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EXPERIENCE WITH USE OF THROMBOELASTOGRAM FOR PATIENTS WITH SEVERE COMBINED PELVIC INJURY Kazhanov I.V., Afonchikov V.S., Kolchanov E.A., Mikityuk S.I., Shalamov D.V., Zhirnova N.A., Samohvalov I.M.

Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine,

Kirov Military Medical Academy, Saint Petersburg, Russia

 

Among severe combined injuries, the incidence of pelvic injuries achieves 10-42 %, including unstable pelvic injuries in 39-81.4 % [1, 2]. The mortality in patients with combined injuries and stable hemodynamics achieves 3 %. For unstable hemodynamics, it achieves 33-58 % [3, 4]. A patient with severe combined pelvic injury (CPI) and ongoing bleeding has little probability of survival without appropriate intensive care, early surgical hemostasis and adequate replacement hemotransfusion therapy.

Massive hemotransfusion therapy is accompanied by complications. So, for infusion volume > 2,000 ml, coagulopathy develops in more than 40 % of patients, > 3,000 − more than in 50 %, 4,000 ml and more − > 70% [5]. The most severe complications with blood clotting disorders in acute period of trauma include early traumatic coagulopathy (ATC), the extreme condition of which is DIC, which significantly worsens the course of traumatic disease and final prognosis [1]. In 25-35 % of cases, patients with severe combined injuries demonstrate hemostasis disorders, which often cause lethal outcomes and complications [6, 7, 8].

The factors of early traumatic coagulopathy are variable. They include excessive consumption of components of external and internal ways of hemostasis system which are used for prevention and arresting of intrapelvic bleeding, activation of coagulation cascade and fibrinolytic system due to vascular wall damage and changes relating to hypovolemia, hypothermia and acidosis [1, 9, 10]. Therefore, monitoring of hemostasis system for identification and timely correction of coagulopathy acquires high importance during process of treatment of patients with severe concomitant pelvic injuries and massive blood loss due to ongoing intrapelvic bleeding. The use of thromboelastography (TEG) allows receiving all data of all clotting phases with a single analysis, as well as indirect estimation of fibrinogen level, clot quality and lysis. In our study, we estimated the role of this technique for diagnosis and correction of hemostasis disorders in patients with severe concomitant pelvic injury with ongoing intrapelvic bleeding.

Objective − a comprehensive assessment of the blood coagulation system in patients with severe CPI and pelvic hemorrhage for the correction of transfusion therapy.

MATERIALS AND METHODS

The study materials were the data on treatment of 21 patients with severe combined pelvic injuries with intrapelvic bleeding in acute period of traumatic disease. All patients were admitted to the level 1 trauma center in 2017-2020 immediately from the accident site. The table 1 shows the structure of materials.

Table 1

Structure of studied materials, n = 21

Way of distribution, value		Characteristic
		Abs. number	%
Age, years		36.1 ± 10.6
Gender	male	18	85.7
	female	3	14.3
Injury causes:	road traffic accident	11	52.4
	falling from height	8	38.1
	compression	2	9.5
Time of delivery to trauma center	< 1 hour	11	52.4
	> 1 hour	10	47.6
	average, min	70.1 ± 4.0
SAP, mm Hg		91.8 ± 20.3
HR, beats per min		107.4 ± 21.1
Pelvic injury according to classification by М. Tile и М.Е. Muller – AO/ASIF	pelvic ring injuries	19		90.5
	acetabular fracture	2		9.5

As the table 1 shows, patients with CPI had severe and extremely severe injuries, and conditions with unfavorable prognosis. There were 18 (85.7 %) men and 3 (14.3 %) women. Among all patients with CPI, 11 patients had vertical unstable injuries (type C), 8 rotation unstable (type B) pelvic injuries and 2 complex acetabular fractures according to the classification by M. Tile and M.E. Muller − AO/ASIF (1996, 2007). A pattern of the pelvic ring injury was determined according to results of radiography and/or SCT of the pelvis.

