Method for evaluating anticoagulant-fibrinolytic blood potential at burn disease

FIELD: medicine, diagnostics.

SUBSTANCE: the present innovation deals with blood sampling, separating plasma against erythrocytes, moreover, in plasma on should detect activity of antithrombin III, proteins C and S, XIIa-dependent fibrinolysis and concentration of plasminogen obtained results should be expressed as relative units followed by calculating integral parameter that characterizes the state of anticoagulant-fibrinolytic potential (IPAFP) by the following formula: IPAFP = [(C1 + C2)/(C3 + C4)] x 100, where C1 - the ratio of observed value of antithrombin III activity to the value of inferior border of the range of analogous parameter norm; C2 - the ratio of observed value for the activity of proteins C and S system to the value of inferior border of the range of this parameter norm; C3 - the ratio of the value of inferior border of plasminogen concentration under normal conditions to observed value of analyzed parameter; C4 - coefficient calculated with the help of regression equation: C4 = 0.9 + (0.01 x X), where X - terms of lysis of patient's euglobulin clot/min, and at IPAFP value of 101.4 U and higher one should state anticoagulant-fibrinolytic blood potential to be in norm, in interval of 64.8 - 101.3 -as insufficient, and at 64.7 and below - as critical. The present method simplifies the procedure of evaluating the state of endogenous anticoagulants and activity of XIIa-dependent fibrinolysis.

EFFECT: increased diagnostic value of obtained results.

3 ex, 1 tbl

 

The invention relates to medicine, more specifically, to methods for estimating the depth of a system disorders of endogenous anticoagulants and activity XIla-dependent fibrinolysis blood in patients with burns, and can be used in clinics thermal defeats by medical combustiologists, and medical technicians biochemical and hemostatic laboratories relevant medical institutions with the aim of early detection of this pathology and the timely correction of violations of this system.

Existing methods study system state of endogenous anticoagulants and XIIa-dependent fibrinolysis based on the result of the determination in the patient's blood activity of anti-thrombin III, protein C and S, XIIa-dependent fibrinolysis, as well as the concentration of plasminogen, which are dissected and tests each of the study results is evaluated independently (Barkagan SS, Momot A.P. bases of diagnostics of disorders of hemostasis. - M.: Novamed-AO, 1999. - 224 S.).

No integral indicator, based on which it is possible judgment about the state of the system of endogenous anticoagulants and XIIa-dependent fibrinolysis, makes it difficult to assess the state of the system as a whole, especially in cases where there are multi-directional changes of the studied parameters (depression of one of the systems can be compensated for accounts the activation of another).

The present invention is the elimination of the existing fault - simplified assessment of the mechanisms of endogenous anticoagulants and XIIa activity-dependent fibrinolysis test results for the characteristics of the different parts of these systems, as well as increasing the diagnostic value of the test.

The problem is solved due to the fact that patients with burns away the blood, separates the plasma and in the last using known methods to determine the activity of anti-thrombin III (AT III), protein C and S, Ha-dependent fibrinolysis (Ha PD), and the concentration of plasminogen. The results are expressed in relative units, where the activity of AT III (K1) and proteins C and S (K2- found in a patient size indicator to the lower limit of the normal range of the corresponding parameter; K3- the ratio of the lower border of the indicator of the concentration of plasminogen in the conditions of the rules to found the patient to the value of the analyzed parameter; K4- coefficient, calculated using the regression equation: K4=0,9+(0,01×X), where X is the time of lysis euglobulin clot patient (min). To4written as a dimensionless quantity. Integral parameter characterizing the state of anticoagulant-fibrinolytic capacity of the blood (IAFP), Vychisl the t according to the formula:

IPAPP=[(K1+K2)/(K3+K4)]×100,

where K4-K4- as described above. The multiplier 100 is used to represent the values obtained in whole units. IPAPP expressed in conditional units.

When the value IPAPP 101,4% and above of anticoagulant-fibrinolytic potential in patients with thermal injury is assessed as being within normal limits, in the range from 64,8 to 101,3% as insufficient, and when 64,7% and below as critical. Identification of patient failure or critical state of anticoagulant-fibrinolytic potential is the basis for an appropriate therapy for the correction of impaired mechanism of this system of blood.

The method is as follows. In patients with burns away the blood, separates the plasma and in the last using known methods to determine the parameters characterizing the status of the various links of the system of endogenous anticoagulants and XIIa-dependent fibrinolysis.

Examine the activity of AT III (major physiological anticoagulant body), which according to our data in terms of norms is within 80,8-level 113.0% (M±2σ), which corresponds to literature data (M is the arithmetic mean of the indicator, σ - standard deviation - Sigma). Diagnostically important drop p is the index of activity of AT III below 81%. Depth of irregularities in the system of endogenous anticoagulants by decreasing the activity indicator AT III increases. The value of the analyzed parameters of the patient is expressed as the dimensionless ratio K1, which is calculated as the ratio of the values of activity of AT III (X1) to the lower limit of the control parameter values (K1=X1/81). If the activity of AT III the examined patient is 81% and above (any value more than 81%), K1always equal to 1.0% decrease of the activity of AT III in a patient with burns, for example, up to 65% recorded in the form of K1less units, 0,80%(65:81=0,80).

