FIV and the CBC



  •   1.  Introduction

  •   2.  Red Cell Values and Anemia

  •   3.  White Cell Values

  •   4 . White Cell Differential

  •   5.  Neutrophils

  •   6.  Lymphocytes

  •   7.  White Cell Summary

  •   8.  Platelets

  •   9.  Pancytopenia

  • 10. Normal CBC Reference Ranges (opens in a separate window)

  • Click here to open a Glossary of Terms in a separate window.


  • 1. Introduction

  • The CBC (Complete Blood Count) is a blunt instrument for making FIV-related judgments until it is very well advanced. But it is worthwhile to have a basic understanding of what its elements mean and what they do or don't have to say not only about FIV disease advancement, but about secondary problems that may or may not have a relation to FIV induced immune suppression. While not all vets are sympathetic to the idea, asking for copies of CBCs and other test results is a good practice for people with FIV+ cats. People with HIV are encouraged to have CBCs every six to twelve months if they are asymptomatic, and every six months if they are symptomatic. A particular challenge in the case of FIV is that bloodwork often is not done when a cat is not showing symptoms of an illness. Finding "footprints" of FIV-related immunosuppression in a cat whose CBC is already registering the effects of the problem that occasioned it is not easy, even when FIV disease has progressed. Close attention to physical findings, to disease history, to the presence, absence, and pattern of fever, and to range of symptoms in providing a context for the CBC is crucial in this regard.

  • It is also important to understand that the figures on the CBC represent a snapshot in time of a dynamic process. All blood cells arise out of stem cells in the bone marrow and, if there is a need for their action, disappear into bodily tissue. Between occurs a complex process of differentiation and maturation, reserve duty in the stand-by pool, circulation in the peripheral blood, sequestration in the spleen, and "margination" (adhesion) to endothelial cells in the walls of blood vessels. All of these processes potentially affect the numbers reported. This is one reason why values derived from CBCs taken not too far apart may produce different results, indicating a dynamic disease process or simply normal fluctuation. Because varying values can still be consistent with good health, CBCs contain a column of quite broad "Reference Ranges" indicating the range of normal values for a given item. These values vary from laboratory to laboratory but usually not by much.

  • Some of the values reported on CBCs can be done "in house" so that a vet has some information to make quick judgments with. Even when this is done, though, there is usually a follow-up CBC with Differential (a breakdown of white cell types) done by a lab using automated equipment. The information contained in the report may vary somewhat from lab to lab or in accordance with specific information requested by the vet. But all CBCs contain information on red cells/erythrocytes (which carry oxygen bound in hemoglobin), white cells/leukocytes (responsible for immune response) and platelets/thrombocytes (necessary for clotting). Whatever other information is given about red cells, all CBCs contain a red cell count (RBC), a red cell density percentage (hematocrit/HCT, sometimes called a Packed Cell Volume/PCV), and a hemoglobin estimate (HG). The hematocrit can often be performed in house, and is, in fact, the value most often cited with regard to FIV (and HIV). All CBCs with Differential will also cite a total white cell count and will break those cells down into counts and percentages for individual types. For most purposes, absolute counts are more important than percentages, which may be misleading, for instance, when cell counts are very low. Of the white cells, the neutrophil and lymphocyte reports are those most directly relevant to FIV-status. The other white cells usually reported on -- monocytes, eosinophils, and basophils -- are essentially markers of inflammatory and/or tissue-injury response of one sort or another. As such, they may provide useful information about secondary disease processes. Eosinophils, for instance, are often telltale markers of hypersensitivity and inflammation due to allergy or parasites. Declining platelet counts are important markers for a number of specific pathologies (for instance, worsening leukemia) and may reflect particularly what is going on in the spleen, the organ responsible for filtering out abnormal, dead, or damaged blood cells. Splenomegaly (enlargement of the spleen) is a frequent result of disorders that profoundly affect the blood. So is liver disease.

