Hypercoagulation following brain death cannot be reversed by the neutralization of systemic tissue factor.

Abstract

BACKGROUND:

Cerebral injury and brain death is associated with apparent hypercoagulation and poor organ outcome. This experimental study challenges the hypotheses that i) brain death causes hypercoagulation and microvascular thrombosis and that ii) neutralizing systemic tissue factor (TF) by in vitro addition of a TF inhibitor (recombinant active site-inhibited factor VIIa (ASIS)) can reverse the hypercoagulable profile.

METHODS:

Using a validated pig model of intracranial hemorrhage and brain death, 20 pigs were randomized to either control or brain death. The primary endpoints were coagulation parameters measured with whole blood thromboelastometry (ROTEM), thrombin generation and a porcine TF-sensitive plasma clotting time assay. In vitro spiking experiments with ASIS were performed in parallel with the latter two assessments. The kidneys were examined histologically for microvascular thromboses.

RESULTS:

Brain death induced hypercoagulation, as demonstrated with ROTEM, thrombin generation, and reduced TF-sensitive plasma clotting time. In vitro inhibition of TF with ASIS did not reverse the hypercoagulation. No microvascular thromboses were found in the kidneys.

CONCLUSION:

Brain death causes hypercoagulation; however, inhibition of TF does not reverse the coagulopathy. Thus, TF release does not seem to be the primary cause of this hypercoagulation. Minor changes in the levels of protein C suggest that the protein C pathway may be linked to the observed coagulopathy.

• Authors: Christine L Hvas, Christian Fenger-Eriksen, Søren Høyer, Benny Sørensen, Else Tønnesen
• Journal: Thrombosis research (Thromb Res) Vol. 132 Issue 2 Pg. 300-6 (Aug 2013) ISSN: 1879-2472 [Electronic] United States
• PMID: 23910501 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Thromboplastin

Topics

• Animals
• Blood Coagulation
• Blood Coagulation Tests
• Brain Death (blood, pathology)
• Cerebral Hemorrhage (blood, complications, drug therapy, pathology)
• Disease Models, Animal
• Random Allocation
• Swine
• Thrombelastography
• Thrombophilia (blood, drug therapy, etiology, pathology)
• Thromboplastin (antagonists & inhibitors)