Hemostatic alterations associated with supraceliac aortic cross-clamping

Petros V. Anagnostopoulos, Alexander D. Shepard, Iraklis I Pipinos, Sundara B.K. Raman, Pervaiz A. Chaudhry, Takayuki Mishima, Hideaki Morita, George Suzuki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. Methods: To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (IR) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PLT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and α2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests. Results: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in FLT levels (P = .005), a decrease in FBG levels (P < .001), and a trend toward PTT prolongation (P = .06) compared with baseline. In contrast, there were no changes in PTT, PLT levels, or EBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P = .04), remained elevated 5 minutes after unclamping (P = .08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P < .001) and 5 minutes after unclamping (P = .002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of α2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline. Conclusion: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR and SC AXC result in decreased fibrinolytic activity ("fibrinolytic shutdown") after release of the aortic clamp.

Original languageEnglish (US)
Pages (from-to)100-108
Number of pages9
JournalJournal of Vascular Surgery
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

Tissue Plasminogen Activator
Hemostatics
Constriction
Partial Thromboplastin Time
Antigens
Fibrinolysis
Antifibrinolytic Agents
Prothrombin Time
Fibrinogen
Thrombosis
Swine
Blood Platelets
Serum
Plasminogen Activator Inhibitor 2
Plasminogen Inactivators
Hepatic Veins
Blood Coagulation Factors
Plasminogen Activator Inhibitor 1
Portal Vein
Carotid Arteries

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Anagnostopoulos, P. V., Shepard, A. D., Pipinos, I. I., Raman, S. B. K., Chaudhry, P. A., Mishima, T., ... Suzuki, G. (2002). Hemostatic alterations associated with supraceliac aortic cross-clamping. Journal of Vascular Surgery, 35(1), 100-108. https://doi.org/10.1067/mva.2002.118088

Hemostatic alterations associated with supraceliac aortic cross-clamping. / Anagnostopoulos, Petros V.; Shepard, Alexander D.; Pipinos, Iraklis I; Raman, Sundara B.K.; Chaudhry, Pervaiz A.; Mishima, Takayuki; Morita, Hideaki; Suzuki, George.

In: Journal of Vascular Surgery, Vol. 35, No. 1, 01.01.2002, p. 100-108.

Research output: Contribution to journalArticle

Anagnostopoulos, PV, Shepard, AD, Pipinos, II, Raman, SBK, Chaudhry, PA, Mishima, T, Morita, H & Suzuki, G 2002, 'Hemostatic alterations associated with supraceliac aortic cross-clamping', Journal of Vascular Surgery, vol. 35, no. 1, pp. 100-108. https://doi.org/10.1067/mva.2002.118088
Anagnostopoulos PV, Shepard AD, Pipinos II, Raman SBK, Chaudhry PA, Mishima T et al. Hemostatic alterations associated with supraceliac aortic cross-clamping. Journal of Vascular Surgery. 2002 Jan 1;35(1):100-108. https://doi.org/10.1067/mva.2002.118088
Anagnostopoulos, Petros V. ; Shepard, Alexander D. ; Pipinos, Iraklis I ; Raman, Sundara B.K. ; Chaudhry, Pervaiz A. ; Mishima, Takayuki ; Morita, Hideaki ; Suzuki, George. / Hemostatic alterations associated with supraceliac aortic cross-clamping. In: Journal of Vascular Surgery. 2002 ; Vol. 35, No. 1. pp. 100-108.
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abstract = "Purpose: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. Methods: To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (IR) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PLT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and α2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests. Results: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in FLT levels (P = .005), a decrease in FBG levels (P < .001), and a trend toward PTT prolongation (P = .06) compared with baseline. In contrast, there were no changes in PTT, PLT levels, or EBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P = .04), remained elevated 5 minutes after unclamping (P = .08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P < .001) and 5 minutes after unclamping (P = .002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of α2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline. Conclusion: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR and SC AXC result in decreased fibrinolytic activity ({"}fibrinolytic shutdown{"}) after release of the aortic clamp.",
author = "Anagnostopoulos, {Petros V.} and Shepard, {Alexander D.} and Pipinos, {Iraklis I} and Raman, {Sundara B.K.} and Chaudhry, {Pervaiz A.} and Takayuki Mishima and Hideaki Morita and George Suzuki",
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TY - JOUR

T1 - Hemostatic alterations associated with supraceliac aortic cross-clamping

AU - Anagnostopoulos, Petros V.