  • 2. Red Cell Values and Anemia

  • A possible byproduct of acute inflammation, chronic inflammation, and a variety of other conditions, Anemia is a deficiency in hemoglobin as indicated by the three values (RBC, HCT, HG) characteristically reported on. Other values ("red blood cell indices") appearing on a report (mean corpuscular volume/MCV, mean corpuscular hemoglobin/MCH, and mean corpuscular hemoglobin concentration/MCHC) do not reflect independent measurements of anything. They are values derived by dividing one of the three aforementioned values by another in order to make logical deductions that provide clues to the source of anemia, since anemia is not itself a disease entity but a symptom of some other problem. The MCV, for instance, is derived by dividing the HCT (cell density) by the RBC (cell number). (Modern automated blood analyzers can now calculate MCV by other means as an independent value.) If, for instance, the hematocrit remained constant but the number of cells were decreased, the MCV would rise; the logical deduction would be that the cells themselves were larger. So a higher-than-normal MCV would indicate a "macrocytic" (literally "large-cell") anemia. Macrocytic anemia might be transient (indicating that an unusual number of immature, large red cells are being produced to compensate for blood loss or that the body was attacking and destroying its own red cells) or ongoing (the result of a maturation defect affecting division of cells and resulting in large cells, as for instance with B12/folic deficiencies) [Rebar]. So while there are still numerous possible causes of the anemia, the field has been narrowed. When this information is combined with information derived from the MCH and MCHC and with irregularities of cell appearance ("red cell morphology") provided as separate notations by the pathologist, the field of possibilities is reduced further. (See *Note on red cell morphology at the end of this section.)

  • Another very important piece of information is whether an anemia is regenerative or nonregenerative, that is, whether the bone marrow, where cells are created from progenitor cells, retains adequate capacity to replace lost cells. This information is not generally included on a CBC report, although a pathologist can reach tentative conclusions based on microscopy and might conceivably place a note on the CBC report. However, the gold standard for establishing whether an anemia is regenerative or nonregenerative is a reticulocyte count. Reticulocytes are immature, and therefore newly produced, red cells, a characteristic of a regenerative anemia. Absolute counts of immature red cells are more reliable indicators of "hemolysis" (red cell destruction) or red cell loss through bleeding than percentages [Rebar]. It is possible, however, that a regenerative response typical of a hemolytic anemia may be concealed for a time in cats having a concurrent nonregenerative anemia stemming from chronic disease or other causes [Barger]. Although primary immune-mediated (i.e., auto-immune) hemolytic anemia has been recorded in FIV+ cats, it is uncommon, far less so, certainly, than secondary IMHA caused by parasitic infection [Dowers], discussed further on. The likelihood that an anemia is hemolytic is strong if a blood test for the presence of antibody or complement called a Coombs Test returns a positive result.

  • Anemia in an FIV+ cat has all of the possible causes of anemia in an FIV- cat. So it is premature to suppose that anemia, as a reported CBC finding in an FIV+ cat, is directly related to FIV status; it might not even be indirectly related. One large study did report overall lower scores by FIV+ cats in erythrocyte (RBC) counts, in packed cell volume/hematocrit (PCV/HCT), and in hemoglobin (HG) at month 30 post-infection. [Hofmann-Lehmann]. Another large study of FIV+ cats at all stages of disease found that sick FIV+ cats were neither more nor less likely to display anemia than FIV- cats, but were statistically more likely to show anemia when not displaying a particular pathology [Walker]. The presumption was that the virus was responsible for reduced red cell production. (These statistical statements, of course, might not hold true in any given cat). FIV does not directly infect and kill erythroid precursor cells in the bone marrow [Walker]; while the exact method has not been fully elucidated, it is believed that this and other bone marrow suppression are a result of infection of other ("accessory") cells in the marrow environment and a failure of stimulus as a result of the presence of viral antigen [Linenberger]. A new (2008) study found hematological abnormalities in 24 of 50 FIV-infected asymptomatic cats (48%) in which no other explanatory cause was found. “Anemia only, neutropenia only, thrombocytopenia only, bicytopenia and pancytopenia were observed in 10%, 10%, 6%, 14% and 8%, respectively” [Fujino].

