Heinz Body Anaemia

2012-07-16T19:53:14Z

RebekahMCB:

Heinz Body Anaemia

2012-07-14T20:52:59Z

RebekahMCB:

Heinz Body Anaemia

2012-07-14T20:44:16Z

RebekahMCB: addition to article

[[Heinz body anaemias - Wikiclinical|Heinz body anaemias]]

{{Summary
|cause = Oxidative injury to erythrocytes
|associated = Exposure to oxidative toxins
|differentials = Other causes of anaemia
|diagnosis = Examination of blood smears
|treatment = Supportive
}}

==Introduction==
'''Heinz bodies''' are inclusion bodies that form within erythrocytes as a result of '''oxidative injury''' to the cell. Named after Robert Heinz, the German physician who first described them, they consist of precipitated haemoglobin and their presence can result in premature phagocytosis of erythrocytes <ref name="Schalm"> Weiss, D and Wardrop, K (eds) (2010) '''Schalm's Veterinary Haematology, Sixth edition''' Wiley-Blackwell p. 134</ref>

===Structure of haemoglobin===

Haemoglobin is a conjugated protein consisting of four globin chains, each of which contains a heme group. Its structure allows it to combine reversibly with oxygen and is thus very important in the transportation of oxygen to tissues. Normally the iron within the heme group is in the ferrous (2+) form, the form able to combine with oxygen.

===Pathophysiology of oxidative damage to haemoglobin===

Oxygen can produce reactive free radicals such as hydrogen peroxide. These substances are generated under normal physiologic conditions and there are enzyme mechanisms to prevent damage to the cell. When these mechanisms are overwhelmed, oxidative damage occurs. As erythrocytes have no organelles they are unable to synthesise proteins and so have limited ability to repair themselves.<ref name="Schalm"></ref> The damaged cells have highly rigid membranes and so are more likely to be removed from circulation <ref name="CVT"></ref>

Oxidation results in three major changes to the haemoglobin molecules:

* '''Heinz bodies''' are produced when the sylfhydral groups in the '''globin part of the haemoglobin molecule''' undergoes oxidation, causing the molecule to become unstable. Heinz bodies are formed when the damaged haemoglobin molecules coalesce. <ref name="CVT">Bonagura, J and Kirk, R (eds) (1995) '''Kirk's Current Veterinary Therapy XII''' WB Saunders, p. 444</ref> In most species, Heinz bodies can be removed from erythrocytes by the spleen.

* '''Methaemoglobinaemia''' formation occurs when the '''iron in the haemoglobin molecule''' is oxidised to the ferric (3+) state. In normal circumstances the methaemoglobin reductase enzyme reduces ferric (3+) back to ferrous (2+) but this system can become overwhelmed in some circumstances.<ref name="CVT"></ref> This is the only form of oxidative damage which is reversible.

* '''Eccentrocytes''' have their haemoglobin concentrated on one side of the cell, causing the opposite side of the cell to appear clear. They are probably formed when there is damage to the erythrocyte membrane.

This article will cover only Heinz bodies in detail.

==Substances causing Heinz body formation==

Cats, dogs, horses and ruminants can all suffer from Heinz body anaemias but they are clinically significant mainly in the cat and dog.

Feline erythrocytes are particularly susceptible to oxidative damage as they have eight highly reactive sulfhydryl groups, as opposed to two
less reactive ones in other species. In addition, the cat spleen is less efficient in the removal of Heinz bodies from erythrocytes. These two characteristics mean that cats may have 5-10% of erythrocytes containing Heinz bodies under normal circumstances and makes them very susceptible to developing clinical signs of toxicity on exposure to oxidative substances or secondary to other disease processes. <ref name="Schalm"></ref>

===Cats===

* Paracetamol (acetominophen) - cats have a low level of N-acetyltransferase enzymes, which prevents them from metabolising the drug to non-toxic substances as humans do. (ref name="ACVIM"> McConkey SE , Cribb A . The molecular mechanism of acetaminophen in dogs and cats. In: Proceedings of the 26th Annual American College of Veterinary Internal Medicine Meeting 2008, pp. 610 – 612 </ref>.They are also relatively deficient in methaemoglobin reductase and methaemoglobinaemia is also a feature of paracetamol toxicity in cats.

