(Blood) Red Herrings: What can impact your lab results that doesn’t indicate disease

Lab work is a crucial step in forming a diagnosis, preparing for anesthesia, or deciding what treatment plan to pursue. When you’re getting that lab work back it’s important that you can trust the results or at least be able to parse out the important readings from the (blood) red herrings. There are many things to keep in mind, from what patient you are collecting from, how it goes into a tube, to having the results in front of you.

Species and Breed

The first thing that can affect your lab work is the species and breed you have in front of you. While a veterinary article could cover many different species and their unique make up, we’ll focus on dogs and cats.

Many canine breeds have specific lab work findings that would raise concern if they were any other patient. Many times my stomach has dropped with concern when I see an abnormal lab result, only to remember it fits the breed!

For example, Greyhounds, sighthounds, and some dachshunds are prone to erythrocytosis. This may mean higher pack cell volume, hematocrit, hemoglobin concentration, and red blood cell count. Greyhounds also tend to have slightly lower platelet counts, white blood cell counts, and even higher blood urea nitrogen and creatinine concentrations. Always pair those kidney related findings with a urinalysis. If the urinalysis shows adequate concentration and no proteinuria, it’s safe to say it’s breed-related and monitoring going forward is appropriate.

The beloved Cavalier King Charles Spaniel has congenital macrothrombocytopenia, and unlike their congenital heart disease it is unlikely to affect their daily life. The mutation causing this CBC finding causes platelets to stay together instead of dividing appropriately during production; however, it does not affect clotting times or platelet function.

Our Asian breeds, such as the Akita, Shiba Inu, Jindo, Chow Chow, and Shar pei, are known to have pseudohyperkalemia , often paired with pseudohyponatremia. This phenomenon is caused by the Na-K pump working in red blood cells. The longer plasma is in contact with the red blood cells and the more hemolysis that occurs, the more affected sodium and potassium will be on lab work.

There are also benign familial traits to consider, such as hyperphosphatasemia in Siberian Huskies and Scottish Terriers. At least in Siberian Huskies it’s been shown to be a bone isoenzyme that is familial and autosomal.

Familial hypercholesterolemia is also common in several breeds, including:

• Briards
• Rottweilers
• Doberman pinschers
• Rough Collies
• Shetland sheepdogs

Hydration Status & Most Recent Meal

Aside from breed you might have a patient in front of you affected by many other factors, including hydration status, most recent meal, stress, and age.

While any healthy animal should theoretically be well-hydrated, we do have to keep in mind that they may not always come in with an ideal hydration status. Maybe the cat saw the carrier come out the day before and has been hiding under the bed ever since. Maybe it’s a first morning appointment and the dog didn’t drink any throughout the night. Hydration status can affect a myriad of values, and pairing those increases with the signalment, exam, history, and other lab work (such as urinalysis) is crucial.

The last time the patient ate and how long ago also plays a huge role in blood work. In an ideal world, all samples would be fasted to provide an unbiased baseline. Of course, it’s hard to tell our canine patients not to sneak food off the counter prior to their appointment, compared to our doctor telling us to skip Starbucks prior to ours. Thus, when reading samples we need to keep in mind that peak postprandial glucose is 1-3 hours after a meal, and peak triglycerides are 2-5 hours after a meal. Lipemic samples can interfere with analyzers and cause increased creatinine, albumin, bilirubin, hyponatremia, and hyperproteinemia. Typically, lab companies will provide a lipemic index to decipher whether it’s a “real” value versus the effects of a lipemic sample.

Stress

Once you know what kind of water and food intake your patient has had, the patient is now in your hospital and has unfortunately become a ball of anxiety. We take as many steps as we can to reduce F.A.S., but there will certainly still be some stressed patients.

The classic example is the feline patient with stress hyperglycemia. This can be teased out by assessing how high the hyperglycemia is, along with an urinalysis. True persistent hyperglycemia will result in glucosuria, while transient stress hyperglycemia will not. Anxiety can also lead to the physiologic leukogram (mild neutrophilia, lymphocytosis). Ensuring that the changes are a result of the patient’s fight or flight response should include pairing your findings with current clinical signs and other lab work abnormalities.

This also goes for mild erythrocytosis related to splenic contraction in stressed dogs. If in doubt, the physiologic stress leukogram and erythrocytosis should resolve within 30min of the patient relaxing. A stress leukogram pattern, with neutrophilia, lymphopenia and monocytosis, could be the result of true disease (hyperadrenocorticism, sick patients), but it may be expected if there is exogenous steroid administration. This is where a thorough history of current medications will be important. As evident, “stress” can play a huge role in our lab work outcomes.

Now, pretend you have a happy Saint Bernard puppy in for some pre-castration blood work. He has yet to find out what is coming his way, but he has an increased calcium. Young animals, especially large breeds, tend to have a higher calcium. How do you know if it is a concern? Use the adult reference range plus 0.1–0.5 mmol/L as the high end of the reference interval.

