inflammatory reaction; B) sluggish inflammatory process, going to the en-dothelium, associated with atherogenesis and, as a rule, not associated with acute infection. In recent cases, the concentration of CRP increases only in the highly sensitive range - from 0.05 to 10.0 mg/l. This high-sensitivity measurement of CRP is referred to as hsCRP (hs-high sensitive) [3].
There is no doubt that CRP plays a key role in both atherogenesis and atherothrombosis, and serves as an effective predictor of cardiovascular events. It is believed that an increase in hsCRP is associated with endothelial dysfunction, thrombosis and insulin resistance [3].
It has been shown that CRP recognizes oxidized LDL-C as foreign and stimulates uptake of compound X oxy-LDL-C by macrophages, which leads to the formation and accumulation of foam cells. This acute phase protein increases the synthesis of adhesion molecules (ICAM, VCAM, E-selectin, chemokine MCP-1), activates the differentiation of monocytes into macrophages, induces the secretion of monocyte tissue factor (TF), induces the release of pro-inflammatory cytokines from mono-cytes, predecessors of endothelial cells, activates
smooth muscle cells, which increases the instability of the plaque, blocks the formation of NO and violates the vasoreactivity of the endothelium, increases the synthesis of active forms of oxygen, stimulates the synthesis of matrix metalloprotein-ases in the plaque, increases the activity of the collagenase in monocytes and macrophages, which leads to platelet instability, and finally stimulates thrombosis by suppressing the plasminogen activator inhibitor I (PAI-I) and the tissue plasminogen activator (tPA). As a result, the synthesis and secretion of CRP in the sites of atherosclerotic lesions increase local concentrations of CRP much higher than those levels that are found in plasma. All of the above leads to pro-atherogenic, pro-inflammatory and pro-coagulant effects of this marker. In general, it is believed that the higher the concentration of CRP in the highly sensitive range, the more pronounced endothelial dysfunction is[4, 5, 6, 7, 8].
In 2003, the American Heart Association recommended the use of hsCRP for the assessment of CVD risk, and proposed cardiographic calculation algorithms (formulas) that include six indicators: age, current smoking status, systolic blood pressure, total cholesterol, HDL-C, hsCRP, cases of MI in family history [9].
It is believed that before a highly sensitive definition of hsSRB, it is necessary to measure CRP in the acute-inflammatory range (levels <10 mg/l) to determine if the patient has acute inflammatory processes. If the CRP level is above 10 mg/L, the patient is examined to identify infectious, inflammatory or cancerous diseases [10].
At present, there is no doubt that the outcome of the disease depends on the compliance of the volume of the curative program with the severity of the pathological process. A correct assessment of the patient's condition allows for a differentiated approach to the choice of tactics for the management of a particular patient, which in many respects reduces the risk of com-
plications, and thus contributes to the improvement of the outcome of the disease as a whole [11,12].
In foreign and domestic literature, more than one and a half thousand scales, formulas and calculation systems have been published that directly or indirectly reflect the severity of the patients' condition, allowing to predict the possibility of a fatal outcome. Many of the above scales are either very laborious or do not have sufficient accuracy. Attempts to use simplified systems for assessing the severity of a condition reduce the likelihood of a correct prognosis, and the use of multistage scales is not readily available for clinical practice, requiring the availability of special expensive equipment to determine the parameters indicated therein. In connection with this, it seems promising to search for such biological markers, the determination of which would be available to clinical diagnostic laboratories of practical health care institutions, and at the same time their level would correlate with the severity of the condition of patients assessed by specialized multistage scales [13, 14, 15 , 16, 17].
The connection between the processes of inflammation and changes in the hemocoagulation system is natural: it is mediated by common plasma, cellular and vascular components [18, 19, 20]. Among the "global" markers of inflammation there is, as is well known, C-reactive protein, a representative of the family of acute phase response proteins [19, 20]. In turn, the intensity of activation of intravascular coagulation can be estimated from the quantitative content of D-dimers - products formed during the sequential proteolysis of fibrinogen by thrombin, factor XlIIa and plasmin [20].
The purpose of this work is to evaluate the levels of D-dimers and C-reactive protein as markers of the severity of the condition in patients with purulent-destructive pulmonary diseases.
Materials and methods
A complex examination of 35 patients with purulent-destructive pulmonary diseases (PDPD) was conducted at the Department of Thoracic Purulent Surgery and Reanimation of the City Clinical Hospital No. 5 in Barnaul. Exclusion criteria were patients with oncological, tuberculosis, blood diseases, primary viral immunodeficiency virus (HIV) and viral hepatitis. The average age of patients was 48.2 + 4.8 years. On the basis of gender, the patients were divided as follows: 26 (74.3%) were men and 9 (25.7%) were women.