* Diabetes mellitus - there is increased production of radicals resulting from various disease-induced metabolic compromises. Ketoacidotic cats have significantly higher numbers of Heinz bodies than non-ketoacidotic patients. (<ref name="DM"> Christopher M, Broussard J, Peterson M., (1995). '''Heinz body formation
associated with ketoacidosis in diabetic cats''' . J Vet Intern Med, Vol 9: p. 24 – 31.</ref>

* Hyperthyroidism - one study found increased numbers of Heinz bodies in hyperthyroid cats but patients were not significantly anaemic. (<ref name="Christopher"> Christopher M, (1989). '''Relation of endogenous Heinz bodies to disease and anemia in cats: 120 cases (1978 – 1987)'''. J Am Vet Med Assoc, Vol 194 pp. 1089-1095</ref>

* Lymphoma

<references/>
{{unfinished}}

Heinz Body Anaemia

2012-07-14T13:30:55Z

RebekahMCB:

2012-04-01T21:41:35Z

RebekahMCB: adding information

Previously known as: '''Haemobartonellosis'''

Caused by: '''''Mycoplasma haemofelis''''' , previously known as '''''Haemobartonella felis'''''

==Introduction==
Feline Infectious Anaemia, caused by '''''Mycoplasma haemofelis''''' (Mhf), is a regenerative anaemia of cats. The disease occurs worldwide and should be considered as a differential diagnosis for any cat presenting with anaemia.

==Aetiology==
Mhf is one of a group of organisms known as haemotropic mycoplasmas which infect several other domestic animal species. The causative organism was previously called Haemobartonella felis and thus the disease was known as haemobartonellosis. Polymerase chain reaction (PCR) assays allowing DNA analysis resulted in the reclassification of the organism in 20011. Two other haemotropic mycoplasmas (''Candidatus M. haemominutum'' and ''Candidatus M. turicensis'') have been identified in cats but appear to be less pathogenic2.

Mhf can vary in shape from cocci to rods and are sometimes present in chains on the cell surface.

The mode of transmission of Mhf is poorly understood. It is thought that it may be transmitted through biting and fighting activities, although this has not been able to be demonstrated experimentally. As transmission has been shown to occur through blood transfusion, it is recommended that blood donors been screened3.

==Signalment==
The major group at risk for Mhf infection are young male cats who spend time outdoors. In many areas of the world an association has been shown between Mhf and retroviral infections2. It has been demonstrated that cats infected with Mhf and feline leukaemia virus (FeLV) are likely to develop more severe anaemia that cats infected only with Mhf3.

==Pathogenesis==
The pathogenesis of Mhf is not fully understood. It is thought that the presence of the parasite on the surface of the red blood cells may induce antibody production4. The anaemia, which is primarily extravascular, may be due to direct damage of erythrocytes by the organism or as a result of the antibodies produced by the infected animal 2.

==Clinical signs==

Infected cats most commonly present for lethargy and decreased appetite. Physical examination findings are non-specific and can include signs of anaemia, such as mucous membrane pallor, tachypnoea and tachycardia, pyrexia and occasionally splenomagaly and [[Icterus|jaundice]]. Pyrexia is frequently intermittent and spikes when parasite numbers are highest 3. The anaemia can be severe and rapidly fatal in some cases.

==Differential diagnosis==
There are multiple causes of both regenerative and non-regenerative anaemia in cats which must be considered as differential diagnoses when investigating anaemia in cats.

For cats showing signs of regeneration, causes of blood loss or haemolysis must be considered:
*primary immune-mediated haemolytic anaemia
*Heinz body haemolytic anaemia (onions, garlic,propofol)
*other infectious causes such as "Babesia felis" and "Cytauxzoon felis"
*neoplasia

Major differential diagnoses for cats with non-regenerative anaemia include:
*neoplasia
*chronic inflammatory conditions
*underlying conditions such as diabetes mellitus and renal disease
*Feline Immunodeficiency Virus (FIV) and FeLV infections
*bone marrow diseases

==Diagnosis==

The most commmon findings from complete blood counts from cats with Mhf infections are a marcocytic, hypochromic regenerative anaemia. Reticulocytes and Howell-Jolly bodies may be identified on cytologic examination.

