Biomedical Engineering Reference
In-Depth Information
17.7 BLOOD COMPATIBILITY TESTING
The testing of blood compatibility of medical implants has been laid down in the ISO standard
10993-part 4.
106,107
This norm describes standards, methods, and evaluation procedures that have
to be followed in order to get approval for the use of a blood-contacting device. In general, blood-
contacting devices have to be fully blood compatible, which means that no adverse effect of the
device on blood can occur. Also the blood should not have adverse effects on the function and sta-
bility of the device. Overall, one can imagine that the safety requirements for permanent implants
in contact with blood is quite strict, since the blood circulation can potentially spread a response
initiated by an implant over the entire body.
For a blood-compatible material or surface to be called blood compatible, a number of require-
ments need to be fulfi lled:
a. thrombus formation on the surface should be minimized or eliminated;
b. platelet adhesion and activation should be minimized or eliminated;
c. leukocyte adhesion and activation should be minimized or eliminated;
d. complement activation should be minimized or eliminated;
e. hemolysis, the damage to blood cells, should be minimized or eliminated; and
f. endothelial layer (endothelialization) formation should be promoted (in case of permanent
implants).
Furthermore, the materials from which the blood-contacting device has been constructed should
also not cause general or systemic toxicity (chemicals slowly leaching from the device). The extent
of response that is acceptable depends very much on the time of contact and the place of implanta-
tion (on the skin or inside tissues).
The description of blood compatibility testing in the ISO 10993-4 standard gives guidelines
for systematic testing of blood compatibility.
106
A major problem is that a large number of different
assays and standard materials are being used. This results in many variables in testing of blood-
contacting devices, making comparison of test results complicated and unreliable.
Blood compatibility tests can be performed
in vitro,
ex vivo
, or
in vivo
.
In vitro
testing means
that the device is tested in contact with blood from preferentially human donors outside the body.
Ex vivo
testing makes use of shunting blood from an animal or human directly to the test chamber.
The blood can then be collected for analysis (single pass), or can be directed back into the circula-
tion of the animal. For
in vivo
testing a suitable animal model is chosen, and the device is implanted
in a tissue, that is representative for the intended use in humans. The choice of the animal model
can strongly infl uence the outcome of the
in vivo
experiments, and therefore animal model and
the procedure have to be chosen with care. The most preferred animal model would be nonhuman
primates like chimpanzees or baboons. The use of such animals is bound to strict regulation and is
also very expensive. Therefore, the most used animal models for implantation of blood-contacting
devices are goats, sheep, pigs, and dogs. Extrapolation from the animal model to the human situa-
tion is not straightforward and should be done with extreme caution.
For different devices, different sets of experiments are required. This is determined by the
intended use of the device, therefore if it will only contact the blood outside the body (canules,
blood bags, collection tubes) implantation studies are not required. For short-term blood contact
(catheters, hemodialysis equipment, guidewires, intravascular devices) or when the blood stays in
the patient after contact, of course some
in vivo
testing is required, although long-term implantation
studies are only required for implanted devices (like heart valves and vascular prostheses).
In vitro
testing is always performed in order to avoid complete failure in the more laborious and expensive
in vivo
experiments. In the remaining portion of this chapter some of the test procedures will be
discussed in more detail, focusing on the ones most used.
