JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-P01 (NP)

 

SIGNALMENT: Dog.  

 

HISTORY: Blood smear from a dog. Differential white cell count: Segs - 85% (35-75), Bands 5%, Monos - 8% (1-4), Lymphs - 2% (20-55), nRBC - 18/100 WBC.

 

HISTOPATHOLOGIC DESCRIPTION: Peripheral blood: In this highly cellular, good quality blood smear erythrocytes are decreased in density and widely separated within the monolayer (anemia), with a mild increase in white blood cells (leukocytosis), and a paucity of platelets (thrombocytopenia). The majority of white blood cells are segmented neutrophils with fewer scattered bands neutrophils. There are increased numbers of monocytes (monocytosis) with rare lymphocytes (lymphopenia). There are numerous nucleated red blood cells and a moderate degree of anisocytosis and polychromasia (regenerative anemia). There are numerous 1-µm diameter, basophilic, coccobacillary bacteria on the surface of over 90% of the erythrocytes in this smear. They occur singularly, in pairs and in short chains. There are numerous background crystalline structures (artifact).

 

MORPHOLOGIC DIAGNOSIS: Peripheral blood smear: Regenerative anemia with neutrophilia, left shift, monocytosis, lymphopenia and epicellular erythrocytic bacteria, morphology consistent with Mycoplasma haemocanis, breed unspecified, canine.

 

ETIOLOGIC DIAGNOSIS: Hemotropic mycoplasmas; Erythrocytic mycoplasmosis; Hemoplasmosis 

 

CAUSE: Mycoplasma haemocanis

 

SYNONYMS: Hemobartonella canis; Eperythrozoon spp. 

 

GENERAL DISCUSSION: 

• 0.3 – 3.0 µm, non-acid fast bacteria that lack a cell wall
• Epicellular parasites of erythrocytes that attach to erythrocyte membranes 
• Part of normal flora in the upper respiratory tract of canines
• May cause severe hemolytic anemia in splenectomized or immunosuppressed dogs; rarely causes clinical disease in immunocompetent, non-splenectomized dogs
• Reported worldwide distribution in dogs

 

PATHOGENESIS:

• Transmission: Blood sucking arthropods; fleas or Rhipicephalus sanguineus ticks; in-utero transmission, biting/fighting, and transfusion of infected blood products also possible
• Epicellular parasites: Reside in indentations/invaginations on RBC surfaces
• Predominantly non-pathogenic in dogs except with splenectomy, concurrent Ehrlichia sp., Babesia sp., bacterial or viral infection, or immunosuppressive therapy
• Structural damage caused by association of the organism with the erythrocyte membrane may cause increased fragility and early clearance
• Hemotropic mycoplasmas induce formation of cold agglutinins (reactive at cooler temperatures than normal body temperature), but relation to development of hemolytic anemia is not clear
• Four stages of disease:
  • Preparasitemic: 1 - 3 weeks from initial infection to detectable parasitemia
  • Acute: From between the first and last major parasitemia; parasitemia is cyclic in nature; organism is thought to be sequestered in the spleen during non-parasitemic periods; this phase lasts several months
  • Recovery: Period from last major parasitemia until PCV normalizes
  • Carrier: Clinically normal chronically infected 
• No causative link established between Mycoplasma haemocanis infection and myocarditis / myocardial fibrosis in dogs (Molesan A. Vet Pathol. 2019)

 

TYPICAL CLINICAL FINDINGS:

• Tends to be non-pathogenic in dogs, unless splenectomized or immunosuppressed; may cause hemolytic anemia, lethargy, weight loss, fever and anorexia in splenectomized or immunosuppressed dogs
• Lab findings: Anemia, reticulocytosis and polychromasia, hyperbilirubinemia and bilirubinuria, positive direct Coombs’ test, spherocytosis, autoagglutination

 

TYPICAL GROSS FINDINGS:

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Spleen: Congestion, erythrophagocytosis, macrophage hyperplasia, extramedullary hematopoiesis, increased numbers of plasma cells
• Bone marrow: Erythroid hyperplasia (depending on duration of hemolysis)
• Hypoxia-induced or thromboemboli-induced tissue necrosis