According to the outcomes of the disease, patients were divided into two groups: the first group - 24 (68.6%) patients who recovered; the second group - 11 (31.4%) - the process's chronization. The length of stay in the hospital was in the first group - 23.5 + 3.4 days; in the second group - 32.8 + 1.6 days. In all patients with purulent-destructive pulmonary diseases, clinical and laboratory
signs of the systemic inflammatory reaction syndrome (SIRS - Systemic Inflammatory Response Syndrome) were accepted for the 1st and 7th-10th days after admission to the hospital. They were accepted at the International Conciliation Conference of the American College of Pulmonology and the Society of Critical States Medicine in Chicago (1992) [21].
The severity of the condition of patients with purulent-destructive lung diseases treated was determined on the basis of SIRS scales, which makes it possible to assess the severity of abdominal sepsis; SOFA (Score Sequential Organ Failure Assessment) - for an objective assessment of the severity of abnormalities on the part of the patient's organs and systems and determining the likelihood of an adverse outcome associated with sepsis, and APACHE II (the Acute Physiology, Age, Chronic Heath Evaluation) - possibility of lethal outcome for the patient.
From the day of admission to hospital, patients with purulent-destructive lung diseases underwent conservative treatment, including adequate emptying of purulent cavities and their sanitation (abscess puncture, abscess cavity drainage), measures aimed at prompt lung spreading, massive antibacterial therapy (cephalosporins of III- IV generation, fluoroquinolones, carbapenems), detoxification and immunocorrective therapy, aimed at restoring the functions of vital organs and systems.
The production of blood and plasma stabilized by sodium citrate was performed in patients on the 1st and 7-10 days after hospitalization, in accordance with generally accepted recommendations [22]. Determination of D-dimers was performed in the blood plasma of patients (on an automatic coagulometer Sysmex CA-1500 using the D-dimer Plus reagent kit of Simens / Dade Behring). The level of C-reactive protein (CRP) was determined in the blood serum by the immunometric method on the instrument NycoCard Reader using the reagents "CRB Single Test" from Axis-Shield. To determine the control values, the results obtained from 25 practically healthy people were used.
The data obtained is processed using the statistical functions of Excel 2007 and the STATISTICA 6.0 program. Since many of the results obtained were characterized by a nonparametric distribution, they were expressed as a median (Me), a value that divides the distribution in half, 25th and 75th percentiles (25%-75%), values between which 50% of observations are. A check on the normal distribution of the results was carried out using the Shapiro-Wilk W-test. In a comparative analysis of several independent groups with a nonparamet-ric distribution, the ANOVA test using the Krus-kal-Wallis criterion was used.
Results and discussion
In accordance with the data obtained, the level of CRP in patients on the first day after admission
APACHE II scale was used to determine the severity of the condition for patients with purulent-destructive lung diseases. When assessing the results obtained in the groups under analysis, it is worth noting that the groups were statistically significant (p <0.001) differing in the number of scores obtained on this scale on the 1st
to hospital was significantly increased, to an average of 121.4 ± 3.6 mg/l, with an upper limit of normal values - up to 5.0 mg/l (Table 1, Figure 1).
and on the 7-10th day after admission to the hospital. In patients of the second group, the APACHE II score on the first day was 9.5 (9-11) points, while in the patients of the first group, only 7 (5-8) points. On the 7-10th day of stay in the hospital, there was a decrease in the number of points on the APACHE II scale in the first and second groups.
Figure 1. Dynamics of the level of CRP in patients with purulent-destructive diseases, depending on the course and
outcome of the disease.
Table 1
Dynamics of levels of D-dimers and C-reactive protein in blood plasma in patients with PDPD as a result of assessing the severity of the condition in scores on the scales APACHE II, SOFA on the 1st, and 7-10th day
1st group 2nd group
Indicator Day Ме 25%-75% Ме 25%-75%
SIRS, points 1 1 1 - 2 2 1 - 3
7-10 0 0 - 1 1 1 - 2
APACHE II points 1 7* 5 - 8 9,5* 9 - 11
7-10 3* 3 - 3 7* 5 - 8
SOFA, points 1 1 1 - 2 2 1 - 2,5
7-10 0 0 - 1 0 0 - 1
D- dimers, ng/ml (norm up to 300 1 3392 (V) 2272 - 5427 2895 (V) 2132 - 5105
ng/ml) 7-10 1848 (V) 1250 - 2144 1700 (V) 1472 -2350
CRP, mg/l (norm up to 5.0 mg/l) 1 96* 70 - 160 106* 85 - 155
7-10 92,3* 55,5 - 105 110,2* 98 - 145
Notes: Me - median, [25% -75%] - the 25th and 75th percentile
(V) - the difference in groups on the 1st and 7th-10th days is statistically significant (p <0.01) * - the difference between the 1st and 2nd groups is statistically significant (p <0.05)
To assess the severity of organ failure, the SOFA scale was used. On the first day after admission to the hospital and on the 7-10th day of hospital-ization, the first and second groups did not differ statistically significantly.
