Версия для печати Makshanova G.P., Ustyantseva I.M, Khokhlova O.M.

BLOOD SYSTEM IN PATIENTS WITH POLYTRAUMA AT DIFFERENT TIMEFRAMES OF SURGICAL TREATMENT

Kemerovo State Medical University, Kemerovo, Russia,

Regional Clinical Center of Miners’ Health Protection, Leninsk-Kuznetsky, Russia

One of the actual problems of the modern medicine is polytrauma, which takes the third place (after oncologic and cardiovascular diseases) among the causes of lethal outcomes in working age men (age of 18-40) (the WHO data). In the early period of trauma, a lethal outcome is usually caused by shock and massive blood loss, in the late period – by concurrent complications (thromboembolism, pneumonia and infectious processes).
The polytrauma-associated complications are determined by dynamic changes in coagulation hemostasis and decreasing immunity [1]. It can be caused by disordered functioning of the formed elements [2, 3].

MATERIALS AND METHODS

60 patients with polytrauma after road traffic accidents were examined in the clinical conditions: 43 men and 17 women (age of 25-55, mean age 39.5 ± 3.6) in critical state admitted to the intensive care unit, Regional Clinical Center of Miners’ Health Protection, Leninsk-Kuznetsky, from January to December 2016. The patients were admitted within 2 hours after the injury. They had traumatic shock of degrees 2-3 (APACHE-III ≈ 76), with assumed blood loss of 1,200-1,500 ml (> 20 % of circulating blood volume). The individual estimation of blood loss was conducted with the sum of external and cavitary blood loss in fractures. The inclusion criteria were age from 16 to 65, severe multiple (n = 21) or associated (n = 39) injuries to the locomotor system. The exclusion criteria were severe traumatic brain injury and/or abdominal injury.
Retrospectively, depending on the timeframes of the surgical treatment for the locomotor system injuries, the patients were distributed into 2 groups. The patients of the main (1st) group (23 men and 8 women) received the early surgical treatment within 24 hours after the injury. The comparison (2nd) group included the patients (20 men and 9 women) who received the late surgical treatment (more than 3 days after injury). The control group included 20 almost healthy individuals at the age of 20-50.

Table 1. The characteristics of the examined patients

Indices	Main group (n = 31)	Comparison group (n = 29)	p-value
Age, years	38.8 ± 3.09	40.1 ± 4.18	0.216
Gender, male/female	23 (8)	20 (9)
Injury patterns (n =, (%)): - associated, - multiple	20 (64.5 %) 11 (35.5 %)	19 (65.5 %) 10 (34.5 %)
Severity according to APACHE-III (points)	75.9 ± 12.1	77.1 ± 12.9	0.68
The volume of blood loss (l)	1.29 ± 0.200	1.15 ± 0.160	0.55
HR, per min.	115.0 ± 6.20	110.0 ± 5.80	0.59
mean AP	65.0 ± 2.40	64.0 ± 2.56	0.28

Note: HR – heart rate; mean AP – mean arterial pressure. APACHE III – Acute Physiology and Chronic Health Evaluation, Knaus W., 1985.

The study was conducted in concordance with World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, 2013 with the written approval from the patients for participation in the study (or from their relatives, if a patient’s ability to communication was limited) and the approval from the local ethical committee.
The values of the venous blood were examined upon admission and on the days 1, 2, 3, 5, 7, 10, 15 and 21 after the injury. The hematological parameters were determined (amount of red blood cells, thrombocytes, the level of hemoglobin) with the analyzer Sismex ХТ 4000i (Japan).
The ability of red blood cells to aggregation was estimated with the piesodynamic erythro-agrometer Test-2, the deformation capability of red blood cells – with the rotation viscosimeter (Russia) at the rates from 10 to 200 sec.^-1.
The aggregation capability was estimated with the aggregometer BIO/DATA Corporation (USA). The level of fibrinogen and the prothrombin index (PTI) were measured in the blood plasma with the coagulometer STA COMPACT (Stago, France).
The spontaneous NBT-test (NBT-sp.) was performed according to Park B.N. (1971) with modification by Mayansky A.N. (1983), the stimulated NBT-test (NBT-st.) – according to Baechner R.S. (1968). The estimation of bactericidal activity was conducted with the microbial culture Staphylococcus aureus.
The statistical analysis of the data was conducted with IBM SPSS Statistics 20. The mean arithmetic (M) and the error of mean (m) were calculated. The results were tested for normalcy of distribution with use of Kolmogorov-Smirnov's test. When the distribution law for the measured values could be considered as normal, the intergroup differences were identified with use of one-way analysis of variance with the following procedure of Tukey multiple paired comparisons at the general significance level of 0.05.

RESULTS AND DISCUSSION

There were not any statistically significant differences in condition severity (APACHE-III) between the groups at the moment of hospital admission (the table 1).
The severity of condition in the patients with polytrauma demonstrated the clinical manifestations in view of system hemodynamic disorders: the heart rate was 43 % higher than the control values at the moment of hospital admission (p < 0.05), the mean AP – 28 % lower (p < 0.05). These changes in the system perfusion were determined by the blood loss (the table 1).
Acute posthemorrhagic anemia developed in the patients with polytrauma as result of the blood loss: the amount of red blood cells was decreasing (by 27 %, p < 0.05), as wells as the level of hemoglobin (by 30 %, p < 0.05). It is common for patients with multiple and associated injuries to the locomotor system [4]. Despite of blood loss replacement, anemia was increasing, with the maximal level on the days 3-5 after the injury that is possibly determined by hemodilution [5]. It was found that the phase of hemodilution develops later (on the days 5-8 instead of the days 1-2 after “clean” bleeding) in injuries with acute blood loss [6].
Anemia was continuing to persist up to the end of the follow-up period (21st day), possibly, as result of decrease in plastic functions of red bone marrow and increasing hemolysis of red blood cells [7].
The condition of most patients in the main group improved significantly by the day 7. It was confirmed by the decrease in APACHE-III up to 44 ± 8.5. But the value of APACHE-III was 60 ± 8.5 in the patients with the delayed surgical treatment for the locomotor system (Fig. 1).

Figure 1. The comparative time trends of severity of condition of the patients with polytrauma according to APACHE-III in early (group 1) and delayed (group 2) surgical treatment of locomotor system injuries



* – statistically significant differences between the groups

During the whole follow-up period, the patients ofboth groups demonstrated the higher HR as compared to the normal values, but on the days 5-21 of the follow-up, the mean HR was 10.5 % (p < 0.05) in the patients with the early surgical treatment of the locomotor system than in the patients with the delayed surgery (Fig. 2).

Figure 2. The comparative time trends of HR in the patients with polytrauma in early (group 1) and delayed (group 2) surgical treatment of locomotor system injuries


* – statistically significant differences between the groups

The preservation of the compensatory mechanisms can be testified by the improving patients’ condition and earlier normalization of HR in patients with polytrauma during the early surgical treatment. It is confirmed by the features of changes in the functional properties of red blood cells. As result of total blood volume decrease and anemia, hypoxia of mixed genesis (circulatory and hemic) was developing and it was complicated by increasing aggregation of red blood cells and decreasing deformity [6]. But after the delayed surgical treatment of the locomotor system injuries the patients showed the higher aggregation ability of red blood cells (the aggregation index was at average 33 % higher, p < 0.05), the aggregation coefficient – by 83 % (p < 0.05), the deformation capability – lower than in the patients of the group 1 [3, 8] (the table 2).

Table 2. The time trends of changes in index (J) and coefficient (K) of aggregation and index of deformity (Id) of red blood cells in patients with polytrauma in early (group I, n = 31) and delayed (group II, n = 29) surgical treatment (М ± m)

