Clinical Pathology: Leukocytes, Hemostasis, and Blood Parasites

Comprehensive practice flashcards defining core vocabulary, hematologic disorders, coagulation pathways, and infectious blood parasites from clinical pathology lectures.

Marginal Leukocyte Pool

The pool of white blood cells located primarily within small blood vessels that marginate along and adhere to vascular endothelium, moving at a slower rate than axial blood flow; the ratio of the circulating to marginal pool is approximately $1:1$ in the dog and $1:3$ in the cat.

Proliferating Pool of Neutrophils

The bone marrow compartment of granulocyte precursors capable of mitotic division, comprising myeloblasts, progranulocytes, and myelocytes; myelocytes divide at least $4$ times under normal conditions and represent the final dividing stage.

Maturation and Storage Pool of Neutrophils

The post-mitotic bone marrow reserve of neutrophils that do not divide, consisting of metamyelocytes, band neutrophils, and segmented neutrophils, which are released into the blood in order of maturity to meet tissue demands.

Neutrophil Transmigration

The multistep process by which neutrophils exit blood vessels into tissues, involving selectin-mediated rolling, integrin-mediated sticking/adhesion, spreading, and PE-CAM-mediated diapedesis (extravasation) between endothelial cells.

Respiratory Burst

The metabolic process in activated neutrophils where membrane oxidase converts oxygen into superoxide anion ($\text{O}_2^-$) and hydrogen peroxide ($\text{H}_2\text{O}_2$), which combines with myeloperoxidase (MPO) and chloride to generate hypochlorous acid ($\text{HOCl}$) for microbicidal killing.

Eosinophil

A granulocyte characterized by specific acidophilic lysosomal granules containing digestive enzymes (alkaline and acid phosphatases, peroxidase, profibrinolysin) and histaminase; it neutralizes histamine, serotonin, and bradykinin and specializes in killing metazoan parasites.

Mast Cell

The tissue counterpart of the circulating basophil, derived from hematopoietic stem cells, possessing a round nucleus and dense cytoplasmic granules containing heparin, histamine, and serotonin; unlike basophils, mast cells retain the ability to divide and survive for weeks to months in tissue.

Histiocyte (Tissue Macrophage)

Differentiated mononuclear phagocyte derived from a circulating monocyte that migrates into tissue within $12\text{--}26\text{ hours}$;

it has a lifespan of 100+ days

outnumbers circulating monocytes by $400:1$ in humans,

functions as a primary scavenger, antigen processor, and cytokine producer.

Multinucleated Giant Cell

A large syncytial cell formed by the fusion of multiple macrophages when encountering particulate foreign matter or pathogens (such as Mycobacterium) that are too large for a single phagocyte to ingest.

Corrected Total WBC Count

A calculation applied when more than $5\text{ nucleated RBCs (nRBCs)}$ are counted per $100\text{ leukocytes}$ on a differential smear, calculated as: $\text{Corrected WBC Count} = \frac{100 \times \text{Measured Total WBC Count}}{100 + \text{nRBCs}}$.

Regenerative Left Shift

An inflammatory leukogram pattern characterized by an elevated total leukocyte count where circulating mature (segmented) neutrophils outnumber immature forms (bands, metamyelocytes), indicating an effective bone marrow response to tissue demand.

Degenerative Left Shift

A leukogram pattern in which immature neutrophils outnumber mature segmented neutrophils in the circulation, commonly accompanied by a normal, slightly elevated, or subnormal total WBC count; it indicates that tissue consumption exceeds bone marrow supply and carries an unfavorable prognosis.

Leukemoid Reaction

An extreme non-neoplastic inflammatory leukocytosis characterized by a marked regenerative left shift with leukocyte counts mimicking granulocytic leukemia, seen in severe suppurative disorders such as canine pyometra, deep abscesses, or severe hemolysis.

Right Shift

An alteration in the leukogram characterized by an increased number of hypersegmented neutrophils (five or more lobes), reflecting prolonged circulation time or increased cellular aging, classically seen with corticosteroid exposure or stress.

Stress Leukogram

A hematologic pattern induced by endogenous or exogenous glucocorticoids, characterized by the classic triad of mature neutrophilia, lymphopenia, and eosinopenia, frequently accompanied by monocytosis in dogs.

Physiologic Leukocytosis

A transient, catecholamine-mediated shift in circulating leukocytes induced by epinephrine during fear, excitement, or vigorous exercise, characterized by mature neutrophilia (via demargination) and mature lymphocytosis (via splenic contraction), particularly pronounced in cats and horses.

Toxic Change in Neutrophils

Morphologic cytoplasmic abnormalities in neutrophils arising from disturbed maturation during accelerated granulopoiesis in severe inflammation, characterized by Döhle bodies, cytoplasmic basophilia, foaminess/vacuolation, and toxic granulation.

Cyclic Neutropenia (Gray Collie Syndrome)

An inherited autosomal recessive stem cell defect of rough collies linked to a gray-silver hair coat, characterized by cyclic fluctuations in circulating neutrophils and platelets occurring at approximately $11\text{--}12\text{ day}$ intervals, predisposing pups to recurrent infections.

Pelger-Huët Anomaly

A congenital hereditary trait characterized by failure of granulocyte (especially neutrophil) nuclei to undergo normal segmentation, resulting in persistent hyposegmentation (bilobed or pince-nez configuration) with coarse, mature chromatin and normal cellular function.

Leukocyte Adhesion Deficiency (Bovine Granulocytopathy Syndrome)

An inherited deficiency of the $\text{CD11/CD18}$ integrin adhesion complex described in Holstein cattle and Irish Setters, impairing neutrophil margination, pavementing, and emigration through the vascular endothelium to sites of infection.

Primary Hemostasis

The initial phase of hemostasis involving local vasoconstriction, platelet adhesion to subendothelial collagen mediated by von Willebrand factor, platelet activation, and aggregation to form a temporary, unstable primary hemostatic plug.

Secondary Hemostasis

The enzymatic activation of plasma coagulation cascade proteins on the anionic phospholipid surface of aggregated platelets, culminating in the conversion of prothrombin to thrombin and fibrinogen to a stable, cross-linked fibrin clot.

von Willebrand Factor (vWF)

mediates platelet adhesion to exposed subendothelial collagen

circulates as a carrier and stabilizer for coagulation Factor VIII-coagulant.

large, multimeric plasma glycoprotein synthesized by endothelial cells and megakaryocytes

Thromboxane $\text{A}_2$ ($\text{TxA}_2$)

A labile prostaglandin intermediate with a half-life of $30\text{ seconds}$, synthesized from arachidonic acid via cyclooxygenase and thromboxane synthetase in activated platelets, acting as a potent stimulator of platelet aggregation, secretion, and vasoconstriction.

Contact Activation Factors

The plasma proteins of the intrinsic coagulation pathway activated upon contact with negatively charged surfaces without requiring calcium: Factor XII (Hageman factor), Factor XI (plasma thromboplastin antecedent), High Molecular Weight Kininogen (HMWK), and Prekallikrein (Fletcher factor).

Vitamin K-Dependent Coagulation Factors

Coagulation proteins Factors II, VII, IX, and X, along with anticoagulant proteins C and S, which require vitamin K-dependent post-translational $\gamma$-carboxylation of glutamic acid residues in the liver to bind calcium and assemble on phospholipid surfaces.

Antithrombin III (AT-III)

An $\alpha_2$-globulin anticoagulant synthesized by the liver that serves as the major physiologic inhibitor of thrombin and activated factors IXa, Xa, XIa, and XIIa; its inhibitory activity is accelerated $200\text{-fold}$ in the presence of heparin.

Activated Partial Thromboplastin Time (APTT)

A screening test that evaluates the functional integrity of the intrinsic and common coagulation pathways (Factors XII, XI, IX, VIII, X, V, II, and I); prolongation occurs when individual factor activity drops below $30\%$ of normal.

Prothrombin Time (PT)

A screening test that evaluates the functional activity of the extrinsic and common coagulation pathways (Factors VII, X, V, II, and I); it is the first test to prolong in anticoagulant rodenticide toxicity because Factor VII has the shortest half-life ($4\text{--}6\text{ hours}$).

