Hematology PDF

Hematology 17 CH A P TE R Patricia A. Schenck...

Hematology 17 CH A P TE R Patricia A. Schenck e. Hereditary nonspherocytic hemolytic ERYTHROCYTE DISORDERS anemia I. Anemias (1) Autosomal dominant in poodles A. Blood loss anemia (a) Resembles PK deficiency 1. Causes include trauma, surgery, parasites (b) Persistent macrocytic hypochromic (external and internal), gastric ulcers, gast- anemia; moderate reticulocytosis rointestinal (GI) tumors, urinary tract tumors, (c) Fatal by 3 years of age splenic rupture, coagulation disorders (2) Autosomal recessive in beagles 2. Treatment is administration of whole blood if (a) Can remain undetected for years packed cell volume (PCV) drops acutely below (b) Short RBC lifespan 20% in the dog or 25% in the cat 2. Immune-mediated hemolytic anemia (see below) B. Hemolytic anemia 3. Infectious causes of hemolysis 1. Congenital a. Hemoplasmosis (hemobartonellosis) a. Pyruvate kinase (PK) deficiency (1) Caused by Mycoplasma haemocanis in (1) Autosomal recessive in basenji, beagle, dogs and Mycoplasma haemofelis in cats West Highland white terrier, Cairn terrier, (2) Transmitted by ticks and fleas or from American Eskimo dog, miniature poodle, queens to newborn kittens Chihuahua, pug; Abyssinian, Somali, and (3) Immunosuppression or splenectomy domestic short hair (DSH) cats predisposes (2) Young animals (4) Clinical signs are associated with anemia (3) Anemia, exercise intolerance, tachycar- (5) Epicellular organisms are found on dia, splenomegaly; death by 4 years of blood smears; dogs usually have linear age usually chains of organisms, whereas cats usu- (4) Intense reticulocytosis, frequent nucle- ally have coccoid or ring shapes. PCR ated red blood cells (RBCs) tests are available for cats (Figure 17-1) (5) Polymerase chain reaction (PCR) (6) Treat with doxycycline. Prednisolone genetic test available for some breeds may be needed to suppress the destruc- b. Phosphofructokinase deficiency tion of RBCs. Enrofloxacin can be used (1) Autosomal recessive in English springer in cats if they do not tolerate doxycy- spaniels and American cocker spaniels cline. May need blood transfusions. (2) Increased intracellular pH increases Cats may become latent carriers fragility of RBCs b. Babesiosis (3) Hypoxia, intravascular hemolysis, (1) Caused by Babesia canis or Babesia hemoglobinuria, bilirubinuria, persis- gibsoni in dogs. Babesia felis affects tent reticulocytosis cats (but has not been found in (4) Lethargy, hepatosplenomegaly, myopa- North America). B. canis has been asso- thy, fever. May live a normal lifespan ciated with greyhounds, and B. gibsoni (5) PCR genetic test available has been associated with pitbulls and c. Hereditary stomatocytosis American Staffordshire terriers (1) Autosomal recessive in Alaskan (2) Transmitted by ticks malamutes in association with (3) Clinical signs are associated with ane- chondrodysplasia mia and range from an acute hemolytic (2) Mild anemia with slight reticulocytosis crisis to subclinical signs d. Feline porphyria (4) Large teardrop-shaped organisms are (1) Enzyme deficiency affects synthesis of seen in RBCs on blood smear. Smaller heme signet ring-shaped forms suggest B. gib- (2) Pink urine, pink-brown teeth, severe soni. Immunofluorescent antibody (IFA) anemia, skin photosensitization and PCR tests are available (Figure 17-2) (3) RBCs lyse when exposed to sunlight (5) Treat with imidocarb dipropionate 249 250 SECTION II SMALL ANIMAL membrane surface. Eccentrocytosis has been associated with onion and garlic ingestion in dogs (Figure 17-3) (6) Treatment is to remove the source of oxidant; give blood transfusions and supportive care. Acetominophen toxicity is treated with acetylcysteine b. Snake venom (coral snakes, rattlesnakes) can cause hemolysis. Echinocytosis may be observed c. Zinc toxicity can cause intravascular hemolysis in dogs. Sources of zinc include galvanized wire (from kennel cages), fishing sinkers, and pennies (since 1983). Regenerative anemia results, sometimes Figure 17-1 This blood smear from a domestic cat shows a high proportion with Heinz bodies and spherocytosis of the red blood cells with single scattered or short chains of basophilic cocci 5. Mechanical ragmentation of erythrocytes or faint rings on the cell membrane that are characteristic of Mycoplasma hae- a. Heartworms obstruct blood flow, resulting mofelis organisms. (Diff-Quik stain, original magnification 400.) (From Cowell in anemia from intravascular hemolysis. RL, Tyler RD, Meinkoth JH, DeNicola DB. Diagnostic Cytology and Hematology Schistocytosis, hemoglobinemia, and of the Dog and Cat, 3rd ed. St. Louis, 2008, Mosby.) hemoglobinuria are noted. (See section on cardiovascular disorders) b. Disseminated intravascular coagulopathy (DIC) causes a microangiopathic hemolytic anemia from fibrin deposition in damaged small blood vessels. Thrombocytopenia, decreased clotting factors, and increased fibrin degradation products are noted c. Hypophosphatemia associated with feline diabetes mellitus and hepatic lipidosis may cause hemolysis C. Nonregenerative anemia 1. Infectious agents a. Feline leukemia virus (FeLV) causes a normochromic, normocytic to macrocytic anemia. Severe RBC hypoplasia is common b. Other viruses, such as feline infectious peritonitis (FIP), feline immunodeficiency Figure 17-2 Peripheral blood from a dog with a Babesia canis virus (FIV), feline panleukopenia