AU - Shepard, Alexander D.

AU - Pipinos, Iraklis I

AU - Raman, Sundara B.K.

AU - Chaudhry, Pervaiz A.

AU - Mishima, Takayuki

AU - Morita, Hideaki

AU - Suzuki, George

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Purpose: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. Methods: To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (IR) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PLT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and α2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests. Results: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in FLT levels (P = .005), a decrease in FBG levels (P < .001), and a trend toward PTT prolongation (P = .06) compared with baseline. In contrast, there were no changes in PTT, PLT levels, or EBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P = .04), remained elevated 5 minutes after unclamping (P = .08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P < .001) and 5 minutes after unclamping (P = .002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of α2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline. Conclusion: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR and SC AXC result in decreased fibrinolytic activity ("fibrinolytic shutdown") after release of the aortic clamp.

AB - Purpose: The causative role of consumptive coagulopathy in the development of bleeding complications after supraceliac (SC) aortic cross-clamping (AXC) has been challenged by recent reports that ascribe this coagulopathy to primary fibrinolysis. This theory is made on the basis of evidence that tissue plasminogen activator (t-PA) antigen (Ag) levels increase after SC AXC. However, t-PA Ag levels reflect both active and inactive (bound to serum t-PA inhibitors) forms of serum t-PA, and elevations confirm the presence of fibrinolysis only in conjunction with an increase in t-PA activity. Methods: To investigate the etiology of this coagulopathy, we submitted eight pigs to SC AXC and six pigs to infrarenal (IR) AXC for 30 minutes. Blood was drawn from the portal vein, the hepatic vein, and the carotid artery before AXC, just before unclamping, and 5, 30, and 60 minutes after unclamping. Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FBG), platelets (PLT), thrombin-antithrombin complexes (TAT), t-PA Ag, t-PA activity, plasminogen activator inhibitor-1 (PAI-1), and α2-antiplasmin (AP) activities were measured. Statistical analysis was performed by using repeated measures analysis of variance and t tests. Results: The PT did not differ between the two groups at any point. After unclamping, in the SC group there was a drop in FLT levels (P = .005), a decrease in FBG levels (P < .001), and a trend toward PTT prolongation (P = .06) compared with baseline. In contrast, there were no changes in PTT, PLT levels, or EBG levels in the IR group. TAT, a serum marker of thrombin generation, increased with SC AXC (P = .04), remained elevated 5 minutes after unclamping (P = .08), and returned to normal 30 minutes after unclamping. In contrast, TAT levels did not change in the IR control group. In the SC AXC group, the TAT levels did not differ between the three test sites at any time. SC AXC was associated with an increase in t-PA Ag just before unclamping (P < .001) and 5 minutes after unclamping (P = .002), but IR AXC was not. t-PA activity levels decreased in both experimental groups 30 and 60 minutes after unclamping. Levels of α2-AP activity decreased to a similar degree in both groups after unclamping when compared with baseline. Conclusion: Thirty minutes of SC AXC results in intravascular thrombosis that cannot be localized to the ischemic visceral circulation. This intravascular thrombosis is associated with consumption of clotting factors. Thirty minutes of SC AXC causes an activation of fibrinolytic pathways that does not result in a hyperfibrinolytic state. An increase in t-PA Ag without a rise in t-PA activity does not represent true fibrinolysis, but rather an increase in the bound, inactive forms of serum t-PA. Both IR and SC AXC result in decreased fibrinolytic activity ("fibrinolytic shutdown") after release of the aortic clamp.

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