  • The most characteristic finding for anemia in an FIV+ cat is that it is nonregenerative. The CBC will likely report MCV in normal range (normocytic/normal cell size) and MCHC likewise in normal range (normochromic/normal hemoglobin concentration). Is the anemia caused by FIV suppression of bone marrow regenerative capacity? Not necessarily, not even probably. The most common finding for cats with chronic diseases of any kind is a nonregenerative anemia. This is, in fact, called "anemia of chronic disease," which is caused by a combination of mechanisms, including decreases in iron availability, erythrocyte survival, and response to erythropoietin [Barger]. Not until the degree or duration of anemia expected from competing causes is exceeded might it legitimately be suspected that FIV is involved. The hematocrit usually does not fall below 20% in anemia of chronic disease [Barger]. In some cases, analysis of the marrow itself can provide information pointing to an FIV-related component.

  • Assuming that a mystery anemia points to FIV-induced bone-marrow suppression is problematic for a number of reasons. (1) The bone marrow is only one element of the system involved in regenerating the blood cycle. The kidneys, liver, and spleen are also directly involved, and problems in one or more of those organs might have a long background before significant clinical evidence comes to light. It is by no means unprecedented, on the basis of FIV+ status and a highly significant anemia, that a clinical diagnosis of "late stage" FIV disease is mistakenly given for what turns out to be a liver problem. This is why a chemistry panel and a urinalysis are often necessary adjuncts to a CBC in pinpointing the origin of anemia. (2) Cancers often not easily detected except by advanced diagnostic procedures are capable of producing moderate and severe nonregenerative anemias that are might initially be ascribed to "late stage" FIV. (3) Not all FIV-related anemias are nonregenerative. In a minority of instances, FIV+ cats have displayed highly regenerative anemias without other traceable origins [Pedersen]; they are assumed to be autoimmune in origin and related to a whole variety of autoimmune phenomena, from diabetes to arthritis, observed in FIV+ cats as a result of the high degree of immune activity associated with chronic FIV antigen stimulation.

  • All FIV+ cats displaying moderate to severe anemia and even low-grade fever in the absence of other obvious symptoms suggesting a particular pathology should, in addition to a CBC, receive a chem panel, a urinalysis, a reticulocyte count, and some form of screening for blood parasites. Mycoplasma haemofelis (formerly known as hemobartonella) and in some places throughout the world babesia, are parasites that attach to (but do not infect) red blood cells, resulting in an assault by the immune system on what are perceived to be infected cells requiring lysis (destruction). The result is a massive die-off of blood cells that overwhelms the spleen and liver, downstream organs whose job it is to filter red cells, and that induces the bone marrow to keep churning out new cells to replace the dead ones. Hemobartonella, the commonest and most widespread blood parasite, produces a variety of disease pictures. The consistent feature is a highly regenerative anemia that will be immediately apparent with a reticulocyte count--if there were a reticulocyte count. Since this count is not, however, a characteristic feature of the CBC, it is usually necessary to order a second test after the results of the first establish that there is anemia. The CBC often contains a specific notation of "No blood parasites observed," and in-house microscopy is often done as well. But blood parasites are not always visible under the microscope. Sending a sample off for PCR (a kind of genetic testing) is a worthwhile expenditure if the emergent picture (highly regenerative anemia, liver disturbance, and, usually, fever) is consistent with blood parasites.

  • *Note on red cell morphology. Among the most common notations associated with anemia are anisocytosis and poikilocitosis. Anisocytosis refers to variation in red cell size. A mix of small and normal size cells may indicate iron deficiency; a mix of large and normal size cells may indicate abnormal cell development, such as occurs with FeLV infection. Poikilocytes (cells with abnormal shapes) may be further broken down into subcategories. Spherocytes, for instance, are round red cells (normal ones are bi-concave in shape) that may indicate an immune-mediated anemia. Schistocytes have a "torn" character as a result of squeezing through narrowed capillaries and often accompany DIC (a pathological activation of coagulation mechanisms) and disturbances of the liver and spleen. Target cells (bull's eye shaped) and acanthocytes (with irregular projections) form as a result of abnormal lipid-cell membrane interactions that may reflect liver, spleen, or kidney disturbances [IDEXX].

