What to do when blood work is normal in a sick dog.

Pardon me while I preface this discussion with the following disclaimer. I often get inquiries about sick Shar-Pei and “the blood work is normal”. I will be talking about what I do in such cases. The material contained herein is based on my experience, what I’ve read in the veterinary literature, opinions and observations. Any comments, criticism or questions should be directed to me. I also look at this as a work in progress and fully expect to add to it as experience, new information and discussions with colleagues further enlightens me. I present this material now to provide some insight into what to do with the difficult Shar-Pei case.

I look at the diagnostic workup in any sick animal in terms of levels. These levels may be thought of as the floors of a building and divide out based on the availability of tests, costs of tests, ease of obtaining the test samples, the equipment needed to run the diagnostic tests and the experience and comfort level of the veterinarian in interpreting the test results. The higher you go up in the building the more specific, more specialized and more expensive the tests become.

(CBC), a blood chemistry screen, a urinalysis, a stool sample check and usually a chest and abdominal radiograph or radiographs. The purpose of the basic workup is to provide a sense of direction for additional testing, if needed. Many times the basic workup provides enough information for a diagnosis. The fact that the basic workup doesn’t provide a diagnosis should not be interpreted to mean that the dog is normal or that there is nothing wrong. Normal results more often mean additional testing needs to be done. Another possibility is that the workup was done too early in the course of the disease process before significant changes have occurred. This workup doesn’t adequately evaluate the gastrointestinal system, the endocrine system, the neurological system, the cardiopulmonary system or the musculoskeletal system. It often does not help when evaluating for infectious diseases or immune-mediated disease.

Once the basic workup is complete and has not provided a definitive diagnosis, the third level  of diagnostics come into play. In my scheme of things, this is the level in which the options for diagnostic testing increase dramatically. Hopefully, the information gathered at the first and second levels provides enough information to narrow down the testing choices in this third level. In this category I place serologic testing for leptospirosis, testing for systemic mycoses such as blastomycosis and histoplasmosis,and coccidioidomycosis and aspergillosois these can be diagnosed  from a urine

sample by V[IMiraista  Vista Diagnostics(www.MiraistaVets.,Indianapolis).

testing for tick-borne diseases such as Lyme’s disease, ehrlichiosis,bartonella and others. Other blood tests in this category would include testing for immune-mediated diseases such as autoimmune hemolytic anemia, systemic lupus erythematosus, immune-mediated thrombocytopenia, myasthenia gravis, masticatory myositis, etc. Bacterial culture and sensitivity testing would be included here as would uncommon tests such as urine protein: creatinine ratios and urine cortisol: creatinine ratios. Additional testing could also include tests of the endocrine system such as the ACTH stimulation test and dexamethasone suppression tests for Cushing’s disease, thyroid function tests, insulin levels, etc. Testing of pancreatic digestive function utilizing the TLI (trypsin-like immunoreactivity test) may also fit in this level. Tests of the gastrointestinal system like a B12/Folate blood test or the newer fecal a1- proteinase inhibitor test fit in this level as well. There are quite a few blood tests at this level but bear in mind that the information obtained from the first two levels will provide a direction for the testing here. Other testing here would include contrast radiographic studies, which utilize iodine-containing solutions or barium to highlight the gastrointestinal tract, the urinary bladder, the kidneys, the spinal canal, etc. Electrocardiography and blood pressure measurement might also be used at this level. Also cardiac biomarkers such as BNP and Troponin I used to asses heart muscle damage.

A definitive diagnosis may still be elusive and fourth level diagnostics may be required. Diagnostic tests here include ultrasonography, contrast radiography, MRI, CT, EEG scans,for epilepsy, ,laparoscopy and fiberoptic endoscopy. Various biopsy techniques including the exploratory laparotomy are placed at this level. Please remember this classification is my own way of explaining diagnostic testing. The levels are not written in granite and vary with the availability of equipment and laboratory services. For example, a veterinarian with ultrasound experience and equipment may do an ultrasonographi examination very early in the workup. Likewise a veterinary internist may proceed directly to specialized testing that a general practitioner may not have access to or not do very often.

With the “ain’t doin’ right” Shar-Pei the following disease categories need to be considered specifically:

1. Inflammatory Bowel Disease Gastrointestinal disease often is not demonstrated in the general workup, but I do pay particular attention to the albumin and total protein levels. These are often slightly low due to loss of protein in the GI tract which occurs with IBD. Additional tests which may help to further define the problem include a direct fecal smear to rule out Giardia, a fecal floatation to rule out intestinal parasitism, a trypsin-like immunoreactivity test (TLI) to rule out exocrine pancreatic insufficiency or lack of digestive enzymes, a B12/Folate blood test to rule in protein-losing enteropathy and a relatively new test called a fecal alpha-1 protease inhibitor test which also helps to diagnose protein-losing enteropathy. These tests can be done at many local veterinary labs or more information can be obtained from theGastrointestinal Function Test Laboratory, College of Veterinary Medicine, TAMU 4474, College Station, TX 77843-4474, phone (979) 862-2861. They also have a web site at cvm.tamu.edu/gilab. Ultimately, IBD is a diagnosis based on intestinal biopsies via exploratory abdominal surgery or fiberoptic endoscopy.
2. Familial Shar-Pei Fever A multitude of abnormalities can show up in the blood work in cases of FSF depending on when during the episode blood tests are taken. Usually a moderate to severe stress leukogram is present characterized by a neutrophilia or increase in the neutrophil count. Often there is an increase in the liver function test results due to the release of acute phase reactant proteins. Other changes can include increases in kidney function tests due to dehydration and electrolyte abnormalities due to vomiting and diarrhea. The diagnosis is based on the characteristic fever and fairly quick response to therapy. Complications of FSF need to be considered such as DIC (disseminated intravascular coagulation), STSS (streptococcal toxic shock syndrome), splenic torsion or thrombosis, thromboembolism in general, SIRS (systemic inflammatory response syndrome) and MODS (multiple organ dysfunction syndrome).
3. Cancer, in general, can result in clinical signs of weight loss, changes in behavior, decreased appetite, lethargy, depression, etc. Primary cancer types to think about in Shar-Pei include lymphoma and mast cell cancer. Radiographs often are helpful as are additional diagnostics such as ultrasound, CT scans, MRI and exploratory surgery with biopsy. As an aside, gastrointestinal lymphoma can present with clinical signs similar to IBD.
4. Endocrine diseases are a fourth category in which vague and nonspecific clinical signs often predominate. Hypothyroidism, Cushing’s disease (hyperadrenocorticism), Addison’s disease (hypoadrenocorticism) are diseases, which may not easily show up on routine blood testing and require additional tests to diagnose them.
5. Infectious diseases including tick-borne diseases can also have vague signs and require additional blood testing beyond the routine workup. These diseases include Lyme’s disease, ehrlichiosis, babesiosis, leptospirosis, and others. Systemic mycoses (fungal infections) such as blastomycosis, histoplasmosis and, in some parts of the country, cocciodiodomycosis would be included in this category as well. Chronic bacterial disease such as brucellosis should be considered in appropriate circumstances. Further pursuit of these diseases involves the use of serologic blood testing.
6. Immune-mediated disease including immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediate skin disease such as pemphigus variants, hepatitis, glomerulonephritis, and various neuromuscular disorders such as myasthenia gravis and masticatory myositis fit in this category. Specialized tests are necessary such as various immune panels, acetylcholine receptor antibody levels, 2M muscle antibody levels, etc.
7. The cardiopulmonary system can be further evaluated with the use of an electrocardiogram, cardiac ultrasound. I have seen primary and metastatic (cancer spread from another area to the lungs) neoplasia to the lungs, heart-based tumors and primary heart disease in Shar-Pei. Early in the course of these diseases coughing and breathing problems may not be part of the clinical picture and only decreased activity, weight loss, loss of appetite may be noted.
8. The neurologic system is notorious for being difficult to evaluate. Additional testing involves CSF (cerebrospinal fluid) tap, myelograms, CAT scans and MRI studies. Diseases to rule out include various types for cancer including lymphoma, and discrete tumors involving the brain and spinal cord. Inflammatory disease such as granulomatous meningoencephalomyelitis (GME) and otitis media or middle ear infection need to be considered. Another conditions to be considered here in the Shar-Pei is glaucoma or an increase in intraocular pressure. In some Shar-Pei I’ve seen an early intermittent glaucoma characterized by temporary blindness and pain which may last for only a few hours and then return to normal. Checking intraocular pressure during an episode would be the means of diagnosis. Another aspect of this subject involves Cognitive Dysfunction Syndrome (CDS) also called canine Alzheimer’s disease. Many vague symptoms can fit this syndrome in the older patient. Lastly, emotional and behavioral upsets can often reflect as vague and non-specific signs such as loss of appetite, weight loss, lethargy, etc.
9. The musculoskeletal system is also not evaluated very well in the routine workup. Pain related to degenerative joint disease (arthritis) and/or muscle/ligament strains and sprains can be reflected in vague signs such as decreased activity, decreased appetite, lethargy and changes in behavior. Often diagnosis is based on additional radiographs and, more importantly, response to therapy with pain-relieving medications. Anterior cruciate ligament rupture and luxating patella involve the stfle, hip dysplasia and elbow dysplasia are orthopedic problems seen in Shar-Pei.
10. gait analysis testing is more available.
11. Lastly, in intact animals, the reproductive system can be a source of vague symptoms. In males, I worry about prostate disease whether it be prostatitis, benign prostatic hypertrophy, prostatic abscesses or cysts, testicular torsion or prostatic cancer. In females we need to consider ovarian disease such as ovarian cysts or ovarian cancer and uterine diseases such as endometritis, pyometritis, uterine cancer, etc.
12. Various other tests. A relatively new test has been introduced in the last 7-10 years is a canine

cancer blood test :the TK  canine cancer panel  using chemuminescent and sandwich Immunoassay methodology. (Veterinary Diagnostics Institute,California)VDI) This test combines two indepenent measures of cellular irregularity –Thymidine Kinase Type-1( and a cellular proliferation marker and CRP (c-reactive protein  abiomarker of inflammation.these two markers generate are used to generate a neoplasia  index (NI).

13. (A positive NI signals the presence cancer. The NI can be used to monitor cancer treatment
14. And success of surgery.

One of the tmajor points in the workup is to do it within a reasonable period of time. Too often therapeutic trials are tried as the pet continues to deteriorate and by the time additional testing and/or biopsies are recommended it’s too late. The Shar-Pei owner must decide early in the course of the workup how far to go in terms of finances, time, commitment to the :pet,prognosis,quality of life issues.

etc. Often the delays in the progression of the workup are

due to wavering on the owner’s part.

My intent has been to illustrate the complexities of the workup and the range of diagnostic tests and procedures, which are available to the pet owner and the veterinarian. There are other testing procedures I may have missed and others, which will be available in the future. One thing is always certain – cutting edge technology will never stand still.