When to Say No: Sample Rejection Criteria

As a clinician, you want answers. When a sample is borderline, the temptation is to say, "Just run it and let's see."

In cfDNA testing, this is dangerous. A compromised sample doesn't just give a "blurry" result; it can give a confidence-destroying False Positive (indicating high cell death where there is none) or a False Negative (missing a cancer because the signal was diluted).

Here are the 4 absolute Deal-Breakers. If your nurse brings you a tube like this, reject it.

1. The Clot

* The Sign: A small jelly-like blob in the EDTA tube, or the blood is solid. * The Reality: The clotting cascade has activated. WBCs have lysed. Platelets have degranulated. This is now serum, not plasma. * Action: Redraw. (Check your ratio of blood to anticoagulant next time).

2. The Cherry Soda (Hemolysis >2+)

* The Sign: Plasma is red or dark pink. * The Reality: While we can mathematically correct for mild (straw/light pink) hemolysis, dark red implies massive cellular destruction. The genomic DNA contamination is too high to trust a "negative" cancer result. * Action: Redraw. Use a larger needle or a fresh stick.

3. The Warm Weekender

* The Sign: An EDTA tube drawn Friday arrives at the lab on Tuesday, and the ice pack is melted. * The Reality: The 4-hour stability window is long gone. The sample is effectively a soup of necrotic white blood cells. * Action: Reject. Do not send it. If you must ship over a weekend, use a Streck tube.

4. The "Drop"

* The Sign: You send 0.2 mL of plasma when the lab asked for 1.0 mL. * The Reality: cfDNA is a trace analyte. We often need to extract DNA from a large volume (1–2 mL) to get enough atoms to sequence. If the volume is too low, the sensitivity drops. We might miss the cancer simply because we didn't have enough plasma to find the fragments. * Action: Fill the tube. Ensure you draw enough whole blood (approx 3x the plasma volume needed) to get the yield.

The Bottom Line: A rejected sample causes a delay. A bad result causes a misdiagnosis.