Small Animal News editor, Harriet Woodhall, brings us an article on the Pet Blood Bank, a fantastically important and lifesaving service.
Pet Blood Bank
Harriet Woodhall (Vet News Small Animal News Editor)
The Pet Blood Bank is a UK charity that supplies blood products to veterinary professionals for canine blood transfusions and has recently hit its 5000th donor in its seventh year as a charity.
Like human blood donations, there are certain criteria that dogs need to meet to ensure that donated blood is safe for a transfusion patient and not contaminated. The donor should: weigh more than 25kg, be aged between one and eight years old, have a good temperament, be up to date with vaccinations, never have traveled abroad, be fit and healthy and not be on any medication.
When a blood donation is made, the dog also needs to be blood typed so that any transfusions made are using the correct type. If given an unmatched type, the immune system will recognise the new cells as foreign and prematurely destroy them, which could lead to other complications. What causes the body to recognise foreign or self red blood cells is whether they have aminosaccharide molecules on the red blood cell membranes. As well as the presence/absence of these molecules, there are also very small differences in their structure, giving them antigenic properties.
A canine donor is normally classified as DEA (Dog Erythrocyte Antigen) 1.1 negative or positive, but the other major antigens are 1.2, 3, 4, 5, 6 and 7. DEA 1.1 negative patients should only receive 1.1 negative, whereas patients that are DEA 1.1 positive can receive both 1.1 negative and 1.1 positive. However, due to the lack of DEA 1.1 negative blood, it is always recommended that 1.1 positives receive 1.1 positive, so that supplies of 1.1 negative are preserved. The dog’s blood is screened to check Packed Red Cell Volume (PCV) and Total Solids (TS) before donation. The donors are also micro-chipped so that all blood can be traced, and have annual haematology and biochemistry screens. Once all criteria and tests are met then the dog is suggested to donate blood three to four times a year.
There are a range of blood products available:
Packed Red Blood Cells (PRBC)
Fresh Frozen Plasma (FFP)
Frozen Plasma (FP)
Fresh Whole Blood (FWB)
Stored Whole Blood (SWB)
Blood is taken from the jugular vein in the dog’s neck and put into a collection bag containing anti-coagulants. Once blood is collected from a donor, it is transported to a processing centre and is kept at 20 degrees Centigrade while travelling. The blood is then inspected and logged with a reference number for tracking purposes. Under sterile conditions, the tubing and needle are removed, blood is weighed and then centrifuged (spun at 3800 revolutions per minute) for 15 minutes to allow the red blood cells to separate from the plasma. The plasma and red blood cells are then stored separately and in special conditions to increase shelf life: plasma is stored in a minus eighty degrees Centigrade freezer, once frozen it can then be transferred into a minus thirty four degrees Centigrade freezer where it can be stored for up to five years. Red Blood Cells can only be stored for up to six weeks and are kept at four degrees Centigrade in specialist fridges.
Choosing which blood product to use depends on the reason for transfusion. For example, several diseases causing anaemia would require PRBC whereas conditions such as thrombocytopaenia (platelet deficiency) would need FWB. Some conditions could receive several suitable products but there are often superior products that are favoured if more than one option is available.
At present, only canine blood products are available from the bank. Feline patients that need transfusion can only receive fresh whole blood from emergency donors.
This month we lead into the New Year with a fascinating article by Exotics Editor, Charlotte Hitch, on the news that SeaWorld have developed a treadmill for orcas in an attempt to improve their welfare, a very topical subject.
SeaWorld develops ‘treadmill’ for orcas in attempt to improve welfare of captive whales
Charlotte Hitch (Vet News Exotics Editor)
Following the August release of the critical documentary entitled Blackfish, which depicted the less than desirable lives of captive killer whales forced to perform in popular sea life parks such as Loro Parque in Tenerife and SeaWorld, there has been an outburst of controversy over the ethics of keeping such intelligent, emotionally complex animals confined to small, concrete tanks. In response to this wave of criticism, SeaWorld announced in September that they were working towards a killer whale treadmill, as a way of encouraging their orcas to exercise more and to supposedly add some interest and entertainment to their otherwise desolate tanks. This machine is essentially a pump which will produce currents which the whale can swim against, simulating swimming in a straight line. While some claim this is a good idea, for the majority, it seems like an attempt to improve public relations, instead of addressing the real issue at hand: orca welfare.
One of the main problems that arise when keeping an animal as large as orcas in captivity is, inevitably, space. A fully-grown wild orca is capable of swimming 100 miles in a day, and for a captive orca to swim this distance it would have to circle the perimeter of the main tank at SeaWorld 1900 times. A further problem is the depth of the tanks in sea life centres; only two of the seven tanks at SeaWorld Florida are deeper than their largest bull orca, Tilikum, is long. Captive orcas are hence deprived of the freedom of a three dimensional world in which they can exhibit natural behaviour, and are forced to swim endlessly around the same pool, an activity which lacks mental stimulation.
In captivity, the complex social needs of these intelligent whales are almost always overlooked or misunderstood. Orcas are kept in incompatible groups with others from completely different social groups, and mothers and calves are often separated far too early. It has been reported that in the wild, calves can stay with their mothers for life, aiding in the nursing of further calves and forming complex emotional bonds with a part of their brain which even humans have not developed, which has been linked specifically to their social and emotional capacities. Early separation of calves from mothers in order to sell them to or exchange them with other sea life centres can cause a huge amount of emotional grief and even depression, resulting in poor health and aggressive behaviour towards both other orcas and trainers. Frequent swapping of orcas can result in incompatible animals coming into contact, risking aggression and fatal clashes, which have already claimed the lives of many captive orcas.
Furthermore, the physical needs of these whales are very often neglected. They are fed an unnatural diet of thawed frozen fish as well as beef and pork bones to provide gelatine in order to keep them hydrated. The lack of variety in their diet can often cause vitamin deficiencies, and killer whales are therefore often given supplements as part of their normal diet. Orcas damage their teeth by chewing on metal and concrete edges of their enclosures, most likely out of boredom, and some require painful procedures known as pulpotomies (drilling of the soft, inner part of the tooth with blood and nerve supply), leaving open channels for pathogens to enter the bloodstream. Multiple captive orcas have died of septicaemia, and it seems that the poor dental condition of many orcas may have been a likely cause of this. Dorsal collapse, where the collagen structure inside the dorsal fin progressively degenerates, is also a common implication of a poor diet and too much time spent at the surface of the water.
One of the primary reasons for keeping orcas in captivity, SeaWorld representatives argue, is for educational purposes. Sadly, there is a worrying lack of public knowledge about the species and the conditions in which they live in captivity, with publically available post mortem reports claiming that an 18-year-old orca died of ‘old age’, despite female orcas being capable of reaching the age of 90 years in the wild and males only slightly less. The median survival time in captivity is only 4 years, yet SeaWorld employees are forced to tell visitors that orcas live longer in captivity than in the wild. How can the captivity of orcas possibly be used as an educational tool if SeaWorld and its staff lie to the public on a daily basis?
The figures for life expectancy in captivity indicate that orca captivity is, more often than not, unsuccessful. The problems highlighted show that there is a lot more to improve than simply the orcas’ physical fitness, so while orca treadmills may be a small improvement to their quality of life, orcas are still going to be kept with incompatible tank mates, have poor dental health, be mentally unstimulated and bored to the point of causing harm to themselves or trainers, and be forced to perform in public shows. Despite the efforts of SeaWorld to produce a machine which will make it acceptable for orcas to be kept in captivity, it seems that as long as they are kept away from the open environment of the ocean, their quality of life will always suffer compared to that of wild killer whales.
Blackfish. (2013). Documentary. Directed by Gabriela Cowperthwaite. USA: Magnolia Pictures.
Carwardine, Mark (2001). Killer Whales. London: BBC Worldwide Ltd.
This month our Exotics News Editor, Charlotte Hitch, takes a look at some interesting research being conducted into the treatment of prion diseases using gene switching. Something to whet your biochemistry and genetics appetites!
Treatment of prion and other neurodegenerative diseases with injection of a single protein
Charlotte Hitch (Vet News Exotics Editor)
The prognoses of animals with neurodegenerative diseases may become much more hopeful thanks to new research carried out at the University of Leicester into the promotion of cell growth in damaged brain tissue using biochemical pathways.
Researchers have discovered a way of deactivating neurodegeneration caused by a number of diseases such as canine cognitive dysfunction (CCD) and prion diseases by switching off a pathway which has been identified as the mechanism for neural cell death and resulting encephalopathy.
The research has given new hope to the veterinary world due to its potential to treat previously untreatable neurodegenerative diseases, many of which seem to share a common feature – the build-up of misshapen proteins in cerebral tissue. In CCD, this build-up is of beta amyloid plaque, while in certain prion diseases, the build-up is of the prion itself and the body’s own proteins which are damaged by it.
In mice, it has been shown that the build-up of these mis-folded proteins correlates with cell death inside the brain; by the means of a response mechanism which switches ‘off’ protein synthesis in neural cells when build-ups of these proteins are detected, preventing cell repair and proliferation. There is no switching back ‘on’ of the production of proteins, as the continual build-up of the proteins acts as positive feedback for this system.
The research has now been able to isolate a protein which, when injected into brain tissue, blocks the pathway by which this cycle occurs, allowing protein synthesis to commence once more and aiding the recovery of the brain cells. This has the potential to increase the lifespan of both animals and humans suffering from a range of neurodegenerative conditions, such as Bovine Spongiform Encephalopathy, Exotic Ungulate Encephalopathy, Scrapie, Canine Cognitive Dysfunction, Alzheimer’s disease, Parkinson’s disease, and many more.
Cummings BJ, Head E, Afagh AJ et al. (1996) ‘Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine’, Neurobiology of learning and memory,66(1), pp. 11-23.
Rabies & The Pet Travel Scheme
Harriet Woodhall (Vet News Small Animal News Editor)
Rabies has been frequently in the news over the past couple of months due to increasing concerns that it could enter the UK and due to the presence of World Rabies Day on 28th September. There have been several cases of rabies in the Netherlands and other EU countries recently that have led to increased Government pressure to review UK quarantine laws that were previously relaxed to save pet owners money.
Rabies is a fatal disease that can potentially affect all mammals, even humans. Due to the variable incubation period and ranging characteristics, it is often difficult to diagnose and predict the spread of the disease. Rabies has a wide range of clinical signs; meaning it has to be confirmed in a laboratory; however typical signs include sudden behavioural changes and progressive paralysis leading to death, if without treatment. The disease is mainly transmitted via saliva from a bite of an infected animal; dogs being the source of 99% of human rabies deaths.
Under the Pet Travel Scheme (PETS) dogs, cats and ferrets are allowed to enter the UK without being put in quarantine, provided they have a microchip, rabies vaccination 21 days before travelling and a pet passport; dogs also need tapeworm treatment. If the requirements are not met, the animal is then put into quarantine on arrival into the UK. Only once the requirements of the PETS scheme are met can the animal be released.
A blood test and a wait of 6 months following vaccination was previously needed to enter the UK from the EU or approved countries; this was relaxed in January 2012: blood tests are no longer needed and the wait before entering is now only 21 days. The relaxed wait could be seen as a risk, seeing as the rabies incubation period is so variable and can often be longer than 21 days.
One of the biggest concerns is the increasing numbers of smuggled dogs and puppies entering the UK with forged passports, often without vaccination or vaccination at a too young age. It is thought that since regulation changes, people are less concerned about being caught due to the shorter quarantine time. This is a particularly big problem when the dog’s origin is unknown, as rabies is still endemic in parts of the world. Many vets are now suggesting that quarantine regulations are not strict enough, and are warning of the increased risk of rabies entering the UK. BVA President, Robin Hargreaves also stated that this increase and the case in the Netherlands should “be a serious wake-up call to potential pet owners who must always ask about the animal’s background and ask to see it with its mother”.
Government officials state that the risk of rabies entering the UK is still very low, but several animal welfare charities are still concerned that they are putting their staff at risk, now suggesting that staff themselves are vaccinated against the disease.
How can marine mammals survive for so long underwater?
Charlotte Hitch (Vet News Exotics Editor)
Research at the University of Liverpool into oxygen-carrying proteins in the muscles of marine mammals has recently revealed how these animals are able to hold their breath for up to 90 times longer than humans.
The protein myoglobin, which gives muscle its red colour, is responsible for supplying muscle tissue with the oxygen required for respiration. In seals and other marine mammals, muscles are often almost black in colour due to their high myoglobin content, of which the concentration is about ten times that of bovine muscle. More myoglobin means more oxygen can be stored within the muscle itself, so oxygen from the last breath before a dive can be retained in the blood and used by the vital organs, such as the brain and heart.
By storing their own oxygen, the muscle cells are still capable of carrying out respiration to produce the ATP energy needed for movement (i.e. flipper and tail motion) during the dive, so marine mammals can still be active even when they haven’t inhaled for over half an hour. This is what enables sperm whales to dive 2-3km underwater to catch giant squid, a major constituent of their diet.
The problem with having a high muscle myoglobin content is that the protein has self-associating properties when packed tightly together. When proteins stick together, their function is impaired; in this case the myoglobin would be unable to bind with oxygen properly.
To overcome this problem, marine mammals have developed a modified version of myoglobin – with an overall positive charge on the molecule. This results in repulsion between molecules, preventing self-association.
While the adaptation offers a clear advantage to marine mammals, there are risks involved. There is no problem while the myoglobin is contained in the muscle; however muscle damage from fighting or predators’ attacks may cause it to enter the bloodstream. Myoglobin is toxic to the renal tubular epithelium, so when the blood passes through the kidneys, it can lead to renal failure.
Despite the risk to the kidneys, the outcome of this adaptation has evidently contributed to the evolutionary success of marine mammals; sperm whales can hold their breath for 90 minutes and common seals for 30 minutes. Seals are even able to sleep underwater, taking refuge from land-based predators – a vital part of their survival.
Harriet Woodhall (Vet News Small Animal News Editor)
The intelligence of domestic dogs has been a topic much in the news recently after the discovery of perhaps the “world’s cleverest dog”, Chaser the Border Collie.
One of the reasons this topic is a controversial one could be because of the limited means of testing a dog’s intelligence apart from the amount of words they are able to retain and respond to. One way scientists are trying to evaluate how intelligent the species is to look at its evolution.
It is well known that domestic dogs evolved from wolves, but how this transition came about is thought to be through humans. After a group of wolves took advantage of humans, they actually gained from the interaction and domesticated themselves naturally. It is now thought the increase in intelligence is down to their involvement with us.
Dogs have gained a social intelligence different from their wolf ancestors in which they are able to learn words in a similar way to a small child. One study has shown that dogs work things out with an inferential strategy based on the principle of exclusion: they have words that are attached to items, so when given a new word they know this belongs to a different, new item. Another quite shocking discovery was in several border collies who when shown a 2D picture were able to go and fetch the object in the picture – using something called the principle of iconicity. This was previously thought of as something that only children were able to do.
It is clear that we have much to learn about canine intelligence and are gradually uncovering new insights into their minds. One good example of a recent advance is Chaser the “world’s cleverest dog” who has been able to learn 1,200 words, more than any other non-primate and is estimated to have the intelligence of a 2 and a ½ year old child.
Even further into the field is Brian Hare from Duke University in North Carolina who has come up with a series of scientific tests covering more than just the amount of words learnt – they can also explore empathy, communication, cunning, memory and reasoning. The tests aim to prove that, like humans, dogs have different approaches to challenges. Researchers have created a profile that enables the owner to get a full overview of their dog’s traits and individual skills. The tests, through the website Dognition, are part of a study that aims to get a better understanding of how dogs think, not just for insight into dogs but also into our own intelligence evolution. As dogs learn words much like human babies it may help with our knowledge of our own learning.