  • 3. White Cell Values

  • White cells derive from same multipotential stem cells as red cells. At the first branching of these "hematopoietic" (blood forming) stem cells are myeloid and lymphoid progenitor cells, the first, the myeloid progenitors, giving rise to the cells of the "natural" immune system--and the red/erythroid cells and platelets, as well--, the second, the lymphoid progenitors, giving rise to the cells of the "specific" immune response. The neutrophils, basophils, eosinophils, and monocytes reported on the CBC all descend from the the same "myeloblast" precursor. The "lymphocytes" reported on the CBC are the only representatives of the specific immune response. Although they further divide into B cells, T cells, and NK cells (Natural Killer cells, which, curiously, are part of the natural immune response and are particularly important for tumor cell surveillance), this breakdown is not represented on the CBC. It would be useful if it could be, since T cells are the most significant targets of FIV. The natural immune response is the "as is" branch of the immune system, providing first response to alien antigens. The T and B cells of the "specific" immune response kick in sometime later and require a complex process of tutoring in order to configure themselves to mount a specific response to a specific pathogen. If the pathogen has been encountered previously, memory T and B cells initiate a more rapid specific response.

  • The white cell count alone provides useful information prior to any breakdown into constituent cells. An abnormally depressed white count is always to be regarded as a pathologic circumstance [Sprayberry]. Elevated white counts characterize, among other things, inflammatory processes that may be pathogenic in origin (as with bacteria or parasites outside the GI tract such as toxoplasmosis or hemobartonella), allergic in origin, or non pathogenic in origin (as with chronic pancreatitis or inflammatory bowel disease). A very high count might indicate a severe localized inflammation; a mild elevation might indicate a more diffuse and chronic inflammation [Rebar]. Low white counts in immunocompetent cats are most often due to viral infection. White counts by themselves can also provide confusing information. White counts, particularly lymphocyte counts [Campbell], decline with age, for instance. Bacterial infections, can sometimes cause low white counts, instead of high ones. An elevated white count may also indicate nothing more than a high level of excitement or stress in a cat.

  • It would be nice if it were possible to judge the extent of FIV disease progression by a nicely declining curve in the white cell count as a result of viral influence on cell depletion, but this is not the case. Despite occasionally recorded and unexplained episodes of leukopenia (the -penia suffix indicates abnormal shortage, -osis or -philia an abnormal excess), most field studies of naturally infected cats find no WBC abnormalities in asymptomatic FIV+ cats [Shelton, Bendinelli]; at least one did, but with reservations [Walker]. A study of experimentally infected cats found no WBC abnormalities after 64 months, but did record a variety of red cell values that were abnormal [Hoffman-Lehmann]. Statistical differences that several studies found were largely on the chem panel (glucose, serum protein, gamma globulins, sodium, urea, phosphorus, aspartate aminotransferase, glutamate dehydrogenase, lipase, cholesterol, and triglyceride), indicating energy and lipid metabolic defects, excessive antibody activity, and subclinical kidney and liver dysfunction [Hofmann-Lehmann, Bendinelli, Gleich]. But even these values remained within normal limits. A deficiency of white cells appears to be a possible finding in cats at all symptomatic stages of FIV disease advancement [Shelton], but is not to be expected as a marker of movement from asymptomatic to symptomatic status. WBCs of sick FIV+ cats correlate largely to their disease state, not to their FIV+ status [Walker]. In some cases WBC of symptomatic FIV+ cats settle at an unusually low-normal level, periodically dipping below normal values. Conversely, there have also been reports of leukocytosis (elevated white count) in FIV+ cats unexplained by secondary disease [Bendinelli]. Sustained abnormality of leukocyte counts without an alternative explanation can be regarded as FIV-related, but this is a diagnosis of exclusion. In summary, there is no agreed-upon "characteristic" WBC for FIV+ asymptomatic or symptomatic cats. In any case, since part of the immunosuppressive activity of FIV involves impairment of white cell function--neutrophils as well as lymphocytes--counts alone cannot provide a complete measure of immune status. This impaired functioning is often present without any evidence of leukopenia and increases susceptibility to gram-negative, gram-positive, and fungal infections [Heit]

