Lithium heparin is an anticoagulant used inside blood collection tubes to keep blood samples from clotting. If you’ve had blood drawn into a green-topped tube for chemistry tests, there’s a good chance it contained lithium heparin. It works by preventing the clotting process so the lab can separate plasma from blood cells and run tests on it quickly, which is why it’s the go-to choice for urgent bloodwork in emergency departments.
How It Prevents Blood From Clotting
Heparin is a naturally occurring sugar-based molecule covered in negatively charged sulfate groups. When it enters a blood sample, it latches onto a protein called antithrombin, which is one of the body’s built-in clotting regulators. On its own, antithrombin slowly neutralizes the enzymes that trigger clot formation. But when heparin binds to it, antithrombin’s clot-blocking ability increases roughly 1,000-fold. This burst of activity shuts down thrombin and several other clotting factors almost immediately, keeping the blood sample liquid.
The “lithium” part refers to the lithium salt form of heparin. Lithium was chosen because it doesn’t interfere with most of the blood chemistry tests labs commonly run. Sodium heparin and ammonium heparin also exist, but lithium heparin is the most widely used version for general chemistry panels because lithium ions are rarely measured in routine blood work.
The Green-Top Tube
Blood collection tubes are color-coded by the additive inside them. Green tops contain heparin, most commonly the lithium salt. When your blood fills the tube, it mixes with a pre-measured amount of lithium heparin, typically at a concentration of 10 to 30 USP units per milliliter of blood. That’s enough to prevent clotting without distorting most test results.
Unlike red-top tubes, which produce serum (the liquid left after blood clots and the clot is removed), green-top tubes produce plasma. Plasma still contains fibrinogen and other clotting proteins because they were never activated. This distinction matters because plasma can be separated from blood cells faster than serum, since you don’t have to wait for a clot to form first.
Why Labs Use It for Emergency Testing
Speed is the main advantage. Serum tubes require blood to clot for 20 to 30 minutes before they can be spun in a centrifuge. Lithium heparin tubes skip that waiting period entirely. A standard lithium heparin tube can be centrifuged at 2,000 times gravity for about 10 minutes, or at higher speeds (3,000 to 4,000 times gravity) for as little as 3 to 5 minutes. That time savings adds up fast when a patient in the emergency department needs results immediately.
This is why green-top tubes are the default for “stat” chemistry requests: electrolytes, kidney function markers, liver enzymes, blood sugar, and similar tests that guide urgent treatment decisions.
What It Can and Can’t Be Used For
Lithium heparin tubes work well for a broad range of routine chemistry tests. Most electrolytes, metabolic panels, and enzyme measurements perform reliably in heparinized plasma. The tube is also used for some blood gas analyses, where keeping the sample from clotting is essential for accurate oxygen and carbon dioxide readings.
There are important exceptions. The most obvious one: you cannot use a lithium heparin tube to measure a patient’s lithium level. The lithium salt in the tube would contaminate the sample and produce a falsely elevated reading. Patients on lithium therapy for bipolar disorder have their levels drawn into a different tube type, usually a red-top or gold-top serum tube.
Another documented issue involves certain creatinine assays. Research published in 2021 found that lithium heparin directly interferes with at least one major enzymatic creatinine test, and the problem gets dramatically worse when tubes are underfilled. In samples with only a small amount of blood in the tube, creatinine readings were on average 40.6% higher than the true value. That’s a clinically significant error that could make kidney function appear worse than it actually is. Filling the tube to the correct volume (marked by the fill line) prevents this problem.
How Long Samples Stay Accurate
Once blood is in a lithium heparin tube, the clock starts ticking on sample stability. A 2019 study examined how long common chemistry results remain reliable at room temperature (about 21°C). The key findings paint a practical picture for labs:
- Most analytes: stable for at least 6 hours whether the tube has been centrifuged or not.
- Phosphorus: begins dropping after about 3 hours in uncentrifuged samples, falling roughly 6% from baseline.
- Potassium: decreases modestly (about 3%) after 6 hours if the tube hasn’t been centrifuged. This is the opposite of what happens in serum tubes, where potassium tends to rise over time as it leaks out of red blood cells.
- Bicarbonate: drops nearly 20% after 6 hours in plasma that has already been separated, making it one of the least stable analytes.
These stability windows explain why labs prioritize spinning and analyzing lithium heparin samples promptly, especially for analytes like bicarbonate and phosphorus.
How It Differs From Other Tube Types
The choice of collection tube depends entirely on which test the lab needs to perform. EDTA tubes (lavender tops) are standard for complete blood counts because EDTA preserves cell shape and size. Citrate tubes (light blue tops) are used for coagulation studies because the citrate can be precisely reversed during testing. Lithium heparin tubes occupy the space between: they’re ideal for chemistry and metabolic panels where speed matters and where the lithium and heparin won’t interfere with the assay.
Within the heparin family, lithium heparin is preferred over sodium heparin when sodium is being measured, and over ammonium heparin when ammonia levels matter. Each salt form avoids contaminating the specific analyte it might otherwise affect. For most general chemistry work, lithium heparin covers the widest range of tests with the fewest interference concerns, which is why it has become the default in most hospital and reference laboratories worldwide.