Intrapelvic bleeding was confirmed with presence of big retroperitoneal pelvic hematoma. The incidence, location and volume of retroperitoneal pelvic hematoma was estimated with results of spiral computer tomography (SCT) of the pelvis and abdomen or intrasurgically, during laparotomy or laparoscopy. In some patients, due to severe condition and non-transportability, the assessment was realized with clinical data (subcutaneous bleedings which show the distribution of a pelvic hematoma onto the perineum, anterior abdominal wall, scrotum, vulvar lips in rectal and vaginal manual examination).

The approximate estimation of blood loss degree at admission was realized with summary assessment of the following laboratory values: proportion of the blood, hemoglobin level, hematocrit. The decreasing proportion of the blood below 1,044, hemoglobin < 70 g/l and hematocrit < 23 % were considered as acute massive blood loss with deficiency of circulating blood volume > 30 %.

Along with intrapelvic bleeding, all patients had some other life-threatening consequences of injuries, including two and more consequences in 12 (57.1 %) patients (the table 2). After admission to the anti-shock surgery unit, severity of injuries was estimated with ISS, MFS-I (MI) (Military Field Surgery - Injury (Mechanic Injury)), pathophysiological signs indicating acute massive blood loss (systolic arterial pressure, hemoglobin, platelets), changes in acid-base equilibrium and homeostasis (pH, base excess (BE) in arterial blood), coagulogram data (fibrinogen, APTT, INR). TASH score (trauma-associated severe haemorrhage) was used for estimation of probability of massive replacement hemotransfusion therapy [9].

Table 2

Structure of life-threatening consequences of injuries, n = 21, n (%)

Value	Incidence*
	Abs. number	%
Intraabdominal bleeding	4	19.0
Intrapleural bleeding	1	4.8
External bleeding	1	4.8
Oropharyngeal or nasal bleeding	1	4.8
Opened or tension pneumothorax	5	23.8
Asphyxia of various origin	2	9.5
Brain compression	1	4.8
Costal valve	1	4.8
Acute irreversible ischemia of extremity	1	4.8

Note: * – possibility of more than one life-threatening consequences of injury. 

SAP and HR were registered with Patent Monitor B30 (GE Medical Systems Inc., Germany). Clinical values of the blood were estimated with Sysmex XP-300 (Sysmex, Inc., Japan). Acid-base balance was estimated with the portable gas analyzer ABL80 FLEX (Radiometer Medical Aps., Denmark). Coagulometric values of the bleed were measured with the automatic coagulometer ACL 200 (Instrumentation Laboratory, USA) with reagents HemosIL (Instrumentation Laboratory, USA).

TEG was performed for complex estimation of hemostasis system and for substantiation of qualitative and quantitative composition of blood products for realization of replacement hemotransfusion therapy. TEG was conducted with the hemostasis analysis system TEG 5000 Thromboelastograph (Haemonetics Corporation, USA) with two samples: whole citrate blood and plasma, platelet-poor plasma (PPP).

The qualitative and quantitative composition of components of replacement hemotransfusion therapy was estimated according to TEG parameters with a sample of whole citrate blood. The time course of fibrinogen level was estimated according to TEG maximal amplitude with PPP [10]. For interpretation of graphic data of the hemostasis analyzer, five main parameters of hemocoagulation processes were measured (Fig. 1, the table 3).

Figure 1

Scheme of thromboelastogram (visual presentation of hemostasis in the patient): R – response time; K – coagulation time; α – angle constant; MA – maximal amplitude; LY30 – value of 30-minute lysis.

Table 3

Main parameters of thromboelastogram

TEG parameters	Designation	Characteristic	Reference
Response time, min.	R	It describes phases I and II of clotting or enzymatic part of coagulation cascade or response time (thrombokinase formation).	9 – 27
Coagulation time, min.	K	It characterizes phase III of clotting (thrombin formation time) and reflects time of clot formation.	2 – 9
Angle constant, degrees	α	It characterizes activity of thrombin and level of fibrinogen, and shows increasing strength of a clot.	22 – 58
Maximal amplitude, mm	MA	It shows maximal strength of a clot and characterizes the highest capture of platelets by fibrin fibers	44 – 64
Value of 30-minute lysis, %	LY30	It characterizes the process of clot dissolution − lysis.	0 – 8

All studied TEG values were estimated at admission of a patient and after surgical hemostasis and correction of replacement hemotransfusion therapy (the table 3).

The blood hypercoagulation is characterized with shortening of R and K intervals, and increasing amplitude of MA, for hypocoagulation − lengthening of R and K intervals and decreasing amplitude of MA.

The statistical analysis was conducted with Statistica 7.0 (StatSoft Inc., USA) and Microsoft Office Excel 2007. Kolmogorov-Smirnov test showed normal (5 %) or near normal (1-5 %) distribution of almost all basic values (except for ISS). Therefore, Student's test was used for analysis of differences in mean values of two groups. For ISS, Mann-Whitey's test for independent observations was used (the table 4). Paired Student's t-test was used for analysis of differences in changes in values in each group over time (tables 6, 7, 8). The probability of a difference of 95 % was considered as level of significance (p ≤ 0.05).

Table 4

Characteristics of patients' groups with various blood loss

Value, М ± Ϭ			Acute blood loss degree		(p)
			20-30% of CBV, n1= 13	More than 30% of CBV, n2= 8
Age, years			35.2 ± 9.0	32.9 ± 8.7	0.28
TASH, points			23.6 ± 2.1	25.8 ± 3.3	0.02
ISS, points			36.2 ± 6.9	43.1 ± 6.6	0.01
MPKh-P (MT) Score, points			12.5 ± 3.6	17.4 ± 2.3	0.001
Glasgow Coma Scale, points			13.1 ± 1.7	11.7 ± 2.3	0.03
Transfused blood components (day 1)	RBC suspension	doses	2.9 ± 1.0	5.6 ± 2.6	0.01
		ml	714.0 ± 256.5	1388.0 ± 652.8	0.01
	FFP	doses	2.9 ± 1.1	4.5 ± 2.1	0.04
		ml	728.3 ± 271.1	1115.3 ± 536.3	0.04
	Platelet concentrate	ml	27.7 ± 56.7	150.3 ± 113.4	0.01
	Cryoprecipitate	ml	-	195.0 ± 123.2	-

All patients were included with continuous method. All survivors gave the written consent for participation in the study.

 

RESULTS

For arresting of intrapelvic bleeding, the pelvis was fixed with external fixation device in 13 cases (Ganz frame was used in 2 cases for stabilization of posterior structures, iliosacral screws − for 8 cases). Despite of mechanic stabilization of the pelvis, extraperitoneal tamponade was used in one case, and angioembolization − in 2 cases, due to ongoing intrapelvic bleeding.

At the same time, the patients received surgical interventions for correction of life-threatening consequences of injuries in other body regions: intubation and sanitation of tracheobronchial tree for correction of asphyxia of various origin (2 cases), thoracocentesis and correction of tension pneumothorax (5 cases), decompressive cranial trepanation (1 case), thoracotomy and arresting of intrapleural bleeding (1 case), rib valve fixation (1 case).

For arresting of external bleeding, ligation of vessels in the wound of the extremity was conducted. Laparotomy for abdominal injuries was conducted in 1 case. Extensive retroperitoneal pelvic hematoma was found in all cases.

The patients with severe CPI were distributed into 2 groups according to degree of acute blood loss: 20-30 % and > 30 % of circulating blood volume (CBV) (the table 4).

The table 5 shows the scheme of replacement hemotransfusion therapy with blood products and components in dependence on TEG values of whole citrate blood (the table 5).

Table 5

Scheme of replacement hemotransfusion therapy

TEG value	Hemotransfusion therapy correction
R 11-14 min.	FFP, 10 ml/kg
R > 10 min.	FFP, 15 ml/kg
МА 40-64 mm	1 platelet concentrate
МA < 40 mm	2 platelet concentrates
К > 10 min.	FFP, 15 ml/kg
Angle α < 22о	Blood clotting factor VIII (cryoprecipitate), 1,600-2,000 U
LY30 > 10%	Fibrinolysis inhibitor (tranaxemic acid, 10 ml/kg)

The clinical blood analysis shows the changes in mean values of total blood analysis (Hb, Tr), parameters of acid-base metabolism (pH, BE) and coagulogram over time due to acute blood loss after intrapelvic bleeding in patients with severe CPI (the table 6).

Table 6

Values of clinical blood analysis and acid-base state over time of therapy of patients with severe pelvic injuries, n = 21 (M ± Ϭ) 

Value	Величина острой кровопотери Acute blood loss degree
	20-30 % ОЦК, n1 = 13 20-30 % of CBV, n1 = 13			Более 30 % ОЦК, n2 = 8 More than 30 % of CBV, n2 = 8
	исходные basic	24 ч 24 h	(p)	исходные basic	24 ч 24 h	(p)
Hemoglobin, g/l	119.5 ± 21.8	96.3 ± 7.0	0.001	80.3 ± 21.5	77.5 ± 14.8	0.31
Platelets, ×109/l	252 ± 104	146 ± 48	0.002	148 ± 94	85 ± 39	0.06
INR	1.28 ± 0.20	1.22 ± 0.13	0.76	1.44 ± 0.20	1.58 ± 0.71	0.29
APTT, sec. (25-36)	35.1 ± 14.1	30.4 ± 2.6	0.15	36.6 ± 13.1	31.1 ± 3.8	0.16
Fibrinogen, g/l	1.98 ± 0.5	4.1 ± 0.5	0.23	2.0 ± 0.8	3.6 ± 1.0	0.001
Arterial blood pH	7.26 ± 0.08	7.28 ± 0.09	0.17	7.23 ± 0.09	7.29 ± 0.02	0.13
BE deficiency, mmol/l	- 6.4 ± 2.6	-3.8 ± 3.8	0.08	- 8.2 ± 2.7	-3.9 ± 5.2	0.04

However, it was difficult to talk about complex assessment of blood clotting system. In its turn, the coagulogram values (INR, APTT, fibrinogen level) reflected only some links of hemostasis cascade or a level of some clotting factors. Therefore, along with the basic tests of the coagulogram (INR, APTT), we used TEG for estimation of the whole hemostasis system. Realization of the test for the concrete temperature of the body in a patient with severe CPI gave a possibility for the duty team of the anti-shock surgery room to perform more precise estimation of blood clotting system in the patient. As one knows, at the body temperature differing from 37°C, all phases of blood clotting pass with alternated velocity. The standard coagulogram tests were conducted at temperature of 37°C.

Considering the data of practical realization of the program for balanced and quantitative composition of blood products for replacement of acute massive blood loss due to intrapelvic bleeding, the table 7 and 8 show the increasing rate of the enzymatic part of coagulation cascade (R-value), clot strength kinetics (K-values, α-angle), increasing maximal strength clot (MA value) that indicated the correct direction of our approach for replacement hemotransfusion therapy in patients with severe combined pelvic injury.

Table 7

Parameters of thromboelastogram in time course of hemotransfusion therapy in patients with severe combined pelvic injuries with blood loss of 20-30 % of CBV, (M ± Ϭ), n = 13

Parameters	Blood samples
	Whole citrate blood			Platelet-poor plasma (PPP)
	basic	24 h	(p)	basic	24 h	(p)
Response time (R), min.	11.7 ± 3.1	13.5 ± 4.7	0.17	21.5 ± 11.7	18.3 ± 6.1	0.25
Coagulation time (K), min.	5.3 ± 2.8	4.1 ± 1.0	0.15	9.5 ± 4.7	6.0 ± 2.3	0.12
Angle α, degrees	42.8 ± 8.8	43.2 ± 6.0	0.46	29.2 ± 12.6	37.3 ± 10.6	0.08
Maximal amplitude (MA), mm	45.8 ± 19.7	60.9 ± 14.7	0.04	22.4 ± 7.3	38.0 ± 10.6	0.001
Clot lysis, %	8.5 ± 9.8	0.6 ± 0.8	0.03	0.0	1.4 ± 4.1	0.17