virus, ca- infection. Two piroplasms are seen in a single red blood cell in this field. nine parvovirus, and canine distemper vi- (Wright’s stain, original magnification 330×.) (From Cowell RL, Tyler RD, rus, can cause mild to moderate anemia be- Meinkoth JH, DeNicola DB. Diagnostic Cytology and Hematology of the cause of the suppression of erythropoiesis Dog and Cat, 3rd ed. St. Louis, 2008, Mosby.) c. Leptospirosis can cause hemolysis and coagu- lopathies. (See section on infectious diseases) 4. Chemical or toxic injury of erythrocytes a. Heinz body anemia (1) Produced by oxidant agents that precip- itate hemoglobin; this leads to acceler- ated RBC destruction (2) Agents responsible include acetami- nophen, methylene blue, onions, zinc, vitamin K3, methionine, and propylene glycol (3) In cats, Heinz bodies may be associated with hyperthyroidism, lymphoma, and ketoacidosis (4) Clinical signs include hemoglobinemia, hemoglobinuria, moderate to severe Figure 17-3 Three canine erythrocytes with large Heinz bodies and an anemia, and icterus eccentrocyte (center) can be seen in this field. (Wright’s stain, original (5) Heinz bodies appear as a large pale- magnification 330×.) (From Cowell RL, Tyler RD, Meinkoth JH, DeNicola DB. staining area in RBCs or may appear as Diagnostic Cytology and Hematology of the Dog and Cat, 3rd ed. St. Louis, a blunt projection bulging from the RBC 2008, Mosby.)  CHAPTER 17 Hematology 251 c. Rickettsial diseases such as Ehrlichia and toxic agents. It is also associated with myelo- Anaplasma are associated with mild to dysplastic syndrome and acute myelogenous moderate nonregenerative anemia, along leukemia in cats. Bone marrow aspirate with thrombocytopenia, leukopenia, or produces only blood, with few to no marrow pancytopenia. Intracytoplasmic morulae are particles sometimes observed in mononuclear cells c. Myelonecrosis results from direct injury to or granulocytes endothelium or occlusion of microcirculation d. Leishmaniasis may cause a mild to moder- d. Osteopetrosis is an inherited condition ate normocytic, normochromic anemia resulting in obliteration of marrow cavities e. Cytauxzoonosis causes moderate anemia, by bone, with resulting anemia or leukopenia, and thrombocytopenia, and is pancytopenia in young dogs highly fatal 8. Irradiation can result in pancytopenia and 2. Nutritional deficiencies aplastic bone marrow a. Iron deficiency causes a poorly regenerative 9. Pure erythrocyte aplasia is a significant reduc- anemia from deficient hemoglobin synthesis tion in erythroid stem cells, with no effect on (1) Caused by neoplasia, trauma, parasites, granulocytic or megakaryocytic lines coagulopathies, and GI diseases causing II. Polycythemia blood loss A. Relative polycythemia (2) RBCs show hypochromasia and 1. Usually due to dehydration or hemoconcentra- poikilocytosis tion. Splenic contraction from excitement can (3) Thrombocytosis is common also cause a transient increase in PCV. Grey- b. Cobalamin (vitamin B12) deficiency causes hounds normally have a higher PCV (about 60%) normocytic, normochromic, nonregenera- 2. Mucous membranes are dark red and have a tive anemia slow capillary refill time c. Folate deficiency produces a macrocytic B. Absolute polycythemia anemia 1. Primary erythrocytosis (polycythemia vera) 3. Inflammatory diseases frequently cause results from a stem cell defect, with low serum nonregenerative anemia erythropoietin concentrations a. Cytokine release leads to decreased eryth- 2. Secondary erythrocytosis is a result of over- ropoiesis, reduced iron availability, and production of erythropoietin resulting from decreased RBC survival hypoxia, erythropoietin-producing tumors, or b. Bone marrow is hypocellular pyelonephritis 4. Organic diseases III. Methemoglobinemia a. Chronic renal disease may be accompanied A. Occurs from oxidation of iron in hemoglobin. by normocytic, normochromic, nonregener- Oxidized hemoglobin cannot bind oxygen, ative anemia resulting in hypoxia. Blood appears dark red or b. Liver disease is associated with normocytic, chocolate-colored nonregenerative anemia. Poikilocytosis is B. Results from exposure to oxidant drugs and common chemicals. Methemoglobinemia often occurs 5. Endocrine diseases at the same time as Heinz bodies appear, but a. Hypothyroidism may cause mild anemia methemoglobinemia usually occurs first b. Hyperestrogenism causes moderate to C. Treatment is similar to Heinz body anemia severe anemia with thrombocytopenia and leukopenia LEUKOCYTE DISORDERS c. Hypoadrenocorticism may cause a nonre- generative anemia I. Congenital disorders 6. Drug and toxin-induced diseases A. Pelger-Huet anomaly a. Drugs inducing anemia include estrogens, 1. Inherited disorder of granulocyte maturation phenylbutazone, antineoplastic agents, 2. Nuclei of neutrophils often look like band cells, trimethoprim-sulfadiazine, thiacetarsamide, metamyelocytes, or myelocytes quinidine, meclofenamic acid; decreased 3. No clinical signs; treatment not necessary erythropoiesis and aplastic anemia B. Feline Chediak-Higashi syndrome b. Lead toxicity 1. Rare; occurs in blue-smoke Persian cats with (1) Mild anemia; basophilic stippling yellow eyes observed 2. Neutrophils contain large pink cytoplasmic (2) Large numbers of nucleated RBCs with inclusions normal or decreased PCV 3. Abnormal lysosomal granule formation in gran- 7. Myelophthisis occurs when abnormal cellular ulocytes and monocytes infiltrates crowd the bone marrow, suppressing C. Lysosomal storage disease hematopoiesis 1. Mucopolysaccharidosis and gangliosidosis a. Neoplasia from primary hemolymphatic a. Inherited; caused by enzyme deficiency tumors or metastatic tumors b. Neutrophils contain coarse, red-purple b. Myelofibrosis occurs when bone marrow is granules when stained. Must distinguish damaged by inflammation, necrosis, neoplasia, these from toxic neutrophils 252 SECTION II SMALL ANIMAL c. Urine test for glycosaminoglycans. Also cell 3. Allergies result in the production of immuno- enzyme activity tests globulin E (IgE) with mast cell degranulation 2. Other disorders cause lymphocyte vacuolation and attraction of eosinophils abnormalities. Affected lymphocytes have 4. Tumors such as fibrosarcoma, mammary carci- multiple cytoplasmic vacuoles noma, mast cell tumors, and T-cell lymphomas D. Abnormal granulation syndrome in Birman (cats) cats 5. Feline hypereosinophilic syndrome 1. Pink-purple granules within neutrophil a. Infiltration of eosinophils into organs cytoplasm b. Cause unknown 2. No clinical signs c. Resembles leukemia of well-differentiated II. Neutrophil disorders eosinophils A. Neutrophilia d. Clinical signs include anorexia, weight loss, fe- 1. Physiologic resulting from the release of epi- ver, vomiting, diarrhea, and lymphadenopathy nephrine (transient increase). More common e. Death results from organ infiltration in cats B. Eosinopenia from exogenous or endogenous 2. Corticosteroid administration corticosteroids 3. Inflammation V. Basophilia a. Infectious A. Parasites such as heartworms or hookworms b. Noninfectious such as in pancreatitis, tissue B. Allergies cause IgE production with increased necrosis, thrombosis, and burns mast cells and basophils c. Neoplasia such as metastatic fibrosarcoma C. Hyperlipemia can result in basophilia or renal tubular carcinoma D. Systemic mastocytosis d. Severe abscessation such as pyometra VI. Lymphocyte disorders e. Immune-mediated such as systemic lupus A. Lymphocytosis erythematosus 1. Transient lymphocytosis can occur with stress f. Granulocytopathy syndrome in Irish setters. or extreme exertion Neutrophils have impaired bactericidal 2. Infectious lymphocytosis can occur from anti- activity as a result of adhesion defects gen stimulation in FeLV, E. canis, Rickettsia rick- 4. Paraneoplastic syndrome ettsii, and fungal infections. Vaccination with B. Neutropenia modified live vaccines may also cause a reac- 1. Congenital cyclic neutropenia tive lymphocytosis about a week after vaccina- a. Inherited disorder of gray collies tion. Lymphocytes appear slightly enlarged b. Cyclic decrease of neutrophils, platelets, with a dark basophilic cytoplasm and monocytes in 12-day intervals 3. Neoplastic (see leukemic disorders below) 2. Infection causes a degenerative left shift with B. Lymphopenia an increase of immature cells 1. Corticosteroids (exogenous or endogenous) a. Gram-negative bacteria decrease lymphocytes. Lymphopenia should b. Toxoplasma resolve within a few days of discontinuing cor- c. Systemic fungal disease ticosteroids d. Viruses such as FeLV, FIV, feline panleuko- 2. Infectious agents may cause lymphoid tissue penia virus, canine parvovirus destruction (FeLV, FIV, parvovirus, distemper e. E. canis virus), resulting in lymphopenia 3. Drugs: Many antibiotics (e.g., chloramphenicol, 3. Lymphatic injury such as in chylothorax, lym- trimethoprim-sulfadiazine), antineoplastic phangiectasia, or protein-losing enteropathy agents, and nonsteroidal antiinflammatory causes loss of lymph fluid and lymphopenia drugs (NSAIDs) can cause neutropenia 4. Congenital lymphopenia occurs in basset 4. Endotoxins from gram-negative bacteria hounds and is associated with severe bacterial 5. Immune-mediated neutropenia is due to infections destruction of antibody-coated neutrophils VII. Mastocytosis by macrophages. Drugs responsible include A. Occurs secondary to mast cell tumors methimazole and cephalosporins B. Bone marrow is rarely invaded by mast cells III. Monocytosis A. From corticosteroid administration (along with PLATELET DISORDERS neutrophilia, lymphopenia, and eosinopenia) B. Inflammatory processes that cause a demand for I. Thrombocytopenia macrophages A. Immune-mediated injury (see below under im- C. Neoplasia (see leukemic disorders below) mune disorders) IV. Eosinophils B. Increased platelet consumption or utilization A. Eosinophilia 1. Infectious agents such as E. canis, E. ewingii, 1. Parasites in skin, respiratory tract, or GI tract Anaplasma platys, and A. phagocytophilum 2. Parasites include Ancylostoma, Trichuris vulpis, 2. Canine distemper virus vaccination causes Toxocara canis, Dirofilaria immitis, Dipetalo- transient thrombocytopenia about a week nema reconditum, lungworms, and Paragonimus after vaccination and may persist for several kellicotti weeks  CHAPTER 17 Hematology 253 3. Hemorrhage LEUKEMIC DISORDERS 4. DIC associated with infection, neoplasia, heart- worm disease, pancreatitis, and shock I. Lymphoid leukemia C. Sequestration of platelets by an enlarged spleen A. Acute lymphoblastic leukemia (ALL) D. Decreased platelet production 1. Abnormal proliferation of immature lympho- 1. Congenital thrombocytopenia may be associ- blasts in bone marrow or blood ated with cyclic hematopoiesis in collies 2. Rapidly progressive with poor response to 2. Infectious diseases such as distemper