VET-125 - Ch 5 - Hematologic & Immunologic

Blood functions

Temperature regulation, pH balance, nutritional & hormone transport, waste disposal, & immune response

Blood components

RBCs, WBCs, platelets, & plasma

Plasma

Fluid portion of the blood that contains suspended cells; about 55% total blood volume

90% water, 10% dissolved constituents (protein, hormones, lipids, enzymes, salts, carbs, vitamins, electrolytes, & waste)

Serum

Fluid portion of blood with fibrinogen removed (liquid left after clotting)

RBC production

In red bone marrow

Hemoglobin

Oxygen carrying pigment

Hemoglobin concentration is roughly what percentage of PCV in most pets & domestic animals?

33%

Anemia

Disorder characterized by reduced numbers of RBCs; various causes

Three broad categories = decreased production, increased destruction (eg. immune related), & inappropriate loss

Classified as 2 types = regenerative & nonregenerative

Treatment is aimed at correcting the primary problem & supporting the patient

What is the most common cause of anemia?

Hemorrhage from trauma

Hemorrhagic anemia

Anemia caused by hemorrhage aka blood loss

Hemorrhagic anemia treatment

Should consist of controlling hemorrhage & volume replacement
— blood transfusions (platelet rich), steroid therapy (less common now), & avoid additional trauma

Hemorrhagic anemia other info

With acute blood loss, the hematocrit doesn’t reflect severity of the problem, & as a fluid shift occurs to compensate for blood loss, shock may result
— may act fine otherwise, then go into shock abruptly

Thrombocytopenia accounts for many cases of generalized bleeding

What are the best areas to check for signs of bleeding?

Gingiva, inner ear pinna, lower ventral abdomen, & eyes

Petechiae (pinpoint) & ecchymoses (larger) aka petechial & ecchymotic hemorrhages; dotted or speckled bruising caused by bleeding into the skin, may be caused by bleeding disorders such as IMTP

Iron-deficiency anemia

Iron & hemoglobin lost with external bleeding results in altered RBCs with decreased life spans

Iron-deficiency anemia causes

Possibly chronic external blood loss such as fleas, internal parasites (commonly hookworms), gastric ulceration, & bleeding neoplasms

Iron-deficiency anemia treatment

Correcting cause of blood loss & iron supplementation for 30-60 days

Hemolysis

Destruction of RBCs

Hemolytic anemia

Immune components attach directly or indirectly to the RBC membrane & alter its structure
— in attempt to regain homeostasis, the body removes these cells

Hemolytic anemia causes

Dogs = appears related to underlying inflammatory process

Cats = most common cause is hemobartonellosis (Mycoplasma haemofelis)
— FeLV may stimulate immuno-hemolytic disease

Hemolytic anemia signs

Exercise intolerance, pale mucous membranes, tachycardia, & icterus if severe

Hemolytic anemia treatment

Suppression of immune system (steroids) & supportive therapy; transfusion if hematocrit declines to life-threatening; Doxycycline (antibiotic) for hemobartonellosis

Anemia from blood-borne parasites

Hemobartonellosis (Mycoplasma haemofelis)
— epicellular bacterial parasite attaches to the RBC membrane, resulting in immune related hemolysis
— most common cause of hemolytic anemia in cats

Babesia canis & B. gibsoni = babesiosis
— hemolytic anemia in dogs
— transmitted by brown dog tick

Cytauxzoon felis = cytauxzoonosis
— Protozoan found in southern US, responsible for fatal disease in cats

Babesia sp. (top = B. canis, bottom = B. gibsoni)

Found in cats

Cytauxzoon felis

Toxin-induced anemia aka Heinz body anemia

Most common cause in dogs = onion toxicity

Acetominophen (tylenol) toxicity in dogs & cats (especially fatal in cats) results in methemoglobinemia (brown blood) & anemia

Heinz body

Changes in RBC that may be seen as large eccentric pale structures within feline RBC or as multiple small structures within canine RBC

Which lab abnormality is frequently seen with acetaminophen toxicity in cats?

