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Ancillary
Notes for
Clinical Hematology Notes Menu | Glossary | Search | VM 551 Home | Courses Home | External Web
RBC life-span
Disorders of red blood cells:
Take in to consideration age and breed differences in laboratory reference values before making a diagnosis of anemia or polycythemia. Puppies and kittens have lower values for PCV than adults. Sight hounds (eg greyhounds) have higher PCV’s than other breeds. Additionally some breeds of dogs have morphologic differences in RBCs, for example Akitas have smaller RBC’s (microcytosis) than other breeds.
Animals with a slow onset of anemia will show less severe signs than those which rapidly develop anemia. With a slower development of anemia, compensatory physiologic mechanisms occur which enhance the delivery of oxygen to tissues. Physical evaluation
of the anemic patient The arterial pulses may be hyperkinetic (stronger than normal) or may be weak if the animal is hypovolemic secondary to blood or fluid loss. If general body condition is poor then chronic disease is present. Icterus may be observed due to hemolysis or concurrent liver disease including hypoxic damage to hepatocytes as a sequel of anemia. The presence of hemorrhages suggest a coagulation disorder may also be present and may be causing blood loss that may be causing or contributing to anemia. The liver or spleen may be enlarged in some patients with immune mediated extravascular hemolysis or enlargement may reflect extramedullary hematopoiesis. Brown mucous membranes may be present in cats intoxicated with acetaminophen. Laboratory
evaluation of anemia
Other laboratory tests may be altered in anemic patients, either secondary to anemia, as part of the disease process that caused anemia or as unrelated findings.
Regenerative responses indicate bone marrow response to anemia. Regenerative anemia occurs secondary to blood loss (internal or external) or hemolysis of RBC. Following acute blood loss, signs of regeneration may not observed for 2 to 3 days in cats and 4 to 5 days in dogs. Chronic, external blood loss can initially be regenerative and progress to nonregenerative. 1. Blood loss anemia is regenerative if sufficient blood has been lost to stimulate the bone marrow to produce new cells and there has been sufficient time for regeneration to be observed. Blood loss can be internal or external. Blood loss anemia is usually accompanied by a reduction in total protein. The reduced total protein is due to loss of blood proteins along with cells during hemorrhage as well as dilution of proteins in the blood vessels by fluids drawn into the blood vessels in an effort to maintain blood pressure. When internal blood loss occurs, for example rupture of an abdominal tumor, the blood cells and protein will be reabsorbed into the blood stream. As the proteins are re absorbed faster than the cells, an animal with internal bleeding may show a regenerative anemia with normal total protein. Blood loss into a body cavity does not always clot as the blood may be defibrinated. This is commonly the case with abdominal bleeding secondary to hemangiosarcoma. Chronic external blood loss is microcytic and hypochromic due to depletion of iron. This type of anemia will gradually change from regenerative to non regenerative. 2. Hemolysis of RBC may be immune mediated (involve antibody), may be due to a congenital defect of the RBC such as pyruvate kinase deficiency that makes the RBC more susceptible to hemolysis, or may be secondary to a drug, toxin or parasites (Haemobartonella, Ehrlichia, Babesia). Drugs and toxins can structurally change the RBC making it more susceptible to hemolysis (example: Heinz body formation occurs in cats given acetaminophen, zinc intoxication from ingestion of pennies) or the drug/toxin can adhere to the RBC surface and precipitate antibody formation against the RBC-drug complex (immune mediated). Parasitic anemia can also be mediated by antibody directed against the parasite-RBC complex. Hemolytic anemia is usually accompanied by a normal total protein value, unless concurrent hemorrhage is present. Often the total protein is increased in patients with immune hemolysis because of the inflammatory nature of the disease resulting in increased immunoglobulins. 