Biomedical Engineering Reference
In-Depth Information
17.7.1 T HROMBIN G ENERATION AND T HROMBUS F ORMATION
The activation of the coagulation cascade is one of the most common problems for blood-contacting
devices. The adsorption of plasma proteins can lead, via the activation of the intrinsic pathway, to
the generation of thrombin and subsequent thrombus formation. The formed blood clots can block
blood vessels (thrombosis), and cause hypoxia and dysfunction of downstream tissues and organs.
In the case of stents and synthetic blood vessels, this is the biggest concern. For other devices the
release of small clot fragments (emboli) can result in distant embolization, leading to myocardial
infarction, for instance.
Routinely coagulation disorders are determined in vitro measuring thrombin time (TT), acti-
vated partial thromboplastin time (APTT), or prothrombin time (PTT). 106,108 - 110 These assays depend
on the fact that the formation of a blood clot is determined by the concentrations and activation state
of the coagulation factors. In case of TT, the time in which a certain amount of thrombin results in
a thrombus is determined. For the APTT the blood is challenged by an external stimulus that will
activate the intrinsic pathway of the coagulation cascade. Finally, the PTT measures the clotting
time upon addition of a combination of PL and TF so that the extrinsic pathway is triggered. The
advantage of these methods is that they can be performed almost anywhere, they are very reproduc-
ible, and they are cheap. The disadvantage is that they are relatively insensitive and that they all
depend on an external stimulus. 106,109,110 In fact, in the case of blood-contacting devices, one is not
really interested in these parameters, but the biomaterial-induced thrombin generation is important.
Also these clotting assays in general work with PPP. 110 The role of platelets, leukocytes, and even
the erythrocytes is not taken into account, which is an oversimplifi cation of the in vivo situation.
Therefore, it is preferable to incubate the blood-contacting device with recalcifi ed whole blood and
measure the formation of thrombin and a clot.
The formation of blood clots is a very easy and effective way to estimate the performance of a
blood-compatible surface (Figure 17.13). The device or material is incubated in whole blood, and
the time it takes to form a clot on the surface is determined. This method is very effective in demon-
strating the performance of good blood-compatible surfaces, since no clot will form on their surface
when compared to a bad surface like bare steel, Tefl on (PTFE), or glass.
The formation of a blood clot is preceded by the generation of thrombin, the central enzyme
in coagulation (see Figure 17.4). For quantifi cation, it is better to determine the time course of
Coating
Coating + heparin
10 µ m
10 µ m
FIGURE 17.13 Clot formation on guidewires coated with a hydrophilic polymer. The inclusion of hepa-
rin in the coating inhibits blood clot formation. In the scanning electron micrographs, one can distinguish
erythrocytes and fi brin. On the heparin containing coating, no thrombus was formed.
 
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