  • 4. White Cell Differential

  • Gaining maximum information from white cell counts requires a breakdown into counts of individual white cell types. A broad rule of thumb, for instance, is that viral infections depress neutrophil numbers and percentages relative to lymphocytes, while bacterial infections widen the ratio between them, which normally favors neutrophils already. Rules of thumb can be misleading, though. Viral infections sometimes breed secondary bacterial infections so that over time the ratio may change considerably [Merck]. Or consider the following table illustrating patterns of leukocyte response:
  •  
  •  
  • WBC
  • Neutrophils
  • Band
  • Neutrophils
  • Lymphocytes
  • Monocytes
  • Eosinophils
  • Acute Inflammation
  • Increased
  • Increased
  • Increased
  • Decreased or no change
  • Variable
  • Variable
  • Chronic Inflammation
  • Increased or no change
  • Increased or no change
  • Increased or no change
  • Increased or no change
  • Increased
  • Variable
  • Overwhelming Inflammation
  • Decreased or no change
  • Decreased or no change
  • Increased
  • Decreased or no change
  • Variable
  • Variable
  • Excitement Leukocytosis
  • Increased
  • No change in cats
  • No change
  • Increased in cats
  • No change
  • No change

  • Stress Leukogram
  • Increased
  • Increased
  • No change
  • Decreased
  • Increased or no change
  • Decreased or no change
  • -Rebar AH., Metzger F. Interpreting Hemograms in Dogs and Cats. The Veterinary CE Advisor. 2001          

  • In one instance, an "overwhelming" inflammation may result in a normal white cell count because tissue demands for immune cells are matching or outstripping marrow production. While other factors would undoubtedly indicate that all was not "normal," the only dependable indication on the "Leukogram" is the invariable increase of "band" cells, that is, neutrophils released in an immature state because of high demand upon the bone marrow. (Segmented neutrophils are mature neutrophils.) Or consider again the distinction between "stress" and "excitement" as causes of elevated WBC, the first by the internal release of cortisol, the second of epinephrine, where the important distinction is the decrease of lymphocytes in the first instance and the increase (in cats) in the second. A "stress leukogram" indicates the effect of (1) steroidal drugs, (2) short-term (as little as four to eight hours) stressors such as pain, emotional distress, and bodily insult, (3) or longer-term stressors such as cancer or debilitating illness. The presence or absence of elevated numbers of monocytes, eosinophils, or basophils may further help to pinpoint the reason for abnormal WBC. Monocytosis (elevation), for instance, is particularly associated with the need for "phagocytes," (antigen gobbling cells) to address ongoing tissue damage characteristic of chronic or (sometimes) acute localized inflammatory problems. (Monocytes morph into macrophages when they enter tissue.) Elevation of Basophils is a good indicator of inflammatory processes, and, like eosinophils, may be particularly indicative of parasitic infections or hypersensitivies. Mild eosinophil elevations tend to occur more often in benign situations, but eosinophilia is an important indicator of certain types of bacterial infections (strep or staph), of allergic responses, of a particular allergic response leading to eosinophic granuloma complex, and sometimes mast cell tumors, lymphoma, or other carcinomas [Ishida].

