Today I gave a lecture on hCG testing to 4th year medical students at the University of Utah. Part of that lecture included the tragic ordeal of Jennifer Rufer. In 2001, she was awarded nearly 16 million dollars because of a misdiagnosis of cancer from a false-positive pregnancy test. I previously wrote about false-positive pregnancy tests from urine specimens. This post deals with false-positive results from blood tests.
The same things that can cause false-positive results from urine specimens can also cause false-positive results from blood samples. It might help to review those first. There is another cause of false-positive hCG test results that is unique to blood samples: interfering antibodies.
First, a quick summary:
- Human blood normally contains many different types of antibodies: molecules made by our immune system that identify and neutralize invaders such as bacteria and viruses.
- Animals make antibodies, too, and their antibodies are used to make the components of hCG tests. For example, mouse antibodies that recognize human hCG molecules are used in tests that measure the concentration of hCG. One mouse antibody binds to one part of the hCG molecule (capture antibody) and a second mouse antibody binds to a different part of the hCG molecule. That second mouse antibody has a signaling molecule attached to it. We can measure the strength of that signal and that signal strength will be equal to the amount of hCG that it is bound to:
- Some people's immune systems make antibodies that react against animal antibodies. These "anti-animal" antibodies can cause false-positive hCG test results because they connect the capture antibody and the signaling antibody together even when hCG is not present, like this:
This was the cause of Jennifer Rufer's false-positive pregnancy test. Unfortunately for her, the false-positive result was recognized for what it was only after she had been treated for what her doctors thought was an aggressive type of cancer called choriocarcinoma.
It's uncertain how many people have interfering antibodies in their blood. Some estimate the frequency as high as 10-20%, other studies put that number much lower at <1%. It doesn't really matter how many people have them but what does matter is how doctors and laboratorians work together to identify this problem when it occurs. That's easier said than done.
Why? Because the laboratory that does the testing is nearly always unaware of the medical history of the patient so it's practically impossible for the lab to know if an hCG result is inconsistent with the patient's condition. The lab has to rely on the doctor to question an hCG test result when it don't fit what they are seeing in their patient. If the hCG result doesn't fit the clinical picture and the doctor calls the lab for help, there are investigations the lab can do to help identify if an interfering antibody is present or not. But without that call questioning the result, the lab doesn't have reliable mechanisms for identifying all cases of interfering antibodies.