Maybe the next controversial question that needs answering is: “which are smarter, dogs or cats?”
Hormone Implants for Pet Ferrets with Adrenal Disease
Charlotte Hitch (Vet News Exotics Editor)
Hyperadrenocorticism is arguably one of the most serious and prevalent diseases in pet ferrets in the USA and United Kingdom. There is a particularly high rate of incidence in neutered individuals; studies show that 50-75% of neutered ferrets develop the condition at some point in their lives. Although the prognoses may differ depending on how early in its development intervention occurs, the condition can potentially be life threatening in some cases if inflamed tissue causes anuria. The animal is then unable to remove waste and toxins from its body through urination.
Neutering the animal is considered to be one of the main causes of the onset of the disease, aside from excessive artificial light exposure and genetic predisposition. In the endocrine system, hormones work antagonistically against each other, and the presence of high levels of one hormone in the blood can stimulate the release of a different hormone to counteract the effects of the first. After neutering, there is no negative feedback from the gonads to the pituitary gland, so the pituitary gland continually releases a hormone called Gonadotrophin Releasing Hormone (GnRH) which in turn stimulates the overproduction of gonadotrophins (sex steroids) from the adrenal glands, situated beside each kidney.
One hormone produced in great quantities is Luteinizing Hormone (LH), which stimulates ovulation. The gonads are no longer present to respond to high blood LH levels, so negative feedback does not occur and the levels continue to rise in an unregulated manner. Hyperplasia occurs in the adrenal cortices, and this can lead to adenoma or carcinoma formation.
The main symptoms of the disease include severe alopecia, pruritus (itchiness), polydipsia (excessive drinking), aggressive behaviour, swollen or enlarged vulva/prostate tissue, and muscular atrophy. Adrenocortical hyperplasia may cause malignant tumours to develop; in this case the condition is often life threatening.
Current treatment options include surgery to remove the affected gland, inhibition of the release of GnRH using melatonin, and desensitisation of the pituitary gland using Lupron Depot injections, again stopping the production of GnRH. Unfortunately, surgery has limitations in that only the left gland can be removed safely because ferrets with both adrenal glands absent are likely to develop Addison’s disease, and the right gland is extremely close to the vena cava. Melatonin and Lupron only work to relieve the symptoms; they do not remove the tumour (although Lupron may shrink it).
Recently, subcutaneous deslorelin implants manufactured by Virbac have been legally marketed in the UK. Over the period of about 8 months, the implant releases hormones which antagonise the release of GnRHs, removing the stimulus for the overproduction of sex hormones by the adrenal glands. This treatment is multifunctional because not only can it be used to reduce the effects or prevent the onset of adrenal disease, but it can even be used as an alternative to neutering, saving the ferret the pain and risk associated with surgery. The implants are not yet approved in the USA, but with further research they may have great potential in the treatment of this highly prevalent condition.
Immune Mediated Haemolytic Anaemia (IMHA) in Dogs
Harriet Woodhall (Vet News Small Animal Editor)
In a normal, healthy dog red blood cells (RBCs) live around 4 months and are then destroyed by the immune system to be replaced. In a dog with IMHA the immune system destroys RBCs prematurely as if they were a foreign virus or infection; this means they cannot be replaced at the same rate.
There are two forms of IMHA: primary (idiopathic) and secondary. In primary IMHA the body produces anti-erythrocyte (RBC) antibodies which bind to surface antigens on RBCs and lead to their destruction. Although the exact cause is unknown, there are some breeds more susceptible: Cocker Spaniels, Poodles, Old English Sheepdogs and Irish Setters. Secondary IMHA also results in antibody attachment to RBCs but occurs when the patient is exposed to a drug, toxin or has an underlying neoplastic or infectious disease.
Common symptoms include anaemia, lethargy, tachypnea (increased respiratory rate), anorexia, weakness and vomiting. Most of the symptoms arise from reduced RBCs and lack of oxygen delivery to tissues.
Diagnosis can be particularly difficult and expensive with the primary purpose to demonstrate that antibodies are attached to the surface of the RBCs. A physical exam and history need to be taken along various laboratory tests such as a Complete Blood Count and a Saline Auto-Agglutination (to evaluate the clumping of cells which arise from antibody attachment). Although the most useful starting point is Saline Auto-Agglutination it can often take a lot of laboratory tests to fully diagnose the disease.
At present there is no cure for IMHA, current treatments aim to improve RBC concentration and to stabilise the patient.
Most emergency cases need blood transfusions which try to increase haemoglobin concentrations in the blood. Transfusion products can be whole blood, red blood cells or haemoglobin concentrates with the main goal to improve oxygen delivery to the tissues. While most dogs don’t have naturally occurring alloantibodies, blood typing is still important with the universally accepted blood donor being DEA (dog erythrocyte antigen) 1.1 negative.
Another treatment method is immunosuppressive therapy using corticosteroids to slow down RBC destruction and RBC phagocytosis as well as reducing antibody production.
It is thought that T regulatory cells play a part in autoimmune diseases when there are a reduced number or they have functional defects. Therefore there is the suggestion that replacing the T-regulatory cells with those grown from stem cells would be an effective treatment for the disease. Although this seems feasible a lot more research needs to be done to ensure effective delivery of the cells and whether the treatment is practical and safe.
This month our Small Animal editor, Harriet Woodhall brings us an article on a subject that many of us in practice and those aspiring to be there deal with on a daily basis: rabbit vaccination. This is a great topic to be up to speed on for veterinary interviews.
Harriet Woodhall (Vet News Small Animal Editor)
In the past couple of months the importance of animal vaccinations has been highlighted and was the main topic of focus for World Veterinary Day (27th April). As rabbits are becoming increasingly popular and now a significant part of a small animal practice’s patients, their need for vaccination is also great. According to a PDSA survey in 2011, 54% of rabbits were not vaccinated and 62% did not have regular boosters, emphasizing the need for awareness and effective vaccines.
At present, rabbits can be vaccinated against Myxomatosis and Viral Haemorrhagic disease in the form of two separate injections:
Myxomatosis was first introduced as a control for wild rabbit populations but is now a major threat for domesticated rabbits both indoor and outdoor. It is thought that the severe effect on domestic rabbits is partly due to them lacking genetic immunity that wild rabbits may have developed.
The classic signs of the Myxomatosis are swollen and runny ears, eyes and genitalia. It is spread by biting insects carrying the Myxoma virus such as flea and possibly mosquitoes but also by rabbit-to-rabbit contact. The disease can take 5 to 14 days to show and some rabbits may survive for months after infection. However, a general case often leads to a secondary lung infection and death in 12 days.
The current Myxomatosis vaccines can be given to rabbits over 6 weeks of age and it is recommended to have annual boosters.
Viral Haemorrhagic disease (VHD) is a highly contagious disease that is spread by direct and indirect (clothes) contact and also by fleas. It is also rapidly fatal, killing rabbits within 48 hours of exposure. Often there is not time for rabbits to show symptoms, but bleeding from the nose, mouth and rectum is sometimes seen.
The vaccine is normally given to 10-12 week old rabbits and must be given 14 days apart from the Myxomatosis vaccine, also with annual boosters.
Recent research has found a new recombinant vaccine against both Myxomatosis and VHD that is seemingly effective against both diseases and an improvement of many current vaccines. The vaccine is a live vector constructed from an attenuated (weakened) strain of the Myxoma virus and the capsid (shell of virus particle) protein gene of VHD that can be given in a single vaccination. This generates an immune response against both diseases but does not induce them. The research concluded that all rabbits remained healthy with no adverse effects, promising a step forward in rabbit disease prevention and awareness.