Determine the activity of protein C and S. the Value of the analyzed parameter in healthy people is 0.7% or more (literature data). Diagnostic value has decline by less than 0.7%, the Biggest drop of the analyzed parameter reflects the depth of failure of the system proteins C and S. the value of the activity of protein C and S in a patient with burns writes in the form of K2, which is calculated as the ratio of the values found in the activity of protein C and S to measure the lower limit of normal (2=X2/0,7).

If the activity of protein C and S in a patient with thermal injury equal to or more than 0.7%, the factor K2always equal to 1.0% NR is based on the specific values of the analyzed parameter.

Calculate the K-factor3as the ratio of the lower border of the normal range blood concentrations of plasminogen (76%) found the patient to the value of the analyzed parameter X3(K3=76/X3). According to our data in healthy people, the concentration of plasminogen varies within 76,4-132,0% (M±2σ)that corresponds to the data of the literature. The increase of K3reflects the measure of the failure of the concentration of plasminogen in casualties from thermal injury. Increase To3indicates the decrease in the content of plasminogen, which transforms into plasmin and is involved in the lysis of microthrombi blood. If the patient's concentration of plasminogen 76% or more K-factor3always write as 1.0%

Analyzed system Ha PD. The values of the indicator in terms of norms within 4-10 min (literature data). With the depletion of the main components of the plasma proteolytic systems involved in resorption of microthrombi, slowing lysis euglobulin clot, which is reflected in the lengthening of the time of its destruction. Diagnostic value has prolonged lysis euglobulin bunch more than 10 min, while the metric values below 4 min in patients with thermal injury according to our data, almost never observed. eprese Ha PD (increased more than 10 min) indicates decrease the ability of the fibrinolytic system of blood to effectively participate in the lysis of microthrombi. Time characterizing the state Ha PD, expressed as the ratio To4, which is calculated by the regression equation: K4=0,9+(0,01×X4), where X4the time of lysis euglobulin clot patient in minutes Therefore, lengthening the time of lysis euglobulin clot (decreased fibrinolytic activity of the blood) leads to an increase of K4.

The integral indicator of anticoagulant-fibrinolytic capacity of the blood (IPFP) calculated as the ratio of the sum of the coefficients of K1and K2to the sum of the coefficients K1and K4obtained result is multiplied by 100 for ease of presentation, IPAPP in integers):

IPAPP=[(K1+K2)/(K3+K4)]×100

and when the value of 101.4% or more anticoagulant-fibrinolytic potential blood assessed as being within normal limits, in the range 64,8-101,3% as insufficient, and 64,7% and below as critical.

Thus, the reduction of the sum of the coefficients of K1and K2located in the numerator of the formula proposed for the assessment of anticoagulant-fibrinolytic capacity of blood, reflects a reduction in the functional capacity of anticoagulant system, while increasing the set of coefficients K3and K4(in the denominator form of the s) - the depth of disorders of the fibrinolytic system. This is accompanied by a decrease in the value of the integral indicator of the state system of endogenous anticoagulants and fibrinolysis (IAFP).

Generally, the decline in activity of AT III and protein C and S (system of endogenous anticoagulants) accompanied by a decrease in the blood concentration of plasminogen and depression XIIa-dependent fibrinolysis. Ultimately, the reduction in the value of the integral indicator shows the appearance in the body affected by thermal injury conditions for the formation of Microsystem and progression in varying degrees, expressed blockade of the microcirculation of vital organs and tissues of the kidneys, lungs, liver, brain, adrenal glands, gastrointestinal tract, etc., resulting in them developing hypoxia, accumulation of toxic products of altered metabolism, disruption of specific functions. Timely detection of deep disorders anticoagulation blood systems, impeding the development of these complications, using the proposed test will allow doctors combustiologists promptly appoint adequate therapy, and systematically monitor the effectiveness of this treatment.

The basis for determining the amount IPFP, the value of which may be the judgment of the depths of the failure of anticoagulant-fibrinolytic capacity of the blood from the victims thermal injury, was the research results of this indicator in patients with severe burns on the affected area of the skin over 20% of body surface, were treated in the Russian burn center on the basis of the Nizhny Novgorod research Institute of traumatology and orthopedics. In addition, IPAPP studied in healthy individuals (control group).

In this case, the outcomes of burn disease patients were divided into two groups. Victims of the first group had less severe than in the second group, burns, more favorable course of the pathological process and the positive outcome of burn disease. The patients in this group survived. The period of burn disease patients of the second group appeared to be more severe, which ended all patients fatal.

Comparative analysis IPAPP in both groups of patients with thermal injuries, as well as healthy people have shown the following.

