Bone marrow - nonneoplastic
Infectious / inflammatory
Ehrlichiosis / anaplasmosis

Topic Completed: 1 March 2015

Minor changes: 2 August 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Ehrlichiosis bone marrow

Dragos C. Luca, M.D.
Page views in 2019: 1,022
Page views in 2020 to date: 445
Cite this page: Luca DC. Ehrlichiosis / anaplasmosis. website. Accessed June 1st, 2020.
Definition / general
  • Ehrlichia: obligate intracellular gram negative bacteria belonging to recently reorganized family Anaplasmataceae
  • Species producing disease in humans (3):
    • E. chaffeensis: human monocytic ehrlichiosis (HME)
    • Anaplasma phagocytophilia: human granulocytotropic anaplasmosis (HGA, formally termed human granulocytic ehrlichiosis)
    • E. ewingii: rare granulocytic disease (increased frequency in transplant patients)
  • Vector borne disease transmitted through bite of Ixodes ticks
  • Bacteria is obligate intracellular pathogen that binds to P selectin glycoprotein ligand 1 (PSGL1 / CD162)
  • Susceptibility also associated with expression of CD15s (J Clin Invest 1999;103:407)
  • First described in USA in 1994
  • Geographic distribution of E. chaffeensis (HME) and A. phagocytophilia (HGA) reflects regions of US where their hard tick vectors reside:
    • HME: south central, southeastern and mid Atlantic states
    • HGA: northeastern states, northwest Wisconsin, eastern Minnesota and Pacific northwest states
Clinical presentation and diagnosis
  • HME and HGA have similar clinical symptoms but HME is more often serious with hospitalization in 50% of patients; septic shock-like syndrome possible, especially if immunosuppressed
  • Both present with fever, leukopenia, thrombocytopenia (70 - 90%) and elevated liver enzymes
  • Mortality rate is 2 - 3% for HME and 0.5 - 1% for HGA
  • Particularly severe infections occur in elderly / immunocompromised
  • Characteristic intracytoplasmic morulae (morula is Latin for mulberry): cytoplasmic membrane bound vacuoles with irregular edges containing hundreds to thousands of clustered gram negative bacteria
  • Infected cells typically contain only 1 or 2 morulae although as many as 15 may be seen in immunosuppressed individuals
  • Morulae are present in less than 0.2% of circulating WBCs in HME infection; examination of buffy coats facilitates detection
  • Greatly variable percentage of peripheral blood films with detectable morulae in the literature (3 - 80%) with a higher number seen with HGA infection (50 - 80%) and in immunosuppressed individuals
Case reports
  • Most patients are seronegative during first few weeks of acute infection (60 - 97%), so therapeutic decisions must be based on clinical suspicion, peripheral blood findings and PCR (sensitivity is 60 - 85%, high degree of false positive results)
  • Became a nationally reportable disease to US Centers for Disease Control in 1999
  • Organisms are susceptible to tetracyclines and their derivatives, particularly doxycycline
Microscopic (histologic) description
  • Peripheral blood: buffy coat examination may reveal intracytoplasmic inclusions (morulae - spherical structures with irregular edges) within neutrophils or monocytes
  • Bone marrow: epithelioid granulomas; usually normo or hypercellular with intact trilineage maturation; rare hypoplasia; possible increased megakaryocytes
  • Histopathologic bone marrow findings: inconsistent and likely to change during the course of the disease
  • HGA organisms preferentially infect more mature rather than immature granulocytic cells in bone marrow
Microscopic (histologic) images

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HGA: inclusions in granulocytes

Left: HGA (HGE)

Rhodamine labeled HGE organisms

HGE antigens

Peripheral smear images

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Intracytoplasmic inclusion

Inclusions in granulocytes

Electron microscopy images

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Missing Image

Dense core cells of E. chaffeensis

Several morulae

Bone marrow white blood cell

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