 

ADDITIONAL DIAGNOSTIC TESTS:

• Demonstration of organisms on a Romanowsky stained blood smear
  1. Organisms typically appear as thin chains of cocci on the RBC membrane 
     • May form pleomorphic patterns: Violin bow, figure 8, oval, cross, or occasionally seen as individual rods or cocci
  2. Organisms may detach from RBC membrane as samples age, making identification more difficult
• PCR 

 

DIFFERENTIAL DIAGNOSIS:

• Pathogens that target red blood cells usually produce splenic lesions 
  • Mycoplasma spp; Babesia spp; Plasmodium spp; Anaplasma spp; Theileria spp; Eperythrozoon spp. 

 

COMPARATIVE PATHOLOGY:

• Cats: Mycoplasma haemofelis (H. felis) is the causative agent of feline infectious anemia (FIA); can cause acute hemolytic anemia in immunocompetent cats
  1. Clinical signs: Depression, weakness, anorexia/emaciation, fever
  2. Extravascular hemolysis, icterus, splenomegaly, distended gallbladder
     • Intravascular hemolysis also occurs
  3. Coomb’s positive, regenerative anemia with erythrophagocytosis by blood monocytes in a cat is suggestive of FIA; differential diagnosis includes primary immune-mediated hemolytic anemia and FeLV-induced hemolytic anemia
• Wild felids: Hemotropic mycoplasmas reported in multiple species
  1. Uncertain pathogenicity; disease outcome unclear
• Cattle can have hind limb edema and swelling of the teats
• Mice: Mycoplasma coccoides transmitted by Polyplax spinulosa (sucking louse)
  1. Essentially non-existent in lab mice (both M. coccoides and louse vector)
  2. In natural infections in wild mice, clinical signs from inapparent to death; splenomegaly is prominent feature
• Rats: Mycoplasma haemomuris – Typically infects rats but may infect wild mice as well  
• Llamas & alpacas: Mycoplasma hemolamae - Endemic in North and South American as well as European camelids
  1. Similar to hemotropic mycoplasmas in cats, pigs, cattle; vector not identified
  2. Weight loss, lethargy, anemia (potentially life-threatening)
• Bats: Hemotropic Mycoplasma spp. have been isolated in healthy bats (no clinical disease noted)

 

Hemotropic mycoplasmas, aka hemoplasmas

Cat	M. haemofelis, M. turicensis, M. haemominutum
Dog	M. haemocanis  (H. canis; Bartonella canis)- anemia M. cynos - respiratory disease M. canis - urogenital tract infections
Cattle	Anaplasma marginale / centrale
	Paranaplasma caudatum / discoides
	M. wenyonii - anemia, edema, lymphadenopathy, and fever M. hemobos - pathogenicity is unclear
Sheep, goats	M. ovis - only rarely causes hemolytic anemia
Llamas, alpacas	M. haemolamae - acute anemia, in crias and stressed adults
Swine	M. suis - piglets fever, hemolytic anemia, and hypoglycemia
	E. parvum
Mouse, rat	M. haemomuris
	E. coccoides

 

References: 

1. Agnew D. Camelidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:198-199. 
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016;63,65.
3. Cardona JC, Johnsrude JD, McManus PM, MacWilliams PS. The Spleen. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:346, 351, . 
4. Durham AC, Boes KM. Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:836-837.
5. Farina LL, Lankton JS. Chiroptera. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:620. 
6. Haddad JL, Roode SC, Grindem CB. Bone Marrow. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:494, 496, 500. 
7. Molesan A, Goodman L, Ford J, et al. The Causes of Canine Myocarditis and Myocardial Fibrosis Are Elusive by Targeted Molecular Testing: Retrospective Analysis and Literature Review. Vet Pathol. 2019;56(5):761-777.
8. Raskin RE. Chapter 4: Hemolymphatic System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:162.
9. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:181-182.
10. Terio KA, McAloose D, Mitchell E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:278. 
11. Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6^th ed. St. Louis, MO: Elsevier; 2016:124-125.
12. Zablotsky SM, Walker DB. Peripheral Blood Smears. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:449, 454. 

 

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