Methemoglobinuria (brown urine)

Also brown-colored mucous membranes

Immune-mediated hemolytic anemia (IMHA)

Specific cause unknown, but accelerated RBC destruction occurs because of the presence of antibodies that attach to RBC membrane

Antibodies may attach directly to cell membrane, to a microorganism, or drug that has previously been bound to membrane receptor sites

Adherence of antibodies activates the complement system, causing agglutination & hemolysis

IMHA risk factors

Most commonly in dogs 2-8 years; 4 times more prevalent in females

Breeds = poodles, old english sheepdogs, cocker spaniels, & irish setters

IMHA signs

Pale mucous membranes, anorexia, listlessness, weakness, tachycardia, tachypnea, icterus, hepatomegaly, & splenomegaly

IMHA diagnosis

CBC, agglutination test, direct combs, & direct immunofluorescence assay (detects antibodies against immunoglobulin)

CBC = leukocytosis, neutrophilia with left shift, regenerative anemia, & spherocytes

IMHA treatment

Aimed at improving tissue oxygenation & managing immune response

Glucocorticoids, cyclosporine, & azathioprine
— protectants from gastric ulceration side-effect from these = omeprazole, cimetidine, misoprostol, & sucralfate

Heparin = prevent thromboembolism or disseminated intravascular coagulation (DIC)

IMHA prognosis

Guarded

Agglutination test; 1 drop anticoagulated blood + 1 drop saline, if antibody molecules are present then agglutination will be observed

Thrombocytes

Shortly after vascular injury, platelets become active & stick together, forming a platelet plug that blocks the vessel & prevents hemorrhage

Chemicals contained within thrombocytes are also necessary for the activation & maintenance of blood clotting cascades

Should you scrub puncture site to clean off blood?

No because it will disturb clotting; only dab to clean

Immune-mediated thrombocytopenia (IMTP)

Occurs when platelets become coated with antibodies or complement-antibody complexes

Destruction may occur in spleen, bone marrow, or liver

IMTP causes

Cause unknown

Some drugs associated with this condition = sulfonamide, chlorothiazide, arsenicals, digoxin, & quinidine

IMTP risk factors

Dogs 5-6 years; females twice as likely

IMTP signs

Epistaxis, petechial & ecchymotic hemorrhages, weakness, & lethargy

Epistaxis

Nose bleeds

IMTP diagnosis

Rule out differential, bone marrow exam, & clinical signs with response to treatment

IMTP differential diagnosis

Other causes of thrombocytopenia such as disseminated intravascular coagulation (DIC), lymphoma, & myeloproliferative disease

IMTP treatment

Immunosuppressive drugs (prednisone, azathioprine, cyclosporine, etc. & platelet rich transfusions), splenectomy in refractory cases, & spay females to decrease hormonal stress

IMTP prognosis

Guarded to favorable; relapses may occur

As platelets decline to what level, then what happens?

< approx. 30,000, bleeding problems develop

Hematocrit is aka what?

Packed cell volume (PCV)

Neutrophil

Granulocyte; predominantly phagocytic cells, active in inflammation response

Basophil

Granulocyte; contain histamine & heparin, involved in immune response & blood clotting

Eosinophil

Granulocyte; involved in allergic responses & parasitic infections

Monocyte

Agranulocyte; predominantly phagocytic cells, active in inflammation response

Lymphocyte

Agranulocyte; B & T types; identify & neutralize invaders

T-Lymphocyte

Active in cell-mediate immune responses; recognize & destroy invaders

Nature killer & cytotoxic t-cells are active against tumor cells

B-Lymphocyte

Make up the humoral immune response (antibodies); produce antibodies specifically designed to destroy invaders & activate mechanisms that also aid in destroying invaders

Ehrlichia canis origin

First recognized in the U.S. in 1963; gained prominence due to large losses of military working dogs stationed in Vietnam

Ehrlichiosis (E. canis) transmission

Saliva from ticks (E. canis = brown dog tick, Rhipicephalus sanguineus) & blood transfusions

Ehrlichiosis (E. canis) acute phase signs

Lymphadenopathy, edema of the limbs & scrotum, dyspnea, ocular & nasal discharge, depression, anorexia, fever, & weight loss
— scrotal edema more suspicious of this condition, especially with known tick bite or potential exposures

Ehrlichiosis (E. canis) chronic phase signs

Anterior uveitis, retinal hemorrhages, bleeding tendencies, severe weight loss, debilitation, & abdominal tenderness

Ehrlichiosis (E.canis) diagnosis

Hematology = thrombocytopenia (most common sign), pancytopenia, anemia, positive Coombs test, increased serum proteins, & organism found on blood smear

Serology = SNAP 4Dx plus test & immunofluorescent antibody test (IFA)

Ehrlichiosis (E. canis) treatment

Doxycycline (antibiotic)

Ehrlichiosis (E. canis) prevention & prognosis

Tick control products

Generally good, reinfection may occur

Ehrlichiosis (E. canis) other info??