This Saint Bernard could also have a high alkaline phosphatase. Knowing that he is young can prevent pursuing unnecessary diagnostics out of concern for the liver and gallbladder. Concentrations of ALP are highest in liver and bone; thus, this goes up not only with hepatitis but also with bone growth. Growing animals can have as high as 3-4 times the adult ALP reference interval.

Drawing Blood

Now you’ve seen your patient, understand the breed and physiologic changes that could affect your lab work, and you’re drawing the blood.

Maybe you have that stressed cat that needs a medial saphenous draw. You’re slowly pumping out the blood, trying not to collapse the vein while simultaneously counting the kitty minutes you have left. You get your blood work back, and thrombocytopenia is evident. Knowing how long it took to draw the blood, along with checking the tube for any obvious clots can solve the puzzle. It is also recommended to review a blood film for microscopic platelet clumps, especially if a large clot is not obvious. Placing the blood in appropriate tubes is a no-brainer, but a slow draw or an inappropriate amount of blood placed in the tube can cause a clot and affect our values.

Remember an appropriate sized needle!

As we fly through our busy days we also need to remember an appropriate sized needle, to avoid contamination of additives, and to ensure everything is properly stored for in-house use or to ship off to the lab. Rough handling, such as a small gauge needle spewing blood into a vacuum tube can easily cause hemolysis, resulting in various derangements.

While these derangements can vary greatly with the type of blood, the analyzers used, and storage time, the most common increases in dogs include creatinine phosphokinase, lactic dehydrogenase, aspartate aminotransferase, lipase, and albumin.

When handling tubes, EDTA contamination is particularly common as we often put the blood in a purple top first to prevent it from clotting. If not careful, EDTA can get on your needle and cause hyperkalemia and hypocalcemia. Once I had a foreign body patient wagging his tail visiting with his owners. His recent lab work showed hyperkalemia that was so high he should have been weak and entering ventricular fibrillation! As we suspected, it was contaminated and a repeat electrolyte panel showed normal potassium.

In summary

Understanding lab work is truly a puzzle, and I think solving puzzles is one of the reasons many of us were drawn to the veterinary profession. Hopefully the above red herrings on blood work, caused by breed, artifact, or physiologic factors, can be that reminder of what is “normal”, even if your results look full of scary abnormal values. When in doubt, combine with other diagnostics, repeat what you can, and pair with the overall clinical picture.

References

Allen, Julie. Differential Diagnosis: Hypercholesterolemia. Internal Medicine/Clinical Pathology. 2019 Feb. https://www.cliniciansbrief.com/article/differential-diagnosis-hypercholesterolemia

B. Davis, M. Toivio-Kinnucan, S. Schuller, and M.K. Boudreaux Mutation in b1-Tubulin Correlates with Macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 2008;22:540–545 p. 542

Degen M. Pseudohyperkalemia in Akitas. J Am Vet Med Assoc. 1987 Mar 1;190(5):541-3. PMID: 3558091.

Lawler DF, Keltner DG, Hoffman WE, Nachreiner RF, Hegstad RL, Herndon PA, Fischer BJ. Benign familial hyperphosphatasemia in Siberian huskies. Am J Vet Res. 1996 May;57(5):612-7. PMID: 8723869.

Morissette, Eric. Inflammation, Stress, or Something Else? Clinical Pathology. www.zoetisus.com

Nestor DD, Holan KM, Johnson CA, Schall W, Kaneene JB. Serum alkaline phosphatase activity in Scottish Terriers versus dogs of other breeds. J Am Vet Med Assoc. 2006 Jan 15;228(2):222-4. doi: 10.2460/javma.228.2.222. PMID: 16426191.

O’Neill SL, Feldman BF. Hemolysis as a factor in clinical chemistry and hematology of the dog. Vet Clin Pathol. 1989;18(3):58-68. doi: 10.1111/j.1939-165x.1989.tb00519.x. PMID: 15156513.

Sakals S, Peta HG, Fernandez NJ, Allen AL. Determining the cause of hypercalcemia in a dog. Can Vet J. 2006 Aug;47(8):819-21. PMID: 16933565; PMCID: PMC1524827.

Silva, Nathalia, et al. 2019/02/01. Post-prandial lipemia and glycemia in dogs fed with industrialized pet food. VL 28. Doi: 10.1007/s00580-018-2824-0. Comparative Clinical Pathology.

Sullivan PS, Evans HL, McDonald TP. Platelet concentration and hemoglobin function in greyhounds. J Am Vet Med Assoc. 1994 Sep 15;205(6):838-41. PMID: 7829376.

Washington, Ida, M., et al. The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents, 2012.