Mhf infection can be definitvely diagnosed by identification of organisms on a blood smear, appearing as cocci or rods and sometimes forming short chains of organisms. However, examination of a single blood smear is less than 50% sensitive 5 as the animal's immune response causes organisms to disappear from the blood stream for several days, often to reappear a few days later. It was found in one study that smears should be examined every four days over a minimum of three four day cycles5. As there could be eight days between presentation and diagnosis this is clearly not an ideal means of diagnosis. It also has the potential for misidentification.

The gold standard for diagnosis of Mhf infection is polymerase chain reaction (PCR), which detects the 16S RNA gene. The test is widely available through veterinary diagnostic laboratories.

==Treatment==
Infected cats should be treated with [[Tetracyclines|doxycycline]] for 3 weeks twice daily. [[Fluoroquinolones|Enrofloxacin]] is also a good treatment choice especially in refractory cases when combined with doxycycline.

A [[:Category:Transfusion Medicine|blood transfusion]] may also be required in cases of severe anaemia.

As blood sucking endoparasites, such as [[:Category:Fleas|Fleas]], are thought to spread disease the animal should also receive flea treatment.

Prednisolone is also advised to treat the immune mediated mechanisms and to prevent further erythrophagocytosis.

==Prognosis==
Varied prognosis depending on the severity of the anaemia at presentation. If not treated 1/3 of affected animals will die. Antibiotics do not clear the infection so many cats become carriers of the organism however relapses are uncommon.

{{Learning
|flashcards = [[Small Animal Emergency and Critical Care Medicine Q&A 12]]
|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Mycoplasma+haemofelis%22&occuring1=title&rowId=2&options2=OR&q2=%22Haemobartonella+felis%22&occuring2=title&rowId=3&options3=AND&q3=&occuring3=freetext&x=48&y=12&publishedstart=yyyy&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all ''Mycoplasma haemofelis'' publications]

[http://www.cabdirect.org/search.html?q=%28title%3A%28%22Infectious+Anaemia%22%29+OR+title%3A%28Haemobartonellosis%29+OR+title%3A%28%22Mycoplasma+haemofelis%22%29+OR+title%3A%28%22Haemobartonella+felis%22%29%29+AND+od%3A%28cats%29 Feline Infectious Anaemia publications]
|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2009/20093115252.pdf ''' Diagnosis and management of Hemoplasma infections.''' Lappin, M. R.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 17-21 January, 2009, 2009, pp 655-656, 23 ref.]

[http://www.cabi.org/cabdirect/FullTextPDF/2007/20073119573.pdf ''' Bartonellosis and hemoplasmosis in dogs and cats: emerging issues.''' Lappin, M. R.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Volume 21, Orlando, Florida, USA, 2007, 2007, pp 629-631]
}}

==References==
#Niemark H, Johansson KE, Rikihisa Y, et al (2001) Proposal to transfer some members of the genera ''Haemobartonella'' and ''Eperythrozoon'' to the genus ''Mycoplasma'' with descriptions of Candidatus ''Mycoplasma haemofelis'', Candidatus ''Mycoplasma haemomuris'', Candidatus ''Mycoplasma haemosuis'' and Candidatus ''Mycoplasma wenyonii'' '''Int J Sys Evol Microbiol 51(3) pp891-9
#Sykes, JE (2010) Feline Hemotropic Mycoplasmas '''Vet Clinics of North America: Small Animal Practice''' pp. 1157-1170
#Wardrop J, Reine N, Birkenheuer A et al (2005) Canine and feline blood donor screening for infectious disease '''J Vet Intern Med''' 19(1) pp.135-42
#Hagiwara, MK (2009) Anemia in Cats: Is It Mycoplasma? '''Proceedings of the 34th World Small Animal Veterinary Congress'''
#Ettinger, S.J, Feldman, E.C. (2005) '''Textbook of Veterinary Internal Medicine''' (6th edition, volume 2)''W.B. Saunders Company''
#Czerski A, Gnus J, Agnieszka Rusiecka A, et al (2009) Usefulness of blood films for the feline infectious anaemia diagnosis '''Acta Sci. Pol., Medicina Veterinaria''' 9(4)pp. 21-28

Merck & Co (2008) '''The Merck Veterinary Manual''' (Eighth Edition) ''Merial''

{{review}}
[[Category:Anaemia]]
[[Category:Lymphoreticular and Haematopoietic Diseases - Cat]][[Category:Cat Bacteria]]
[[Category:Expert_Review - Small Animal]]

Feline Infectious Anaemia

2012-04-01T20:23:46Z

RebekahMCB: