4 Anemia in Horses

Anemia in Horses

• Anemia is defined as a decrease in the circulating red blood cell (RBC) mass, measured by packed cell volume (PCV) or RBC count.

Causes of Anemia

• Blood loss
• Destruction/hemolysis
• Decreased production of RBCs

Classification of Anemia

• Pack Cell Volume (PCV) normal range is 33-42%
• RBC normal range is 7-10 x 10^6/ul.
• Hemoglobin concentration normal range is 11-15 g/dl.

Regenerative vs. Non-Regenerative Anemia

• Horses do not release immature RBCs into the peripheral blood like other species.
• A bone marrow biopsy is needed to determine if there is a regenerative response
• Observing an increase in RBC concentration over time (approximately 3 days after hemorrhage) is an alternative to determine regenerative response.

Bone Marrow Aspirate

• Bone marrow aspirates can be taken from the sternum, rib, or tuber coaxe.
• A large needle or bone marrow biopsy punch can be used.
• A fine needle aspirate (FNA) should show bone spicules.
• Hemorrhage caused by the FNA can make results difficult to interpret.
• Normal Myeloid to Erythroid ratio (M:E) is 0.5 to 3.76
• Ratios less than 0.5 can indicate a regenerative response.

Blood Loss Anemia: Acute

• Can be caused by external hemorrhage, such as trauma or guttural pouch mycotic infections
• Iron is lost in external hemorrhage and GI bleeding.

Blood Loss Anemia: Internal

• Examples include middle uterine artery hemorrhage (in post-parturient mare), ingestion of warfarin-like toxins, rib fractures, or hemothorax.
• When bleeding occurs into a body cavity, approximately 2/3 of RBCs are autotransfused back into circulation within 24-72 hours: the remaining RBCs are phagocytized, and iron is reused.

Blood Loss Anemia: Clinical Signs

• Increased heart rate (HR) and respiratory rate (RR)
• Pale mucous membranes
• Poor venous distention
• Weakness
• Fainting
• Heart murmur (due to changes in blood viscosity)

Blood Loss Anemia: Assessment

• PCV and TP may initially appear normal
• Reduction in PCV and TP begins within 4-6 hours
• Complete redistribution of fluid takes up to 24 hours
• Splenic contraction adds RBCs to peripheral blood.
• Accurate determination of blood loss is difficult within the first 24 hours.
• Evidence of RBC regeneration starts at 3 days, with maximal response at 7 days.
• PCV increases by about 1% or less per day.

Blood Loss Anemia: Treatment

• Control the hemorrhage through surgical hemostasis or medical therapy such as aminocaproic acid or Yunnan Baiyo
• Intravenous fluids are indicated in severe acute hemorrhage to restore volume.
• Blood transfusion is necessary based on clinical signs; shock can occur with a PCV of 18 or as low as 10%, depending on the bleeding rate (acute vs. chronic).
• Transfusions should be given slowly.

Blood Transfusions: Donor Options

• Crossmatching: Major cross-match ensures compatibility between donor RBCs and any alloantibody in the patient's plasma
• Crossmatching: Minor cross-match ensures compatibility between alloantibody in the donor's plasma and the patient's RBCs.
• "Universal donors": Horses that don’t have Aa or Qa blood types and lack Aa or Qa antibodies in plasma.
• Geldings or mares that have never been bred
• Most horses without a transfusion history can safely receive a single transfusion.
• A 1000 lb horse can tolerate removal of 5-10 L of blood for donation.

Blood Volume Formula

• Blood volume to be delivered = (BW kg)(0.08)(PCVdesired- PCVobserved)/(PCVdonor blood)
• This formula may not be practical to use with very acute hemorrhage or ongoing hemorrhage.
• PCV desired goal should not be greater than 18-20%.

Chronic Blood Loss

• Examples include chronic GI bleeding (commonly caused by parasites) and GIT neoplasia (rare).

Chronic Blood Loss: Clinical Signs

• Animals tolerate lower PCV compared to acute blood loss.
• Weight loss and ill thrift
• Pale mucous membranes
• Heart murmur (viscosity-related)
• Exercise intolerance
• Signs of shock if blood loss is severe

Chronic Blood Loss: Diagnosis and Treatment

• Determine the site of blood loss
• Iron deficiency can result in non-regenerative anemia
• Treatment includes controlling hemorrhage and supplementing with dietary iron if necessary.

Hemolysis

• Immune-mediated destruction
• Oxidative injury to the RBC
• Infectious agents (may increase RBC fragility and induce IMHA)
• Iatrogenic causes (hypo- or hypertonic drugs)
• Less common: liver and renal issues (hemolytic uremic syndrome)

Intravascular Hemolysis

• Hemoglobinemia (pink plasma)
• Icterus
• Hemoglobinuria (red/brown urine)

Extravascular Hemolysis

• Intense icterus (plasma will be yellow).

