BLOOD LOSS ANEMIA

Acute blood loss in otherwise normal dogs and cats results in reticulocytosis (i.e., regeneration) within 48 to 96 hours. Therefore animals evaluated shortly after a traumatic injury and severe blood loss usually have nonregenerative anemias with low-to-normal serum (plasma) protein concentrations. The source of bleeding should be identified and the bleeding stopped; if the patient is bleeding as a result of a systemic hemostatic defect, it should be identified and specific treatment should be initiated (see Chapter 87). Aggressive intravenous (IV) fluid therapy with crystalloids or colloids or the transfusion of blood or blood products is often required in patients with anemia caused by acute blood loss.

HEMOLYTIC ANEMIA

In human beings the bone marrow is capable of undergoing hyperplasia until its production rate is increased approximately sixfold to eightfold; the same is probably true for dogs and cats. As a consequence, a considerable number of RBCs must be destroyed before anemia develops. As is the case in cats and dogs with blood loss anemia, patients with peracute hemolysis can be in a nonregenerative state at the time of presentation because the bone marrow has not yet been able to mount a regenerative response. In addition, in some dogs with immune-mediated hemolysis, the destruction of erythroid precursors in the bone marrow results in a lack of regeneration.

On the basis of their pathogenesis, hemolytic anemias can be classified as extravascular (i.e., the RBCs are destroyed by the mononuclear phagocytic cells) or intravascular (i.e., the RBCs are lysed by antibody-complement, drugs, toxins, or by hitting fibrin strands). On the basis of the age of the animal at onset, anemias can be classified as congenital or acquired (Table 83-4). Most dogs and cats with hemolytic anemia seen at my clinic have acquired extravascular hemolysis.

TABLE 83-4 Causes of Hemolytic Anemia in Dogs and Cats

PFK, Phosphofructokinase; IHA, immune hemolytic anemia.

Modified from Couto CG et al: Hematologic and oncologic emergencies. In Murtaugh R et al, editors: Veterinary emergency and critical care medicine, St Louis, 1992, Mosby.

In extravascular hemolysis, RBCs are phagocytosed by the mononuclear-phagocytic system (MPS) in the spleen, liver, and bone marrow. Stimuli that trigger RBC phagocytosis consist mainly of intracellular inclusions, such as RBC parasites or Heinz bodies (the latter are commonly seen in cats) and membrane coating with immunoglobulin (Ig) G or M (common in dogs). Congenital RBC enzymopathies can also precipitate extravascular hemolysis. Once abnormal RBCs are recognized, the MPS rapidly phagocytoses them, resulting in a decrease in the number of circulating RBCs and the generation of cells with specific morphologic changes (e.g., spherocytes). Anemia develops if the destruction of RBCs continues. Spherocytes are RBC “leftovers,” in that after a mononuclear-phagocytic cell takes a “bite” of cytoplasm and membrane, the membrane is resealed; the RBC then loses its redundant membrane and consequently its central pallor. Spherocytes are characteristic of immune hemolytic anemia (IHA), although they can occasionally be seen in other disorders, such as Babesia gibsoni infection or zinc toxicity. Immune hemolysis is the most common cause of extravascular hemolytic anemia in dogs at my hospital. Drugassociated hemolysis (e.g., βlactam antiiotics) and mycoplasmosis (formerly known as haemobartonellosis) are the two most common causes in cats, although IHA is now more common in this species. Other causes of extravascular hemolytic anemia in dogs and cats are listed in Table 83-4.

Intravascular hemolysis can occur as a consequence of direct RBC lysis caused by antibodies that activate complement (e.g., immune-mediated hemolysis), infectious agents (e.g., Babesia canis infection), drugs or toxins (e.g., zinc in pennies minted after 1983, in pet carrier bolts, other hardware, and zinc oxide–containing ointments), metabolic imbalances (e.g., hypophosphatemia in dogs and cats with diabetes mellitus treated with insulin), or increased shearing of RBCs (e.g., microangiopathy, DIC). Intravascular hemolysis is considerably less common in dogs and cats than extravascular hemolysis, with the notable exception of DIC in dogs with hemangiosarcoma, zinc toxicity, and hypophosphatemia. Certain congenital enzymopathies (e.g., phosphofructokinase [PFK] deficiency) in dogs also result in intravascular hemolysis.

