Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis

R W G Dujardin; D J B Kleinveld; C E van den Brom; L M G Geeraedts; E Beijer; C Gaarder; K Brohi; S Stanworth; P I Johansson; J Stensballe; M Maegele; N P Juffermans

doi:https://doi.org/10.1097/TA.0000000000004235

Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis

R W G Dujardin, D J B Kleinveld, C E van den Brom, L M G Geeraedts, E Beijer, C Gaarder, K Brohi, S Stanworth, P I Johansson, J Stensballe, M Maegele, N P Juffermans

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages.

METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality.

RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests.

CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups.

LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

Original language	English
Journal	Journal of Trauma and Acute Care Surgery
DOIs	https://doi.org/10.1097/TA.0000000000004235
Publication status	E-pub ahead of print - 8 Dec 2023

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Dujardin, R. W. G., Kleinveld, D. J. B., van den Brom, C. E., Geeraedts, L. M. G., Beijer, E., Gaarder, C., Brohi, K., Stanworth, S., Johansson, P. I., Stensballe, J., Maegele, M., & Juffermans, N. P. (2023). Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis. Journal of Trauma and Acute Care Surgery. Advance online publication. https://doi.org/10.1097/TA.0000000000004235

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title = "Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis",

abstract = "INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages.METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality.RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests.CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups.LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.",

author = "Dujardin, {R W G} and Kleinveld, {D J B} and {van den Brom}, {C E} and Geeraedts, {L M G} and E Beijer and C Gaarder and K Brohi and S Stanworth and Johansson, {P I} and J Stensballe and M Maegele and Juffermans, {N P}",

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Dujardin, RWG , Kleinveld, DJB, van den Brom, CE, Geeraedts, LMG , Beijer, E, Gaarder, C, Brohi, K, Stanworth, S, Johansson, PI, Stensballe, J, Maegele, M & Juffermans, NP 2023, 'Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis', Journal of Trauma and Acute Care Surgery. https://doi.org/10.1097/TA.0000000000004235

TY - JOUR

T1 - Older females have increased mortality after trauma as compared to younger females and males, associated with increased fibrinolysis

AU - Dujardin, R W G

AU - Kleinveld, D J B

AU - van den Brom, C E

AU - Geeraedts, L M G

AU - Beijer, E

AU - Gaarder, C

AU - Brohi, K

AU - Stanworth, S

AU - Johansson, P I

AU - Stensballe, J

AU - Maegele, M

AU - Juffermans, N P

PY - 2023/12/8

Y1 - 2023/12/8

N2 - INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages.METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality.RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests.CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups.LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

AB - INTRODUCTION: Female sex may provide a survival benefit after trauma, possibly attributable to protective effects of estrogen. This study aims to compare markers of coagulation between male and female trauma patients across different ages.METHODS: Secondary analysis of a prospective cohort study at six trauma centers. Trauma patients presenting with full trauma team activation were eligible for inclusion. Patients with a penetrating trauma or traumatic brain injury were excluded. Upon hospital arrival, blood was drawn for measurement of endothelial and coagulation markers and for rotational thromboelastometry (ROTEM) measurement.Trauma patients were divided into four categories: males <45 years, males ≥45 years, females <45 years and females ≥45 years. In a sensitivity analysis, patients between 45 - 55 years were excluded to control for menopausal transitioning. Groups were compared with a Kruskall-Wallis test with Bonferroni correction. A logistic regression was performed to assess whether the independent effect of sex and age on mortality.RESULTS: 1345 patients were available for analysis. Compared to the other groups, mortality was highest in females ≥45, albeit not independent from injury severity and shock. In the group of females ≥45 there was increased fibrinolysis, demonstrated by increased levels of plasmin-antiplasmin complexes with a concomitant decrease in α2-antiplasmin. Also, a modest decrease in coagulation factors II and X was observed. Fibrinogen levels were comparable between groups. The sensitivity analysis in 1104 patients demonstrated an independent relationship between female sex and age ≥ 55 years and mortality. ROTEM profiles did not reflect the changes in coagulation tests.CONCLUSION: Female trauma patients past their reproductive age have an increased risk of mortality compared to younger females and males, associated with augmented fibrinolysis and clotting factor consumption. ROTEM parameters did not reflect coagulation differences between groups.LEVEL OF EVIDENCE: Level III prognostic and epidemiological data.

U2 - https://doi.org/10.1097/TA.0000000000004235

DO - https://doi.org/10.1097/TA.0000000000004235

M3 - Article

C2 - 38079234

SN - 2163-0755

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

ER -