3. Immune mediated hemolysis occurs commonly in dogs and cats. The antibody can be directed against RBC antigens (autoimmune) or against foreign antigens on the RBC cell surface (immune-mediated). Often it is unknown if there exits an inciting antigen on the RBC surface. Immune destruction of RBC may be associated with drugs, parasites, viral or neoplastic antigens on the surface of the RBC. Hemolysis may occur intravascular or extravascular. This is discussed in the section on clinical immunology. 4. Isoimmune disease which is the destruction of RBC of newborns due to differences in blood types between dam and offspring are not as common in dogs and cats as in horses. This type of hemolytic anemia may occur in kittens with type A blood born to queens with type B blood, sired by males with type A blood. 5. Anemia associated with DIC: DIC can result in physical destruction of RBC (hemolysis) as they are sheared by passing through fibrin strands in the small blood vessels. The magnitude of anemia by this mechanism is usually mild. DIC can also be associated with anemia if the animal is hypocoagulable and this results in blood loss (blood loss anemia). 1. Nonregenerative anemia can be associated with nutritional deficiencies including malnutrition, vitamin/mineral deficiency, and protein deficiency but nutritional deficiencies are uncommon sole causes of anemia. Nutritional deficiencies may contribute to the severity of anemia from other causes. 2. Bone marrow suppression Bone marrow suppression most often results in suppression of all three cell lines (RBC, WBC, platelets) but occasionally only the red cell series is suppressed. The bone marrow may be suppressed by:
3. Anemia of chronic renal disease - is nonregenerative, normocytic and normochromic. It is caused by deficiency of erythropoietin releasing factor, erythroblast inhibition, reduced survival of RBC, iron deficiency (blood loss, impaired absorption), myelofibrosis, chronic infection, or loss due to coagulation abnormalities. 4. Anemia of chronic inflammatory disease and malignancy is due to impaired reutilization of iron that is sequestered by macrophages. The anemia is usually mild in magnitude (~25-35%PCV); normochromic normocytic and nonregenerative. The general diagnostic approach to the anemic patient From the history and physical examination the extent and nature of concurrent disease should be defined. If the animal is in good physical condition and the history suggests acute onset of signs the anemia is probably due to RBC loss or destruction and will probably be regenerative unless insufficient time has passed for regeneration to take place. If the patient is debilitated with a chronic history of illness the anemia is more likely to be nonregenerative. Approach to regenerative anemia: Regenerative anemia is usually due to blood loss or destruction (hemolysis) of RBC
*Places to search for physical evidence of loss should include feces, urine, body cavities (pleural space or peritoneal cavity) and evaluation for external parasites (eg fleas). Approach to nonregenerative anemia Rule-out chronic external loss of weeks to months especially if the RBC morphology is consistent with iron deficiency (microcytic and hypochromic). Search the same sites as listed above. Determine if intra-marrow or extra-marrow disease is present, intra-marrow diseases are often accompanied by reductions in WBC and platelets where-as extra-marrow diseases tend to involve only RBC Indications for examination of the bone marrow include:
Aspiration vs core:
Needle types
Technique Dogs will often tolerate procurement of a marrow aspirate using only local anesthesia whereas heavy sedation or general anesthesia is required to collect a core sample. General anesthesia is required for either aspiration or core in the cat. The area for bone puncture should be aseptically prepared and sterile gloves are worn
Place a small drop of marrow on each slide.
The top slide is drawn in this direction -->.
Interpretation of bone marrow cytology The interpretation of bone marrow cytology is complicated and likely will be performed by a speciality laboratory. The veterinarian should evaluate the cellularity of the sample before submitting the sample for analysis both grossly and microscopically. If the sample is low in cellularity, a second sample can be collected. The sample on the left is moderately cellular, the one on the right contains no marrow elements, only RBC.