Dogs with congenital (frequently familial) hemolytic anemias may have relatively prolonged clinical courses at the time of presentation, with the notable exception of English Springer Spaniels with PFK deficiency–induced hemolysis, in which acute hemolytic episodes occur after they hyper ventilate during excitement or field work (i.e., alkaline hemolysis). Dogs and cats with acquired hemolytic anemias are usually evaluated because of acute clinical signs consisting of pallor, with or without icterus (in my experience, only approximately half of dogs and a lower percentage of cats with hemolytic anemia are icteric); splenomegaly may be a prominent finding. If the patient has associated thrombocytopenia (e.g., Evans syndrome, DIC), petechiae and ecchymoses may be present. Clinical signs and physical examination findings associated with the primary disease can also be present in cases of secondary hemolytic anemias; however, as opposed to human beings, they are extremely rare in dogs and cats.

In the evaluation of dogs or cats with hemolytic anemia, a careful examination of the blood smear is mandatory. Morphologic abnormalities pathognomonic for or highly suggestive of a particular etiology are often detected with this method (see Table 83-2). The sample should also be tested for autoagglutination; this is done by placing a large drop of anticoagulated blood on a glass slide at room temperature and at 4° C. Agglutination can be distinguished from rouleaux formation by diluting the blood 5 : 1 or 10 : 1 in saline solution (this disaggregates rouleaux); rouleaux formation is common in cats but rare in dogs. A direct Coombs test to detect RBC-bound Ig should always be performed in dogs and cats with suspected hemolysis (see below). As a general rule, the presence of Ig coating on the RBCs indicates immune-mediated hemolysis. A positive Coombs test result should be interpreted with caution, however, because certain drugs and hemoparasites can induce formation of antibodies that bind to the RBCs, thus causing secondary immune hemolysis (e.g., cats with mycoplasmosis). The pretreatment of an animal with corticosteroids may also result in decreased binding of Ig molecules to the surface of the RBC, thus resulting in false-negative results. Direct Coombs tests are usually not necessary in animals with autoagglutination because this phenomenon connotes the presence of Ig on the surface of the RBCs (i.e., biologic Coombs test). Cryoagglutination (i.e., the agglutination of RBCs if the blood sample is refrigerated for 6 to 8 hours) occurs in a large proportion of cats with mycoplasmosis and is usually associated with IgM coating on the RBCs.

If an etiologic agent cannot be identified (e.g., RBC parasite, drug, pennies in the stomach), the patient should be treated for primary or idiopathic IHA while further test results (e.g., serologic tests or polymerase chain reaction [PCR] for hemoparasites) are pending. As previously mentioned, primary IHA is considerably more common in dogs than in cats; thus every effort should be made to identify a cause of hemolysis in cats, such as drugs or hemoparasites. A detailed discussion of IHA is presented below.

Hemolytic anemias not associated with immune destruction of the RBCs are treated by removal of the cause (e.g., drug, infectious agent, gastric foreign body) and supportive therapy. Corticosteroids (see below) can be administered to suppress MPS activity while the etiologic agent is being eliminated, although this is not always beneficial. Doxycycline (5 to 10 mg/kg PO q12-24h for 21 to 42 days) usually results in resolution of the signs in dogs and cats with mycoplasmosis and in dogs with ehrlichiosis.

Immune Hemolytic Anemia

IHA constitutes the most common form of hemolysis in dogs (see Chapter 104). Although two pathogenetic categories of hemolytic anemia are recognized (primary, or idiopathic, and secondary), most cases of IHA in dogs are primary (i.e., a cause cannot be found after exhaustive clinical and clinicopathologic evaluation). The immune-mediated destruction of RBCs can occur in association with drug administration (e.g., βlactam antibiotics, barbiturates) or vaccination. With the exception of the immune hemolysis secondary to hemoparasitism, IHA is rare in cats (although its prevalence is higher than 5 years ago). The clinical course in dogs is typically acute, but peracute presentations are also common.

In IHA, the RBCs become coated primarily with IgG, which leads to the early removal of the coated cells by the MPS, mainly in the spleen and liver. As a consequence spherocytes are generated; therefore the presence of spherocytes in the blood smear of a dog with anemia is highly suggestive of IHA. Spherocytes are difficult to identify in cats.

The typical patient with IHA is a middle-aged, female spayed Cocker Spaniel or small breed dog, although I have recently noticed a higher prevalence of IHA (and other immune-mediated cytopenias) in Golden Retrievers. Clinical signs in dogs with IHA include depression of acute (or peracute) onset, exercise intolerance, and pallor or jaundice, occasionally accompanied by vomiting or abdominal pain. Physical examination findings usually consist of pallor or jaundice, petechiae and ecchymoses (if immune thrombocytopenia is also present), splenomegaly, and a heart murmur. As previously noted, jaundice can be absent in dogs with IHA. A subset of dogs with acute (or peracute) IHA with icterus (and usually autoagglutination) shows clinical deterioration within hours or days of admission, resulting from multifocal thromboembolic disease or a lack of response to conventional therapy. I treat these dogs more aggressively than the typical dog with IHA (see next page).

Hematologic findings in dogs with IHA typically include strongly regenerative anemia, leukocytosis from neutrophilia with a left shift and monocytosis, increased numbers of nucleated RBCs, polychromasia, and spherocytosis. The serum (plasma) protein concentration is usually normal to increased, and hemoglobinemia or bilirubinemia may be present (i.e., pink or yellow plasma). As previously noted, autoagglutination is prominent in some dogs. Thrombocytopenia is also present in dogs with Evans syndrome or DIC.

The presence of polychromasia with autoagglutination and spherocytosis in a clinically ill dog with anemia of acute onset is virtually pathognomonic of IHA. In these cases a direct Coombs test is usually not necessary to confirm the diagnosis. In dogs that lack some of these physical examination and hematologic findings, a direct Coombs test should be performed to detect Ig adsorbed to the RBC membrane.

The direct Coombs test is negative in approximately 10% to 30% of dogs with IHA, yet they tend to respond to immunosuppressive therapy (see below). In these cases enough Ig or complement molecules may be bound to the RBC membrane to induce the MPS to stimulate phagocytosis but not enough to result in a positive Coombs test. Hemolysis can occur in human beings with approximately 20 to 30 molecules of Ig bound to the RBC, whereas the direct Coombs test can only detect more than 200 to 300 molecules of Ig per cell. Another explanation for the findings in this subset of patients is that the previous administration of exogenous corticosteroids has resulted in decreased antibody binding to the surface of the RBCs.

Immunosuppressive doses of corticosteroids (equivalent to 2 to 4 mg/kg of prednisone q12-24h in the dog and up to 8 mg/kg q12-24h in the cat) constitute the treatment of choice for primary IHA. Although dexamethasone can be used initially, it should not be used as maintenance therapy for prolonged periods because of its higher potential to cause gastrointestinal tract ulceration or pancreatitis; in addition, if given on an alternate-day basis, it causes interference with the hypothalamic-pituitary-adrenal axis. In equivalent doses dexamethasone does not appear to be more beneficial than prednisone in dogs. In cats with IHA, I have used dexamethasone (4 mg/cat, PO, q1-2wk) with a high degree of success.

A high percentage of dogs treated with corticosteroids shows a marked improvement within 24 to 96 hours (Fig. 83-1). Corticosteroids act mainly by three different mechanisms: they suppress MPS activity, decrease complement and antibody binding to the cells, and suppress Ig production. The first two effects are rapid in onset (hours), whereas the third effect is delayed (1 to 3 weeks).

FIG 83-1 Response to treatment in a dog with immune hemolytic anemia (IHA) and immune-mediated thrombocytopenia (Evans syndrome). PCV, Packed cell volume; , PCV; , platelets; ↓, treatment administered.

I have observed a high number of dogs with acute or peracute IHA generally associated with icterus and autoagglutination that show a rapid deterioration and that usually die of thromboembolism of the liver, lungs, or kidneys despite aggressive corticosteroid therapy. Such animals are treated with cyclophosphamide (Cytoxan) at a dosage of 200 to 300 mg/m² given orally or intravenously in a single dose over a 5- to 10-minute period in conjunction with a single IV dose of dexamethasone sodium phosphate (1 to 2 mg/kg). I also advocate the use of prophylactic heparin therapy because dogs with hemolysis are at high risk for DIC and thrombosis. In my practice heparin therapy of 50 to 75 IU/kg is routinely given subcutaneously every 8 hours. These dosages of heparin usually do not result in therapy-related prolongation of the activated clotting time (ACT) or the activated partial thromboplastin time (Aptt), tests used routinely to monitor heparinization. The use of low- or mini-dose aspirin (0.5 mg/kg q24-48h) has been associated with lower mortality rates in dogs with IHA. Because dogs with IHA are at high risk for thromboembolic events, I refrain from placing central venous lines; thrombosis of the anterior vena cava commonly leads to severe pleural effusion in these dogs. Aggressive fluid therapy should be administered in conjunction with these treatments in an attempt to flush the microaggregates of agglutinated RBCs from the microcirculation (Note: circulating blood does not clot). Importantly, however, is that depending on the degree of anemia, the resultant hemodilution may be detrimental to the patient. If deemed necessary, oxygen therapy should also be used, but it is rarely beneficial unless the HCT or Hb can be increased.

I have been using human intravenous IgG (HIVIGG-0.5 to 1.5 g/kg IV infusion, single dose) with a high degree of success in dogs with refractory IHA. This treatment is aimed at blocking the Fc receptors in the MPS with a foreign Ig, thus minimizing the phagocytosis of antibody-coated RBCs. This treatment appears to have other immunomodulatory effects as well. However, the product is moderately expensive (approximately $300 to $400 per dose for a 10-kg dog). This approach has had such an impact, however, that I frequently use it as the first line of therapy in dogs with severe IHA.

Drugs used for the maintenance treatment of dogs with IHA include prednisone (1 mg/kg PO q48h) and azathioprine (50 mg/m² PO q24-48h), used either singly or in combination. Azathioprine is associated with few adverse effects, although close hematologic and serum biochemical monitoring is necessary because of its potential to suppress bone marrow function and cause mild hepatopathy. A dose reduction is necessary if myelosuppression or hepatotoxicity occurs; occasionally azathioprine must be discontinued in dogs with hepatotoxicity. In cats, chlorambucil is an effective immunosuppressor with very low toxicity; I have used it successfully in cats with IHA, immune-mediated thrombo cytopenia, or other cytopenias at a dosage of 20mg/m² PO q2wk. In general, dogs and cats with IHA require prolonged (often lifelong) immunosuppressive treatment. Whether an animal requires continuous treatment is determined by trial and error; decremental doses of the immunosuppressive drug(s) are administered for a given period (usually 2 to 3 weeks), at which time the patient is reevaluated clinically and hematologically. If the PCV has not decreased or has increased and the patient is clinically stable or has shown improvement, the dose is reduced by 25% to 50%. This procedure is repeated until the drug is discontinued or the patient relapses. In the latter case, the previously used dosage that had beneficial effects is used again. In my experience, more than two thirds of dogs with IHA require lifelong treatment.

Alternative treatments for dogs with refractory IHA include danazol (5 to 10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12-24h), and possibly splenectomy. However, splenectomy has rarely been of benefit in dogs with IHA treated at my clinic.

Chlorambucil (20 mg/m² PO q2wk) appears to be the best induction and maintenance agent in cats with IHA refractory to corticosteroids or in those who develop corticosteroid-induced diabetes mellitus. In my experience azathioprine causes pronounced myelosuppression in this species and should not be used.

One of the biggest dilemmas the clinician faces in the treatment of a dog with IHA is whether to administer a transfusion of blood or blood products. As a general rule, a transfusion should not be withheld if it represents a lifesaving procedure. However, because patients with IHA are already destroying their own antibody-coated RBCs, they may also be prone to destroying transfused RBCs (although this has not been scientifically proven). My recommendation is to administer a transfusion to any animal with IHA that is in dire need of RBCs (i.e., withholding a transfusion would result in the animal’s death). I usually pretreat these patients with dexamethasone sodium phosphate (0.5 to 1 mg/kg IV), administer fluids through an additional IV catheter, and continue the heparin therapy. Although cross-matching is indicated, time is usually of the essence; therefore non–cross-matched universal donor blood is frequently administered; moreover, if autoagglutination occurs, the results of a cross-match may be difficult to interpret.

Another issue pertaining to transfusion in dogs with IHA autoagglutination deals with blood typing; if blood typing cards are used, the results will be false-positive for DEA 1.1 (see Principles of Transfusion Therapy, p. 1221). Finally, no rule of thumb exists (e.g., PCV value, lack of response to oxygen therapy) regarding when to administer a transfusion. The clinician should use his or her best clinical judgment to determine when a transfusion of blood or blood products is necessary (e.g., does the patient exhibit tachypnea, dyspnea, or orthopnea?). If available, universal donor packed RBCs should be used instead of whole blood because they deliver a high oxygen-carrying capacity in a smaller volume and administration usually does not result in hypervolemia.

A polymer of bovine Hg has been available for use in dogs with acute anemia that are in dire need of oxygen-carrying capacity (Oxyglobin, Biopure Corp., Cambridge, Mass.). This compound has a long shelf life; it does not require refrigeration, blood typing, or cross-matching. Administration of Oxyglobin typically results in clinical improvement of the signs associated with anemia, but the duration of response is limited (2 or 3 days). Because of the nature of this compound, the PCV does not increase after infusion (the Hg concentration does increase). Some laboratory test results may be difficult to obtain after infusion of Oxyglobin because of interference with colorimetric analysis. Unfortunately this product is not readily available for veterinarians at this time.

ANEMIA OF CHRONIC DISEASE

ACD is the most common form of nonregenerative anemia in cats and dogs; however, because it is mild, it almost never results in clinical signs of anemia and the patients are usually evaluated as a consequence of their primary disorder (e.g., cancer, infection). ACD develops secondary to a variety of chronic inflammatory, degenerative, or neoplastic conditions. Although the term anemia of chronic disease implies a chronic onset, it has recently been established that cats can develop ACD in as little as 2 weeks. However, some of those cats were receiving fluid therapy that may have resulted in hemodilution (Ottenjan et al., 2006). In most cats with ACD the PCV percentage values range from the high teens to the mid-20s, whereas in dogs they range from the mid-20s to the low 30s. Therefore ACD can usually be excluded in dogs with PCVs of less than 20% and in cats with PCVs of less than 17% to 18%. The RBC indices are normocytic and normochromic, and the CBC may also reflect the nature of the primary problem (e.g., leukocytosis, neutrophilia, monocytosis, hyperproteinemia resulting from a polyclonal gammopathy); some cats with ACD have microcytic hypochromic RBC indices, a condition that mimics IDA.

Sustained inflammatory or neoplastic processes cause iron to be sequestered within the bone marrow MPS, and it is therefore not available to the erythroid precursors for normal erythropoiesis. This unavailability of iron is mainly mediated by lactoferrin and other acute-phase reactants released from neutrophils during inflammation. In cats and dogs with ACD, the serum iron concentration and total iron-binding capacity (TIBC, or transferrin concentration) are usually decreased and the Hb saturation is low, but iron stores in the bone marrow are increased (Table 83-5). Although serum ferritin concentrations are the main feature that distinguishes ACD from IDA (i.e., high in ACD and low in IDA) in human beings, the results of ferritin assays in dogs and cats with IDA and ACD are not as clear cut. Therefore, to conclusively differentiate ACD from IDA, evaluation of bone marrow iron stores by Prussian blue staining is important. After a diagnosis of ACD has been confirmed, every effort should be made to identify the cause of the problem if it is not already evident.

TABLE 83-5 Distinguishing Features of ACD and IDA in Dogs

ACD, Anemia of chronic disease; IDA, iron deficiency anemia; ↓, low; ↓↓, markedly low; ↑, high; ,↑↑ markedly high; N, normal; +(−), positive or negative.

Dogs and cats with ACD usually do not require specific or supportive therapy because treatment of the primary disorder causes the anemia to resolve. Although some have advocated the use of anabolic steroids in dogs and cats with ACD, these agents appear to be of little or no benefit.

BONE MARROW DISORDERS

Neoplastic, hypoplastic, or dysplastic bone marrow disorders can result in anemia and other cytopenias. In these conditions a “crowding out” of the normal erythroid precursors by neoplastic or inflammatory cells (myelophthisis), a paucity or absence of erythroid precursors (hypoplasia or aplasia, respectively), or a maturation arrest of the erythroid precursors (dysplasia) occur. All these disorders, with the exception of pure RBC aplasia (PRCA) (see following section), typically affect more than one cell line and the patients are bicytopenic or pancytopenic (see Chapter 86). In general, these disorders are chronic and the clinical signs are those of anemia (see p. 1209) with or without signs of the underlying disorder. Although some information regarding the pathogenesis of this type of anemia can be obtained by evaluating the clinical and hematologic data, a definitive diagnosis is usually made on the basis of the cytologic or histopathologic appearance of a bone marrow specimen and, possibly, the results of serologic tests or PCR for infectious agents (e.g., FeLV, FIV, Ehrlichia canis).

ANEMIA OF RENAL DISEASE

The kidney is the main site of production of Epo, the principal stimulus of erythropoiesis. In addition, in dogs and cats with chronic renal failure, the life span of RBCs is considerably shorter and subclinical to clinical gastrointestinal tract bleeding is present; high concentrations of parathyroid hormone also suppress erythropoiesis. Because of these factors, anemia is common in such patients. The anemia is usually normocytic and normochromic, with few or no reticulocytes. HCT levels in dogs and cats with anemia of renal disease (ARD) are usually in the 20% to low 30% range, although HCT levels in the teens are common. Of note, the HCT in these patients is usually that low only after they have undergone intensive fluid therapy (i.e., on presentation the anemia is not that severe because the patients are markedly dehydrated).

Improvement in renal function may result in marginal increases in the RBC mass. Anabolic steroids are rarely beneficial in improving the anemia in these patients. Human recombinant Epo (Epogen, Amgen, Thousand Oaks, Calif.) has been used successfully to treat anemia in cats and dogs with chronic renal failure. A dose of 100 to 150 IU/kg given subcutaneously twice weekly is administered until the HCT returns to a target value (usually 20% to 25%); the interval between injections is then lengthened for maintenance therapy. The HCT usually returns to normal within 3 to 4 weeks of the start of treatment. Given the fact that this Epo is foreign to dogs and cats, an appropriate antibody response usually nullifies the beneficial effects of long-term therapy (6 to 8 weeks) in more than 50% of the patients.

ACUTE AND PERACUTE BLOOD LOSS OR HEMOLYSIS (FIRST 48 TO 96 HOURS)

After an acute episode of blood loss or hemolysis, bone marrow takes approximately 48 to 96 hours to release enough reticulocytes to result in regeneration. Therefore blood loss and hemolytic anemias are nonregenerative during the initial phases of recovery.

In most dogs and cats with acute blood loss, profound bleeding is either historically or clinically evident. If no obvious cause of bleeding is found or if the patient is bleeding from multiple sites, the hemostatic system should be evaluated in search of a coagulopathy (see Chapter 89). Sites of internal bleeding should be evident after a complete physical examination is performed.

Once the bleeding has been stopped, the anemia typically resolves within days to weeks. The initial management of a bleeding episode should include supportive therapy and IV crystalloids or plasma expanders. If necessary, blood or packed RBCs or Hg solutions should be administered.

The management of dogs with peracute hemolysis was discussed earlier in the chapter.

IRON DEFICIENCY ANEMIA

IDA is traditionally classified as nonregenerative even though mild to moderate regeneration usually occurs. Moreover, as previously discussed, the RBC indices in dogs and cats with IDA are microcytic and hypochromic, distinguishing it from other forms of nonregenerative anemia, which are normocytic and normochromic. When evaluating the CBC of a dog with microcytic hypochromic anemia, the clinician must remember that microcytosis occurs in some breeds (e.g., Akita, Shiba Inu, Sharpei) and in dogs with other disorders, such as portosystemic shunts (see Table 83-2).

This form of anemia is well characterized in dogs with chronic blood loss. In cats, IDA has been well documented only in weanling kittens, in whom iron supplementation results in rapid resolution of the clinical and hematologic abnormalities. IDA is extremely rare in adult cats, and I have seen it primarily in association with chronic blood loss in cats with gastrointestinal (GI) lymphoma. Given its rarity in cats, the following discussion of IDA pertains primarily to dogs.

Chronic blood loss leading to iron depletion is common in dogs with GI tract bleeding caused by neoplasia, gastric ulcers, or endoparasites (e.g., hookworms) and in those with heavy flea infestation. Other causes of chronic blood loss, such as urogenital bleeding and iatrogenic bloodletting, are extremely rare. In my experience the most common cause of symptomatic IDA in dogs that present for evaluation of signs associated with anemia is GI neoplasia.

Dogs with IDA are typically evaluated because of the signs of the anemia or because of GI tract signs such as diarrhea, melena, or hematochezia. Mild IDA is occasionally recognized during the routine evaluation of heavily parasitized dogs (mostly pups). Hematologically, most dogs with IDA have microcytic, hypochromic indices, mild reticulocytosis (1% to 5%), a high RBC distribution width (RDW) with an occasional bimodal population of RBCs, thrombocytosis, low serum iron and TIBC (transferrin) concentrations, an extremely low percentage of saturation (usually less than 10%), a low serum ferritin concentration, and low iron stores in the bone marrow (see Box 83-5). The RDW generated by a particle counter represents a histogram of RBC sizes; a high RDW is indicative of anisocytosis. The typical tetrad of hematologic abnormalities in dogs with IDA is microcytosis, hypochromasia, mild regeneration, and thrombocytosis.

Because the most common cause of IDA in adult dogs is chronic GI tract bleeding, the stools should always be evaluated for occult blood with commercially available kits (see Chapter 29); if the results are negative, they should be evaluated again two or three times during a period when the animal is not eating canned dog food (myoglobin in canned dog food can occasionally result in false-positive reactions). If occult blood is present in the stool, a GI tract neoplasm should be ruled out. Tumors commonly associated with IDA in dogs include GI stromal tumors (GISTs), such as leiomyomas, leiomyosarcomas, and true GISTs; lymphomas; and carcinomas. In dogs with IDA, positive fecal blood test results, and lack of clinical signs associated with the GI tract, the most likely diagnosis is a jejunal tumor (usually a GIST); I refer to these tumors as the “silent” GI neoplasms.

Another condition that can lead to IDA is chronic upper GI tract bleeding secondary to gastroduodenal ulceration, although most of these dogs have overt clinical signs associated with the GI tract (e.g., vomiting, hematemesis, weight loss). In pups or kittens with IDA, fecal flotation or a direct smear for hookworms and a thorough physical examination (to search for fleas) are mandatory because these are the two most common causes of IDA in young dogs and cats.

IDA usually resolves within 6 to 8 weeks after the primary cause has been eliminated. Oral or intramuscular iron supplementation is usually not necessary to hasten the resolution of the hematologic abnormalities; a sound commercial diet usually achieves the same effect. As a general rule, if the cause can be eliminated, I do not use iron supplementation. The dietary iron requirement for adult dogs and cats is approximately 1.3 mg/kg/day.

BLOOD GROUPS

Several blood groups have been recognized in dogs; these include dog erythrocyte antigen (DEA) 1.1 and 1.2 (formerly known as blood group A) and DEA 3 through 8. Dogs do not have naturally occuring antibodies against blood group antigens; therefore they can only acquire them after receiving a transfusion or after pregnancy. Transfusion reactions can occur if blood positive for DEA 1.1, 1.2, or 7 is transfused, so donors should be negative for those antigens. However, clinically relevant acute hemolytic transfusion reactions are extremely rare in dogs. Transfusion of blood from a donor who has not been typed and has never been pregnant or transfused to a recipient, independently of their blood types, is generally safe.

Blood groups in cats include A, B, and AB. Cats tested in the United States have almost exclusively been type A; the prevalence of type B cats varies greatly from region to region and among breeds. Breeds in which 15% to 30% of the cats are type B include Abyssinian, Birman, Himalayan, Persian, Scottish Fold, and Somali; breeds in which more than 30% of cats are type B include the British Shorthair and the Devon Rex. Because fatal transfusion reactions commonly occur in type B cats receiving type A blood, cats should always be cross-matched or typed before receiving a transfusion. In those cases a type B cat should be used as a donor. All the type B cats seen in our clinic in the past 5 years have been domestic short-haired cats. Blood typing is also vital in cattery situations to prevent neonatal isoerythrolysis in type A or AB kittens born to type B queens.

CROSS-MATCHING AND BLOOD TYPING

Cross-matching is an alternative to blood typing in in-house donors or animals that have had prior transfusions, in cats, or in animals that will require multiple transfusions. Cross-matching detects many incompatibilities but does not guarantee complete compatibility. Rapid, cage-side blood typing cards for DEA 1.1 in dogs and for groups A and B in cats are commercially available (RapidVet-H, DMS Laboratories, Flemington, NJ). A kit for rapid cross-matching will soon be commercially available.

BLOOD ADMINISTRATION

Refrigerated blood may be warmed before or during administration, particularly in small dogs or cats; excessive heat should be avoided, however, because fibrinogen precipitation or autoagglutination may occur. I typically do not warm blood or pRBCs before administration. The administration set should have a filter in place (Baxter International, Deerfield, Ill.) to remove clots and other particulate matter, such as platelet aggregates. The blood is usually administered by way of the cephalic, saphenous, or jugular veins. However, intraosseous infusion may be performed in small animals, neonates, or animals with poor peripheral circulation. To administer fluids or blood intraosseously, the skin over the femur is surgically prepared and the skin and periosteum of the femoral trochanteric fossa are anesthetized with 1% lidocaine. A bone marrow needle (18 gauge) is placed into the marrow cavity parallel to the shaft of the femur. Suction with a 10-mL syringe should yield marrow elements (fat, spicules, and blood), confirming correct placement of the needle. The blood is administered through a standard blood administration set.

The recommended rate of administration is variable but should not exceed 22 mL/kg/day (up to 20 mL/kg/hr can be used in hypovolemic animals). Dogs and cats in heart failure may not tolerate a rate of more than 5 mL/kg/day. To prevent bacterial contamination, blood should not be exposed to room temperature during administration for longer than 4 to 6 hours (blood is considered to be contaminated if it is at room temperature for more than 6 hours). If necessary, two smaller volumes of blood can be administered in succession. Blood should never be administered with lactated Ringer’s solution because of the calcium chelation with citrate and consequent clot formation that may occur. Normal saline solution (0.9% NaCl) should be used instead. A simple rule of thumb to predict the increase in the recipient’s HCT is to remember that 2.2 mL/kg (or 1 mL/lb) of transfused whole blood will raise the HCT by 1% if the donor has an HCT of approximately 40%.

COMPLICATIONS OF TRANSFUSION THERAPY

Transfusion-related complications can be divided into those that are immunologically mediated and those that are of nonimmunologic origin. Immune-mediated reactions include urticaria, hemolysis, and fever. Non–immune-mediated complications include fever resulting from the transfusion of improperly stored blood, circulatory overload, citrate intoxication, disease transmission, and the metabolic burden associated with the transfusion of aged blood. Signs of immediate immune-mediated hemolysis appear within minutes of the start of transfusion and include tremors, emesis, and fever; these are extremely rare in dogs but common in cats receiving incompatible blood products. Delayed hemolytic reactions are more common and are manifested primarily by an unexpected decline in the HCT after transfusion over days, in association with hemoglobinemia, hemoglobinuria, and hyperbilirubinemia. Circulatory overload may be manifested by vomiting, dyspnea, or coughing. Citrate intoxication occurs when the infusion rate is too great or the liver is not able to metabolize the citrate. Signs of citrate intoxication are related to hypocalcemia and include tremors and cardiac arrhythmias. If signs of a transfusion reaction are recognized, the transfusion must be slowed or halted.