Ask Dr. Stephan Moll

These questions have been submitted by folks on the mailing list and answered by Dr. Moll, Director of the Thrombophilia Program at the Carolina Cardiovascular Biology Center, Department of Medicine, Division of Hematology-Oncology, UNC Chapel Hill (North Carolina, USA). Why am I doing this?

31. Factor V Leiden: Laboratory tests

Q1: "Why do some test results for factor V Leiden (FVL) come back "normal"? It seems to reason that test results should come back either positive or negative for FVL. Since there continues to be confusion between factor V Leiden and factor V deficiency, is the latter at times tested in place of testing for FVL? Since the test results came back quot;normal" for 2 of my relatives, could they have been tested for factor V deficiency? If not, what is a person to conclude upon discovering their test results are "normal"?
A1: It is incorrect and confusing terminology to say that the factor V Leiden test was "normal". The wrong test can, indeed, have been performed. The patient needs to ask her/his physician to clarify the issue.

Q2: "I had an abnormal APC resistance test. Does this mean I have factor V Leiden? Should I still get the genetic test"?
A2: To have an abnormal APC resistance test does not necessarily mean that you have factor V Leiden. There are other causes for an abnormal APC resistance test. Yes, the patient should still get the genetic test.

The diagnosis of FV Leiden is either made by

• genetic testing, called PCR (= polymerase chain reaction) or,
• by APC-resistance assay (= activated protein C resistance assay). There are important limitations to this latter test.

When performing the genetic test for factor V Leiden, the lab should report that the patient either:

1. does not have factor V Leiden, or
2. is heterozygous for factor V Leiden, or
3. is homozygous for factor V Leiden

The same unambiguous terminology should be used by the physician who passes the test results on to the patient. When performing the APC-resistance test, the lab should report that the patient either

• has a normal APC resistance test, or
• abnormal test suggesting that the patient may be heterozygous for factor V Leiden, or
• abnormal test suggesting that the patient may be homozygous for factor V Leiden

Since abnormal APC resistance tests can be due to other reasons than factor V Leiden (such as antiphospholipid antibodies and other, yet unknown, reasons), an abnormal test does not prove that the patient has factor V Leiden. An abnormal APC resistance test result should always be followed by the genetic factor V Leiden test to confirm that the patient does, indeed, have factor V Leiden. Up to 37 % of patients with an abnormal APC resistance test do not have factor V Leiden [references 1 and 2]. On the other hand, a normal APC resistance test means that the patient does not have factor V Leiden and a confirmatory genetic test is not necessary.

The phrase that the "factor V Leiden test was normal" is unfortunately used by some physicians, often with the meaning that the factor V Leiden mutation was not discovered on genetic testing, i.e. that the patient does not have factor V Leiden. However, the terminology "normal" is inaccurate and confusing, particularly because at times the wrong test (factor V activity test) is ordered instead of the genetic test. A normal factor V activity test means that the patient does not have factor V deficiency, but does not exclude factor V Leiden. The issue is further discussed in Q/A 7. What is a person to conclude upon being told their test result is "normal"? The person should ask her/his physician what test was really done. If it was the genetic test, then the patient should ask: "Do I have factor V Leiden, am I heterozygous, or am I homozygous?" If the APC resistance test was performed and was normal, then the patient does not have factor V Leiden; if it was abnormal, the patient should ask for the confirmatory genetic test to be done. If the factor V activity test was performed, then the wrong test was done. The best thing would be for the patient to ask for a copy of the lab report and keep it with her/his own medical records.

References:

1. Journal of Vascular Surgery 1998;28:624-629;
2. Clinical & Laboratory Haematology 1997;19:67-71

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