Biomedical Engineering Reference
In-Depth Information
The Vroman effect is seen on most surfaces. This is the turnover at the same
surface site of one protein by another as time progresses, which also may later be
replaced by a third.
Many proteins may be deposited at their own times (and conditions of flow) that
have not yet been investigated.
Blood Coagulation and Fibrinolysis
When blood is exposed to damaged tissue or to an artificial surface, blood
coag-
ulation
takes place, which comprises a series of consecutive enzymatic reactions
(a cascade) that leads to the conversion of
fibrinogen
into a
fibrin clot
. Intimately
associated with coagulation is the process of
fibrinolysis
, the enzymatic breakdown
of fibrin (usually by
plasmin
). The dynamic steady state of coagulation and fib-
rinolysis maintains the patency of the circulatory system. Fibrin formation is a
major contributor to thrombosis. There are two pathways for coagulation, which
at a certain level merge into a common pathway.
The
intrinsic pathway
is triggered by collagen or other subendothelial compo-
nents (or negatively charged surfaces) that on contacting factor XII activate it into
factor XIIa. In this process, two other plasmatic components are involved as well,
high molecular weight kininogen (HMWK) and kallikrein. Factor XIIa activates
factor XI into XIa, which in turn, in the presence of Ca
2
C
activates factor IX into
IXa. Then IXa in the presence of platelet membrane phospholipids, Ca
2
C
, and factor
VIII converts factor X into Xa. This activated factor Xa, together with factor V and
in the presence of Ca
2
C
, binds to platelet membrane phospholipids. The complex
formed (sometimes referred as prothrombinase) catalyzes factor II (prothrombin) to
thrombin
(factor IIa). There are positive feedback mechanisms involving thrombin
and the previous reactions, where factors V and VIII are involved.
The extrinsic pathway
is triggered by tissue thromboplastin (made available
either by subendothelium or by stimulated leukocytes, or by activated endothelial
cells). Thromboplastin in the presence of Ca
C
2
complexes with factor VII to activate
X into Xa. This is a point of convergence with the intrinsic pathway.
The generation of thrombin, therefore, is the key point of both coagulation path-
ways to make the final coagulation product, i.e., fibrin fibers. As it is the case in
most situations, the process of activation of the circulating clotting factors has a
counteraction. Indeed, there are a number of naturally occurring protease inhibitors,
including antithrombin-III (AT-III). Deficiency of AT-III in a patient is associated
with an increased risk of venous thrombosis.
Fibrinolysis
also follows intrinsic or extrinsic pathways and depends on the
plasma protein
plasminogen
.
In summary if an artificial or natural surface, negatively charged, comes in
contact with blood, coagulation is initiated. This contact system of coagulation con-
sists of four proteins: factors XII, XI, prekallikrein and HMWK. Activation of the
contact system initiates the intrinsic and extrinsic coagulation pathways, intrinsic
fibrinolysis, and the complement, kinin and renin-angiotension systems.