Multiplies within mononuclear cells, both circulating & fixed (liver, spleen, & lymph nodes), which can infect other organs

Results in vascular endothelial damage, platelet consumption, RBC destruction, & bone marrow suppression resulting in aplastic anemia

Dogs unable to mount an adequate immune response become chronically infected

What is the most common diagnostic finding in dogs with Ehrlichiosis?

Thrombocytopenia

Aplastic anemia

Blood disorder where bone marrow doesn’t produce enough blood cells (including RBCs, WBCs, & platelets)

von Willebrand Disease (vWD)

Most common inherited disorder of hemostasis (aka clotting disorder)

In healthy dogs, the von Willebrand clotting factor (vWF) promotes platelet clumping, but in affected dogs the gene causes a decrease or absence of vWF & results in a bleeding disorder

In most dogs, inheritance is autosomal dominant with incomplete penetrance, so dogs that carry this gene will demonstrate varying severity of bleeding tendencies

vWD risk factors

Identified in 54 breeds; in U.S. overrepresented in german shepherds, doberman’s & labs

vWD signs

Easy bruising & prolonged bleeding during estrus, venipuncture, etc.

vWD diagnosis

Buccal mucosal bleeding time (BMBT) > 4 minutes, decreased vWF in plasma, DNA confirmation of gene defect, & positive enzyme-linked immunosorbent assay (ELISA)

vWD treatment

Bleeding episodes managed with plasma or cryoprecipitate infusion

Desmopressin acetate to control bleeding during surgery

What is recommended before surgery in dogs that carry the gene for vWD?

Buccal mucosal bleeding time (BMBT) assessment

Feline lymphoma

Accounts for 90% of all feline hematopoietic tumors

Multicentric disease is the most common form

May be classified by location or extent of disease

Feline lymphoma causes & risk factors

FeLV (70%), average presentation at 4 years (multicentric)

Canine & feline lymphoma signs

Depend on location & size of tumors

Enlarged peripheral lymph nodes, dyspnea, anemia, vomiting, diarrhea, lethargy, & weight loss
— 85% of cases in dogs involve regional or generalized lymphadenopathy

Canine & feline lymphoma diagnosis

Fine needle aspirate (FNA) or surgical biopsy = cytology

Canine & feline lymphoma treatment

No cure

Goal of therapy is to induce remission, improve comfort, & prolong life

Chemotherapy, which some protocols have up to 80% remission rates in cats & up to 90% in dogs

Canine lymphoma

Malignant lymphoma (aka lymphosarcoma) is the most common hematopoietic tumor in dogs

Canine lymphoma risk factors

Boxers, mastiffs, basset hounds, st. bernards, & scottish terriers

Radiation or Chemotherapy

Body surface area is a more accurate method of dosing toxic materials; doses are in mg per square meter

Negative side effects = anorexia, vomiting, leukopenia, renal toxicity, & hemorrhagic cystitis
— leukopenia is a concern because decreased immunity can cause dangerous secondary infections & patient may be unable to continue therapy

When was FIV first isolated?

1987

Are free roaming males or females at greater risk for FIV?

Males; 1.5-3x more likely than females

What cells does FIV affect?

Lymphocyte

Lymphopenia, loss of memory cell function, & decrease in antibody production for T-cell-stimulated lymphocytes leave the cat open for opportunistic infections

What must be looked at to determine if an anemia is regenerative or non-regenerative?

Absolute reticulocyte count

What is the tick vector responsible for the spread of canine ehrlichiosis (E. canis)?

Brown dog tick (Rhipicephalus sanguineus)

What might a buccal mucosal bleeding time (BMBT) > 4 minutes in a healthy, young Doberman indicate?

von Willebrand disease (vMD)

True or false? Few cats with feline lymphoma will test positive for FeLV.

False

List some drugs that are useful in the treatment of canine lymphosarcoma

Prednisone, cytoxan, l-asparaginase, vincristine, & doxorubicin

True or false? According to the new protocols for vaccination, all cats should be vaccinated for FIV

False, vaccination may result in positive tests in the future, making it more difficult to distinguish actual infection versus vaccine-induced antibodies

What is the main disadvantage to vaccinating young cats for FIV

Vaccinated cats will test positive in the future, so it will be difficult to determine if they contracted the disease prior to being vaccinated or not

When dosing toxic drugs, which method should be used instead of by weight?

Body surface area

What is Haemobartonella felis now called?

Mycoplasma hemofelis

Animals demonstrating intravascular hemolytic disease will have what color plasma?

Red