Immune Mediated Hemolytic Anemia (IMHA)

• Antibodies attach to RBC surface, resulting in extravascular (most common) or intravascular hemolysis: caused by the antibody fixes and activates complement.

Types of IMHA

• Primary (very rare) true autoantibody
• Secondary (more common): caused by drugs, neoplasia, infectious agents, or Ag-Ab coating of RBCs.

IMHA: Clinical Signs

• Vary depending on intra- or extravascular hemolysis
• Fever may be present in cases of hemorrhage or infectious disease.

IMHA: Bloodwork

• Anemia (+/- pink plasma in intravascular hemolysis)
• Increased total and indirect bilirubin

IMHA: Diagnosis

• Detection of antibody on RBC.
• Coomb’s test detects antibodies coating RBCs
• Direct immunofluorescence via flow cytometry

IMHA: False Negatives

• Use of steroids prior to testing
• Rapid hemolysis of RBCs with antibodies
• If there is autoagglutination, Coombs test is unnecessary.

IMHA: Causes in Horses

• Drugs (penicillin)
• Infectious agents (equine infectious anemia- streptococcal, & clostridal infections)
• Neoplasia (lymphosarcoma)
• Maternal antibody (neonatal isoerythrolysis)
• Idiopathic IMHA

IMHA: Treatment

• Stop any previously administered drugs or treat underlying disease if possible.
• Use immunosuppression (steroids)
• Blood transfusions
• Prevent hemoglobin-induced nephrotoxicity by using fluids.

Oxidative Injury to RBC

• Oxidizing agents cause Heinz body formation and methemoglobinemia (heme iron oxidized from ferrous to ferric).
• Heinz bodies appear as round, blue-black granules on the RBC membrane.
• Heinz bodies result in damage to RBC membrane- resulting in RBC intravascular hemolysis.
• Methemoglobin can’t carry oxygen, causing brown mucous membranes.

Oxidative Injury: Causes

• Wilted Red Maple Leaves (Acer rubrum) is the most common (toxic agent unknown)
• Wild onions (toxic agent n-propyl disulfide)
• Phenothiazines (older anthelmintic drugs)
• Nitrate poisoning only results in methemoglobin, not Heinz body creation

Red Maple Leaves

• Must be wilted to cause toxicity
• Hemolysis and methemoglobin levels vary among horses, causing variable clinical signs such as rapid death, hemoglobinuria, brown mucous membranes, and high heart rate.

Oxidative Injury: Diagnosis

• Rule out IMHA
• Look for Heinz bodies
• Methemoglobinemia (normal less than 1.77% of total hemoglobin)
• Red Maple leaf toxicity results in methemoglobin concentrations up to 50% of total hemoglobin.

Oxidative Injury: Prevention and Treatment

• Eliminate access to leaves
• Treat exposed horses with mineral oil
• Blood transfusions may be needed
• Use fluids to prevent hemoglobin-induced nephrotoxicity
• Large doses of vitamin C
• Dexamethasone
• Supportive care

Non-Regenerative Anemia

• Most common causes are anemia of chronic disease (very common, but anemia is mild), iron deficiency (uncommon), and bone marrow suppression (due to drugs or neoplasia)

Anemia of Chronic Disease

• Mild to moderate anemia
• Normocytic, Normochromic
• Non-regenerative anemia
• Anemia is mild, so it does not result in clinical signs and treatment is not necessary.

Anemia of Chronic Disease: Pathophysiology

• Basic cause is lack of iron mobilization (not low iron stores).
• Inflammation results in increased production of hepcidin (protein produced by the liver).
• Hepcidin decreases ferroportin (a transmembrane protein that transports iron out of the cell).
• Ferroportin is present on enterocytes, macrophages and liver cells.
• Iron is trapped intracellularly, unavailable for red cell production.

Anemia of Chronic Disease: Diagnosis

• Mild anemia and chronic disease.
• Bone Marrow (to document non-regenerative anemia)
• Serum iron concentrations are decreased, but indices of iron storage (ferritin, bone marrow staining for iron) are normal.

Iron Deficiency

• Uncommon, as most diets have enough iron
• Possible with chronic external blood loss (parasites)
• Non-regenerative anemia, microcytic, hypochromic
• Serum iron concentrations are decreased, and indices of iron storage are decreased

Bone Marrow Suppression

• Can be drug induced from recombinant human erythropoietin, SMZ, or other drugs
• Neoplasia (myelophthisis) is the accumulation of abnormal cells in bone marrow (very rare)
• Viral causes include Equine Infectious Anemia
• Chronic Renal Failure caused by a lack of erythropoietin production.