virus, therapy parvovirus, FeLV, and E. canis 3. Clinical signs include fever, abdominal pain, 3. Drugs such as cisplatin, cyclophosphamide, anorexia, splenomegaly, and pale mucous chlorambucil, doxorubicin, and hydroxyurea membranes II. Thrombocytosis 4. Most have leukocytosis with abnormal lympho- A. Physiologic thrombocytosis occurs during heavy cytes. About 10% have aleukemic leukemia, exercise or from epinephrine release which is bone marrow involvement without B. Reactive thrombocytosis peripheral blood involvement 1. From acute blood loss, iron deficiency anemia, 5. Cytochemical stains may be necessary to trauma, surgery, inflammation, splenectomy, differentiate from other forms of leukemia hyperadrenocorticism 6. Poor prognosis 2. Tumors causing thrombocytosis include mast B. Chronic lymphocytic leukemia (CLL) cell tumors, hemangiosarcoma, osteosarcoma, 1. Abnormal proliferation of mature lymphocytes lymphoid leukemia, and myeloid leukemia in bone marrow or blood 3. Vincristine administration can cause 2. Clinical signs include lethargy, inappetance, thrombocytosis polyuria, polydipsia, intermittent lameness, 4. Pseudohyperkalemia may be observed due to and episodes of collapse leakage of potassium from clotted platelets 3. Most have normocytic, normochromic, C. Neoplastic (see leukemic disorders below) nonregenerative anemia with thrombocyto- penia. About one third of dogs have hyper- proteinemia, many with monoclonal gammo- DYSPLASTIC DISORDERS pathies. Bence-Jones protein in the urine I. Congenital dysplasia indicates B-cell origin, but most cases of A. Inherited erythrocyte macrocytosis in miniature CLL are of T-cell origin and toy poodles 4. Treat if symptomatic, if there are significant 1. Macrocytosis and megaloblastosis with no cytopenias, or if lymphadenopathy or spleno- signs of anemia megaly are present. Treat with prednisone 2. Not responsive to folate or vitamin B12 and chlorambucil B. Inherited macroplatelets in Cavalier King Charles 5. Prognosis is better for CLL than for ALL spaniels II. Myeloid malignancy II. Infectious causes A. Myelodysplastic syndrome A. Typically from FeLV or FIV 1. Persistent cytopenia in one or more B. Dysplastic changes include macrocytosis, megalo- hematopoietic cell lines, accompanied by blastosis, large hypersegmented neutrophils, and abnormal maturation. Associated with FeLV small megakaryocytes in cats C. Cytopenia may occur 2. Clinical signs include lethargy resulting III. Drug-induced from anemia, hemorrhage, and chronic A. Drugs such as chloramphenicol, vincristine, infections cyclophosphamide, and azathioprine can cause 3. Bone marrow is hypercellular with mild in- dyserythropoiesis with macrocytosis, nuclear crease in myeloblasts. Cells have dysplastic fragmentation, sideroblastosis, megaloblastoid changes, including macrocytosis, megalob- changes, and siderocytosis lastosis, nuclear fragmentation, abnormal B. Changes are not associated with folate deficiency, granulation, hypersegmentation or hyposeg- and normal morphology returns a few days after mentation, micromegakaryocyte or macro- drug therapy is stopped thrombocyte formation, and cell giantism IV. Nutritional 4. Treat supportively. May respond to prednisone A. Malabsorption of vitamin B12 in giant schnauzers and erythropoietin causes erythroid dysplastic changes with neutro- B. Acute myeloid leukemia (classified as M1 to M7, philic hypersegmentation depending on which blast cells predominate in B. Folate deficiency the bone marrow) 1. Neoplasia, intestinal malabsorption, liver dis- 1. Acute myeloblastic leukemia (M1, M2) ease can cause folate deficiency, resulting in a a. Relatively common; often associated with macrocytic nonregenerative anemia FeLV in cats 2. Anticonvulsants and some antibiotics and b. Severe nonregenerative anemia, antineoplastic agents can inhibit folate thrombocytopenia with leukocytosis metabolism, causing megaloblastic changes c. Leukemic cells have pale basophilic cyto- in erythroid precursors plasm containing small, red granules 254 SECTION II SMALL ANIMAL d. Blast cells are variably positive for peroxi- Lameness is secondary to bone pain. Epistaxis or dase, Sudan black B, chloroacetate esterase, gingival bleeding occurs secondary to hypervis- leukocyte alkaline phosphatase, and acid cosity syndrome or thrombocytopenia phosphatase with cytochemical staining C. Diagnosis 2. Acute myelomonocytic (M4) 1. Most have monoclonal gammopathy, either IgG a. Common form involving the stem cell for or IgA both granulocytes and monocytes 2. Bence-Jones proteins may be observed in the b. Both monoblasts and myeloblasts are urine observed with cytochemical staining 3. Often associated with nonregenerative, normo- 3. Acute monocytic (M5) cytic, or normochromic anemia. Some also a. Increased monoblasts in bone marrow. Cells have thrombocytopenia have a basophilic cytoplasm without granu- 4. About 20% of dogs have hypercalcemia lation, and irregular nuclei with prominent D. Diagnosis is based on the presence of plasma- nucleoli cytosis, evidence of osteolytic bone lesions, b. Cytochemical staining is positive for non- and serum or urine myeloma proteins specific esterase and acid phosphatase E. Differentials for monoclonal gammopathy include 4. Erythroleukemia (M6) ehrlichiosis and benign hypergammaglobulinemia a. Associated with FeLV in cats in the dog. Ehrlichiosis, carcinomas, connective b. Rubriblasts may predominate. Megaloblas- tissue disorders, liver disease, and hypersensitiv- tosis, neutrophil giantism, or hypersegmen- ity states are differentials for plasmacytosis tation may also be present F. Prognosis in the dog is good but poor in the cat c. Nucleated RBCs and normochromic macro- G. Treatment with melphalan and prednisone cytes are observed induces remission in about 90% of dogs 5. Megakaryoblastic (M7) IV. Polycythemia vera a. Rare. May be associated with radiation in A. Rare the dog B. Increased hematocrit (PCV 65% to 82%). Blood b. Severe nonregenerative anemia, leukopenia, is hyperviscous, and mucous membranes are and variable platelet count dark red c. Megakaryoblasts appear in circulation, and C. Treat with phlebotomy, hydroxyurea, or platelets may be giant and have abnormal radiophosphorus granulation V. Primary thrombocythemia d. Immunocytochemical stains are helpful A. Rare proliferation of platelets C. Chronic myeloproliferative diseases B. Characterized by splenomegaly and platelet func- 1. Chronic granulocytic (neutrophilic) leukemia tion abnormalities (bleeding, thromboembolism) a. Increased numbers of progranulocytes C. Treat with melphalan, hydroxyurea, or radiophos- to metamyelocytes in blood and bone phorus marrow. Myeloblasts in the bone marrow D. May transform to chronic myelogenous leukemia are decreased VI. Idiopathic myelofibrosis b. Leukocytes are markedly elevated, with mild A. Uncommon to moderate anemia B. Intramedullary and extramedullary hematopoiesis c. Differentiate from highly suppurative infec- with reactive or secondary marrow fibrosis tions such as pyometra that cause a leuke- C. Granulocytic and megakaryocytic cells infiltrate moid reaction the spleen and liver 2. Eosinophilic leukemia D. Leukoerythroblastic reaction in which the periph- a. Rare. Has been associated with FeLV in eral blood has both immature granulocytes and the cat erythroid cells. Poikilocytosis and dacryocystosis b. High eosinophil count with immature forms. are present May appear similar to hypereosinophilic conditions (e.g., allergies, parasites) COAGULATION DISORDERS c. Eosinophils infiltrate lymph nodes, liver, and spleen I. Diagnostic tests (Figure 17-4) 3. Basophilic leukemia A. Quick assessment of coagulation a. Rare, mostly in the dog 1. Assessment of platelet number on blood smear. b. Mature and immature basophilia in blood or Thrombocytopenia is ruled out if under oil bone marrow. Associated with thrombocy- immersion there are 7 to 10 platelets per field in tosis and anemia the dog and 10 to 15 platelets per field in the cat c. Must differentiate from mast cell leukemia 2. Activated clotting time d. Cytochemical staining with -exonuclease is a. Test of the intrinsic clotting system helpful b. Do not sample from the jugular vein be- e. Treat with hydroxyurea cause of the risk of hematoma formation III. Multiple myeloma c. Using a Vacutainer, collect 2 mL of blood A. Plasma cell neoplasm into a plain tube, then collect 2 mL into a B. Usually in older dogs; clinical signs include an- tube containing siliceous earth. Warm this orexia, listlessness, polyuria, and polydipsia. tube to 37° C before sampling  CHAPTER 17 Hematology 255 Intrinsic system Extrinsic system 5. von Willebrand factor (vWF) assay a. Specific measurement of vWF concentration PK Tissue b. If vWF is below the reference range, the dog HMWK Factor XII is at risk for carrying or expressing vWD XI VII 6. Diagnosis of DIC IX a. Based on clinical signs and coagulation tests VIII b. High plasma fibrin, fibrinogen degradation Common pathway products, or cross-linked fibrin fragments c. Decreasing platelet count, low antithrombin X activity, prolongation of aPTT, PT, TCT, and V presence of schistocytes II APTT I OSPT II. Coagulation factor deficiencies ACT XIII A. Acquired deficiencies are common 1. Coagulation factors are produced in the liver; conditions decreasing liver function or mass Fibrin will result in decreased coagulation factors 2. Vitamin K deficiency occurs with ingestion of Figure 17-4 The traditional intrinsic, extrinsic, and common coagulation anticoagulant rodenticides, posthepatic biliary pathways. PK, Prekallikrein; HMWK, high-molecular-weight kininogen; obstruction, or infiltrative bowel disease. APTT, activated partial thromboplastin time; ACT, activated coagulation Vitamin K is required for activation of factors II, time; OSPT, one-stage prothrombin time. (From Nelson RW, Couto CG. Small Animal Internal Medicine, 3rd ed. St. Louis, 2003, Mosby.) VII, IX, and X 3. Heparin inhibits fibrin clot formation by in- creasing the activity of antithrombin III. Excess d. Immediately invert to mix blood with sila- heparin results from overdosage in the treat- ceous activator and place in a 37° C heating ment of thrombotic disorders or from release block of heparin from mast cell tumor granules e. After 45 seconds, remove tube every 5 to 4. Increased concentration of fibrin degradation 10 seconds and check for clotting. Normal products in DIC can interfere with fibrin clot dogs clot within 60 to 120 seconds; normal formation cats clot within 60 to 70 seconds B. Inherited deficiencies 3. Bleeding time tests 1. Hemophilia is the most severe coagulation a. Buccal mucosa bleeding time test factor deficiency (1) May require sedation a. Inherited X-linked recessive trait. Spontane- (2) Evert lip, encircle muzzle with gauze to ous mutations causing hemophilia are not cause the buccal veins to engorge uncommon (3) Make two parallel incisions in mucosa b. Males express hemophilia, whereas females of upper lip are asymptomatic carriers (4) Normal dogs and cats stop bleeding from c. Hemophilia A is more common and is both incisions within 2 to 4 minutes caused by a defect in the factor VIII gene. (5) Prolonged in those with acquired and Hemophilia B is caused by a defect in the inherited platelet dysfunction and von factor IX gene Willebrand disease (vWD). Normal with d. German shepherd dogs (especially from coagulation factor deficiencies and in European stock) have the highest incidence some with DIC of hemophilia A b. Toenail bleeding time test 2. Deficiencies of other factors (XI, X, VII, II, (1) Perform only if sedated or anesthetized fibrinogen) have been described (2) Cut nail at cuticle and allow blood to 3. Factor XII deficiency is common in cats but flow freely does not cause bleeding (3) Normal dogs stop bleeding in 5 to 4. Combined deficiency of factors II, VII, IX, and 6 minutes X has been reported in Devon Rex cats and (4) Prolonged in significant coagulation Labrador retrievers factor deficiencies, vWD, platelet dys- III. von Willebrand disease (vWD) function, and DIC A. Most common hereditary bleeding disorder in B. Coagulation screening assays measure the time dogs. Occurs in both males and females for fibrin clot formation in vitro B. Breeds with a high prevalence of vWD include 1. Activated partial thromboplastin time (APTT) the Doberman pinscher, Scottish terrier, Shetland detects deficiencies of intrinsic and common sheepdog, German wirehaired pointer, German coagulation pathways shorthaired pointer, Pembroke Welsh corgi, 2. Prothrombin time (PT) detects deficiencies of Chesapeake bay retriever, and Australian shep- extrinsic and common pathways herd, but it can occur in any breed, including 3. Fibrinogen concentration measures plasma mixed-breed dogs fibrinogen C. Bleeding in those with vWD is exacerbated by 4. Thrombin clotting time (TCT) detects defi- other underlying conditions such as infection, en- ciency and dysfunction of fibrinogen docrinopathies, or concurrent thrombocytopenias 256 SECTION II SMALL ANIMAL D. Three subtypes occur in dogs: 3. Desmopressin acetate may improve hemosta- 1. Type 1 vWD is mild to moderate, with low vWF sis in some dogs with vWD concentration but normal vWF structure 4. Heparin therapy is typically used to treat 2. Type 2 vWD causes severe bleeding with low thrombotic DIC. Close monitoring is required vWF concentration and abnormal vWF structure 3. Type 3 vWD causes severe bleeding as a result IMMUNE DISORDERS of the complete lack of vWF IV. Disseminated intravascular coagulopathy (DIC) I. Immune-mediated hemolytic anemia (IMHA) A. Caused by activation of the coagulation cascade. A. Cause is unknown Clot formation leads to thrombosis and occlusion B. Breeds with a higher incidence include cocker of blood vessels, decreased blood supply to spaniels, poodles, and old English sheepdogs. tissues, and activation of fibrinolytic pathways Vaccination, stress, or infection may trigger IMHA B. DIC is usually associated with severe inflamma- C. Clinical signs include weakness, collapse, pale tion, sepsis, neoplasia (lymphoma, hepatic neo- gums, discolored urine, fever, hepatosplenomeg- plasia, hemangiosarcoma, prostatic carcinoma, aly, tachycardia, and tachypnea mammary carcinoma), burn wounds, pancreatitis, D. Laboratory findings include anemia, reticulocyto- and intravascular hemolysis sis, spherocytosis, and leukocytosis with left C. Bleeding develops as coagulation factors and shift. Coombs’ test is usually positive. Liver platelets are consumed in the thrombotic process enzymes may be elevated as a result of hypoxic D. Clinical signs include spontaneous hemorrhage or damage. Spontaneous autoagglutination of RBCs excessive bleeding after surgery or trauma. The may occur (Figure 17-5) presence of petechiae is a common sign of throm- E. DIC and thromboembolism are complications bocytopenia. Bleeding is usually severe, and signs F. Test cats for FeLV, FIV, and hemoplasmosis of underlying disease are typically present G. May occur in conjunction with immune-mediated E. Diagnosis is through a combination of clinical thrombocytopenia signs, history, radiography to detect bleeding in H. Treatment body cavities, and laboratory findings, especially 1. Intravenous (IV) fluids and blood transfusion if elevated fibrinogen degradation products PCV is below 15% V. Treatment 2. Prophylactic therapy with heparin or aspirin to A. Transfusion therapy is necessary to supply coag- prevent thromboembolism ulation factors in those with severe deficiencies 3. In mild cases, treatment with prednisone or 1. Stored whole blood or RBCs do not contain re- prednisone  azathioprine placement levels of coagulation factors or vWF. 4. Cases in which bilirubin is greater than 3 mg/dL Fresh whole blood (within 4 to 6 hours of col- or the PCV is rapidly dropping require aggres- lection) will supply coagulation factors, but sive therapy. Treat with IV fluids, heparin, there is a higher risk of transfusion reactions prednisone, and azathioprine. Human 2. Transfusion of plasma products along with immunoglobulin and cyclosporine can also stored whole blood or packed RBCs is the equiv- be used alent to fresh whole blood, and this combination reduces the risk of transfusion reactions 3. Do not treat