Table

The integral indicator of anticoagulant-fibrinolytic potential of blood in healthy people and those suffering from thermal injury (M±m), a unit
ControlPatients with burns (survivors)Patients with burns (deceased)
123
103,2± 0,2482,7±5,6352,8±5,31
(12)(36)(12)
 P1<0,001P2<0,001
  P3<0,001
Note: in parentheses are the number of studies; P1- significance of differences in the analyzed parameters in column 1 and 2; P2in column 1 and 3; P3in column 2 and 3.

The average IPAPP healthy individuals (control) according to our data is 103,2±0,24% (M±m) and ranges of 101.5-104.9% (M±2σ). It is seen that as the surviving and dead patients IPAPP statistically significantly different from the values of the analyzed parameter in terms of the norm (P1<0,001; P2<0,001). Patients with unfavorable outcome of the pathological process (the second group) recorded lower values IPAPP than in surviving patients (the first group), 1.6 times with a high degree of confidence (P3<0,001).

With the aim of obtaining the highest possible sensitivity and information content of the method of the border IPAPP to detect failure or diagnosis of a critical state of anticoagulant-fibrinolytic capacity of the blood in patients with thermal injury were identified who received at different values of the ratio of mean-square deviation (M± 0,67σ; M±σ and M1,5σwhere M is the arithmetic mean, σ - standard deviation). The most optimal for making satisfactory ranges IPAPP characteristic failure or critical state of anticoagulant-fibrinolytic potential blood was scope within M±0,67σ. In the group with signs of failure of anticoagulant-fibrinolytic potential (surviving patients) IPAPP varied within 64,3-101,2, and when a critical state of this system 40,5 from 65.1%

Since the curves of the distribution of each of the three statistical aggregates in the marginal zones of variational series intersect, then the intersection point of these curves, it is advisable to lay down boundaries, which are the benchmarks for assessment of anticoagulant-fibrinolytic potential blood-largest IPAPP. When the range IPAPP from 101,4% and above of anticoagulant-fibrinolytic potential is estimated as being within normal limits, from 64,8 to 101,3% as insufficient, and in the range from 64.7% and below as critical.

Below are a few examples to illustrate the validity of the proposed method of assessment of anticoagulant-fibrinolytic capacity of the blood from the victims thermal injury, which correlates with the depth of t is the TV of the blood coagulation system, the severity of the pathological process and outcome of burn disease.

Example 1.

The patient M s N.A. (the East. b-nor N 191817), 45 years old, 22.03.00, entered the Russian burn center on the basis of the Nizhny Novgorod research Institute of traumatology and orthopedics in connection with the burn of flame II-III AB-IV degree of trunk, upper extremity, both the lower limbs in the area of 50% of the body surface. IAFP on the 5th day after the burn unit 117, on the 9th day of 129 units of the State IPAPP assessed as being within normal limits. After standard treatment and repeated operations plastic skin, the patient was discharged 14.07.00, in a satisfactory condition.

Example 2.

The victim Sa-l P.I. (East. b-nor N195088), 55 years old, was admitted to the burn center 26.12.00, with a diagnosis of scald II-AB-IV degree of the trunk, of both lower extremities in the area of 45% of the body surface. On the 7th day after thermal injury IPFP was 84%, which was assessed as insufficient. After a course of adequate remedial measures, including repeated surgeries plastic skin, the patient was discharged in satisfactory condition, 22.03.01

Example 3.

Sick EP-VA S.A. (East. b-nor N194684), 67 years old, was admitted to the clinic of thermal lesions NIETO 22.11.00, about burn the flame of the face, neck and both upper limbs, back and front surface of the chest on the area of 32% of the skin is of okrolov depth AB-IV degree. IAFP on the 9th day after burn 36% State of anticoagulant-fibrinolytic capacity of blood is estimated as critical. In spite of intensive treatment, the patient died 10 days after thermal injury with symptoms of progressive multiple organ failure.

Method of assessment of anticoagulant-fibrinolytic potential of blood in burn disease, including blood collection and separation of plasma from red blood cells, characterized in that the plasma determine the activity of anti-thrombin III, protein C and S, Ha-dependent fibrinolysis and the concentration of plasminogen, the results are expressed in relative units, calculate the integral parameter characterizing the state of anticoagulant-fibrinolytic potential (IPFP) by the formula IPAPP=[(K1+C2)/(K3+C4)]×100, where K1- found respect patient values activity of anti-thrombin III to the magnitude of the lower border of the normal range of similar parameter; K2- the ratio found in the examined values of the indicator system activity of protein C and S to measure the lower limit of the normal range for this parameter; K3- attitude indicator lower limit of the concentration of plasminogen in the conditions of the rules to found the patient to the value of the analyzed parameter; K4- to fficient, calculated using the regression equation: K4=0,9+(0,01×X), where X is the time of lysis euglobulin clot patient in the mines, and when the value IPAPP 101,4% and above of anticoagulant-fibrinolytic potential blood assessed as being within the normal range in the interval from 64,8 to 101,3% as insufficient, and when 64,7% and below as critical.



 

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