Activated Coagulation Time (ACT)

A point-of-care whole blood clotting test evaluating the intrinsic and common pathways, utilizing diatomaceous earth as a contact activator; it requires individual factor deficiencies below $5\%$ to prolong and can be prolonged by severe thrombocytopenia ($<10,000/\mu\text{L}$).

Buccal Mucosa Bleeding Time (BMBT)

An in vivo test of primary hemostasis measuring the duration of bleeding following a standardized incision on the oral mucosa; it is the preferred clinical screening test for platelet function defects and von Willebrand's disease (normal: $<5\text{ minutes}$ in dogs, $<2.5\text{--}3\text{ minutes}$ in cats).

Fibrin Degradation Products (FDPs)

Digested breakdown fragments of fibrinogen or cross-linked fibrin produced by plasmin-mediated cleavage; elevated serum levels ($>40\,\mu\text{g/mL}$) indicate excessive systemic fibrinolysis and are strongly indicative of disseminated intravascular coagulation (DIC).

D-Dimer

Specific plasminolytic degradation products generated exclusively from the breakdown of factor XIIIa cross-linked fibrin; their presence in circulation specifically confirms secondary fibrinolysis and intravascular thrombus formation.

Disseminated Intravascular Coagulation (DIC)

A consumptive thrombohemorrhagic syndrome triggered by massive endothelial injury, tissue procoagulant release, or sepsis, characterized by widespread microvascular thrombosis, consumption of platelets and clotting factors, and secondary hyperfibrinolysis.

Hemophilia A

An X-linked recessive bleeding disorder caused by a deficiency of coagulation Factor VIII-coagulant activity, characterized clinically by deep tissue hematomas, hemarthrosis, prolonged APTT/ACT, and normal PT and vWF antigen levels.

Hemophilia B (Christmas Disease)

An X-linked recessive congenital coagulopathy resulting from a deficiency in Factor IX activity, clinically and diagnostically identical to Hemophilia A with prolonged APTT and ACT and normal PT.

Canine Thrombopathia

An inherited, intrinsic platelet function defect described in Basset Hounds characterized by impaired dense granule release and defective stimulus-response coupling; affected dogs exhibit mucosal bleeding despite normal platelet numbers and a normal clot retraction test.

Thrombasthenic Thrombopathia

An inherited intrinsic platelet disorder of Otterhounds characterized by abnormal clot retraction, giant bizarre platelets ($30\text{--}80\%$), and reduced membrane glycoproteins II and III, failing to aggregate in response to ADP, collagen, or thrombin.

Glanzmann's Thrombasthenia

An inherited intrinsic platelet disorder recognized in Great Pyrenees dogs caused by a deficiency or marked reduction of membrane glycoprotein IIb/IIIa, resulting in failure of platelet aggregation and abnormal clot retraction.

Anticoagulant Rodenticide Toxicity

Toxicosis caused by ingestion of coumarins or indanediones that inhibit epoxide reductase, preventing the recycling of vitamin K and depleting functional Factors II, VII, IX, and X; characterized by prolonged PT first, followed by prolonged APTT and ACT.

Tissue Plasminogen Activator (TPA)

An extrinsic serine protease released by vascular endothelial cells that converts plasminogen to active plasmin exclusively on the surface of a fibrin clot, protecting systemic circulation from indiscriminate proteolysis.

Cytauxzoon felis

A tick-borne apicomplexan protozoan of felids

transmitted by Dermacentor variabilis (reservoir: North American bobcat)

it exhibits a leukocytic phase with schizonts obstructing venules in macrophages and an erythrocytic phase with signet-ring piroplasms, causing a rapidly fatal febrile, icteric, and hemolytic syndrome in domestic cats.

Hepatozoon americanum

A tick-borne protozoan that causes canine hepatozoonosis (protozoal myositis) in the southern United States, transmitted by ingestion of the Gulf Coast tick (Amblyomma maculatum); it produces marked periosteal bone proliferation, severe neutrophilic leukocytosis, and characteristic 'onion-skin' cysts in skeletal and cardiac muscle.