Table 8

Parameters of thromboelastogram in time course of hemotransfusion therapy in patients with severe combined pelvic injury with acute blood loss > 30 % of CBV, (M ± Ϭ), n = 8  

Parameters	Blood samples
	Whole citrate blood			Platelet-poor plasma (PPP)
	basic	24 h	(p)	basic	24 h	(p)
Response time (R), min.	14.6 ± 9.2	18.1 ± 10.8	0.28	11.3 ± 0.6	25.3 ± 13.2	0.06
Coagulation time (K), min.	9.1 ± 4.7	8.0 ± 7.2	0.37	14.4 ± 1.5	14.6 ± 6.6	0.22
Angle α, degrees	27.3 ± 12.6	34.1 ± 13.1	0.2	24.3 ± 4.0	21.1 ± 10.0	0.3
Maximal amplitude (MA), mm	39.9 ± 10.3	55.8 ± 15.6	0.03	31.3 ± 17.5	31.9 ± 21.1	0.48
Clot lysis, %	0.9 ± 1.9	0.2 ± 0.3	0.22	0.0	0.2 ± 0.4	-

There were not any significant differences in TEG MA in PPP in patients with deficiency of CBV > 30 % at admission and after 24 hours. For such patients, the scheme of replacement hemotransfusion therapy, which is based on TEG values of citrate blood, requires for modernization in view of increasing volume of transfused doses of platelet concentrate.

The analysis of the treatment results showed the absence of hemorrhagic complications, which could be considered as manifestations of coagulopathy, i.e. gastrointestinal bleedings, recurrent internal bleedings, pulmonary bleedings, hematuria and bleedings from injuries and surgical wounds in the studied group in the acute period of trauma. In two patients, the unfavorable course of traumatic disease resulted in lethal outcomes from complications (pneumonia and sepsis) in later period.

Clinical case

A patient, male, age of 24, fell from the third floor. He was examined after admission. The diagnosis was made: "Severe combined injury to the head, chest, spine, pelvis and extremities. Closed traumatic brain injury. Brain concussion. Closed chest injury with multiple fractures of ribs to the right. Tension right-sided pneumothorax. Lung contusion. Closed spinal injury without disorder of spinal cord conductance. Fractures of both transverse processes of L1-L3 vertebrae. A closed pelvic injury with a vertical unstable injury to pelvic ring: rupture of pubic symphysis, a fracture of left ischial bone, a middle L-shaped fracture of sacrum with transverse component at S3 level. Ongoing intrapelvic bleeding. A closed fragmented fracture of both bones of the left forearm. A closed fragmented fracture of right calcaneal bone with displaced fragments. Acute massive blood loss. Traumatic shock of degree 3".

The general condition was severe at admission. Arterial pressure was 75 and 50 mm Hg. Pulse was rhythmical (115 per minute). No consciousness. The injured pelvic ring was temporarily stabilized with anti-shock dressing. Ultrasonic abdominal study showed little amount of free fluid in hepatorenal fossa and small pelvis. Contrast SCT of abdomen and pelvis was performed after stabilization of hemodynamic values. Pelvic retroperitoneal hematoma (V~ 510 c.u. cm³) without signs of contrast extravasation was diagnosed. ISS was 34, MFS-I (MI) was 8.1 points. Diagnostic laparoscopy was conducted for exclusion of abdominal injuries. It showed a retroperitoneal pelvic hematoma extending to the level of the lower pole of kidneys.

Considering the relatively stable hemodynamic values and presence of an unstable pelvic ring injury, we conducted the combined osteosynthesis of multiple fractures of pelvic bones. The anterior pelvic structures were fixed with the external fixation apparatus, a sacral fracture − with two iliosacral cannulated screws at S1-S2 level. The external fixation apparatus was dismounted on the 2nd day, and the pubic symphysis was fixed with the plate (Fig. 2).

Figure 2

X-ray images and SCT of the patient G. before and after surgery: a) 3D-reconstruction of pelvis: pubic symphysis rupture, fracture of left ischial bone, median fracture of sacrum; b) pelvic outlet (outlet view); c) 3D-reconstruction of pelvis after osteosynthesis. 

 

The main values of laboratory analysis of the blood at admission: hemoglobin − 67 g/l, hematocrit − 20.2 %, red blood cells − 1.87 × 10¹²/l, platelets − 65 × 10⁹/l, INR − 1.71, APTT − 32.9 sec., fibrinogen − 1.7 g/l, arterial blood pH − 7.23, BE deficiency − -8.6 mmol/l. The probability of massive replacement hemotransfusion therapy was 30 points according to TASH. TEG, which was conducted at admission of the patient G. with CBV deficiency > 30 %, showed the increased response time (R, min.), decreasing maximal amplitude (MA, mm) and decreasing α-angle constant. It supposed a decreasing rate of formation of thromboplastin and density of a clot due to increased consumption of fibrinogen and platelets (Fig. 3a).

Considering the above mentioned data of TEG, replacement hemotransfusion therapy was corrected (4 doses of single-group packed red blood cells and fresh frozen plasma were transfused, as well as 10 doses of cryoprecipitate). The blood values on the next day after admission: hemoglobin − 85 g/l, hematocrit − 29.4 %, red blood cells − 2.43 × 10¹²/l, platelets − 75 × 10⁹/l, INR − -1.01, APTT − 30.5 sec., fibrinogen − 5.1 g/l, arterial blood pH − 7.38, BE deficiency − -3.1 mmol/l. 24 hours later, TEG (Fig. 3b) showed a decrease in response time (R, min.) and increasing maximal amplitude (MA, mm). It supposed right correction of acute traumatic coagulopathy. Therefore, we received the possibility to assess the efficiency of replacement hemotransfusion therapy and to determine the hemostasis links requiring for correction.

Figure 3

Thromboelastogram of the patient G.: a) at admission; b) after surgical hemostasis and correction of replacement hemotransfusion therapy.

 

On the day 12, we conducted internal osteosynthesis for fractures of left forearm and right calcaneal bone. 3 weeks after injury, the patient was allowed to stand up and walk in the ward with use of crutches. The patients was discharged from the hospital on 27th day. After 6 months, fractures of pelvic bones united, and the patient could move independently.

 

DISCUSSION

Patients with severe CPI, with signs of consumption coagulopathy due to ongoing intrapelvic bleeding, demonstrate significantly higher mortality in the acute period of trauma. Presence of traumatic coagulopathy must be identified in early period by means of specific tests (TEG rotation thromboelastometry), which are conducted immediately in the anti-shock surgery or intensive care unit [11, 12, 13, 14, 15].

As known, routine coagulometry tests allow analyzing the influence of separate clotting factors or only some separate clotting phases, but not the whole cascade of hemostasis system. So, INR parameter indicated only "the external way" of clotting, and APTT − "the internal way" (however, both values can be increased in disorders with "general" pathway), considering only activity of plasma factors of clotting without participation of platelets. In our study, besides general techniques for estimation of hemostasis (total blood analysis (hemoglobin, red blood cells), coagulogram (INR, APTT), we used thromboelastography, which gives more precise estimation of changes in hemostasis system in the body of the patient with severe API at concreted body temperature, which is important for correct interpretation of results and for accept of appropriate solution for correction of replacement hemotransfusion therapy.

 

CONCLUSION

Thromboelastography showed the increasing rate of phases of initiation and amplification (R value), kinetics of fibrin clot formation (K values, α-angle), and maximal amplitude (MA), which characterizes mechanical features of formed clot in patients with severe API. It allowed us to estimate the efficiency of replacement component hemotransfusion therapy.

TEG presents the main technique for estimation of adequacy of replacement hemotransfusion therapy, which allows correction of qualitative and quantitative composition of blood components and products.

For patients with CBV deficiency > 30 %, the scheme of replacement hemotransfusion therapy should be based on not only TEG values of whole blood, but also on platelet-poor plasma.

 

Information on financing and conflict of interests

The study was conducted without sponsorship. The authors declare the absence of any clear and potential conflicts of interests relating to publication of this article.