Page 2143 - Hematology_ Basic Principles and Practice ( PDFDrive )

1904 Part XII Hemostasis and Thrombosis

When operating properly, this system of blood leakage attenu- FUTURE DIRECTIONS
ation displays the appropriate level of procoagulant required to
obstruct blood loss but is precluded from systemic activation of This chapter describes the process of blood coagulation (extrinsic and
the coagulation system. The converse to hemostasis occurs when intrinsic pathway) by dividing it into sections based on procoagulant,
the damaging insult for the vasculature is internal to the vessel anticoagulant, and fibrinolytic enzymes, cofactors, and inhibitors in
lumen. 338 the overall process of fibrin formation and fibrin dissolution. When
all of the players are present, the overall process of blood coagulation
and fibrinolysis is best described as a dynamic threshold-limited,
Elimination and Fibrinolysis complex, intertwined process that together promotes hemostasis.

The hemostatic or pathologic thrombus is structurally composed of
aggregated platelets and cross-linked fibrin. The steps in thrombin ACKNOWLEDGEMENTS
generation of a cross-linked fibrin clot are shown diagrammatically
in Fig. 126.11. Other plasma proteins and blood cells are also trapped We the authors would like to thank Matthew Gissel in the prepara-
within the clot. Clot formation is integrated with clot dissolution by tion of this chapter. The authors were supported by the NIH-DOD
plasmin to maintain hemostatic balance. The plasminogen system has TACTIC study 1-UM-1-HL120877-2, the Systems Biology program
two roles: t-PA generates plasmin at the fibrin surface and governs ARO-W911NF-10-1-0376, and by the United States Naval Health
fibrin homeostasis, and u-PA binds to a cellular u-PA receptor Research Center contract W911QY-15-C-0027.
(u-PAR) and generates pericellular plasmin, which plays an important
role in tissue remodeling and cellular migration. 339,340 The latter
function is, to a great extent, mediated by plasmin activation of
matrix metalloproteinases, which degrade ECM. t-PA and u-PA are SUGGESTED READINGS
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