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2304 Part XII: Hemostasis and Thrombosis Chapter 135: Fibrinolysis and Thrombolysis 2305

Figure 135–1. Overview of the fibrino-
lytic system. A. Fibrin–based plasminogen
activation. The zymogen plasminogen (Plg)
is converted to the active serine protease,
plasmin (PN), through the action of tis-
sue plasminogen activator (t-PA) or uroki-
nase (u-PA). The activity of t-PA is greatly
a 2 -PI enhanced by its assembly with Plg through
lysine residues (K) on a fibrin–containing
thrombus. u-PA acts independently of fibrin.
Both t-PA and u-PA can be inhibited by plas-
Plg minogen activator inhibitor–1 (PAI–1), the
main physiologic regulator of plasminogen
activator activity. By binding to fibrin, PN
is protected from its major inhibitor, α –
2
plasmin inhibitor (α –PI). Fibrin-bound
2
plasmin degrades crosslinked fibrin, giving
rise to soluble fibrin degradation products
(FDPs). B. Cell surface plasminogen acti-
vation. Although many cell types express
receptors for Plg, urokinase, and t-PA, only
A the endothelial cell is depicted here. The
annexin A2 heterotetramer, consisting of
two copies each of annexin A2 (A2) and
protein p11 (p11), binds both t-PA and
Plg, thereby augmenting the efficiency of
plasmin generation on endothelial cells.
Plg may also bind to other endothelial cell
receptors, including histone H2B (H2B),
Plg α-enolase, and may be activated by u-PA
Plg bound to its receptor, uPAR, to effect plas-
min generation.

B

TABLE 135–1. Fibrinolytic Proteins
A. MAJOR PROTEASES
Property Plasminogen t-PA u-PA
Molecular mass 92,000 72,000 54,000
Amino acids 791 527 411
Chromosome 6 8 10
Site of synthesis Liver Endothelium Endothelium, kidney
Plasma concentration
nM 1500 0.075 0.150
mcg/mL 140 0.005 0.008
Plasma half-life 48 h 5 min 8 min
N-glycosylation (%) 2 13 7
Form 1 – Asn117, Asn184, Asn448 Asn302
Form 2 Asn288 Asn117, –, Asn448 –
O-Glycosylation
α-Fucose – Thr61 Thr18
Complex Thr345 – –
(continued )

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