Infectious hemoylytic anemias: Look for an underlying cause
Q. Could you review current diagnostic and treatment trends for infectious hemolytic anemias in dogs and cats?
A. Dr. Adam J. Birkenheuer, at the 2006 American College of Veterinary Internal Medicine Forum in Louisville, Ky., gave a lecture on infectious hemolytic anemias. Here are relevant points from the lecture:
Most hemolytic anemias (both idiopathic as well as those associated with an underlying disease) either are documented or presumed to be immune mediated with a smaller percentage mediated through oxidative damage, red blood cell (RBC) fragility or microangiopathic destruction.Most immune-mediated hemolytic anemia (IMHA) cases are associated with IgG antibodies attached to the RBC surface and subsequent extravascular hemolysis by the reticuloendothelial system.
Less frequently, hemolysis is mediated through the complement system resulting in intravascular hemolysis characterized by hemoglobinemia and hemoglobinuria.
Despite the frequency with which we recognize IMHA, an underlying cause is identified in a minority of cases, including those cases without restrictions on the types or amounts of diagnostics pursued.
The inability to identify an underlying cause for IMHA means that immune suppression remains the mainstay treatment. Concerns about potential negative effects of this immune suppression exist, especially if an occult underlying infectious cause of IMHA was missed during the diagnostic work-up. Recent advances in technology have improved the ability to rapidly and accurately identify several infectious diseases that can cause IMHA.
Infectious causes of feline hemolytic anemias
Idiopathic IMHA is diagnosed less frequently in cats than in dogs. It is of utmost importance to search for an underlying cause. Bacterial, viral and protozoal causes of IMHA have been described in cats.
Hemotropic Mycoplasma species (formerly Haemobartonella) are the most commonly diagnosed infectious cause of IMHA in cats. Several species can infect cats. The majority of clinical information exists regarding Mycoplasma haemofelis and candidatus Mycoplasma haemominutum. The cat flea, Ctenocephalides felis, is presumed to transmit Mycoplasma haemofelis, although recent transmission studies have failed to demonstrate this. Unlike M. haemofelis, M. haemominutum is not considered highly virulent and is not usually associated with clinical disease unless there is concurrent retroviral infection. These organisms have never been cultured in vitro, and there are no commercially available serologic tests.
The diagnostic modalities available include microscopy and molecular techniques such as polymerase chain reaction (PCR). Microscopy is generally considered to have poor sensitivity since the number of organisms present in circulation can wax and wane. It is important that PCR-based tests are able to differentiate between the M. haemofelis and M. haemominutum; a positive result with the latter species appears to be less clinically significant.
The treatments of choice are doxycycline (5 mg/kg PO BID), enrofloxacin (10 mg/kg PO Q24) or marbofloxacin (2.5 mg/kg PO Q24) for 14 days to 21 days. Since the anemia is immune-mediated, concurrent treatment with prednisone (2-4 mg/kg PO daily) may be indicated as well. To date, no treatments appear to result in complete clearance of the organisms. Therefore, infected cats are at risk of recurrence and may serve as reservoirs of infection. Flea prevention may be important for the prevention of disease transmission.
The feline leukemia virus and feline immunodeficiency virus infections have been associated with anemia in infected cats. The anemia caused by retroviruses in cats can be due to several underlying mechanisms including immune-mediated hemolysis, bone-marrow suppression, chronic inflammation and neoplasia. Of these, IMHA appears to be an uncommon cause of anemia. Usually, the diagnosis is made using commercially available in-house ELISA tests and can be confirmed in some cases by either PCR or Western blot assays. Treatment of IMHA in these cases is still directed toward the immune response and typically consists of prednisone (2-4 mg/kg PO daily).
The primary protozoal diseases associated with IMHA in cats are Cytauxzoon felis and Babesia felis. C. felis is a tick-transmitted infection that is endemic to the Southeastern, Midwestern and Mid-Atlantic regions of the United States. It is characterized typically by an acute febrile illness associated with decreases in one or more cell lines. The disease occurs most often between the months of April and September, which correlates with peak tick activity.