Thrombin generation and procoagulant microparticle profiles after acute trauma

A prospective cohort study

Myung (Michelle) S Park, Ailing Xue, Grant M. Spears, Timothy M. Halling, Michael J. Ferrara, Melissa M. Kuntz, Sabtir K. Dhillon, Donald H. Jenkins, William S. Harmsen, Karla V. Ballman, Paul Harrison, John A. Heit

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

OBJECTIVE The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma. METHODS Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]). RESULTS Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days. CONCLUSION Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters. LEVEL OF EVIDENCE Epidemiologic study, level III.

Original languageEnglish (US)
Pages (from-to)726-731
Number of pages6
JournalJournal of Trauma and Acute Care Surgery
Volume79
Issue number5
DOIs
StatePublished - Nov 1 2015

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Thrombin
Cohort Studies
Prospective Studies
Wounds and Injuries
Length of Stay
Thrombin Time
Injury Severity Score
Phlebotomy
Venous Thromboembolism
Epidemiologic Studies
Healthy Volunteers
Flow Cytometry
Hospitalization
Blood Platelets
Hemorrhage
Mortality

Keywords

  • cohort
  • microparticle
  • prospective
  • thrombin
  • Trauma

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Surgery

Cite this

Thrombin generation and procoagulant microparticle profiles after acute trauma : A prospective cohort study. / Park, Myung (Michelle) S; Xue, Ailing; Spears, Grant M.; Halling, Timothy M.; Ferrara, Michael J.; Kuntz, Melissa M.; Dhillon, Sabtir K.; Jenkins, Donald H.; Harmsen, William S.; Ballman, Karla V.; Harrison, Paul; Heit, John A.

In: Journal of Trauma and Acute Care Surgery, Vol. 79, No. 5, 01.11.2015, p. 726-731.

Research output: Contribution to journalArticle

Park, MMS, Xue, A, Spears, GM, Halling, TM, Ferrara, MJ, Kuntz, MM, Dhillon, SK, Jenkins, DH, Harmsen, WS, Ballman, KV, Harrison, P & Heit, JA 2015, 'Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study', Journal of Trauma and Acute Care Surgery, vol. 79, no. 5, pp. 726-731. https://doi.org/10.1097/TA.0000000000000839
Park, Myung (Michelle) S ; Xue, Ailing ; Spears, Grant M. ; Halling, Timothy M. ; Ferrara, Michael J. ; Kuntz, Melissa M. ; Dhillon, Sabtir K. ; Jenkins, Donald H. ; Harmsen, William S. ; Ballman, Karla V. ; Harrison, Paul ; Heit, John A. / Thrombin generation and procoagulant microparticle profiles after acute trauma : A prospective cohort study. In: Journal of Trauma and Acute Care Surgery. 2015 ; Vol. 79, No. 5. pp. 726-731.
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abstract = "OBJECTIVE The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma. METHODS Whole blood was collected by venipuncture into 3.2{\%} trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]). RESULTS Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7{\%} male; 95{\%} with blunt mechanism; mortality, 3.2{\%}), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5{\%}) values reflecting a possible {"}hypercoagulable state{"} (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible {"}hypocoagulable state{"} (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days. CONCLUSION Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters. LEVEL OF EVIDENCE Epidemiologic study, level III.",
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AU - Xue, Ailing

AU - Spears, Grant M.

AU - Halling, Timothy M.

AU - Ferrara, Michael J.

AU - Kuntz, Melissa M.

AU - Dhillon, Sabtir K.

AU - Jenkins, Donald H.

AU - Harmsen, William S.

AU - Ballman, Karla V.

AU - Harrison, Paul

AU - Heit, John A.

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N2 - OBJECTIVE The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma. METHODS Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]). RESULTS Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days. CONCLUSION Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters. LEVEL OF EVIDENCE Epidemiologic study, level III.

AB - OBJECTIVE The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma. METHODS Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]). RESULTS Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days. CONCLUSION Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters. LEVEL OF EVIDENCE Epidemiologic study, level III.

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