  • 5. Neutrophils

  • Unlike lymphocytes, which take several days to configure but can be recycled into circulation, neutrophils have been compared to expendable "pac men," constantly circulating in the peripheral blood, at the ready. Because neutrophils have rapid turnover, remaining in circulation only for about 48 hours, CBCs will register spikes or depressions more rapidly than with lymphocytes. Because they are the chief immune defense against bacterial and fungal invaders, elevated neutrophils are most often associated with these types of infection. When demand is high, ready reserves can be called in from a "storage pool," but a significant infection may necessitate highly accelerated production in the bone marrow. A typical acute inflammation is characterized by neutrophilia (elevation) with what is termed a "left shift," meaning the presence of significant numbers of immature neutrophils. This phenomenon is sometimes labeled "with left shift" on the CBC report or may be indicated simply by the presence of significant numbers of band cells. Normally, the Bands column will read zero or close to it. The left shift may be noted as "regenerative" if mature cells outnumber immature cells, "degenerative" if the reverse is true. The latter would indicate a guarded prognosis and might occur in cases of septicemia (the presence of infectious microbes or their toxins in the blood) or impaired marrow production. Concurrent lymphopenia and monocytosis if there is tissue damage are expected findings where left shift indicates acute inflammation [Sprayberry]. Chronic inflammatory diseases, if low grade and diffuse, are characterized by a high normal or slightly elevated neutrophils, no left shift, and normal lymphocyte counts, indicating a regained balance between marrow production and tissue demand and the ramping up of the specific immune response. Monocytes are usually slightly elevated because of ongoing tissue injury. If the inflammation is more focal, as with, say, an abscess, neutrophil counts may remain high and left shifted. Some bacteria evoke more intense neutrophil response than others. Very high WBC are almost always caused by very high neutrophil counts. The CBC report may also carry a notation of "toxic neutrophils," followed by a number from +1 to +4 indicating grade of toxicity and/or pathologist's comment noting specific cell abnormalities. (Döhle bodies are often noted, indicating extranuclear bodies in the cellular cytoplasm.) Toxic neutrophils are abnormal in appearance (taking on some of the granular characteristics of basophils) and most often occur as a result of bacterial toxins or excessive demand on neutrophil precursors. Gram negative bacteria release substantial amounts of endotoxins when they are destroyed because the endotoxin is a structural component of their cell wall. In some cases, bacterial infections can cause neutropenia, a dearth of neutrophils. Endotoxemia, for instance, causes increased expression of adherence molecules on the walls of blood vessels, in turn causing neutrophils to stick to them and decreasing counts in the circulating blood [Sprayberry]. Neutrophils are especially sensitive to the effect of toxic substances and drugs, sometimes even common drugs such as cimetidine (Tagamet) or penicillin and cephalosporin antibiotics. Neutropenia is usually evident also in the early stages of viral infections. A low ANC (absolute neutrophil count) for a length of time considerably heightens the risk of opportunistic infection.

  • FIV-associated neutropenia occurs both early and late in FIV infection. Severe neutropenia without concurrent anemia is a common feature of initial acute FIV infection and lingers for weeks before receding. One study found week 6 post-infection as the mean time for appearance, with a duration of about six weeks [Linenberger]. It concluded that infection of cells in the bone marrow microenvironment and a dearth of growth promoting substances, not infection of neutrophil precursor cells, were the likely causes. This stage of infection is probably not often caught in clinical practice, so neutropenia is unlikely to be detected and reported on a CBC at that time. If the finding were registered on a CBC and FIV+ status later came to light, this could be one means of dating the time of infection. In one study of cats mostly at a symptomatic stage of FIV disease, neutropenias occurred in 34%, only slightly less than anemias (36% in this study) [Shelton]. A more recent large study found neutropenia the most common differential [Gleich]. The mechanisms involved have never been fully elucidated. FIV rarely infects neutrophils; whether late-stage FIV infects precursors in the bone marrow is uncertain, although some studies do find fewer of them in advanced infection. Autoimmune attack by host antibodies may also be involved. However, the best documented causes of neutropenia in advanced FIV disease are the same as with acute infection: infection of accessory cells in the bone marrow and altered immune-signalling [Tanabe] [Linenberger]. A cat with neutropenia reported on a CBC without explanatory secondary disease features should be suspected of FIV disease advancement to an ARC-like or AIDS-like stage. However, as previously noted, functionality, as well as numbers, is important. One study of FIV+ cats found impaired function of circulating neutrophils at several stages involved in recruitment to infected tissue. Whether this is related to reduced T cell numbers is unclear. GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor), a major regulator of neutrophil function, is primarily produced by the T cells lost to FIV infection, so this is perhaps evidence of the way in which what happens in the specific immune system affects the natural immune system, as well [Heit]. Conversely, when cats show a remarkable degree of neutrophilia without any obvious focus of infection, "paraneoplastic syndrome" should be suspected, with GM-CSF (and other hematopoietic signaling proteins) enhancing the production of neutrophils and their release from bone marrow into the peripheral blood [Lucas]. This reaction can occur with gastrointestinal and other lymphomas to which FIV+ cats are liable.

