Does plasmin have anticoagulant activity?
The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.
Hoover-Plow
Jane
J
Joseph J Jacobs Center for Thrombosis and Vascular Biology, Department of Cardiovascular Medicine, Lerner Research Institute Cleveland Clinic, Cleveland, Ohio 44195, USA. hooverj@ccf.org
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000378:metabolism; D005164:Factor IX / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice
D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005165:Factor V; D005169:Factor VIII; D005164:Factor IX; D005170:Factor X; D005341:Fibrinolysin
J Biol Chem. 2009 May 8;284(19):12917-23
19286661
Blood. 1986 Jun;67(6):1649-54
2939896
Cancer Res. 1981 Nov;41(11 Pt 1):4629-36
6458354
J Biol Chem. 1987 Jul 15;262(20):9750-5
2954962
Br J Dermatol. 2008 Jul;159(1):49-60
18460030
J Biol Chem. 1995 Aug 18;270(33):19217-24
7642592
Blood. 1997 Aug 1;90(3):944-51
9242522
Am J Pathol. 2007 Sep;171(3):1066-77
17640967
Nat Genet. 1995 May;10(1):119-21
7647782
N Engl J Med. 2008 Dec 18;359(25):2651-62
19092151
J Thromb Haemost. 2008 Feb;6(2):339-45
18036190
J Thromb Haemost. 2003 Feb;1(2):307-13
12871505
BMC Blood Disord. 2006 Oct 05;6:6
17022820
Blood. 1973 Jan;41(1):105-11
4118107
Circulation. 1999 Jun 15;99(23):3050-5
10368124
Thromb Haemost. 2007 Jan;97(1):38-44
17200769
J Biol Chem. 2001 Jul 6;276(27):25022-9
11342539
Blood. 2000 Feb 1;95(3):943-51
10648407
J Biol Chem. 1996 Jul 12;271(28):16614-20
8663221
Stroke. 2003 Dec;34(12):2975-9
14615621
Nature. 1996 Nov 7;384(6604):66-8
8900278
Thromb Res. 2009;123 Suppl 4:S56-61
19303506
J Biol Chem. 2004 Aug 6;279(32):33104-13
15166225
Blood. 2000 Dec 15;96(13):4222-6
11110695
Arch Pathol Lab Med. 2007 Jun;131(6):866-71
17550313
Blood. 2005 Nov 1;106(9):3055-7
15985536
Thromb Haemost. 2001 Sep;86(3):923-8
11583328
Curr Drug Targets. 2007 Sep;8(9):966-1002
17896948
Thromb Res. 2008;122 Suppl 3:S20-6
18701142
Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2273-81
16123318
Biochemistry. 2001 May 29;40(21):6293-302
11371191
Blood. 2000 Jul 1;96(1):153-60
10891445
Circulation. 1998 Mar 17;97(10):1002-8
9529269
J Biol Chem. 1999 Mar 26;274(13):8500-5
10085082
FASEB J. 1995 Jul;9(10):939-45
7615163
J Biol Chem. 1993 Sep 5;268(25):18917-23
8360181
Thromb Haemost. 1999 Apr;81(4):601-4
10235447
Am J Ophthalmol. 2002 Apr;133(4):451-5
11931777
Pediatr Res. 1998 Mar;43(3):403-9
9505281
Circulation. 2001 Jan 30;103(4):576-83
11157725
Dev Ophthalmol. 2009;44:26-30
19494649
J Thromb Thrombolysis. 2003 Feb;15(1):19-23
14574072
J Thromb Haemost. 2004 Sep;2(9):1617-21
15333039
Thromb Haemost. 2002 Jan;87(1):98-104
11848464
J Ocul Pharmacol Ther. 2009 Aug;25(4):379-84
19650710
Thromb Haemost. 2008 Oct;100(4):563-75
18841277
Cleve Clin J Med. 2004 Jan;71(1):20, 23-5, 29-30 passim
14740966
Blood. 2000 Jan 15;95(2):577-80
10627465
Blood. 1989 Jan;73(1):185-90
2521293
Thromb Haemost. 1999 Aug;82(2):259-70
10605712
J Biol Chem. 2001 Jun 8;276(23):19929-36
11278280
J Thromb Haemost. 2007 Oct;5(10):2087-94
17883703
Thromb Haemost. 2001 Jul;86(1):324-33
11487021
Curr Drug Targets Cardiovasc Haematol Disord. 2002 Jun;2(1):27-42
12769655
Stroke. 1994 Oct;25(10):2072-8; discussion 2078-9
8091454
Br J Haematol. 2008 Mar;140(5):488-95
18275426
Biochim Biophys Acta. 2008 May;1784(5):753-63
18329389
Thromb Haemost. 1998 Sep;80(3):423-7
9759622
Thromb Res. 1998 Sep 15;91(6):255-85
9772009
J Biol Chem. 2001 May 25;276(21):18614-23
11278331
Stroke. 2002 Sep;33(9):2279-84
12215599
J Thromb Haemost. 2005 Apr;3(4):695-702
15733058
J Thromb Haemost. 2004 May;2(5):785-96
15099286
J Clin Invest. 2008 Sep;118(9):3012-24
18677407
Thromb Haemost. 2000 Feb;83(2):185-90
10739370
Blood. 1973 Nov;42(5):749-51
4270477