Biomedical Engineering Reference
In-Depth Information
spreading, occupying more surface area until the fully spread morphology is reached, which is asso-
ciated with full activation of the platelets. It has been shown that activated blood platelets shed small
vesicular structures called microvesicles. 51 - 53 The microvesicles are highly thrombogenic and they
have been proposed to play a role in coagulation and atherosclerosis, although some investigators
doubt that these microvesicles actually occur in vivo . These investigators claim that the formation
of microvesicles only occurs upon contact with foreign, synthetic surfaces. Fact is that in blood and
blood products used for transfusion purposes these microvesicles are present.
Additionally, thrombin can activate platelets, increasing the amount of available negatively
charged surface, resulting in rapid clot formation and clot propagation. This means that a combina-
tion of platelet adhesion and activation, and thrombin generation will induce blood clot formation
on blood-contacting devices. In summary, platelets have an important role in coagulation and exten-
sive adhesion and activation of platelets on synthetic surfaces should be avoided.
17.5.4 C OMPLEMENT S YSTEM
The complement system is the fi rst line of defense against pathogens invading in the blood. 4,17,54 It
consists of a family of proteins that function or as proteases or as binding proteins. These proteins
are also organized in a cascade (Figure 17.9) similar to the coagulation system (Figure 17.6). There
are two pathways of complement activation. The classical pathway is mainly activated by anti-
gen-antibody complexes. This will lead to the activation of the C1q,r,s complex that can proteolyti-
cally cleave C4 and C2. This results in the formation of the C3 convertase, C4b2a. The alternative
pathway is triggered by the presence of foreign surfaces like bacteria or fungi or biomaterials. This
pathway also results in a C3 convertase, namely C3bBb. In fact this pathway is always activated in
Classical pathway
activators
C4
C3
Alternative pathway
activators
C1q,r,s
C1q,r,s
C4a
C3a
C4b
C3b
B
C2
C4b2
C3bB
C3
D
Ba
C2b
C4b2a
C3bBb
C3a
C3b
C6
C7
C9
C8
C5
C5b
C5a
C5b67
C5b-9
FIGURE 17.9 Complement system activation. The classical pathway is activated by antigen-antibody com-
plexes, while the alternative pathway is being activated by the presence of cell walls of fungi or bacteria. Both
pathways generate C3 convertase complexes (C4b2a and C3bBb), which results in cleavage of C3 into C3a and
C3b. C3b can act as an opsonin or can induce the formation of the membrane attack complex (C5b-9), which
can lyse cells or unicellular pathogens.
 
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