Transfusion of blood and blood products Indications
Known incompatibilty is the major contraindication for blood transfusion. Dogs do not possess naturally occuring antibodies which will result in a major transfusion reaction during the first transfusion. Antibodies will form if an incompatible transfusion is administered and these antibodies will lead to a serious or fatal reaction on subsequent transfusions with the same blood type. Therefore although it is not imperative to cross match before the first transfusion to a dog, it is wise to do so when transfusing a patient which is likely to require multiple transfusions (eg a dog with a congenital coagulation disorder or with chronic reanl disease). At WSU we typically cross match before all transfusions. Cats can have natural occuring antibodies even if they have never been previously transfused. These naturally occuring antibodies can result in serious or fatal transfusion reactions during the first transfusion. Interspecies transfusions will result in rapid destruction of the transfused cells. The administration of dog blood to a cat will result in 50% of the cells being destroyed in destroyed in 6 hours and 95% destroyed in 24 hours. Blood groups and compatibility (KNOW the difference between typing and crossmatching blood) Blood typing is the identification of antigens expressed on the RBC surface. Typing is performed in just a few veterinary laboratories and requires a week or longer to obtain results. Blood cross matching is the mixing of plasma and cells from donor and recipient in order to determine if the cells and plasma are compatible. Cross matching is usually an in-house test and requires about 30 minutes to perform. Agglutination of cells is the end point of the cross match that indicates incompatibilty. Blood donor animals should be blood typed. Most patients are cross-matched against the hospital donors. Dogs have several of 8 unique antigens on the surface of RBC called Dog Erythrocyte Antigens (DEA) or Canine Erythrocyte Antigens (CEA). Nomenclature of Canine Erythrocyte Antigens
From Ball, R.W.: New knowledge about blood groups in dogs. Proceedings Gaines Veterinary Symposium. 1973 DEA 1.1 and 1.2 are the antigens that are most potent with regard to the abilty to stimulate antibody production if transfused into an animal that does not pocess these antigens on their own cells. If the dog subsequently receives blood containing DEA 1.1 and 1.2, they will have a serious reaction. DEA 7 is an antigen against which dogs can have naturally occuring antibodies even if they have never been transfused before. (Isoantibodies are naturally occurring antibodies that exist prior to transfusion). DEA 7 isoantibodies are weak and do not cause serious transfusion reactions but the presence of these antibodies can shorten the survival of transfused cells. There are 3 blood types in cats:
Most cats have type A blood although family groups of "unusual " breeds of cats eg; Devon Rex and Sphinx have a higher frequency of type B blood. AB is a very rare type. Isoantibodies are naturally occurring antibodies that exist prior to transfusion. Cats with type B blood have high anti A titers and cats with type A blood have low anti B titers. Life threatening immediate reactions may occur following the first transfusion of A blood to B cats.
cats:
dogs: There are several anticoagulants that can be used to prevent clotting of dog or cat blood. If there is intent to store the blood for later use, use an anticoagulant that will preserve RBC viabilty. When collecting blood using a commercial collection system, the anticoagulant is already in the collection container in a volume appropriate for the amount of blood that should be collected in that container. A standard unit of blood is ~450ml.
Blood and blood products are administered to the recipient through a filter to remove large particulate matter.
Volume of blood On the average, a transfusion of 10-20 ml/kg will increase the PCV by ~ 10% The goal of a transfusion is to relieve the patients signs of hypoxia, not to normalize PCV You can make a more accurate estimate of the amount of blood needed using this formula: ml of donor blood = wt (kg) x 90 (dog) or 70 (cat) x desired PCV - recipient PCV / PCV of donor Site of administration Blood can be administered by either the IV, IP or intrameduallry route. Blood administered IP will be absorbed up to ~80% of the cells, 50% within the first 24 hours and then the remainder over about 2 weeks. Blood given SC will be virtually 100% destroyed.
Rate of administration The initial rate of administration of blood should be very slow for the first 15 minutes ~1 - 5 ml/kg/hr, if the animal does not show any adverse reactions the rate can be increased to ~ 5 to 10 ml/kg/hr. If the animal is in hypovolemic shock then the rate of delivery should be ~ 20ml/kg/hr.If the animal needs RBC but cannot tolerate the volume of a whole blood transfusion packed RBC can be administered. Packed RBC have a PCV of ~70%. In most patients, if they can tolerate packed cells they can also handle the volume of a whole blood transfusion. Creating packed cells allows one to remove the plasma while it is still fresh and rich in coagulation factors and fresh the plasma as fresh frozen plasma. Fresh frozen plasma is removed from whole blood within 6 hours of collection. The coagulation factors will remain viable for ~ 1 year. Plasma frozen in excess of one year can still be used as a source of proteins. Plasma can be separated from blood that has been stored in the refrigerator and used