Follow-up period	Group	Aggregation index (J • 102)	Aggregation coefficient (К • 102)	Deformity index (Id)
Admission	Control	3.61 ± 0.190	1.44 ± 0.220	1.12 ± 0.003
	I	4.71 ± 0.170*	3.73 ± 0.220*	1.09 ± 0.008*
	II	4.72 ± 0.180*	3.7 ± 0.21*	1.09 ± 0.008*
1-е сутки day 1	I	4.34 ± 0.150*	2.21 ± 0.190*	1.11 ± 0.003*,**
	II	5.98 ± 0.150*,**	3.97 ± 0.210*,**	1.08 ± 0.004*
5-е сутки day 5	I	6.09 ± 0.220*	6.15 ± 0.200*	1.10 ± 0.007*
	II	6.97 ± 0.170*,**	6.64 ± 0.190*	1.06 ± 0.005*,**
7-е сутки day 7	I	6.86 ± 0.230*	5.02 ± 0.180*	1.11 ± 0.005
	II	7.3 ± 0.20*	7.18 ± 0.220*,**	1.08 ± 0.006*,**
10-е сутки day 10	I	5.04 ± 0.130*	3.45 ± 0.160*	1.11 ± 0.004*
	II	7.06 ± 0.180*,**	7.9 ± 0.23*,**	1.09 ± 0.006*,**
15-е сутки day 15	I	4.7 ± 0.13*	3.02 ± 0.160*	1.11 ± 0.006
	II	6.02 ± 0.170*,**	4.88 ± 0.170*,**	1.10 ± 0.007*
21-е сутки day 21	I	4.6 ± 0.15*	2.72 ± 0.150*	1.12 ± 0.008
	II	5.78 ± 0.200*,**	4.39 ± 0.200*,**	1.11 ± 0.005

Note: (*) – statistically significant changes according to Stident's test in comparison with control values; (**) – between groups, p < 0.05.

The described disorders of the aggregation and deformation capability of red blood cells in the comparison group could lead to perfusion disorders in the microcirculatory bed vessels, with worsening hypoxia in some organs and tissues and promoting the development of local complications such as endobronchitis (19.6 %), osteomyelitis (7.8 %), necrosis and bed sores (4.2 %), acute urethritis (3.9 %) [3].
Besides the local complications, the patients with polytrauma often suffered from pneumonia (23.5 %) and ARDS (23.5 %). The development of such threatening complications could be determined by the immune system dysfunction in polytrauma [9, 10]. The total amount of the complications was almost 3 times higher in the comparison group (50.1 % vs. 17.2 %, p < 0.05) than in the main group [3]. Possibly it was determined by more intense disorder of the function of the non-specific link of immunity.
This assumption was confirmed by the decrease in the functional activity of neutrophils in the patients with the delayed surgery. So, the examination of the bactericidal action of neutrophils (with living cultures) showed that the bactericidal action of neutrophils was increasing at the moment of hospital admission in the patients with the early surgical treatment (increase by 30 %, p < 0.05), with maximal increase on the days 2 and 3, but this value increased for short time in the patients with the delayed surgery, with the peak value on the first day of the follow-up. Moreover, the patients of the group 2 did not show any changes in the stimulated NBT-test and showed some positive time trends of spontaneous NBT-test (the table 3).

Table 3. Time trends of bactericidal action of neutrophilic granulocytes, NBT-spontaneous (NBT-sp.) and NBT-stimulated (NBT-st.) in patients with polytrauma in early (group 1, n = 28) and delayed (group II, n = 27) surgical treatment (М ± m)

