The intrinsic pathway of coagulation is essential for thrombus stability in mice
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The intrinsic pathway of coagulation is essential for thrombus stability in mice. / Renné, Thomas; Nieswandt, Bernhard; Gailani, David.
In: BLOOD CELL MOL DIS, Vol. 36, No. 2, 2006, p. 148-51.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The intrinsic pathway of coagulation is essential for thrombus stability in mice
AU - Renné, Thomas
AU - Nieswandt, Bernhard
AU - Gailani, David
PY - 2006
Y1 - 2006
N2 - Blood coagulation is a highly regulated process involving interactions between platelets, plasma coagulation factors, and the vessel wall. During coagulation in vivo, fibrin formation is thought to be initiated when plasma factor VIIa forms a complex with the membrane protein tissue factor. Coagulation factor XII (FXII, Hageman factor) is required for some in vitro coagulation systems; however, FXII deficiency is not associated with hemorrhage, leading to the conclusion that it is not necessary for hemostasis. We generated FXII-deficient mice to study the contributions of FXII to thrombosis and hemostasis in arterial injury models and in models of acute arterial occlusion. FXII-deficient mice do not experience excessive injury-related bleeding; however, intravital fluorescence microscopy and blood flow measurements in three separate arterial beds revealed a severe defect in formation and stabilization of platelet-rich occlusive thrombi induced by different methods of injuries. Similar findings were observed for mice deficient in factor XI, a substrate of activated FXII. Infusion of human FXII into FXII null mice restored thrombus formation. These findings demonstrate that FXII-mediated fibrin formation is crucial for pathological arterial thrombosis but not for hemostasis and suggest that FXII could be an ideal target for safe anticoagulation.
AB - Blood coagulation is a highly regulated process involving interactions between platelets, plasma coagulation factors, and the vessel wall. During coagulation in vivo, fibrin formation is thought to be initiated when plasma factor VIIa forms a complex with the membrane protein tissue factor. Coagulation factor XII (FXII, Hageman factor) is required for some in vitro coagulation systems; however, FXII deficiency is not associated with hemorrhage, leading to the conclusion that it is not necessary for hemostasis. We generated FXII-deficient mice to study the contributions of FXII to thrombosis and hemostasis in arterial injury models and in models of acute arterial occlusion. FXII-deficient mice do not experience excessive injury-related bleeding; however, intravital fluorescence microscopy and blood flow measurements in three separate arterial beds revealed a severe defect in formation and stabilization of platelet-rich occlusive thrombi induced by different methods of injuries. Similar findings were observed for mice deficient in factor XI, a substrate of activated FXII. Infusion of human FXII into FXII null mice restored thrombus formation. These findings demonstrate that FXII-mediated fibrin formation is crucial for pathological arterial thrombosis but not for hemostasis and suggest that FXII could be an ideal target for safe anticoagulation.
KW - Animals
KW - Blood Coagulation
KW - Blood Coagulation Factors
KW - Factor XII
KW - Factor XII Deficiency
KW - Homeostasis
KW - Mice
KW - Mice, Knockout
KW - Thrombosis
U2 - 10.1016/j.bcmd.2005.12.014
DO - 10.1016/j.bcmd.2005.12.014
M3 - SCORING: Journal article
C2 - 16466946
VL - 36
SP - 148
EP - 151
JO - BLOOD CELL MOL DIS
JF - BLOOD CELL MOL DIS
SN - 1079-9796
IS - 2
ER -
