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Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality.

Curry N, Raja A, Beavis J, Stanworth S, Harrison P - J Extracell Vesicles (2014)

Bottom Line: Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury.Patients who died (n=9, 18%) had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived.Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted.

View Article: PubMed Central - PubMed

Affiliation: Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals Trust, Churchill Hospital, Oxford, UK.

ABSTRACT

Background: Microvesicles (MV) have been implicated in the development of thrombotic disease, such as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Trauma patients are at increased risk of late thrombotic events, particularly those who receive a major transfusion. The aims of this study were: (a) to determine whether there were increased numbers of pro-coagulant MV following injury; (b) to determine their cellular origin; and (c) to explore the effects of MV with clinical outcomes; in particular red cell transfusion requirements and death.

Methods: Trauma patients were recruited at a Level 1 trauma centre. The presence of MV procoagulant phospholipid (PPL) was assessed using 2 activity assays (PPL and thrombin generation). Enumeration and MV cellular origin was assessed using 2 colour flow cytometry.

Results: Fifty consecutive patients were recruited; median age 38 (IQR: 24-55), median ISS 18 (IQR: 9-27). Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury. Red cell/AnnV+ and platelet/AnnV+ MV numbers were 6-fold and 2-fold higher than controls, respectively. Patients who died (n=9, 18%) had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived.

Conclusions: MV are elevated following traumatic injury and may be implicated in the increased risk of trauma patients to pro-thrombotic states such as MOF and ARDS. Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted.

No MeSH data available.


Related in: MedlinePlus

Association between procoagulant microvesicle number, procoagulant derived thrombin generation and mortality. (a). Numbers of procoagulant MV of platelet origin (CD41+/AnnV+) in the plasma of samples at admission to hospital from trauma survivors and non-survivors. There is a significantly greater number of platelet derived procoagulant MV in plasma from survivors (n=41, median=202.1 per µL; IQR: 93.4–561.7) when compared to participants who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) (p=0.015). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). (b). Endogenous thrombin potential values in admission samples from trauma survivors and non-survivors. Box plots of median ETP values (PRP reagent) comparing survivors with non-survivors. The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1466–1973.9) (p=0.025).
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Figure 0002: Association between procoagulant microvesicle number, procoagulant derived thrombin generation and mortality. (a). Numbers of procoagulant MV of platelet origin (CD41+/AnnV+) in the plasma of samples at admission to hospital from trauma survivors and non-survivors. There is a significantly greater number of platelet derived procoagulant MV in plasma from survivors (n=41, median=202.1 per µL; IQR: 93.4–561.7) when compared to participants who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) (p=0.015). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). (b). Endogenous thrombin potential values in admission samples from trauma survivors and non-survivors. Box plots of median ETP values (PRP reagent) comparing survivors with non-survivors. The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1466–1973.9) (p=0.025).

Mentions: The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1,466–1973.9) (p=0.025, Mann–Whitney U, 2 tailed). In keeping with this finding, absolute numbers of CD41/Annexin V-positive MV were significantly lower in trauma patients who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) compared to patients who survived (n=41, median=202.1 per µL; IQR: 93.4–561.7) to day 28 (p=0.015, Mann–Whitney U, 2 tailed) (see Fig 2). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). Median platelet counts were significantly lower 197×10−9L (IQR: 145–223) in the cohort of patients that died compared with 273×10−9 L (IQR: 223–301) in those that survived (p=0.004, Mann–Whitney U, 2 tailed). The platelet count and CD41/AnnV+ MV numbers did not show a correlation with each other (r=−0.12; p=0.44).


Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality.

Curry N, Raja A, Beavis J, Stanworth S, Harrison P - J Extracell Vesicles (2014)

Association between procoagulant microvesicle number, procoagulant derived thrombin generation and mortality. (a). Numbers of procoagulant MV of platelet origin (CD41+/AnnV+) in the plasma of samples at admission to hospital from trauma survivors and non-survivors. There is a significantly greater number of platelet derived procoagulant MV in plasma from survivors (n=41, median=202.1 per µL; IQR: 93.4–561.7) when compared to participants who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) (p=0.015). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). (b). Endogenous thrombin potential values in admission samples from trauma survivors and non-survivors. Box plots of median ETP values (PRP reagent) comparing survivors with non-survivors. The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1466–1973.9) (p=0.025).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216813&req=5

Figure 0002: Association between procoagulant microvesicle number, procoagulant derived thrombin generation and mortality. (a). Numbers of procoagulant MV of platelet origin (CD41+/AnnV+) in the plasma of samples at admission to hospital from trauma survivors and non-survivors. There is a significantly greater number of platelet derived procoagulant MV in plasma from survivors (n=41, median=202.1 per µL; IQR: 93.4–561.7) when compared to participants who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) (p=0.015). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). (b). Endogenous thrombin potential values in admission samples from trauma survivors and non-survivors. Box plots of median ETP values (PRP reagent) comparing survivors with non-survivors. The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1466–1973.9) (p=0.025).
Mentions: The PRP ETP result at admission was significantly lower in patients who died (median=1524.5 per µL; IQR: 1155.5–1551.5) relative to those who survived to day 28 (median=1732.3 per µL; IQR: 1,466–1973.9) (p=0.025, Mann–Whitney U, 2 tailed). In keeping with this finding, absolute numbers of CD41/Annexin V-positive MV were significantly lower in trauma patients who died (n=9, median=40.2 per µL; IQR: 38.6–133.5) compared to patients who survived (n=41, median=202.1 per µL; IQR: 93.4–561.7) to day 28 (p=0.015, Mann–Whitney U, 2 tailed) (see Fig 2). Survival correlated positively with CD41/AnnV+ MV numbers (p=0.01, r=0.35). Median platelet counts were significantly lower 197×10−9L (IQR: 145–223) in the cohort of patients that died compared with 273×10−9 L (IQR: 223–301) in those that survived (p=0.004, Mann–Whitney U, 2 tailed). The platelet count and CD41/AnnV+ MV numbers did not show a correlation with each other (r=−0.12; p=0.44).

Bottom Line: Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury.Patients who died (n=9, 18%) had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived.Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted.

View Article: PubMed Central - PubMed

Affiliation: Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals Trust, Churchill Hospital, Oxford, UK.

ABSTRACT

Background: Microvesicles (MV) have been implicated in the development of thrombotic disease, such as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Trauma patients are at increased risk of late thrombotic events, particularly those who receive a major transfusion. The aims of this study were: (a) to determine whether there were increased numbers of pro-coagulant MV following injury; (b) to determine their cellular origin; and (c) to explore the effects of MV with clinical outcomes; in particular red cell transfusion requirements and death.

Methods: Trauma patients were recruited at a Level 1 trauma centre. The presence of MV procoagulant phospholipid (PPL) was assessed using 2 activity assays (PPL and thrombin generation). Enumeration and MV cellular origin was assessed using 2 colour flow cytometry.

Results: Fifty consecutive patients were recruited; median age 38 (IQR: 24-55), median ISS 18 (IQR: 9-27). Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury. Red cell/AnnV+ and platelet/AnnV+ MV numbers were 6-fold and 2-fold higher than controls, respectively. Patients who died (n=9, 18%) had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived.

Conclusions: MV are elevated following traumatic injury and may be implicated in the increased risk of trauma patients to pro-thrombotic states such as MOF and ARDS. Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted.

No MeSH data available.


Related in: MedlinePlus