Teresa Kelley THE INFLUENCE ON MORBIDITY AND MORTALITY WHEN BLOOD PRODUCTS ARE TRANSFUSED USING CONVENTIONAL COAGULATION TESTS VERSUS TEG OR ROTEM IN TRAUMA PATIENTS PERIOPERATIVELY

Committee Members Dr. Alberto Coustasse, DrPH, MD, MBA, MPH Committee Chair Graduate College of Business Marshall University Dr. Priscilla Walkup CRNA, DMP Principle Investigator Charleston Area Medical Center School of Nurse Anesthesia Kathy James, CRNA Charleston Area Medical Center Health System Memorial Hospital

Background Coagulopathy in trauma patients occurs due to tissue injury The onset of coagulopathy begins with the initial tissue injury and evolves rapidly and is referred to as the acute traumatic coagulopathic phase Trauma-induced coagulopathy is due to hemodilution, infusion of hypo-coagulable blood products (e.g. packed red blood cells), acidosis, hypothermia, continued blood loss, and depletion of clotting factors Notes: -Coagulopathy occurs due to tissue injury -It begins with the initial tissue injury and evolves rapidly (this is referred to as the Acute traumatic coagulopathic phase) -Then there is trauma induced coagulopathy which is due to hemodilution, infusion of hypo-coagulable blood products such as PRBCs , it can be due to acidosis, hypothermia, hemorrhaging, and depletion of clotting factors

Background Many factors need consideration when determining resuscitative treatment for the trauma victim Amount of time for extraction from the field Transport time to a trauma center appropriate to the event Associated weather Treatment provided in route

Background Laboratory Evaluation Routine laboratory tests include: PT/INR, aPTT, and PLT function (using plasma samples) Viscoelastic laboratory tests include: TEG/ROTEM using (whole blood samples)

Introduction Deaths due to trauma are a result of hemorrhaging and are generally related to coagulopathy Laboratory test results impact the diagnosis of coagulopathy and influence the interventions needed to maintain homeostasis Research indicates that the timing of laboratory evaluation is imperative to identify the source of coagulopathy This study compares the morbidity and mortality of two laboratory pathways

Introduction Acute Traumatic Coagulopathy Includes: Protein C cleaving Factors V and VIII which are essential cofactors in the production of thrombin and fibrinous clot formation Thrombomodulin (TM) a transmembrane glycoprotein on the surface of endothelial cells and thrombin is formed locally at the site of injury, but is released systemically if there is extensive injury Systemic release produces the “Thrombin Switch” causing thrombomodulin to convert thrombin to an anticoagulant by binding to protein C and enhancing its activation 5-20 fold causing fibrinolysis

Introduction Trauma-induced Coagulopathy Includes: Hemodilution resulting from massive fluid resuscitation leading to acidosis or hemorrhaging Acidosis is considered a pH of less than 7.4 and causes an alteration in platelet formation Consumption of clotting factors results from an initial increase in coagulation Extensive endothelial damage causes a depletion of clotting factors Hypothermia is considered a body temperature below 96.8 F or 36 C: Decreases thrombin production and increases the time of clot formation

Literature Review Conventional Laboratory Tests Conventional laboratory tests are insufficient to determine the probability of bleeding and only evaluates less than a minute of the initial clot formation (Chowdhury et al., 2004) Conventional assays are performed on platelet reduced plasma and cannot evaluate the clot strength which can produce negative results (Simmons et al., 2014) Conventional laboratory tests are used to analyze bleeding disorders such as PT/INR, aPTT, and PLT function. Enhanced knowledge of the clotting cascade provides a better understanding of the function at the cellular level of WBC, RBC, and platelets (Chitlur et al., 2011) Conventional laboratory tests use plasma and does not include platelets or cellular elements (Da Luz et al., 2013) Literature Review shows that Conventional Laboratory Tests are: - insufficient to determine the probability of bleeding and only evaluates less than a minute of the initial clot formation - also they are performed on platelet reduced plasma or cellular elements and cannot evaluate the clot strength which can produce negative results - Finally, conventional laboratory tests are used to analyze bleeding disorders such as PT/INR, aPTT, and PLT function and enhanced knowledge of the clotting cascade provides a better understanding of the function at the cellular level which include the WBC, RBC, and platelets

