Nghiên cứu tình trạng đông cầm máu và giá trị xét nghiệm rotem (rotation thromboelastometry) trong định hướng xử trí rối loạn đông máu ở bệnh nhân đa chấn thương ttta

HANOI MEDICAL UNIVERSITY TRẦN THỊ HẰNG STUDY OF COAGULATION AND TEST VALUE OF ROTEM ROTATION THROMBOELASTOMETRY IN THE MANAGEMENT OF COAGULATION DISORDER FOR PATIENTS WITH MULTIPLE TRA

HANOI MEDICAL UNIVERSITY

TRẦN THỊ HẰNG

STUDY OF COAGULATION AND TEST VALUE OF ROTEM (ROTATION THROMBOELASTOMETRY) IN THE MANAGEMENT OF COAGULATION DISORDER FOR

PATIENTS WITH MULTIPLE TRAUMA

Major : Hematology – Blood transfusion

Major Id : 9720107

MEDICAL DOCTORAL THESIS SUMMARY

HÀ NỘI - 2023

Supervisors:

1 Assoc Prof Phd Nguyen Thi Nu

2 Professor Phd Trinh Hong Son

1 Trần Thị Hằng et al Kiểm soát rối loạn đông máu dựa trên

kết quả xét nghiệm đàn hồi co cục máu ở bệnh nhân chấn

thương Journal of Practical Medicine, Vol February 2017,

1035, 34-39

2 Trần Thị Hằng et al Khảo sát tình trạng rối loạn đông máu

trên bệnh nhân đa chấn thương tại Bệnh viện Hữu Nghị Việt

Đức Vietnam Medical Journal, special issue, May 2018, 467,

766-772

3 Trần Thị Hằng et al Đặc điểm xét nghiệm đông máu thường

quy và ROTEM ở bệnh nhân đa chấn thương tại thời điểm

nhập viện Version B of Vietnam Science and Technology

Magazine, September 2021, 63(9)

4 Trần Thị Hằng et al Vai trò ROTEM trong chẩn đoán rối

loạn đông máu và dự đoán nhu cầu truyền máu ở bệnh nhân đa

chấn thương Vietnam Medical Journal, special issue,

November 2022, 520, 102-117

INTRODUCTION

Multiple trauma is a very serious surgical emergency with a high mortality rate Mortality in patients with multiple trauma due to many different causes, of which, death due to blood loss is a major cause, ranking second only to severe traumatic brain injury Bleeding in trauma patients may be directly due to large vessel lesions, which require surgical intervention to stop bleeding This may also be due to disturbances in the coagulation process Coagulation disorder (coagulopathy)

in patients with multiple trauma is a complex complication that is the result of many different factors In recent years, although there have been many advances in resuscitation of patients with multiple trauma, coagulation disorder in these patients still exists as a major challenge for surgeons as well as resuscitation anesthesiologists

Rotem test using whole blood can quickly identify the patient's coagulation disorder and guide the treatment of coagulation disorders This test has been used

in cardiovascular surgery, liver transplantation and has recently begun to be used in treatment of trauma However, there are not many studies on the threshold test values in the diagnosis of coagulation disorder, blood transfusion guidelines and

mortality risk prediction “The study of haemostasis and test value of ROTEM (rotation thromboelastometry) in the management of coagulation disorder for patients with multiple trauma" is implemeted with 2 main objectives:

1 Description of coagulation and some related factors in multi-trauma patients

2 Evaluation of the value of ROTEM test in guiding early management of coagulation disorder and some prognostic factors in patients with multiple trauma

Thereby, the study will provide more scientific information for doctors to use as a basis for assessing the status of coagulation disorders, and in order to properly prescribe blood transfusions and blood products

The urgency of the study

Coagulation is a common complication of multiple trauma These disorders aggravate the patient's condition, increasing the mortality rate The rapid, timely and accurate investigation of these disorders not only helps to decrease blood loss, decrease mortality At the same time, it helps surgeons prepare timely and conduct surgery safer for patients, avoiding bleeding complications during and after surgery However, the common coagulation tests used in medical facilities are first line coagulation test, including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) With these indicators, only basic disorders are investigated, in theory and practice, sometimes they do not evaluate all possible disorders in the patient's body This can result in missed lesions as well as affect the surgical preparation process Therefore, research on application of Rotem test in guiding the management of coagulation disorder in patients with multiple trauma is essential to save and cure patients especially in emergency situations and in surgery

New contributions of the study

This is the first study in Vietnam that provides some dysfunctional thresholds

of Rotem parameters in the decision to transfuse blood products In addition, the study also demonstrates the role of Rotem parameters in the indications for large-volume transfusion and mortality prognosis in patients with multiple trauma

