CONTRIBUTION OF HEMODILUTION, FIBRINOLYSIS, ACIDOSIS, AND HYPOTHERMIA TO DERANGEMENT OF CLOT FORMATION IN THE IN VITRO MODEL OF TRAUMA-INDUCED COAGULOPATHY
(Abstract release date: 05/19/16)
EHA Library. Budnik I. 06/09/16; 132542; E993
Mr. Ivan Budnik
Contributions
Contributions
Abstract
Abstract: E993
Type: Eposter Presentation
Background
Trauma-induced coagulopathy (TIC) develops often after major trauma and may be diagnosed before any therapeutic intervention is provided. Pathophysiology of TIC includes tissue injury and severe hypoperfusion which cause endothelial activation of the protein C pathway and release of tissue plasminogen activator (tPA) resulting in systemic anticoagulation and hyperfibrinolysis. Subsequent hemodilution due to massive transfusions as well as hypothermia and acidosis exacerbate the hemostatic derangement and may lead to uncontrollable postoperative hemorrhage in severely traumatized patients.
Aims
To investigate the relative contribution of hemodilution, fibrinolysis, acidosis, and hypothermia to the derangement of clot formation in the in vitro TIC model.
Methods
The study was approved by the local research ethics committee. Citrated venous blood was obtained from adult healthy volunteers who signed an informed consent form. The in vitro TIC model included hemodilution combined with hyperfibrinolysis, acidosis, and hypothermia. Hemodilution (40%) was produced by mixing the blood with TRIS/saline solution. Fibrinolysis was induced by treating the blood with 165 ng/mL tPA. Acidosis (pH 7.0–7.1) was produced by treating the blood with 1.2 mg/mL lactic acid. Hypothermia (31°C) was achieved by setting the appropriate temperature while running the test. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotational thromboelastometry (ROTEM) device (Pentapharm, Germany). Clotting time (CT, s), maximum clot firmness (MCF, mm) and lysis onset time (LOT, s) were measured using the EXTEM test with 1:50 pre-diluted reagent and presented as Mean±SD.
Results
In control, CT was 349±66 s, and none of the factors (hemodilution alone or in combination with tPA-induced fibrinolysis, hypothermia, and/or acidosis) affected this parameter. In control, MCF was 64±3 mm. Hemodilution reduced MCF to 54±4 mm (P<0.001 vs. control). Combination of hemodilution and hypothermia produced the same effect. Combination of hemodilution and hyperfibrinolysis reduced MCF to 46±7 mm (P<0.001 vs. hemodilution alone). Combination of hemodilution, hypothermia, and hyperfibrinolysis had the greatest inhibitory effect on MCF reducing it to 38±8 mm (P<0.001 vs. combination of hemodilution and hyperfibrinolysis). Acidosis did not modify the effect of the other factors on MCF. No clot lysis was observed in control. Hemodilution did not lead to clot lysis unless hyperfibrinolysis was induced; in these conditions, LOT was 1766±324 s. When additionally combined with hypothermia, LOT was prolonged to 2380±530 s (P<0.001). Acidosis had no effect on LOT at either blood temperature.
Conclusion
Differential effect of TIC constituents on clot formation is revealed. Latent processes that precede clot formation (CT) were not affected by any of the factors studied. Clot strength (MCF) was reduced in the presence of hemodilution, further reduced if combined with hyperfibrinolysis, and maximally reduced if additionally combined with hypothermia. tPA-initiated clot lysis was delayed by hypothermia. Acidosis had no effect on clot formation. The data presented may be helpful to better understanding the pathogenesis of TIC and elaboration of individually-tailored treatment strategy.
Session topic: E-poster
Keyword(s): Coagulopathy, Fibrinolysis, Trauma
Type: Eposter Presentation
Background
Trauma-induced coagulopathy (TIC) develops often after major trauma and may be diagnosed before any therapeutic intervention is provided. Pathophysiology of TIC includes tissue injury and severe hypoperfusion which cause endothelial activation of the protein C pathway and release of tissue plasminogen activator (tPA) resulting in systemic anticoagulation and hyperfibrinolysis. Subsequent hemodilution due to massive transfusions as well as hypothermia and acidosis exacerbate the hemostatic derangement and may lead to uncontrollable postoperative hemorrhage in severely traumatized patients.
Aims
To investigate the relative contribution of hemodilution, fibrinolysis, acidosis, and hypothermia to the derangement of clot formation in the in vitro TIC model.
