Haematological Changes Associated With Tick-Borne Diseases
World Small Animal Veterinary Association World Congress Proceedings, 2004
Remo Lobetti, BVSc, MMedVet (Med), DECVIM (Internal Medicine)
Internist Bryanston Veterinary Hospital Professor, Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria
Onderstepoort, South Africa

Tick-borne diseases can directly or indirectly affect haematological parameters. It is thus imperative that any animal that has a haematological abnormality be screened for possible underlying parasitic infection. Tick-borne organisms that can result in haematological changes include the rickettsias, mycoplasma, bacteria, and protozoa. As there are no specific haematological changes with tick-borne viral encephalitis and Lyme borreliosis, they will not be discussed further in this paper.

Rocky mountain spotted fever

Rocky Mountain Spotted Fever is caused by Rickettsia rickettsii, an obligate intracellular bacterial organism. The organism is transmitted by Dermacentor variabilis, D. andersoni, Rhipicephalus sanguineus, and Amblyomma cajennense. Within the body the organism invades and replicates in the endothelial cells of small arteries and venules, resulting in a necrotic vasculitis with subsequent activation of platelets and the coagulation system.

Mild-to-moderate normocytic normochromic anaemia occurs with the disease. During the early course of the disease mild leukopenia develops that is followed by moderate left shift neutrophilic leukocytosis. Toxic neutrophils may also be present. The most consistent haematological change is severe thrombocytopenia with megathromocytes often evident. The most common coagulation abnormality is prolongation of the ACT, however, severe cases may show DIC with prolongation of PT, PTT, TT, and elevated FDP and D-dimer.

The diagnosis requires identification of antigen by direct immunofluorescent in tissues, serologic testing, or PCR.

Feline haemobartonellosis (mycoplasmosis)

The 2 organisms associated with feline mycoplasmosis are Mycoplasma hemophilus (pathogenic variant) and M. hemominutum (non-pathogenic variant). The disease is transmitted by Rhipicephalus sanguineus. Cats infected with M. hemophilus typically show regenerative anaemia, whereas those infected with M. hemominutum may show no haematological changes. Leukocyte changes with M. hemophilus are inconsistent. Thrombocytopenia occurs in cats with M. hemophilus infection but not with M. hemominutum.

During the acute phase of the disease, the cat may become anaemic (haematocrit < 20% and even < 10%). The anaemia is variable and is produced by a progressive, periodic (7 to 11 days) series of extravascular haemolytic episodes. During each episode the haematocrit falls precipitously for a day or so and then, remarkably, recovers over the next one or two days. This "response" or recovery is much more than bone marrow regeneration can explain and can be attributed to two mechanisms. First, some of the anaemia is caused by intravascular sequestration of erythrocytes and these cells are "released" during the response phase. Second, many of the erythrocytes are sequestered in the spleen, liver, lungs and bone marrow, where it has been shown that they are "cleansed" of parasites by macrophages and returned to the general circulation as "clean" cells although their half-life is reduced due to an increased fragility. These episodes of anaemia are usually associated with a febrile reaction and often preceded by a short-lived increase in leukocyte count. Cats that survive this series of haemolytic crises, during which they become progressively more anaemic, then enter a recovery phase (which is unremarkable, the haematocrit approaching the low-normal range within a month) and a subsequent asymptomatic carrier phase ensues.

Most cats will show a positive Coomb's positive test and often, there is macroscopically detectable autoagglutination (occasionally shown to be associated with cold agglutinins) and usually a microscopically detectable autoagglutination. It is believed that both immunoglobulins and complement are involved. The decrease in the erythrocyte size has been attributed to increased osmotic fragility and decreased erythrocyte life span. Erythrophagocytosis can be evident in peripheral blood, bone marrow and, spleen.

Mycoplasmosis can morphologically be diagnosed on Romanowski-stained blood smears. The organisms occur as blue staining, small rings (0,5mm), cocci or rods attached to the erythrocyte membrane. The organisms may occur singly, in clusters and in chains. In recent years, PCR techniques have been become the diagnostic "gold standard" for the diagnosis of Mycoplasmosis.

Canine haemobartonellosis (mycoplasmosis)

Mycoplasma hemocanis is an opportunistic pathogen that can cause a mild anaemia in dogs that are either splenectomised or treated with cancer chemotherapeutics or immune suppressive drugs. The anaemia can vary from mild to severe and the disease is usually detected when an animal is examined for other concurrent disease. The anaemia is typically regenerative and often of a haemolytic nature. In some dogs, spherocytosis and a positive Coombs' test may be evident. Leukocyte and thrombocyte changes are inconsistent.

Ehrlichiosis

Canine ehrlichiosis is an acute to chronic disease characterized by infection of monocytes and lymphocytes, with the intracellular gram-negative bacteria, Ehrlichia canis, E. chaffeesis (monocytic ehrlichiosis), and E. ewingi (granulocytic ehrlichiosis). The vector for the disease is Rhipicephalus sanguineus.

The typical haematological changes include anaemia, leucopenia, and thrombocytopenia. Infection may result in either a regenerative or non-regenerative anaemia. In the acute disease although there anaemia due to destruction of progenitor and proliferative cells in the bone marrow occurs, bone marrow is usually hypercellular suggestive that there is also cell destruction in the peripheral blood. As the erythrocyte lifespan is long, the anaemia is usually mild or absent. The organism can also trigger a secondary immune mediated haemolytic anaemia. In the chronic phase of the disease pancytopenia is evident because of stem cell injury with an associated hypocellular bone marrow, which appears to be more common in the German shepherd dog. Lymphocytosis has been reported to occur with ehrlichiosis and may mimic lymphocytic leukaemia, especially if there is also an associated monoclonal gammopathy on serum protein electrophoresis.