Leishmania donovani

A protozoan parasite transmitted by phlebotomine sandflies that multiplies as amastigotes within vacuoles of macrophages and reticuloendothelial cells, recognized by a small purple nucleus and perpendicular rod-shaped kinetoplast, causing chronic visceral and cutaneous disease in dogs and humans.

Trypanosoma cruzi

A hemoflagellate protozoan transmitted by reduviid (kissing) bug feces that causes Chagas' disease (American trypanosomiasis)

infects vertebrate hosts, forming intracellular amastigote pseudocysts in cardiac myocytes and autonomic neural tissue

circulates as flagellated trypomastigotes in peripheral blood.

Mycoplasma hemofelis

epicellular, gram-negative mycoplasmal parasite of feline red blood cells (formerly Hemobartonella felis)

transmitted primarily by fleas,

cocci, short rods, or small rings on RBC membranes

induce cyclical parasitemia & severe regenerative immune-mediated hemolytic anemia (feline infectious anemia).

Babesia canis

A large, tick-borne intraerythrocytic piroplasm transmitted by Rhipicephalus sanguineus, measuring $2.4\,\mu\text{m} \times 5.0\,\mu\text{m}$ and characteristically appearing as paired piriform (pear-shaped) bodies in stained red blood cells, causing acute intravascular and extravascular hemolytic anemia and thrombocytopenia.

Ehrlichia canis

An obligate intracellular bacterium transmitted by the brown dog tick (Rhipicephalus sanguineus) that infects circulating monocytes and tissue macrophages, dividing to form intracytoplasmic morulae; it causes Canine Monocytic Ehrlichiosis (tropical canine pancytopenia) with severe thrombocytopenia, hypergammaglobulinemia, and marrow hypoplasia.

Ehrlichia ewingii

The causative agent of Canine Granulocytic Ehrlichiosis, primarily transmitted by Amblyomma americanum; it forms intracytoplasmic morulae in neutrophils and causes a syndrome featuring mild fever, nonerosive polyarthritis, lameness, and transient thrombocytopenia.

Anaplasma platys

An intracellular bacterium (formerly Ehrlichia platys) that specifically infects canine blood platelets, replicating to form morulae and causing cyclic episodes of marked thrombocytopenia occurring at $10\text{--}14\text{ day}$ intervals.

Rickettsia rickettsii

An obligate intracellular bacterium transmitted by Dermacentor ticks that causes Rocky Mountain Spotted Fever; it directly invades vascular endothelial cells and smooth muscle, causing necrotizing vasculitis, microvascular hemorrhage, edema, and thrombocytopenia ($75,000\text{--}150,000/\mu\text{L}$).

Reed-Sternberg Cell

A distinctive, large multinucleated or bilobed giant cell with prominent nucleoli that is pathognomonic for Hodgkin-like lymphoma, arising within nodular lymphoid lesions.

Waldenström's Macroglobulinemia

A slowly progressive malignant lymphoproliferative neoplasm characterized by proliferation of plasmacytoid B lymphocytes that do not form discrete tumor masses and secrete a monoclonal IgM paraprotein, resulting in severe blood hyperviscosity.

Multiple Myeloma

A malignant neoplasm of plasma cells arising in the bone marrow, causing myelophthisic cytopenias, osteolytic 'punched-out' bone lesions, hypercalcemia (often mediated by cytokines such as IL-6), and a distinct monoclonal gammopathy on serum protein electrophoresis.

Hemangiosarcoma

A highly malignant neoplasm of vascular endothelial cells, most commonly primary in the canine spleen and right atrium of the heart, frequently complicated by microangiopathic hemolytic anemia, schistocytosis, and acute DIC.

Chediak-Higashi Syndrome

An autosomal recessive disorder characterized by abnormal giant lysosomal granulation in leukocytes, melanocytes, and platelets, partial albinism (e.g., blue-smoke Persian cats, Aleutian mink), defective dense granules, bleeding tendencies, and marked susceptibility to infection.