The study has described the picture of coagulation disorder in patients with multiple trauma, with 54.9% of patients having coagulation disorders, mainly thrombocytopenia, prolonged PT, and decreased fibrinogen Research results also show that there are many factors related to coagulation disorder in patients with multiple trauma such as number of damaged organs, degree of injury, degree of blood loss

Layout of study

The thesis consists of 123 pages, 49 tables, 11 charts, 3 diagrams, 3 figures and

149 references Including 1 pages of problem statement, 33 pages about overview, 21 pages regarding object and methods, 65 pages research results and discussion, and about 2 pages of conclusions and recommendations

CHAPTER 1 LITERATURE REVIEW 1.1 Multiple trauma

* Definition

Multiple traumas means having several serious injuries from something like

a fall, an attack, or a crash The injuries could cause severe bleeding or break large bones They might include damage to the brain or to organs such as the lungs or spleen

* Assess severity of injury

Injury Severity Score (ISS) was developed by Baker et al., based on the Abbreviated Injury Scale (AIS) Over the years, the ISS scale has been revised and completed many times Up to now, the ISS scale is still the most used scale in assessing severity in patients with multiple trauma

1.2 Trauma-induced coagulation disorder (coagulopathy in patients with multiple trauma)

The pathogenesis of coagulation disorder in patients with multiple trauma is complex and often involves a combination of factors:

- Main factor: due to the massive release of plasminogen-activating factors from damaged tissues causing activation of coagulation and excessive fibrin consumption

detecting abnormalities in coagulation, the next test can be carried out quickly to determine the components and factors causing the abnormality, helping to effectively target treatment

* Method application

- Over the world

Thromboelastography (TEG) was first applied in the world in 1942 during World War II After a period of widespread application in the 1950s and 1960s, interest in TEG declined in the 1970s because the classical TEG method took too long (about 120 minutes) and the technique was gradually replaced by other coagulation analysis techniques However, in the 1980s, the TEG method was revived, especially in the United States, because it was then that the limitations of other methods of coagulation analysis were recognized In 1993, the ROTEM® Thromboelastometry system was produced to replace the manual method and up to now, Thromboelastography has become one of the routine and mandatory clinical tests in many fields, especially: Cardiovascular surgery, multi-traumatic surgery, liver transplant, obstetrics, in many advanced countries in the world such as Japan, USA, etc Currently, there are more than 2500 laboratories around the world using ROTEM® method

prognosis

CHAPTER 2 RESEARCH SUBJECTS AND METHODS

2.1 Research subjects: 297 patients who were diagnosed with multiple trauma at

Viet Duc Hospital

2.2 Duration: 2017 to 2021

2.3 Research method:

2.3.1 Research design: Descriptive cross-sectional study

2.3.2 Research variables

2.3.2.1 Variables assessing routine coagulation changes: PT, APTT, fibrinogen,

platelet count, d-dimer

2.3.2.1 Coagulation parameters variables according to Rotem: includng 3 tests

Intem, Extem, Fibtem with the indicators: CT, A5, A10, MCF, CFT

2.3.2.2 Variables assessing the association with coagulation disorder:

Age, sex, cause of accident, degree of blood loss, number of damaged organs, location of damaged organs, severity of injury, level of blood transfusion

2.3.2.3 Variables related to predictive value of coagulation disorder: using the

threshold of coagulation disorder with indication for blood transfusion according to the European guidelines 2019 to determine the cut-off point, sensitivity, specificity, area under the ROC curve of Rotem test indices

2.3.2.4 Variables associated with predictive value of massive blood transfusion: determine the cut-off point, sensitivity, specificity, area under the ROC

curve of the Rotem indexes based on the rate of large volume of blood transfusion

2.3.2.5 Variables related to mortality predictive value: determine the cut-off

point, sensitivity, specificity, area under the ROC curve of Rotem indices based on mortality

2.3.3 Method of data analysis Univariate and multivariate analysis The data

were processed using the statistical software SPSS 16.0 Using statistical tests commonly used in research

CHAPTER 3 RESEARCH RESULTS 3.1 Sociodemographic characteristics

Table 3.1 Characteristics of age and gender

Traffic accidents are the leading cause of injuries, accounting for 59% of the cause of trauma, followed by occupational accidents and every-day life accidents

with the rate of 20.5%

3.3 Prevalence of coagulation disorder according to baseline coagulation test

Table 3.2 Prevalence of coagulation disorder according to baseline coagulation test

3.4 Prevalence of coagulation disorder according to ROTEM

Table 3.3 Prevalence of coagulation disorder according to ROTEM

Fibrinogen and decreased PT with the rate of 27.7% and 15.9%, respectively The

lowest was a decrease APPT by 7.2%

3.5 Association of coagulation disorder and the number of damaged organs

Table 3.4 The association of coagulation disorder and the number of damaged

3 (n=104)

≥ 4 (n=37)