The thrombocytopenia and thrombocytopathy that occurs in the acute phase of the disease is associated with both immunologic and inflammatory mechanisms which results in increased platelet consumption and reduced platelet life span. Reported immunologic mechanisms are platelet associated antibodies and platelet migration-inhibition factor.

Ehrlichia platys (Anaplasma platys) infects canine platelets and results in cyclic, moderate to severe thrombocytopenia. Transient leukopenia and mild anaemia may also be associated with the disease.

Haematological changes that have been report with feline ehrlichiosis include non-regenerative anaemia, thrombocytopenia; and either leukopenia or leukocytosis, the latter characterized by neutrophilia, monocytosis, or lymphocytosis.

In both the dog and cat, ehrlichiosis may be complicated by concurrent infection with babesiosis and mycoplasmosis. Diagnosis of ehrlichiosis is based on visualization of the morulae, detection of antibodies, and ideally PCR.

Babesiosis

In the dog babesiosis is caused by Babesia canis (3 strains) or B. gibsoni; whereas in the cat the causative organism is B. felis. Infection typical results in a regenerative anaemia due primarily to erythrocyte destruction by the parasite itself or because of a secondary immune mediated haemolytic anaemia. Babesiosis is solely a tick-borne disease with B. c. canis being transmitted by Dermacentor reticulatus; B. c. vogeli and B. gibsoni by Rhipicephalus sanguineus; and B. c. rossi by Haemaphysalis leachi.

The primary haematological abnormalities in canine babesiosis are anaemia, thrombocytopenia, and leukocytosis. Haematological profiles, however, vary in different parts of the world: mild anaemia and thrombocytopenia has been reported in France; in the Philippines, only mild anaemia; and in Nigeria in peracute cases severe anaemia and leukocytosis and mild-to-moderate anaemia in the acute and chronic cases. In South Africa severe anaemia, left shift neutrophilia, monocytosis, eosinopenia, and thrombocytopenia are the typical haematological changes evident with canine babesiosis. These variations in the haematological profile is most likely due to various strains of Babesia canis.

The anaemia in canine babesiosis is initially mild, normocytic and normochromic that then becomes macrocytic, hypochromic, and regenerative as the disease progresses. The reticulocytosis is proportional to the severity of the anaemia. Leukocyte abnormalities are inconsistently observed but may include leukocytosis, neutrophilia, neutropenia, lymphocytosis, and eosinophilia. In-saline agglutination of erythrocytes is a common finding and a positive Coombs' test occurs in the majority of cases, making a diagnosis of immune mediated haemolytic anaemia difficult. Moderate to severe thrombocytopenia is common. Uncommonly reported haematological changes are a relative polycythaemia with normal plasma protein concentration and a leukaemoid response.

In feline babesiosis the anaemia is typically macrocytic, hypochromic, and regenerative. There is no characteristic change in total or differential leukocyte counts and the thrombocyte count is usually normal with thrombocytopenia an inconsistent finding. The in-saline agglutination test may also be positive.

The diagnosis is made by demonstrating Babesia organisms within infected erythrocytes on a blood smear stained with a Romanowski-type stain. Large (2x5mm) pear-shaped organisms usually present in pairs are indicative of B. canis infection, whereas smaller (1x3mm), singular, round to oval organisms are B. gibsoni. Babesia felis parasites are approximately 1/3 of the size of B. canis and various shapes can be seen. In less endemic areas, serology and PCR may be more reliable methods for detecting occult parasitemia.

Cytauxzoonosis

An infrequent but usually fatal, disease of domestic cats caused by the Theileria-like protozoan Cytauxzoon felis. The vector of the disease is thought to Dermacentor variabilis. Infection results in mild to moderate non-regenerative anaemia because of peracute erythrocyte destruction. Differentiation needs to be made between C. felis and the smaller feline parasites: Babesia felis and Mycoplasma hemophilus.

The primary haematological abnormalities are mild to moderate normocytic normochromic non-regenerative anaemia, mild to marked leukopaenia with neutropenia and band neutrophilia, and marked thrombocytopenia.

The diagnosis of C. felis is made by demonstrating organisms within infected erythrocytes on a blood smear or histological identification of schizonts in tissues. Differentiation needs to be made between C. felis and the smaller feline parasites, Babesia felis and Mycoplasma hemophilus, as well as Howell-Jolly bodies. PCR can be used to differentiate between these feline parasites.

Hepatozoonosis

Hepatozoonosis is a protozoal parasite that only infects dogs once they have ingesting ticks that contain Hepatozoon sporozoites. Once ingested they penetrate the intestinal wall and form macromerozoites, which then penetrate into skeletal muscle, myocardium, lungs, lymphoid tissue, and liver. From here micromerozoites are formed that then enter the leukocytes. There are two types of the disease, the one caused by Hepatozoon americanum (transmitted by Amblyomma maculatum) and the other by H. canis (transmitted by Rhipicephalus sanguineus). The former is a more virulent form of the disease.

Haematological changes that occur with H. americanum infection are left shift neutrophilic leukocytosis, eosinophilia, thrombocytosis, and mild-to-moderate regenerative anaemia. Approximately 1% of peripheral leukocytes contain gametocytes.

Haematological changes that occur with H. canis infection are variable neutrophilic leukocytosis and mild regenerative anaemia. A large percentage of peripheral leukocytes contain gametocytes (60-90%).

Definitive diagnosis is based on the identification of gamonts in neutrophils or monocytes on Romanowski-stained blood smears or by the demonstration of organisms in muscle biopsy sections.

Speaker Information
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Remo Lobetti, BVSc, MMedVet (Med), DECVIM (Internal Medicine)
Department of Companion Animal Clinical Studies
Faculty of Veterinary Science, University of Pretoria
Onderstepoort, South Africa


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