Follow-up  period	Group	Bactericidal action, % microbial killing	NBT-sp. • 109	NBT-st. • 109
Admission	Control	39.2 ± 0.89	0.14 ± 0.020	0.4 ± 0.03
	I	51.1 ± 0.90*	0.19 ± 0.030	0.42 ± 0.090
	II	51.9 ± 0.80*	0.189 ± 0.0200	0.41 ± 0.080
day 1	I	57.3 ± 1.10*	0.27 ± 0.050*	0.56 ± 0.050*
	II	56.4 ± 1.20*	0.26 ± 0.030*	0.4 ± 0.03**
day 2	I	64.3 ± 1.30*	0.34 ± 0.040*	0.58 ± 0.060*
	II	46.3 ± 1.30*,**	0.24 ± 0.020*,**	0.42 ± 0.040**
day 3	I	66.1 ± 1.50*	0.29 ± 0.020*	0.57 ± 0.050*
	II	40.4 ± 1.70*,**	0.22 ± 0.020*,**	0.44 ± 0.030**
day 5	I	55.2 ± 1.04*	0.26 ± 0.020*	0.49 ± 0.030*
	II	42.1 ± 1.30*,**	0.20 ± 0.020*,**	0.48 ± 0.020*
day 7	I	53.3 ± 1.10*	0.17 ± 0.010	0.49 ± 0.020*
	II	31.3 ± 0.92*,**	0.19 ± 0.020	0.44 ± 0.030
day 10	I	45.3 ± 0.99*	0.16 ± 0.010	0.48 ± 0.010*
	II	30.4 ± 0.99*,**	0.16 ± 0.040	0.36 ± 0.040**
day 15	I	42.5 ± 0.97*	0.15 ± 0.030	0.42 ± 0.030
	II	34.2 ± 1.20*,**	0.15 ± 0.020	0.42 ± 0.040
day 21	I	40.1 ± 0.98	0.14 ± 0.030	0.40 ± 0.050
	II	36.1 ± 0.99*,**	0.15 ± 0.020	0.40 ± 0.030

Note: (*) – statistically significant changes according to Stident's test in comparison with control values; (**) – between groups, p < 0.05

The decrease in neutrophil activity in the patients with the delayed surgery was possibly associated with probable progression of systemic inflammatory response [11]. Macrophages are the key cells in development of systemic inflammatory response. Macrophages release cytokines including tumor necrosis factor-alpha, IL-1 and IL-6. The time course of traumatic disease demonstrates the strong correlation relationship between the values of cytokines and hemocoagulation [12]. Therefore, we investigated the time course of hemostasis system in the patients with polytrauma.
Hypercoagulation developed in the patients with polytrauma. It is known that two subsequent phases are available in hemostasis system: short term hypercoagulation (immediately after injury) and prolonged subsequent hypercoagulation [4]. The increasing prothrombin index (PTI), which is observed up to the 10th day of follow-up, confirmed the intensifying blood clotting, i.e. activation of the external way of hemostasis system [13]. Hypercoagulation was more intense in the comparison group than in the main group (higher PTI during the whole follow-up) (the table 4).
The important factor of hypercoagulation is increasing blood level of fibrinogen [12]. The level of fibrinogen was increasing within the first day after injury, with the maximal level on the days 5-7 (3.7-fold increase, p < 0.001), without significant differences between the groups during the whole follow-up (the table 4).

Table 4. Time trends of PTI, level of fibrinogen and platelets, aggregation capability of platelets (with use of the inducers: ADP, adrenaline, ristomycin) in blood of patients with polytrauma in early (group I, n = 31) and delayed (group II, n = 29) surgical treatment (М ± m)

