Hemolytic Effect Test: ISO 10993-4 and Medical Device Safety

Biocompatibility Test Methods for Medical Devices (ISO 10993 Series)

Materials used in blood-contact devices, such as intravenous catheters, hemodialysis sets, blood transfusion sets, vascular prostheses, need to be assessed for blood compatibility to ensure their safety. All materials are incompatible with blood to some degree as they can disrupt blood cells (hemolysis) or activate coagulation pathways (thrombogenicity) and/or the complement system.

What is a Hemolytic Effect?

Hemolysis is the process by which red blood cells (erythrocytes) break down and free hemoglobin is released into the blood. When a device that is incompatible with blood is used, the surface or material of this device can cause damage to cells when it interacts with blood cells. This is known as the hemolytic effect. The hemolytic effect can directly affect the biocompatibility of medical devices and can lead to serious health problems.

Hemolysis testing is a recommended test method for all devices or device materials except those in contact with intact skin or mucous membranes. The Hemolytic Effect (Blood Compatibility) (ISO 10993-4) test is performed to measure the damage to red blood cells when exposed to the material or extracts and compared to positive/negative controls.

Coagulation tests measure the effect of the sample on human blood clotting time. Hemolytic Effect (Blood Compatibility) Testing is recommended for all blood-contact devices.

Prothrombin Time Assay (PT): A general screening test for the detection of clotting abnormalities in the extrinsic pathway.
Partial Thromboplastin Time Assay (PTT): Performed to detect clotting abnormalities in the intrinsic pathway.

The most common test for thrombogenicity is in vivo methods, and for medical devices that are not suitable for this test method, testing is required in each of the four categories covered by the ISO 10993-4 standard: coagulation, platelets, hematology and complement system.

For implant devices in contact with blood, complement activation testing is recommended. This in vitro test complements activation in human plasma as a result of exposure of plasma to the test substance or extract and aims to demonstrate that the test substance is capable of inducing a complement-induced inflammatoryimmune response in humans.

Interpretation of the Results of the Hemolytic Effect Test

ISO 10993-4 sets certain limits on the interpretation of results from the hemolytic effect test. Generally, the hemolysis rate is evaluated as follows:

0-2% Hemolysis: Usually negligible and the device is considered to be compatible with blood.
2-5% Hemolysis: There may belimited effect, but device compatibility can still be ensured. Relevant regulatory bodies may require repeat testing or additional analysis.
Over 5% Hemolysis: This is ahigh risk situation and means that the device is not compatible with blood. In this case, the device may require reformulation or design changes.

Nanolab Laboratories Group continues to provide services within the scope of Medical Device Analysis.

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