Literature Review TEG or ROTEM Whole Blood Assay Data indicates that TEG/ROTEM viscoelastic whole blood assays identify and distinguish which type of coagulopathy is present (Ostrowski et al., 2011) Viscoelastic whole blood assays have been used to direct and monitor transfusion interventions in hemorrhaging trauma patients. TEG is specifically responsive to shifts in fibrin and platelet function. It is beneficial for the initial discovery of trauma or perioperative related changes and defects in the body’s blood clotting ability. Thromboelastography provides immediate results of clot strength and reliable data on coagulation activity, and executes target-directed transfusion treatment for trauma patients (Bollinger et al., 2012) The Literature review states that TEG or ROTEM whole blood assays: - Provide data that identifies and distinguishes which type of coagulopathy is present - These assays have been used to direct and monitor transfusion interventions in hemorrhaging trauma patients - Research shows that TEG and ROTEM is specifically responsive to shifts in fibrin and platelet function and is also beneficial for the initial discovery of trauma or perioperative related changes and defects in the body’s blood clotting ability - Finally, TEG and ROTEM provides immediate results of clot strength and coagulation activity

Hypothesis The working hypothesis for this study was trauma patients who received blood transfusions guided by TEG/ROTEM whole blood assays received fewer blood products and had a decreased morbidity and mortality rate than those who received blood transfusions guided by Conventional Coagulation tests

Research Design Retrospective, Case-Control Study This study was chosen because data was available from the trauma registry within the Charleston Area Medical Center (CAMC) where patient records could be accessed This design allowed for the comparison of the morbidity and mortality rate of the Conventional Coagulation tests vs TEG or ROTEM whole blood assays and statistical analysis of those laboratory pathways

Study Setting Charleston Area Medical Center (CAMC) General Hospital in West VA CAMC serves as a Level I trauma center and provides trauma services to over 3,000 patients annually

Sample Population A review of medical records was performed on adult trauma patients at CAMC General Hospital who required blood transfusions due to blunt force trauma or penetration to the abdomen between the dates of January 1, 2006 and August 31, 2016 A total of 136 patients were selected: 43 patients received the ROTEM whole blood assay (case group) 93 patients received the Conventional Coagulation test (control group) The Sample population consisted of a total of 136 patients where: -ROTEM was performed on 43 patients and was considered the case group -And Conventional Coagulation tests were performed on 93 patients and was the control group

Inclusion Criteria Male or female 18 years of age or older Patients involved in blunt force trauma or penetration to the abdominal cavity and admitted to the CAMC General Hospital Trauma Center Emergency Department Trauma patients designated as Priority (P1) or Priority (P2)

Exclusion Criteria Patients younger than 18 years of age Any patient undergoing elective surgery Any patient considered non-trauma

Independent and Dependent Variables Independent variables: Baseline Labs (TEG or ROTEM whole blood assays or Conventional Coagulation tests) The number of Blood products transfused Age Gender Body Mass Index (BMI) Injury Severity score (ISS) Dependent variables: Morbidity (CHF or Pulmonary Edema) Mortality rate

Data Collection This study was a retrospective investigation of existing data utilizing the patient’s Electronic Medical Records through Sorian (EMR) Each patient was given a number, letter, or both categorizing the data as it was collected and safeguarded the patient’s identification This data came from emergency department records, anesthesia records, and other units at CAMC where patients received care during their hospital stay The demographic and clinical information obtained included: Age, ISS, BMI, TEG or ROTEM whole blood assay test results, Conventional Coagulation test results, length of stay (LOS), morbidities (CHF or Pulmonary Edema), and mortality rate

Results The results indicated that the mortality rate was higher among the ROTEM group 9 (20.9%) compared to 8 (8.6%) in the Conventional group and was found to be statistically significant with (p<0.05) Clinical significance could not be determined due to: The limited amount of ROTEM cases (43) compared to Conventional Coagulation Cases (93)