Follow-up  period	Group	Value
		PTI (%)	Fibrinogen (g/l)	Amount of  platelets (• 1011/l)	Platelet aggregation
					ADP	Adrenaline	Ristomycin
Admission	Control	90.5 ± 1.66	2.89 ± 0.230	232.7 ± 5.57	60.7 ± 2.31	56.99 ± 2.980	65.7 ± 2.30
	I	95.5 ± 1.29*	2.41 ± 0.400	206.6 ± 7.22*	66.5 ± 3.69	60.8 ± 2.98	69.4 ± 2.34
	II	96.2 ± 1.89*	2.28 ± 0.310	202.9 ± 6.07*	67.1 ± 3.12	61.99 ± 2.130	69.9 ± 2.04*
day 1	I	96.7 ± 1.39*	3.81 ± 0.230*	162.3 ± 5.25*	64.1 ± 3.31	64.8 ± 3.18	65.1 ± 3.70
	II	112.4 ± 2.55*,**	4.27 ± 0.350*	199.6 ± 13.71*,**	67.5 ± 3.50	65.9 ± 3.12*	66.5 ± 2.13
day 2	I	99.2 ± 1.87*	7.05 ± 0.420*	140.1 ± 3.24*	70.9 ± 3.21*	67.4 ± 3.05*	66.5 ± 3.17
	II	111.7 ± 2.83*,**	6.84 ± 0.650*	188.7 ± 16.05*,**	70.99 ± 2.320*	65.4 ± 2.50*	67.8 ± 2.59
day 3	I	105.4 ± 1.60*	7.87 ± 0.530*	161.9 ± 3.84*	69.1 ± 2.18*	65.4 ± 2.71*	78.9 ± 2.11*
	II	106.5 ± 2.85*	7.74 ± 0.660*	164.8 ± 12.10*	70.8 ± 2.34*	66.3 ± 2.51*	72.8 ± 2.12*,**
day 5	I	102.8 ± 1.79*	9.21 ± 0.650*	203.1 ± 9.94*	62.5 ± 2.56	71.2 ± 2.73*	72.1 ± 2.16*
	II	107.4 ± 2.29*	9.07 ± 0.600*	186.2 ± 12.09*	75.2 ± 2.16*,**	79.9 ± 3.14*,**	77.8 ± 2.21*
day 7	I	101.3 ± 1.72*	8.37 ± 0.650*	244.9 ± 9.04	62.0 ± 3.15	69.1 ± 2.40*	66.9 ± 2.64
	II	102.4 ± 2.09*	8.77 ± 0.320*	245.6 ± 8.86	74.7 ± 2.61*,**	78.4 ± 2.01*,**	78.6 ± 2.23*,**
day 10	I	95.8 ± 1.91*	7.61 ± 0.52*	364.2 ± 14.96*	61.5 ± 2.64	69.3 ± 2.16*	66.2 ± 2.64
	II	102.5 ± 1.42*,**	7.93 ± 0.69*	329.1 ± 12.11*	72.7 ± 2.19*,**	74.8 ± 2.86*,**	78.4 ± 2.88*,**
day 15	I	94.6 ± 2.21	6.99 ± 0.600*	380.5 ± 13.29*	61.7 ± 2.82	64.5 ± 2.18*	66.4 ± 2.09
	II	100.1 ± 2.20*	6.99 ± 0.550*	380.3 ± 14.49*	69.8 ± 2.22*,**	71.6 ± 2.17*,**	78.1 ± 3.09*,**
day 21	I	91.3 ± 1.89	6.77 ± 0.40*	328.0 ± 6.59*	60.4 ± 1.64	57.7 ± 2.07	65.5 ± 1.96
	II	95.5 ± 1.44*	7.09 ± 1.23*	368.0 ± 9.14*,**	61.9 ± 1.55	64.3 ± 1.71*,**	72.0 ± 2.99

Note: (*) – statistically significant changes according to Stident's test in comparison with control values; (**) – between groups, p < 0.05.

Thrombocytopenia (the amount of platelets decreased by 11 %, p < 0.05), which was observed in the patients with polytrauma during 5 days, was possibly determined by hemodilution [14]. Also the increase in the aggregation capability of platelets was observed during the use of the various inducers (ADP, adrenaline, ristomycin). It was more intense in the patients with the delayed surgery. So, the use of ADP as the inducer resulted in the increasing platelet aggregation on the days 5-15, the increase in adrenaline on the days 5-21, ristomycin – on the days 7-15 of the follow-up in the patients of the group 2 (the table 4).
The microcirculatory disorders could be the caused by more serious hemostasis disorders in the patients with delayed surgical treatment of the locomotor system [15]. The microcirculatory disorders worsen the tissue hypoxia and initiate the vicious circle that can influence on the regeneration processes and development of complications.CONCLUSION

1. Acute posthemorrhagic anemia develops in polytrauma. In case of the delayed surgical treatment of the locomotor system it is accompanied by more intense (as compared to early surgery) disorders of erythrocytic deformity with increasing aggregation capability that testifies the changes in stability of membranes and worsening gas transport function of these cells.
2. The early surgery of the locomotor system in polytrauma promotes the improvement in the functional condition of red blood cells and platelets, hemodynamics and general condition of patients.
3. During the early surgical treatment the functional activity of neutrophilic granulocytes is characterized by increasing bactericidal activity that possibly determines the increasing antimicrobial resistance of the body and results in lower amount of complications.

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