with antihistamine or corticoste- roids before transfusion of blood products 4. In cats, use blood products that are blood type and crossmatch compatible 5. In dogs, use dogs negative for dog erythrocyte antigen (DEA) 1 and DEA 7 as “universal donors” B. Provide supportive care to minimize the risk of hemorrhage. Do not give sulfas or NSAIDs that can cause platelet inhibition C. Drug therapy 1. Treat any underlying disorder that may impair clotting ability (hyperestrogenism, hypothy- roidism, hyperadrenocorticism) 2. Vitamin K therapy is only useful if there is vitamin K deficiency a. The most common cause of vitamin K defi- ciency is anticoagulant rodenticide toxicity Figure 17-5 A blood smear from a dog with immune-mediated hemolytic anemia. Note the marked anisocytosis resulting from a mixed population b. Warfarin is short-acting, and treatment for of small spherocytes and large, immature, and normal red blood cells. The about 1 week is usually adequate. Treat spherocytes are dense staining and lack central pallor. A few polychromato- with subcutaneous vitamin K1, followed by phils are in the shape of codocytes. (Wright’s stain, original magnification oral vitamin K1 250.) (From Cowell RL, Tyler RD, Meinkoth JH, DeNicola DB. Diagnostic c. Long-acting anticoagulants (such as brodi- Cytology and Hematology of the Dog and Cat, 3rd ed. St. Louis, 2008, facoum) require treatment for 4 to 6 weeks Mosby.)  CHAPTER 17 Hematology 257 5. Monitor CBC daily until stable, then weekly SPLENIC DISORDERS until PCV is greater than 25%. Treat for a minimum of 6 months I. Anatomy and function I. Prognosis is fair for mild cases and guarded for A. Located in the left cranial abdomen attached to severe cases. Relapses occur unpredictably the greater curvature of the stomach. The canine II. Immune-mediated thrombocytopenia (IMT) spleen is sinusoidal, whereas the cat spleen is A. Cause is unknown. IMT is suspected when a nonsinusoidal “healthy” animal presents with petechiae or B. The primary function of the spleen is filtration mucosal bleeding of peripheral blood. RBCs and other circulating B. Clinical signs include epistaxis, oral cavity cells are removed as they age, and inclusions are bleeding, petechiae or ecchymoses, hematuria, removed from the RBCs. Inclusions removed melena, pale gums, splenomegaly, fever, or retinal include Howell-Jolly bodies, Heinz bodies, and hemorrhage hemoparasites C. Diagnosis is by finding severe thrombocytopenia C. The spleen has an important immunologic (i.e., less than 25,000/ L) in a healthy appearing function as it is the largest lymphoid organ in animal the body 1. If platelets number more than 25,000/ L, 1. The marginal zone of the white pulp contains consider other causes both B and T lymphocytes, whereas most of 2. Chemistry and coagulation profiles are the B cells are in the germinal center and usually normal. There may be a mild mantle zones. If antigen is present on lympho- elevation of fibrin degradation products cytes, they undergo activation and proliferation due to hemorrhage 2. Important in defense against polysaccharide- D. May occur in association with IMHA encapsulated bacteria and other circulating E. Treatment particulate antigens 1. Treat most cases with prednisone or prednisone 3. Surface immunoglobulins on RBCs are removed  azathioprine by splenic macrophages 2. Vincristine can be used once to help elevate D. Reservoir function the platelet count 1. Blood cells are stored in the spleen, and the 3. Do not use cyclophosphamide spleen is capable of holding a large volume 4. Monitor platelet counts daily until greater than of blood 25,000/ L, then weekly. Treat for a minimum of 2. The spleen normally stores about 10% to 20% 6 months of the total blood volume, but it can hold up F. Prognosis is guarded until the platelet count to a third of the dog’s RBCs begins to rise. Relapses occur unpredictably E. Hematopoietic function III. Systemic lupus erythematosus (SLE) 1. The normal adult spleen has no hematopoietic A. Antibodies are produced against nuclear, cyto- capacity, but the red pulp retains the ability for plasmic, and cell membrane molecules; these extramedullary hematopoiesis (EMH) if needed antibodies directly damage tissues through the 2. Disorders associated with EMH include heman- formation of immune complexes giosarcoma, lymphoma, multiple myeloma, B. Clinical signs are varied since almost any organ leukemia, IMHA, eosinophilic gastroenteritis, can be affected in SLE estrogen-induced bone marrow hypoplasia, 1. Immune-mediated polyarthritis is most com- pyometra, and ehrlichiosis monly recognized in combination with immune- 3. EMH is not as common in cats as in dogs mediated skin disease, glomerulonephritis, 4. With EMH, immature red and white cell precur- hemolytic anemia, or thrombocytopenia sors may be present in the peripheral blood 2. Skin signs include erythema, scaling, crusting, F. Other functions of the spleen include storage and depigmentation, and alopecia. Skin and oral activation of factor VIII, formation and degradation ulcers may occur of angiotensin-converting enzyme, modulation of C. A positive antinuclear antibody (ANA) test with norepinephrine concentrations and prostaglandin two manifestations of autoimmunity or three E2 activity, and iron storage and recycling of iron manifestations of autoimmunity with negative to bone marrow ANA supports a diagnosis of SLE II. Causes