Results The following mean for ISS is 26.29, BMI 28.68, Age 43.15, Number of blood products transfused 20.36, and LOS in the hospital was 19.8 days Of the 136 patients, 101 (74.1%) were male, 35 (25.9%) were female, 4 (2.9%) developed CHF, 12 (8.8%) developed pulmonary edema and the mortality rate was 17 (12.5%)

Conventional Coagulation Test Table 1: Demographic and Clinical Characteristics of Adult Trauma Patients who received Blunt Force Trauma or Penetration to the Abdomen   Variable Total Sample Study Groups Statistical Value  Total N=136 Mean (SD) TEG/ROTEM Whole Blood Assay N=43 (31.6%) Mean (SD) Conventional Coagulation Test N=93 (68.4%) p-Value Age (years)  43.15(18)  44.56(20)  42.49(16.9)  NS Gender N (%) Male (1) Female (2)  100(74.1%) 36 (25.9%)  30 (69.8%) 13 (30.2%)  71 (76.3%) 22 (23.7%) NS Mortality N (%) 1- 118 (86.8%) 2- 17 (12.5%) 1- 34 (79.1%) 2- 9 (20.9%) 1- 85 (91.4%) 2- 8 (8.6%) 0.043* Pulmonary Edema 12 (8.8%) 4 (9.3%)   8(8.6%) CHF N(%) 4(2.9%) 1(2.3%) 3(3.2%)

Table 1: Demographic and Clinical Characteristics of Adult Trauma Patients who received Blunt Force Trauma or Penetration to the Abdomen   Variable Total Sample Study Groups Statistical Value  Total N=136 Mean (SD) TEG/ROTEM Whole Blood Assay N=43 (31.6%) Mean (SD) Conventional Coagulation Test N=93 (68.4%) p-Value ISS  26.29 (12.1)  22.95 (11.5)  27.83 (12.1)  NS BMI (kg/m2)  28.68 (11)  30.12 (17.5)  28.01 (16.9) Hospital LOS (days)  19.81(24.64)  18.51 (4.13)  20.41(62.4) Number of Blood Products  20.36 (34.94)  28.28(51.4)  16.70(23.3)

Table 2: Fisher’s Exact Test Comparing ROTEM and Conventional Coagulation tests with Pulmonary Edema   Value df Asymp. Sig. (2-sided) Exact Sig. (1-sided) Pearson Chi-Square 0.018 1 0.894 Continuity Correction 0.000 1.000 Likelihood Ratio Fisher's Exact Test 0.562 Linear-by-Linear Association 0.18 N of Valid Cases 136

Table 3: Fisher’s Exact Test Comparing ROTEM and Conventional Coagulation Tests with CHF   Value df Asymp. Sig. (2-sided) Exact Sig. (1-sided) Pearson Chi-Square 0.083 1 0.773 Continuity Correction 0.000 1.000 Likelihood Ratio 0.087 0.768 Fisher's Exact Test 0.623 Linear-by-Linear Association 0.83 N of Valid Cases 136

Table 4: Pearson Chi-Square Analysis of the ROTEM (case group) and the Mortality rate   Value df Asymp. Sig. (2-sided) Exact Sig. (1-sided) Pearson Chi-Square 4.086 1 *0.043 Continuity Correction 3.036 0.081 Likelihood Ratio 3.819 0.051 Fisher's Exact Test 0.054 0.044 N of Valid Cases 136

Table 5: T-test Analysis comparing LOS between ROTEM Whole Blood Assay and Conventional Coagulation Tests TEG/ROTEM Whole Blood Assay    N Mean Std. Deviation Std. Error Mean Length of Stay (LOS) 0 1 93 43 20.41 18.51 23.91 26.42 2.48 4.03 

Table 6: Logistic Regression Analysis Comparing ROTEM with Mortality among Adult Trauma Patients Who Received Blood Products Following a Traumatic Blunt Force or Penetration to the Abdomen B S.E. Wald df Sig. Age 0.010 0.015 0.454 1 NS Gender 0.578 0.579 0.997 BMI 0.038 0.030 1.645 ISS -0.002 0.026 0.009 TEG/ROTEM 0.843 0.569 2.193 # Of Blood Products 0.005 0.007 0.589 Constant -4.665 1.482 9.915