Methods
The study was approved by the local research ethics committee. Citrated venous blood was obtained from adult healthy volunteers who signed an informed consent form. The in vitro TIC model included hemodilution combined with hyperfibrinolysis, acidosis, and hypothermia. Hemodilution (40%) was produced by mixing the blood with TRIS/saline solution. Fibrinolysis was induced by treating the blood with 165 ng/mL tPA. Acidosis (pH 7.0–7.1) was produced by treating the blood with 1.2 mg/mL lactic acid. Hypothermia (31°C) was achieved by setting the appropriate temperature while running the test. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotational thromboelastometry (ROTEM) device (Pentapharm, Germany). Clotting time (CT, s), maximum clot firmness (MCF, mm) and lysis onset time (LOT, s) were measured using the EXTEM test with 1:50 pre-diluted reagent and presented as Mean±SD.
Results
In control, CT was 349±66 s, and none of the factors (hemodilution alone or in combination with tPA-induced fibrinolysis, hypothermia, and/or acidosis) affected this parameter. In control, MCF was 64±3 mm. Hemodilution reduced MCF to 54±4 mm (P<0.001 vs. control). Combination of hemodilution and hypothermia produced the same effect. Combination of hemodilution and hyperfibrinolysis reduced MCF to 46±7 mm (P<0.001 vs. hemodilution alone). Combination of hemodilution, hypothermia, and hyperfibrinolysis had the greatest inhibitory effect on MCF reducing it to 38±8 mm (P<0.001 vs. combination of hemodilution and hyperfibrinolysis). Acidosis did not modify the effect of the other factors on MCF. No clot lysis was observed in control. Hemodilution did not lead to clot lysis unless hyperfibrinolysis was induced; in these conditions, LOT was 1766±324 s. When additionally combined with hypothermia, LOT was prolonged to 2380±530 s (P<0.001). Acidosis had no effect on LOT at either blood temperature.
Conclusion
Differential effect of TIC constituents on clot formation is revealed. Latent processes that precede clot formation (CT) were not affected by any of the factors studied. Clot strength (MCF) was reduced in the presence of hemodilution, further reduced if combined with hyperfibrinolysis, and maximally reduced if additionally combined with hypothermia. tPA-initiated clot lysis was delayed by hypothermia. Acidosis had no effect on clot formation. The data presented may be helpful to better understanding the pathogenesis of TIC and elaboration of individually-tailored treatment strategy.
Session topic: E-poster
Keyword(s): Coagulopathy, Fibrinolysis, Trauma
Abstract: E993
Type: Eposter Presentation
Background
Trauma-induced coagulopathy (TIC) develops often after major trauma and may be diagnosed before any therapeutic intervention is provided. Pathophysiology of TIC includes tissue injury and severe hypoperfusion which cause endothelial activation of the protein C pathway and release of tissue plasminogen activator (tPA) resulting in systemic anticoagulation and hyperfibrinolysis. Subsequent hemodilution due to massive transfusions as well as hypothermia and acidosis exacerbate the hemostatic derangement and may lead to uncontrollable postoperative hemorrhage in severely traumatized patients.
Aims
To investigate the relative contribution of hemodilution, fibrinolysis, acidosis, and hypothermia to the derangement of clot formation in the in vitro TIC model.
Methods
The study was approved by the local research ethics committee. Citrated venous blood was obtained from adult healthy volunteers who signed an informed consent form. The in vitro TIC model included hemodilution combined with hyperfibrinolysis, acidosis, and hypothermia. Hemodilution (40%) was produced by mixing the blood with TRIS/saline solution. Fibrinolysis was induced by treating the blood with 165 ng/mL tPA. Acidosis (pH 7.0–7.1) was produced by treating the blood with 1.2 mg/mL lactic acid. Hypothermia (31°C) was achieved by setting the appropriate temperature while running the test. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotational thromboelastometry (ROTEM) device (Pentapharm, Germany). Clotting time (CT, s), maximum clot firmness (MCF, mm) and lysis onset time (LOT, s) were measured using the EXTEM test with 1:50 pre-diluted reagent and presented as Mean±SD.
Results
In control, CT was 349±66 s, and none of the factors (hemodilution alone or in combination with tPA-induced fibrinolysis, hypothermia, and/or acidosis) affected this parameter. In control, MCF was 64±3 mm. Hemodilution reduced MCF to 54±4 mm (P<0.001 vs. control). Combination of hemodilution and hypothermia produced the same effect. Combination of hemodilution and hyperfibrinolysis reduced MCF to 46±7 mm (P<0.001 vs. hemodilution alone). Combination of hemodilution, hypothermia, and hyperfibrinolysis had the greatest inhibitory effect on MCF reducing it to 38±8 mm (P<0.001 vs. combination of hemodilution and hyperfibrinolysis). Acidosis did not modify the effect of the other factors on MCF. No clot lysis was observed in control. Hemodilution did not lead to clot lysis unless hyperfibrinolysis was induced; in these conditions, LOT was 1766±324 s. When additionally combined with hypothermia, LOT was prolonged to 2380±530 s (P<0.001). Acidosis had no effect on LOT at either blood temperature.
Conclusion
Differential effect of TIC constituents on clot formation is revealed. Latent processes that precede clot formation (CT) were not affected by any of the factors studied. Clot strength (MCF) was reduced in the presence of hemodilution, further reduced if combined with hyperfibrinolysis, and maximally reduced if additionally combined with hypothermia. tPA-initiated clot lysis was delayed by hypothermia. Acidosis had no effect on clot formation. The data presented may be helpful to better understanding the pathogenesis of TIC and elaboration of individually-tailored treatment strategy.
Session topic: E-poster
Keyword(s): Coagulopathy, Fibrinolysis, Trauma
Type: Eposter Presentation
Background
Trauma-induced coagulopathy (TIC) develops often after major trauma and may be diagnosed before any therapeutic intervention is provided. Pathophysiology of TIC includes tissue injury and severe hypoperfusion which cause endothelial activation of the protein C pathway and release of tissue plasminogen activator (tPA) resulting in systemic anticoagulation and hyperfibrinolysis. Subsequent hemodilution due to massive transfusions as well as hypothermia and acidosis exacerbate the hemostatic derangement and may lead to uncontrollable postoperative hemorrhage in severely traumatized patients.
Aims
To investigate the relative contribution of hemodilution, fibrinolysis, acidosis, and hypothermia to the derangement of clot formation in the in vitro TIC model.
Methods
The study was approved by the local research ethics committee. Citrated venous blood was obtained from adult healthy volunteers who signed an informed consent form. The in vitro TIC model included hemodilution combined with hyperfibrinolysis, acidosis, and hypothermia. Hemodilution (40%) was produced by mixing the blood with TRIS/saline solution. Fibrinolysis was induced by treating the blood with 165 ng/mL tPA. Acidosis (pH 7.0–7.1) was produced by treating the blood with 1.2 mg/mL lactic acid. Hypothermia (31°C) was achieved by setting the appropriate temperature while running the test. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotational thromboelastometry (ROTEM) device (Pentapharm, Germany). Clotting time (CT, s), maximum clot firmness (MCF, mm) and lysis onset time (LOT, s) were measured using the EXTEM test with 1:50 pre-diluted reagent and presented as Mean±SD.
Results
In control, CT was 349±66 s, and none of the factors (hemodilution alone or in combination with tPA-induced fibrinolysis, hypothermia, and/or acidosis) affected this parameter. In control, MCF was 64±3 mm. Hemodilution reduced MCF to 54±4 mm (P<0.001 vs. control). Combination of hemodilution and hypothermia produced the same effect. Combination of hemodilution and hyperfibrinolysis reduced MCF to 46±7 mm (P<0.001 vs. hemodilution alone). Combination of hemodilution, hypothermia, and hyperfibrinolysis had the greatest inhibitory effect on MCF reducing it to 38±8 mm (P<0.001 vs. combination of hemodilution and hyperfibrinolysis). Acidosis did not modify the effect of the other factors on MCF. No clot lysis was observed in control. Hemodilution did not lead to clot lysis unless hyperfibrinolysis was induced; in these conditions, LOT was 1766±324 s. When additionally combined with hypothermia, LOT was prolonged to 2380±530 s (P<0.001). Acidosis had no effect on LOT at either blood temperature.
Conclusion
Differential effect of TIC constituents on clot formation is revealed. Latent processes that precede clot formation (CT) were not affected by any of the factors studied. Clot strength (MCF) was reduced in the presence of hemodilution, further reduced if combined with hyperfibrinolysis, and maximally reduced if additionally combined with hypothermia. tPA-initiated clot lysis was delayed by hypothermia. Acidosis had no effect on clot formation. The data presented may be helpful to better understanding the pathogenesis of TIC and elaboration of individually-tailored treatment strategy.
Session topic: E-poster
Keyword(s): Coagulopathy, Fibrinolysis, Trauma
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