- The rate of disorders of the indicators of coagulation disorder increased

gradually according to the number of damaged organs

- There is an association between decreased PT%, Fibrinogen and decreased platelet count with the number of damaged organs, p<0.05

3.6 Association between coagulation disorder and injury severity

Figure 3.5 Association between coagulation disorder and injury severity

Severe (n=139)

The rate of coagulation disorder increases with the severity of the injury, there

is an association between PT% reduction with the severity of injury, the risk of

PT% reduction increases 3.5 times in the Profound trauma group compared with the Severe trauma group, the result is significant with p<0.05

3.7 Association between coagulationdisorder and degree of blood loss

Table 3.6 Association between coagulationdisorder and degree of blood loss

Coagulation test

indicator

Degree of blood loss

p Class I

(n=101)

Class II (n=87)

Class III (n=71)

Class IV (n=38)

- The rate of coagulation disorder increases with the degree of blood loss

- There is an association between decreased PT% and decreased platelet count with the degree of blood loss, the result is significant with p<0.01

3.8 Association between large volume blood transfusion and coagulation

- The rate of coagulation disorder increases when patients receive massive blood transfusions, especially PT%, Fibrinogen and platelet counts

- There is an association between decreased PT%, decreased Fibrinogen and decreased platelet count with massive blood transfusions

- The risk of decreased PT%, decreased Fibrinogen and decreased platelet count increased by 5.1; 3.8 and 12.1 when the patient had a massive blood transfusion, statistically significant with p<0.01

3.9 Multivariate analysis and coagulation disorder

Table 3.8 Multivariate analysis and coagulation disorder

Associate factors Odds ratio

(OR)

Confidence interval (CI) (95%)

p

Massive blood transfusion 3.7 1.04 – 13.5 <0.05

The degree of blood loss and massive blood transfusion are two independent

factors leading to coagulation disorders in multi-trauma patients with OR of 5.8 and 3.7 with CI 2.39 – 14.83 and 1.04 – 13.5 respectively, statistically significant

with p < 0.05

3.10 Coagulation disorder’s predictive value of ROTEM parameters

according to blood transfusion thresholds

Table 3.9: Coagulation disorder’s predictive value of ROTEM parameters

according to blood transfusion thresholds

Status Predictive value Rotem

parameters

Sensitivity (%)

A5Ex ≤ 33 mm 100,0 71,0 0,910 < 0,01 A5In ≤ 32 mm 100,0 72,0 0,914 < 0,01 Platelet <100

G/L (n = 17)

A5Ex ≤ 34 mm 81,3 75,6 0,837 < 0,001 A5In ≤ 33mm 81,3 76,6 0,831 < 0,001

Low Fibrinogen

Fibrinogen

< 1,0 g/L (n = 14)

A5Fib ≤ 6 mm 100,0 74,6 0,943 < 0,01 A10Fib ≤ 7 mm 100,0 72,8 0,942 < 0,01 A5Ex ≤ 30 mm 100,0 79,8 0,950 < 0,01 A10Ex ≤ 42 mm 100,0 78,1 0,945 < 0,01

Fibrinogen

< 1,5 g/L (n = 23)

A5Fib ≤ 6 mm 95,0 83,2 0,950 < 0,01 A10Fib ≤ 7 mm 95,0 81,2 0,957 < 0,01 A5Ex ≤ 33 mm 90,0 81,2 0,920 < 0,01 A10Ex ≤ 44 mm 95,0 77,2 0,925 < 0,01

Figure 3.2: ROC Curve of Extem parameters predicts INR > 1.5

ROC Curve predict Platelet < 50 g/L ROC Curve predict Platelet < 100 g/L

Figure 3.3: ROC Curve of Extem parameters predicts Platelet count

ROC curve predicts fibrinogen <1,0

g/L

ROC curve predicts fibrinogen <1,5 g/L

Figure 3.4: ROC Curve of Extem parameters predicts fibrinogen

The thresholds for predicting coagulation disorder of ROTEM parameters according to blood transfusions have high sensitivity and specificity: The threshold for predicting decreased PT (INR > 1.5) of CFT Extem is 170 mm and

of A5 Extem is 30 mm; The threshold for predicting Platelet count < 50 G/L of A5 Extem is 33 mm and A5 Intem is 32 mm; The threshold for predicting Platelet count < 100 G/L of A5 Extem is 34 mm and A5 Intem is 33 mm; The predicted threshold for fibrinogen < 1.0 g/L of A5 Extem is 30 mm, A10 Extem is 42 mm, A5 Fibtem is 6 mm and A10 Fibtem is 7 mm; The predicted threshold for fibrinogen < 1.5 g/L of A5 Extem is 33 mm, A10 Extem is 44 mm, A5 Fibtem is

6 mm and A10 Fibtem is 7 mm