Does plasmin have anticoagulant activity?

Figures & data

Figure 1 The plasminogen system.

Notes: Plasminogen activators are tPA and uPA; PAI-1 inhibits tPA and uPA reducing activation of plasminogen to plasmin; α₂-antiplasmin inhibits plasmin activity.
Abbreviations: PAI-1, plasminogen activator inhibitor-1; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator.

Figure 2 Plasmin substrates in the coagulation pathways.

Notes: Shaded boxes are plasmin substrates. Cleavage by plasmin inactivates the substrates. Extrinsic, intrinsic, and common pathways are indicated.

Table 1 Thrombosis formation and lysis after carotid injury

Mouse genotype	Model	Time to occlusion	Patency	Reference
Plg^−/−	Photochemical	Decreased	Decreased	^Citation39
AP^−/−		Increased	Increased
PAI-1^−/−	Photochemical	Increased	Increased	^Citation39,Citation40
AP^−/−		Increased	Increased
PAI-1^−/−	Photochemical	Increased		^Citation41
VN^−/−		Increased
PAI-1^−/−	Photochemical	Increased	Increased	^Citation42
tPA^−/−		NC	Decreased
uPA^−/−		NC	NC
Plg^−/−	FeCl3	NC	Decreased	^Citation43
PAI-1^−/−	FeCl3	ND	Increased	^Citation44
PAI-1^−/−	FeCl3	Increased	Increased	^Citation45
VN-1^−/−	FeCl3	Increased	Increased
VN-1^−/−	FeCl3	Decreased	ND	^Citation46

Abbreviations: AP, α₂-antiplasmin; NC, no change; ND, not determined; PAI-1, plasminogen activator inhibitor-1; Plg, plasminogen; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator; VN, vitronectin.

Table 2 Plg^−/− mice have increased bleeding time and PAI-1^−/− mice have reduced clot stability time in the tail bleeding/rebleeding assay

	Tail bleeding/rebleeding assay
	Bleeding time (sec)	Rebleeding time (sec)
WT	79 ± 5 (28)♦	207 ± 38 (28)
Plg^−/−	130 ± 15 (9)♦	188 ± 86 (9)
B6	99 ± 17 (34)	189 ± 25 (34)*
PAI-1^−/−	123 ± 26 (21)	108 ± 30 (21)*

Notes: The mouse tail is warmed in saline, clipped and remains in the saline during the time measurements. Bleeding time is the time between the start of bleeding (after tail clip) and rebleeding time is the time between the cessation of the bleeding and the start of the second bleeding. Statistical difference

♦ P < 0.05 between WT/Plg^+/+ mice and Plg^−/− mice, and

* P < 0.0001 for B6 mice compared to PAI-1^−/− mice. (Hoover-Plow et al. modified from Figure 1, Ref. ⁴⁸).

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