  • 6. Lymphocytes

  • Lymphocytes provide both a nonspecific (immediate) response to alien pathogens and tumor cells and a specific (configured) response. They are particularly important in the defense against viruses. B lymphocytes give rise to plasma cells that produce antibodies. T lymphocytes destroy infected cells to prevent the spread of infection. Inversion (called “reversal”) of the ratio of lymphocytes to neutrophils is a mark of some types of viral infection. A normal ratio in cats is around 2:1 favoring neutrophils, although considerable latitude for normal variation exists. A sharp decline in neutrophils rather than a sharp rise in lymphocytes is usually most responsible for reversal. Actual lymphocytosis (elevation) is unusual in cats and would indicate epinephrine-mediated excitement [Feldman], inflammation of lymphatic tissues, chronic antigenic stimulation as in some types of infection, chronic lymphocytic leukemia, or lymphoma [Barger]. Presence of abnormal immature blast cells strongly in the context of lymphocytosis suggests malignancy such as high grade lymphoma, acute lymphoblastic leukemia or other myeloproliferative disorders [Ishida]. Lymphocytes will often decline in the initial phases of some viral infections [Merck]. In infection situations, a reversed N:L ratio that continues to grow in favor of lymphocytes would indicate an acute viral infection becoming chronic. A CBC report will sometimes contain a notation on "reactive lymphocytes." Reactive lymphocytes are atypically large and, like some neutrophilic band cells, may assume a basophilic character. They are sometimes found in viral diseases and certain protozoal infections (e.g., toxoplasmosis), as well as following vaccination. This is called reactive lymphocytosis, and will end when recovery occurs. A few reactive lymphocytes are not uncommon, but if there are more than a few, then the body is responding to antigenic stimulation of some sort [DeNicola] An ongoing lymphocytosis with immature lymphocytes in the blood lacking the basophilic morphology most often indicates lymphoma [Barger]. Lymphopenia is far more common than lymphocytosis, typically occurring (as already noted) in stress reactions, bacterial infections, and the early stage of many viral infections.

  • In one early study, FIV+ cats with ARC-like or AIDS-like clinical features exhibited lymphopenia (sometimes called lymphocytopenia) more than any other cell abnormality, in more than half (53%) of all cases [Shelton]. In another study, healthy FIV+ cats displayed lymphopenia (accompanied in some cases by eosinopenia) more than healthy FIV- cats [Walker]. T lymphocytes are the cells most commonly infected by FIV. Although some are lost to infection, many more are lost to spontaneous cellular destruction ("apoptosis") as a result of ongoing exposure to viral antigen. (Neutrophils have also been observed to have shorter lifespans in FIV+ and HIV+ individuals because of apoptosis.) The growing gap between the target Helper-T (T4/CD4+) lymphocytes and both the Cytotoxic-T (cell killing, T8/CD8+) lymphocytes and antibody-precursor B-lymphocytes is explained by a loss of Helper-T's, not by a gain in the other lymphocyte lines. Still a steady decline in Helper T cells in asymptomatic or symptomatic cats may not noticeably affect the white cell or the lymphocyte counts. At a late stage of infection absolute losses in Cytotoxic-T and B cell groups also occur. In HIV medicine lymphocyte counts of fewer than 1250 cells are sometimes used to predict an AIDS-defining Helper T cell count (<200) in places where T cell testing is unavailable, but no one has suggested applying a similar rule of thumb to cats.