To determine the severity of abdominal sepsis in patients with purulent-destructive lung diseases, the SIRS scale was used. The obtained results showed that all the patients included in the study had one or more signs of SIRS on the first day after hospitalization (depending on the group of patients).
In the course of further observations, patients were stratified according to this integral index of the activity of the inflammatory reaction. In particular, on the 7-10th day in the patients of the first
and second groups the concentration of CRP remained at an extremely high level, although the reliability of the differences between them was established (p <0.001). Initially, high values of this parameter in such patients progressively decreased on the 7-10th day of the survey. These observations allow us to conclude that the severity of the disease was associated with the subsidence of the inflammatory process, the depression of this external aggression defense mechanism.
The second marker, fibrinolysis products, or D-dimers, reflecting the intensity of hemostatic processes, was sharply increased in all patients with PDPD irrespective of the established observation time (Figure 2).
Figure 2. Dynamics of the level of D-dimers in patients with purulent-destructive diseases, depending on the course and
outcome of the disease.
Along with this, it was noted that in the case of a favorable course of the disease, there was a weak, albeit reliably expressed, positive dynamics in reducing the level of D-dimers (on the 7th-10th day of observations) in patients who had recovered in the subsequent time.
In the course of further analysis, a strong correlation was found between the level of D-dimers, the concentration of CRP, the severity of the condition of patients (according to the APACHE II scale) and the appearance of signs of organ failure on the first and third days after the initiation of therapy (Table 2).
Nevertheless, there was no correlation between the level of D-dimers and the severity of SIRS in the first day, which is probably due to the fact that the level of D-dimers in the systemic blood flow is increased in all patients who have an inflammatory process in the pleural cavity.
A strong correlation was found on the 7-10th day between the level of CRP and the severity of SIRS.
Conclusions:
1. Levels of D-dimers in plasma and C-reactive protein in serum can serve as laboratory criteria for assessing the prognosis of the course with purulent-destructive lung diseases.
2. In a comprehensive examination of patients with purulent-destructive pulmonary diseases, it is necessary to determine the levels of CRP and D-dimers in the dynamics as markers of the prognosis and course of the disease.
References
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Table 2
Correlation between the level of D-dimers, CRP and assessment of the severity of the condition on the scales APACHE II, SOFA and SIRS on the 1st and 10th days after admission to hospital in patients with purulent-destructive
pulmonary diseases
Comparison of indicators Day Correlation coefficient (r) p-level
D-dimers and APACHE II 1 0,42 0,0012
7-10 0,42 0,0001
D-dimers and SOFA 1 0,35 0,0031
7-10 0,38 0,0001
CRP and APACHE II 1 0,15 0,0635
7-10 0,26 0,0001
CRP and SOFA 1 0,23 0,0021
7-10 0,30 0,0001
D-dimers and CRP 1 0,54 0,0001
7-10 0,42 0,0001
D-dimers and SIRS 1 -0,52 0,9154
7-10 -0,54 0,9945
CRP and SIRS 1 0,32 0,0038
7-10 0,82 0,0439
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Contacts
Corresponding author: Momot Andrey Pavlov-ich, Doctor of Medical Sciences, Professor, senior researcher of the Laboratory of hematology CSRL ASMU on the basis of the Regional Clinical Hospital, Barnaul.
656056, Barnaul, ul. Lyapidevskogo, 1. Tel.: (3852) 566994. Email: science@agmu.ru
Kapitulin Stanislav Yuryevich, Candidate of Medical Sciences, Associate Professor of the Department of Faculty Surgery named after Professor I.I. Neimark, hospital surgery with course of FVE of the Altai State Medical University, Barnaul. 656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
Fokeyev Sergei Dmitriyevich, Doctor of Medical Sciences, Professor of the Department of Faculty
Surgery named after Professor I.I. Neimark, hospital surgery with course of FVE of the Altai State Medical University, Barnaul. 656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
Medvedev A.A., resident of the Department of Faculty Surgery named after Professor I.I. Neimark, hospital surgery with course of FVE of the Altai State Medical University, Barnaul. 656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
Belokrylova Yulia Gennadiyevna, assistant of the Department of Faculty Surgery named after Professor I.I. Neimark, hospital surgery with course of FVE of the Altai State Medical University, Barnaul.
656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
Zhelkombaeva Maria Alexandrovna, assistant of the Department of Faculty Surgery named after Professor I.I. Neimark, hospital surgery with course of FVE of the Altai State Medical University, Barnaul.
656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
Shoikhet Yakov Nakhmanovich, corresponding member of RAS, Doctor of Medical Sciences, Professor of the Department of Faculty Surgery named after Professor I.I. Neimark, hospital surgery with the course of FVE of the Altai State Medical University, Barnaul.
656045, Barnaul, Zmeinogorsky Trakt, 75. Tel.: (3852) 268233. Email: science@agmu.ru