as a source of protein even after the coagulation factors have become non functional. Cryoprecipitate is plasma that is formed from fresh frozen plasma that is thawed at refrigeration temperatures until a white precipitate forms. This precipitate can be separated from the rest of the plasma and refrozen. This is cyroprecipitate. It is rich in factor VIII and von Willibrands factor. It can be administered in small volumes to patients with hemophilia or von willebrands disease. Platelet rich plasma is plasma collected shortly after centrifuging fresh whole blood at a low G-force so the platelets stay in suspension in the plasma, rather than packing with the RBC. Platelet rich plasma must be used within a few hours of preparation. There are commercial companies that will ship blood and blood products from dogs and cats around the country by overnight shipment so it is not imperative that all small animal practices maintain blood donor animals or bank blood products. Complications of blood transfusions Immunologic reactions can be immediate or delayed depending upon whether the dog or cat has antibodies to the transfused cells. If a dog has been previously transfused or a cat that has isoantibodies, an immediate life threatening hemolytic reaction can take place. Signs may include tachycardia, hypotension, vomiting, salivation, muscle tremors, hemoglobinemia, and hemoglobinuria. Transfusion reactions may precipitate DIC. Treatment includes stopping the transfusion, administration of epinephrine, glucocorticoids and isotonic fluids to maintain vascular volume. If the animal makes antibodies to transfused cells, the survival of the transfused cells will be decreased. Less serious immediate reactions to platelet, protein or WBCs can result in fever, vomiting or urticaria. These can be treated with glucocorticoids and slowed rate of administration. Nonimmunologic complications of blood transfusion can include vascular overload or sepsis following administration of contaminated blood. Autotransfusion is collection of blood from a body cavity which is anticoagulated, and reinfused through a filter into the patients circulation or is collection of patient's own blood which is stored for reinfusion at a later date. Autotranfusion can be performed after trauma with bleeding into the abdominal cavity. Autotranfusion has the disadvantages of possible infusion of microemboli of fat or cellular aggregates that might result in organ infarction or DIC or of inducing sepsis if the patient has damaged intestine. In most circumstances autotransfusion is not recommended. Animals will autotransfuse themselves by reabsorbing blood from body cavities. Anabolic, androgenic steroids such as testosterone, nandrolone decanoate, or Stanzolol (Winstrol V) are sometimes suggested to Increase RBC production. In general the response to these drugs is MINIMAL - you may hold the PCV stable or achieve a small increase but more ofteh there is no response. Human recombinant erythropoietin is used in patients with chronic renal disease. A marked increase in PCV can occur. Animals may develop an antibody response to this product and after achieving an increase PCV you may observe a precipitous decline necessitating discontinuation of the drug. Splenectomy may play a role in the treatment of animals with for immune hemolytic anemia. The response is quite variable. A good plane of nutrition with adequate levels of dietary protein for protein anabolism and adequate amounts of vitamins and minerals should be fed to the anemic animal. Hemoglobin solutions Oxyglobin® solution is a
polymerized hemoglobin of bovine origin in a modified Lactated Ringer’s
Solution. It received FDA clearance for canine use in 1998. Oxyglobin® use is contraindicated in dogs at risk for volume overload such as those with advanced heart disease. Other side effects observed during safety trials included: a transient discoloration of sclera and urine, vomiting, and over-expanded vascular volume when administered at a higher than recommended rate. Less frequent adverse events that may or may not have been related to the administration of Oxyglobin included diarrhea, fever, arrhythmia and tachypnea. Oxyglobin® at a dosage of
30 mL/kg results in a mild decrease in PCV by dilution immediately after
infusion. PCV and RBC count are not accurate measures of the degree of anemia
for 24 hours following administration. Dilutional effects are not seen at lower
dosages. Link to Biopure: source of oxyglobin Most animals with increased PCV have relative polycythemia due to hemoconcentration. Splenic contraction can increase PCV by 10 to 15%. Absolute polycythemia is an increased total hemoglobin/RBC mass with normal plasma volume. Absolute polycythemia can be a primary myeloproliferative disorder called polycythemia vera. The signs of polycythemia vera can include polyuria and polydipsia, bleeding from small capillary rupture, neurologic disturbances caused by increased viscosity of blood. Treatment includes phlebotomy , removing 20-30 blood at 2-4 day intervals until PCV is normal. Phlebotomy may need to be repeated at 2-3 month intervals. Chemotherapy using chlorambucil may be effective. Secondary polycythemia is stimulated by hypoxia and may occur with primary cardiac or pulmonary disease or methemoglobinemia (e.g., acetaminophen intoxication in cats). Secondary polycythemia can also occur with renal tumors that elaborate erythropoietin. Notes Menu | Glossary | Search | VM 551 Home | Courses Home | External WebThis page was last edited on
December 15, 2003 by CRD |
