Activation of fibrinolytic pathways is associated with duration of supraceliac aortic cross-clamping.
OBJECTIVE
The cause of the coagulopathy seen with supraceliac aortic cross-clamping (SC AXC) is unclear. SC AXC for 30 minutes results in both clotting factor consumption and activation of fibrinolytic pathways. This study was undertaken to define the hemostatic alterations that occur with longer intervals of SC AXC.


METHODS
Seven pigs underwent SC AXC for 60 minutes. Five pigs that underwent infrarenal aortic cross-clamping (IR AXC) for 60 minutes and 11 pigs that underwent SC AXC for 30 minutes served as controls. No heparin was used. Blood samples were drawn at baseline, 5 minutes before release of the aortic clamp, and 5, 30, and 60 minutes after unclamping. Prothrombin time, partial thromboplastin time, platelet count, and fibrinogen concentration were measured as basic tests of hemostatic function. Thrombin-antithrombin complexes were used to detect the presence of intravascular thrombosis. Fibrinolytic pathway activation was assessed with levels of tissue plasminogen activator antigen and tissue plasminogen activator activity, plasminogen activator inhibitor-1 activity, and alpha2-antiplasmin activity. Statistical analysis was performed with the Student t test and repeated measures of analysis of variance.


RESULTS
Prothrombin time, partial thromboplastin time, and platelet count did not differ between groups at any time. Fibrinogen concentration decreased 5 minutes (P =.005) and 30 minutes (P =.006) after unclamping in both SC AXC groups, but did not change in the IR AXC group. Thrombin-antithrombin complexes increased in both SC AXC groups, but were not significantly greater than in the IR AXC group. SC AXC for both 30 and 60 minutes produced a significant increase in tissue plasminogen activator antigen during clamping and 5 minutes after clamping. This increase persisted for 30 and 60 minutes after clamp release in the 60-minute SC AXC group. Tissue plasminogen activator activity, however, increased only in the 60-min SC AXC group during clamping (P =.02), and 5 minutes (P =.05) and 30 minutes (P =.06) after unclamping, compared with both control groups.


CONCLUSIONS
Thirty and 60 minutes of SC AXC results in similar degrees of intravascular thrombosis and fibrinogen depletion. Although SC AXC for both 30 and 60 minutes leads to activation of fibrinolytic pathways, only 60 minutes of SC AXC actually induces a fibrinolytic state. Fibrinolysis appears to be an important component of the coagulopathy associated with SC AXC, and is related to the duration of aortic clamping.


CONCLUSIONS
The coagulopathy frequently associated with thoracoabdominal aortic aneurysm repair is thought to revolt visceral ischemia-reperfusion. The nature of this coagulopathy is controversial. The current study demonstrates that the major hemostatic alteration associated with supraceliac aortic cross-clamping is activation of fibrinolytic pathways. The magnitude of this fibrinolytic response is directly related to the duration of supraceliac aortic occlusion. Future efforts to treat this coagulopathy may well include judicious use of autofibrinolytic agents.
Haithcock
Benjamin E
BE
Department of Surgery, Division of Vascular Surgery, Henry Ford Hospital, Detroit, MI 48202, USA.
Shepard
Alexander D
AD
Raman
Sundra B K
SB
Conrad
Mark F
MF
Pandurangi
Keshav
K
Fanous
Nervin H
NH
D000818:Animals; D000990:Antithrombin III / Q000502:physiology; D001014:Aortic Aneurysm / Q000503:physiopathology* / Q000601:surgery; D003250:Constriction; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000503:physiopathology*; D005342:Fibrinolysis / Q000502:physiology*; D023421:Models, Animal; D010447:Peptide Hydrolases / Q000502:physiology; D013552:Swine; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000502:physiology; D014656:Vascular Surgical Procedures / Q000009:adverse effects*
C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator