Evaluation of the Anemic Patient
Anemia develops from one or more of three main pathophysiologic mechanisms: blood loss, hemolysis, and Decreased erythrocyte production. More specific causes are often categorized in terms of these three main mechanisms (Boxes 24.1 and 24.2).
Specific causes of anemia are also sometimes grouped in terms of whether they cause regenerative or nonregenerative anemia. Anemias that are the result of blood loss or hemolysis are typically regenerative, whereas those that are the result of decreased erythrocyte production will be nonregenerative.A regenerative response in the ruminant is best identified by a moderate to marked degree of polychromasia or a reticu- locytosis. Note that following an acute episode of hemorrhage or hemolysis in ruminants, it takes 2 to 4 days for the bone marrow to respond by beginning to release increased numbers of polychromatophilic cells/reticulocytes into circulation. Peak bone marrow response generally occurs within 7 days. This time frame must be kept in mind when assessing peripheral blood for indicators of regeneration. Other findings that can support the regenerative nature of an anemia would be an increased MCV, a decreased MCHC, basophilic stippling, nRBCs, increased numbers of Howell-Jolly bodies, and increased anisocytosis. It may take 2 to 4 weeks or more in ruminants for the HCT to return to normal after an episode of hemorrhage or hemolysis.
As noted previously, classifying an anemia as regenerative or nonregenerative is more difficult in the horse because of the relative absence of peripheral indicators of regeneration (e.g., polychromasia, reticulocytosis). In these patients, serial CBCs can be performed to detect increasing HCT over time. Similar to ruminants, it takes about 4 days for the bone marrow to begin to respond to an episode of hemorrhage or hemolysis. Mild increases in the MCV can be seen in some horses with regenerative anemias.
The bone marrow response to anemia in horses is relatively sluggish compared with other species, and it may take up to 1 to 2 months following severe hemolysis or 2 to 3 months following severe hemorrhage for HCT values to return to normal.13 In both horses and ruminants, the■ BOX 24.1
Causes of Anemia in the Horse
Common Causes
Blood Loss
Trauma
Surgery Ectoparasites (lice, ticks) Endoparasites (strongyles)
Gastrointestinal bleeding (ulcers, neoplasia) Immune-mediated thrombocytopenia Equine purpura hemorrhagica
Hemolysis
Neonatal isoerythrolysis
Red maple leaf toxicosis
Equine infectious anemia
Decreased Erythrocyte Production
Anemia of inflammatory disease (chronic inflammation, neoplasia) Chronic abscessation
Chronic pneumonia or pleuritis Lymphoma
Less Common Causes
Blood Loss
Bleeding diathesis associated with disseminated intravascular coagulation (DIC)
Guttural pouch mycosis Hematuria
Hemoabdomen
Moldy sweet clover toxicosis Rodenticide toxicity (brodifacoum)
Congenital coagulation factor deficiencies (hemophilia A)
Platelet function disorders (von Willebrand disease, Glanzmann thrombasthenia)
Hemolysis
Fragmentation (DIC, vasculitis) Immune-mediated hemolytic anemia (idiopathic) Immune-mediated hemolytic anemia (secondary)
Clostridial infections
Penicillin therapy Lymphoma
TheileriosisTabesiosis
Onion toxicosis
Phenothiazine toxicosis
Glucose-6-phosphate dehydrogenase deficiency
Decreased Erythrocyte Production
Anemia of chronic renal failure
Bone marrow neoplasia (leukemia, metastatic neoplasia) Myelofibrosis
Aplastic anemia (idiopathic, drugs including phenylbutazone)
regenerative response to hemolysis is generally considered to be somewhat more vigorous than the response to hemorrhage. It is suggested that this may be in part due to the fact that in hemolysis, iron (from Hgb) is not lost from that body and is then made available for production of new erythrocytes.
Evaluation of bone marrow can also be performed in horses to evaluate for a regenerative response. Enumeration of polychromatophilic cells and reticulocytes in the bone marrow, assessment of overall cellularity, and calculation of the myeloid- to-erythroid ratio (M:E) are used to determine if a regenerative response is present. Excessive hemodilution of the bone marrow sample and the variable M:E ratios present in normal animals, however, can complicate interpretation in some cases.■ BOX 24.2
Causes of Anemia in Ruminants
Common Causes
Blood Loss
Trauma
Endoparasites (Haemonchus sp. and liver flukes14) Ectoparasites (lice, ticks)
Abomasal ulcers, bleeding
Acute severe Salmonella hemorrhagic diarrhea Oak toxicosis with hemorrhagic diarrhea
Hemorrhagic bowel syndrome (jejunal hemorrhage syndrome)
Hemolysis
Bovine viral diarrhea virus vaccine Anaplasmosis
Brassica spp. toxicosis Leptospirosis
Onion toxicosis
Clostridial infections Chronic copper toxicosis
Water deprivation or salt poisoning followed by ingestion of fresh water
Decreased Erythrocyte Production
Anemia of inflammatory disease (chronic inflammation, neoplasia) Chronic pneumonia
Chronic abscessation
Johne's disease
Chronic bovine virus diarrhea infection
Lymphoma
Less Common Causes
Blood Loss
Hemorrhagic enteritis Hemoabdomen
Bleeding diathesis associated with disseminated intravascular coagulation
Moldy sweet clover toxicosis Caudal vena cava syndrome Severe acute pyelonephritis
Bovine viral diarrhea and mucosal disease complex22
Hemolysis
Babesiosis/theileriosis Mycoplasma spp. infection Postparturient hemoglobinuria
Immune-mediated hemolytic anemia
Decreased Erythrocyte Production
Anemia of chronic renal failure
Bracken fern toxicosis (also hemorrhage in enzootic hematuria) Radiation toxicosis
Myelofibrosis (pygmy goats) Myelophthisis
Blood Loss
Immediately following an episode of acute blood loss, the HCT and plasma protein concentration are generally within the reference interval.
The HCT in horses can actually increase mildly above baseline in some cases as a result of splenic contraction. It is only after fluid shifts have occurred from the interstitial space into the vasculature that the HCT and plasma protein concentration begin to decrease. Increased thirst and renal conservation of free water contribute to the fluid shifts that will continue to occur over a 24- to 48-hour period as vascular volume is restored. Hypoproteinemia concurrent with anemia is supportive of hemorrhage as the cause, assuming there are no other significant sources of protein loss (e.g., gastrointestinal [GI] or renal). Evidence of regeneration should also be present if sufficient time has passed since the episode of blood loss. In some cases, the source of blood loss is obvious (e.g., trauma, surgery, severe epistaxis), whereas in other cases more abstruse sources of blood loss must be investigated. Evaluation of the patient for endoparasites, ectoparasites, hematuria, GI blood loss (e.g., ulcers, neoplasia), and hemoabdomen is warranted in these instances. Chronic blood loss, commonly from parasitic causes,14 GI ulcers, or GI neoplasia, can result in an iron deficiency anemia. Supportive findings for iron deficiency anemia are decreased MCV, decreased MCHC, hypochromic erythrocytes, and a mild degree of erythrocyte fragmentation (i.e., schistocytes and keratocytes). Iron-deficiency anemia is initially regenerative but, if ongoing, can become poorly regenerative to nonregen- erative. Hypoproteinemia may be present; however, protein concentration is within the reference interval in some animals because protein loss is compensated by increased production by the liver. Iron deficiency anemia can also occur in young foals and calves as a result of low dietary intake.15 An iron panel can be performed to confirm iron deficiency.Hemolysis
Hemolysis results in a regenerative anemia often with a normal to increased plasma protein concentration.
Erythrocyte morphology should be assessed for evidence of Heinz bodies, eccentrocytes, schistocytes, erythrocyte parasites, and agglutination. Hemolyzed plasma and hemoglobinuria are supportive of an intravascular hemolytic process, whereas icterus and hyperbilirubinemia support extravascular hemolysis. Hemoglobinuria, however, should be differentiated from hematuria and myoglobinuria, and liver disease and anorexia (in the horse) should be ruled out as causes of the icterus and hyperbilirubinemia. Feed and/or pasture should be evaluated if ingestion of an oxidant is suspected. Additional diagnostics to consider in cases of hemolytic anemia are Coombs testing (IMHA) and Coggin’s testing (equine infectious anemia).Decreased Erythrocyte Production
Anemia of inflammatory disease, often the result of infection, inflammation, or neoplasia, is the most common cause of a mild to moderate nonregenerative anemia. An inflammatory leukogram and hyperfibrinogenemia would be supportive of the presence of a systemic inflammatory response. Chronic renal failure can also result in a nonregenerative anemia of variable severity (moderate to severe) and can initially be assessed by a serum biochemical profile and urinalysis. Feed and/or pasture conditions and drug history should be determined to prioritize other causes of anemia resulting from decreased erythrocyte production. Bone marrow evaluation is indicated to investigate unexplained nonregenerative anemias, especially when other cytopenias are present.