Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma: A prospective cohort study

Myung (Michelle) S Park, Grant M. Spears, Kent R Bailey, Ailing Xue, Michael J. Ferrara, Amy Headlee, Sabtir K. Dhillon, Donald H. Jenkins, Scott P. Zietlow, William S. Harmsen, Aneel Arjun Ashrani, John A. Heit

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Abstract

BACKGROUND: Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. METHODS: In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011-2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at -80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95% CI). RESULTS: Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). CONCLUSION: The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE. LEVEL OF EVIDENCE: III (Diagnostic test or Criteria)

Original languageEnglish (US)
JournalJournal of Trauma and Acute Care Surgery
DOIs
StateAccepted/In press - Mar 30 2017

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Venous Thromboembolism
Thrombin
Cohort Studies
Prospective Studies
Wounds and Injuries
Thrombin Time
Phlebotomy
Patient Admission
Thromboplastin
Proportional Hazards Models
Routine Diagnostic Tests
General Anesthesia
Phospholipids
Body Mass Index
Blood Platelets
Biomarkers
Mortality

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma : A prospective cohort study. / Park, Myung (Michelle) S; Spears, Grant M.; Bailey, Kent R; Xue, Ailing; Ferrara, Michael J.; Headlee, Amy; Dhillon, Sabtir K.; Jenkins, Donald H.; Zietlow, Scott P.; Harmsen, William S.; Ashrani, Aneel Arjun; Heit, John A.

In: Journal of Trauma and Acute Care Surgery, 30.03.2017.

Research output: Contribution to journalArticle

Park, Myung (Michelle) S ; Spears, Grant M. ; Bailey, Kent R ; Xue, Ailing ; Ferrara, Michael J. ; Headlee, Amy ; Dhillon, Sabtir K. ; Jenkins, Donald H. ; Zietlow, Scott P. ; Harmsen, William S. ; Ashrani, Aneel Arjun ; Heit, John A. / Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma : A prospective cohort study. In: Journal of Trauma and Acute Care Surgery. 2017.
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abstract = "BACKGROUND: Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. METHODS: In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011-2015. Blood was collected by venipuncture into 3.2{\%} trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at -80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95{\%} CI). RESULTS: Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71{\%} male, 96{\%} with blunt mechanism, mortality 3.2{\%}), 83 developed symptomatic VTE within 92 days after injury (35 [42{\%}] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). CONCLUSION: The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE. LEVEL OF EVIDENCE: III (Diagnostic test or Criteria)",
author = "Park, {Myung (Michelle) S} and Spears, {Grant M.} and Bailey, {Kent R} and Ailing Xue and Ferrara, {Michael J.} and Amy Headlee and Dhillon, {Sabtir K.} and Jenkins, {Donald H.} and Zietlow, {Scott P.} and Harmsen, {William S.} and Ashrani, {Aneel Arjun} and Heit, {John A.}",
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T1 - Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma

T2 - A prospective cohort study

AU - Park, Myung (Michelle) S

AU - Spears, Grant M.

AU - Bailey, Kent R

AU - Xue, Ailing

AU - Ferrara, Michael J.

AU - Headlee, Amy

AU - Dhillon, Sabtir K.

AU - Jenkins, Donald H.

AU - Zietlow, Scott P.

AU - Harmsen, William S.

AU - Ashrani, Aneel Arjun

AU - Heit, John A.

PY - 2017/3/30

Y1 - 2017/3/30

N2 - BACKGROUND: Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. METHODS: In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011-2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at -80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95% CI). RESULTS: Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). CONCLUSION: The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE. LEVEL OF EVIDENCE: III (Diagnostic test or Criteria)

AB - BACKGROUND: Reliable biomarkers predictive of venous thromboembolism (VTE) after acute trauma are uncertain. The objective of the study was to identify risk factors for symptomatic VTE after trauma, including individual plasma coagulome characteristics as reflected by thrombin generation. METHODS: In a prospective, case-cohort study, trauma patients were enrolled over the 4.5 year period, 2011-2015. Blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24 and 72 hours after injury, and at hospital discharge. Platelet poor plasma was stored at -80°C until analysis. Thrombin generation, as determined by the calibrated automated thrombogram (CAT) using 5 pM tissue factor (TF)/4 uM phospholipid (PS), was reported as peak height (nM thrombin) and time to peak height (ttPeak [minutes]). Data are presented as median [IQR] or hazard ratio (HR) with (95% CI). RESULTS: Among 453 trauma patients (ISS=13.0 [6.0, 22.0], hospital LOS=4.0 [2.0, 10.0] days, age=49 [28, 64] years, 71% male, 96% with blunt mechanism, mortality 3.2%), 83 developed symptomatic VTE within 92 days after injury (35 [42%] after hospital discharge). In a weighted, multivariate Cox model that included clinical and CAT characteristics available within 24 hours of admission, increased patient age (1.35 [1.19,1.52] per 10 years, P<0.0001), body mass index (BMI) ≥ 30 kg/m (4.45 [2.13,9.31], p <0.0001), any surgery requiring general anesthesia (2.53 [1.53,4.19], P=0.0003) and first available ttPeak (1.67[1.29, 2.15], p <0.00001) were independent predictors of incident symptomatic VTE within 92 days after trauma (C-statistic=0.799). CONCLUSION: The individual’s plasma coagulome (as reflected by thrombin generation) is an independent predictor of VTE after trauma. Clinical characteristics and ttPeak can be used to stratify acute trauma pts into high and low risk for VTE. LEVEL OF EVIDENCE: III (Diagnostic test or Criteria)

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