Table 7: Logistic Regression Analysis Comparing ROTEM with Congestive Heart Failure (CHF) among Adult Trauma Patients Who Received Blood Products Following a Traumatic Blunt Force or Penetration to the Abdomen   B S.E. Wald df Sig. Age 0.213 0.109 3.823 1 NS Gender 1.572 1.629 0.931 BMI -0.089 0.125 0.515 ISS -0.280 0.200 1.960 TEG/ROTEM -2.869 2.130 1.815 # Of Blood Products 0.034 0.993 Constant -11.378 6.259 3.305

Table 8: Logistic Regression Analysis Comparing ROTEM with Pulmonary Edema among Adult Trauma Patients Who Received Blood Products Following a Traumatic Blunt Force or Penetration to the Abdomen   B S.E. Wald df Sig. Age 0.009 0.018 0.277 1 NS Gender 0.439 0.675 0.422 BMI 0.016 0.019 0.654 ISS 0.040 0.027 2.100 TEG/ROTEM 0.045 0.738 0.004 # Of Blood Products 0.007 0.322 Constant -5.049 1.572 10.322

Discussion The use of ROTEM for trauma patients at CAMC began in 2014 This study presented 43 ROTEM cases for comparison and 93 Conventional Coagulation cases

Discussion Comparison of the case-control groups did not show a statistical significance between the independent variables and ISS, Age, BMI, Hospital LOS, or Number of blood products given with a (p>0.05). Comparison of case-control groups did not show a statistical significance between the independent variables and gender, Abbreviated Injury Scale (AIS), or Priority level with a (p>0.05)

Discussion Research showed that whole blood assay tests provided personalized therapy according to the needs of the trauma patient in contrast to the predetermined protocol of dispensing allogenic blood products The individualized care decreased the risks of underestimating or overestimated the number of blood products needed This present study revealed a statistical significance between the mortality rate and the ROTEM group indicating a higher percentage compared to the control group It is difficult to determine if there is clinical significance due to the limitations of this study and the limited number of cases to support ROTEM use

Discussion Therefore, there was not a sufficient sample size to support the hypothesis for this study Research has shown that TEG or ROTEM have been recommended as a point of care for trauma patients and more facilities need to be trained how to use, calibrate, and understand the specialized variances in performing the test

Limitations 1st - A limited number of ROTEM cases for adequate comparison 2nd - The ROTEM cases that were found also included conventional coagulation tests results and provided no indication as to which test the interventions were prescribed 3rd - Finally, Unknown preexisting co-morbidities or prescribed medications could influence the treatment and outcome of trauma patients perioperatively

Implications and Recommendations Future research needs to be conducted at CAMC General Hospital on the use of ROTEM whole blood assay tests once sufficient time has passed and enough ROTEM data is available for collection Also, a prospective study could be done as ROTEM whole blood assay is being used for trauma cases to determine if there is clinical significance between the two laboratory pathways and the interventions provided

Implications and Recommendations Next, several studies on ROTEM use should be conducted to include a detailed prediction of the type and number of blood products to be given according to the ROTEM algorithm and the outcomes compared with Conventional Coagulation tests Finally, another study should be conducted comparing the timing of the TEG or ROTEM results provided for trauma patients with that of the timing of Conventional Coagulation tests results

Conclusion In this present study, clinical significance could not be determined, supporting the hypothesis, due to the limited number of ROTEM cases available Statistical significance was found between the mortality rate and the case group indicating a higher percentage with a (p<0.05) Conclusion: To restate that in this present study, clinical significance could not be determined supporting the hypothesis, due to the limited number of ROTEM cases available But, Statistical significance was found between the mortality rate and the case group indicating a higher percentage with a p value of <0.05

This is an example of how TEG and ROTEM present the normal levels of clotting time, formation, and strength

This is an example of a TEG and ROTEM graph as the clot is forming

And Finally, this is an example of an algorithm for TEG and ROTEM and the interventions needed according to the results of the test

Questions?