  • 7. White Cell Summary

  • One educational source summarizes with the following suggestions for interpreting the white cell portion of the CBC:
  • --Neutrophilia with slight left shift and with persistence of eosinophils suggests a mild infection.
  • --Neutrophilia with a relative lymphopenia and an absolute eosinopenia indicates a moderately severe to severe infection.
  • --A falling total white count with a reduction in neutrophils and a return of lymphocytes and eosinophils to normal levels represent the changes in convalescence.
  • --Leukopenia is common to viral diseases but is also present in bacterial infection with septicemia, and there may be a degenerative left shift.
  • --Bacterial infection with localization and pus formation stimulates marked neutrophilia.
  • --Before the abscess becomes encapsulated, the total leukocyte count may be marked to extreme.
  • --Neutrophilia is associated with a variety of noninfectious conditions which induce the stress reaction, e.g., malignancy; metabolic intoxication, as in uremia; hemolytic crisis or acute blood lost; and in the postoperative state.
  • --Left shift with immature neutrophils in excess of mature neutrophils indicates an unfavorable prognosis.
  • --A severe infection is indicated when toxic changes in neutrophils . . . are prominent. Prognosis should be guarded.
  • --An extremely high leukocyte count consisting mainly of neutrophils is an unfavorable sign.
  • --A marked absolute reduction in lymphocytes which persists justifies a poor prognosis.
  • -Leukocyte Function and Clinical Interpretation        

  • 8. Platelets

  • Thrombocytopenia (shortage of platelets) is more common on CBC reports than in actual fact. Undercount of platelets is a common testing "artifact" of a CBC, artifact meaning a result of the test procedure itself rather than of whatever it is the test is supposed to be measuring. Platelet clumping is a common phenomenon and prevents accurate automated or manual platelet counting. The "platelet estimate" is the best indicator of the adequacy of platelet numbers in such situations. Thrombocytopenia may be found in some immune disorders such as lupus or thrombocytic purpura, where the platelets are coated with antibody and marked for destruction. Primary immune-mediated thrombocytic purpura (ITP) is rare, but ITP secondary to some viral infections has been recorded. Splenomagaly (enlargement of the spleen) frequently accompanies ITP, the spleen being the location for the platelet destruction. In one study, FIV+ cats were numbered among cases where the cause was immune-mediated [Kohn], but it does not appear to be as common a finding as in HIV infection. Association with feline leukemia and feline distemper (panleukopenia) is stronger [Barger]. Sepsis (a systemic inflammatory response to infection) and certain cancers are other likely causes of thrombocytopenia[Rebar], although abnormalities in other cell types will likely be evident. Thrombocytopenia is the least common of FIV-related deficiencies among the major cell types (erythrocytes,lymphocytes,and neutrophils). In one study of naturally infected FIV+ cats in a clinical setting only 8% of the cats so presented, vs 36%, 53%, 34%, respectively for deficiencies of the other cells [Shelton]. A German study of 40 FIV+ cats at all disease stages that focused on platelets found only 4 cats to be thrombocytopenic, although FIV+ cats generally showed a degree of clotting abnormality [Hart]. However, true thrombocytopenia unaccompanied by other red or white cell abnormalities would be an unlikely FIV-related finding in most circumstances.

  • 9. Pancytopenia

  • Pancytopenia (deficiency in all blood cell lines) is an uncommon finding in cats. A University of Minnesota review of 2011 CBCs found only 56 instances (2.8%). Although infectious disease was the most common cause (14 instances), there were a number of other causes: drug-associated disorders, immune-mediated haematological diseases, chronic renal failure, idiopathic aplastic anaemia, and additional undescribed causes. The study defined pancytopenia as a PCV < 26%, segmented neutrophils < 3000/wl, and platelets< 200,000/wl [Weiss]. Pancytopenia is not a common finding in FIV+ cats in whom other causes are lacking. Given the strong association of FIV and lymphoma, a bone marrow biopsy would be justified in an FIV+ pancytopenic cat. The absence of cancer would certainly rule in AIDS, although pancytopenia is not a necessary finding in order to justify assigning a cat to end-stage FIV disease status. Moreover, by one estimate fewer than 10% of clinically ill FIV+ cats present with AIDS, and only a minority of FIV+ cats will ever progress to AIDS before dying of some other cause. Where infectious disease is the cause, pancytopenia is more likely to be found in cats with feline leukemia (with or without concurrent FIV) and feline distemper (panleukopenia) [Merck].

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  • References

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  • http://vetclinpath.net/Documents/Complete%20Blood%20Cell%20Count.pdf

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