D. Treatment A. Localized splenomegaly 1. Avoid exposure to sunlight, which may exacer- 1. Primary or metastatic neoplasia bate SLE a. Hemangiosarcoma is the most common 2. Lameness can be treated with NSAIDs neoplasm in the spleen of the dog. Heman- (carprofen, etodolac, or meloxicam) giomas also occur. Breeds at higher risk for 3. More severe signs are treated with corticoste- hemangiosarcoma of the spleen include roids or corticosteroids  azathioprine. Treat German shepherd dogs, golden retrievers, for a minimum of 6 months and Labrador retrievers E. Prognosis is usually good, although signs may b. In cats, systemic mastocytosis and wax and wane. Patients should be monitored for lymphoma are the most common splenic the development of renal disease tumors 258 SECTION II SMALL ANIMAL c. Other tumors in the spleen include the D. Hyposplenism is a decrease in splenic function. sarcomas, histiocytoma, lipoma, mesen- Characteristics include target cells, acanthocytes, chymoma, and lymphoma. Metastatic Howell-Jolly bodies, nucleated RBCs, reticulocyto- carcinomas are rare sis, and thrombocytosis 2. Nodular hyperplasia III. Clinical signs a. Single or multiple nodules that are benign A. Signs are nonspecific and related to the underlying accumulations of lymphoid cells, hemato- disease process poietic cells, and plasma cells B. Signs include weight loss, anorexia, weakness, b. Common in older dogs vomiting, diarrhea, abdominal distension, poly- 3. Hematoma from trauma, causing a mass that uria, and polydipsia. Collapse with pale mucous cannot be differentiated from neoplasia on membranes suggests splenic rupture morphology IV. Diagnosis 4. Abscesses are rare but may occur from A. History hematogenous spread of bacteria (especially 1. Intermittent collapse and pale mucous Staphylococcus in the dog). In the cat, abscess membranes suggest hemangiosarcoma has been associated with cholangiohepatitis 2. Acute abdominal distention may suggest B. Generalized splenomegaly torsion 1. Inflammatory or infectious disease 3. Tick exposure suggests ehrlichiosis or Rocky a. Causes of suppurative inflammation Mountain spotted fever include bacterial endocarditis, septicemia, B. Physical examination splenic torsion, migrating foreign body, 1. The spleen is normally palpable in many dogs penetrating abdominal wounds, toxoplas- and cats. The position of the spleen can vary by mosis, mycobacteriosis, and infectious breed, body weight, and food in the stomach canine hepatitis 2. Lymphadenopathy may suggest lymphoma, b. Causes of necrotizing inflammation include leukemia, or infectious diseases splenic torsion, splenic neoplasia, infectious C. Hematology and serum biochemistry may suggest canine hepatitis, and salmonellosis the underlying disorder c. Causes of lymphoplasmacytic inflammation D. Diagnostic imaging include chronic infectious canine hepa- 1. On radiography, rounded or blunted margins titis, ehrlichiosis, Rocky Mountain are characteristic of enlargement. A mid- spotted fever, pyometra, brucellosis, abdominal mass on a lateral view abdominal and hemobartonellosis radiograph is most likely a splenic mass d. Causes of granulomatous inflammation 2. Ultrasound is useful for determining size, include histoplasmosis, mycobacteriosis, location, and presence of masses. The spleen and leishmaniasis, and causes of pyogranu- is normally hyperechoic lomatous inflammation include blastomyco- E. Fine needle aspiration (FNA) is most useful in sis, sporotrichosis, and feline infectious diffuse splenic disease and should be performed peritonitis with ultrasound guidance. FNA should not be 2. Hyperplastic splenomegaly performed in those with suspected hemangiosar- a. Common in immune-mediated diseases, coma or if there is a large cavitary lesion including IMHA and IMT F. Needle biopsy is also used for diffuse splenic b. Also common in dogs with bacterial endo- disease carditis and chronic bacteremia. Also asso- V. Treatment ciated with SLE A. Splenectomy is indicated in splenic rupture, 3. Congestive splenomegaly splenic torsion, or splenic masses a. Can occur as a result of smooth muscle B. In cats, splenectomy prolongs life expectancy in relaxation in the splenic capsule, especially systemic mastocytosis by phenothiazine and barbiturates. Up to C. With hemangiosarcoma there is a high risk of 30% of blood may pool in the spleen rupture, so splenectomy should be performed b. Right-sided congestive heart failure, caudal D. Splenectomy is not recommended in IMHA or IMT vena cava obstruction, and intrahepatic except as a last resort obstruction can cause splenic congestion E. In some patients with lymphoma and leukemia, c. Splenic torsion results in marked spleno- splenectomy may be an option megaly, and may be associated with gastric F. Treat the underlying disease process dilatation-volvulus 4. Infiltrative diseases include hypereosinophilic Supplemental Reading syndrome of cats and splenic amyloidosis. EMH is common in dogs but rarely causes Brooks MB. Coagulation diseases. In Brichard SJ, Sherding splenomegaly RG, eds. Manual of Small Animal Practice, 3rd ed. St Louis, C. Hypersplenism can be primary or secondary to 2006, Saunders, pp. 256-264. an underlying disease. Characteristics include Cowell RL, Tyler RD, Meinkoth JH, DeNicola DB. Diagnostic splenomegaly with cytopenia that resolves with Cytology and Hematology of the Dog and Cat, 3rd ed. splenectomy St Louis, 2008, Mosby.