Many vets will know John Angles is a small animal medicine specialist who leads the medicine team at the Animal Referral Hospital in Canberra and prior to that the team at the Animal Referral Hospital, Sydney. Less vets will know he started in dairy practice and initially aspired to be a surgeon!
John spent 6 years in private practice before completing his residency at the University of California Davis. He then moved to Ireland and lectured in Small Animal Medicine at the University College Dublin before returning to Australia. He has completed a PhD investigating autoimmune disease in dogs.
I had the opportunity to interview John recently on the approach to pallor and the anaemic patient.
“The very first thing you are going to look at is the animal. You’ll have some history so you [will] very quickly get a sense of why they are in. Are they collapsing? Are they weak? Often times with anaemia they've also got reduced appetites, so it can be really non-specific.” In most cases you will recognise the animal has pale mucous membranes. You then need to assess how the animal is coping, including checking their respiratory rate and heart rate.
John notes the species will influence his approach. Cats need to be taken seriously. If they arrive pale and you handle them too much they may die, whereas dogs tend to cope better because they are more likely to show symptoms earlier. “Sometimes they will come in with profound anaemia where they are sitting at 7-8% percent and they just have enough oxygen to live.”
Stabilising the acute patient
Acute and chronic patients will present differently. Generally, chronic cases will have lower red cell levels but will show less severe symptoms and be more stable. However, be aware these chronic cases may be close to decompensating!
Acute cases are usually very unstable. Their red cell levels drop quickly and they will show severe clinical signs. “They’re the ones that can crash very quickly if you do too much too quickly. If they start to breathe hard or look stressed just pull right back instantly.”
After examining the acute animal, John’s steps of stabilisation are:
- Place a catheter
- Assess hydration and blood pressure
- If it’s traumatic and there’s haemorrhage start fluid resuscitation
- Assess the anaemia by collecting blood for packed cell volume (PCV) and total plasma protein (TPP) (More on this later)
- Oxygen boxes and sedation can be used to settle patients depending on the situation
“People run scared of giving fluids to animals that are bleeding but you need to think the reverse way round. If they are going to keep bleeding, you are going to need to do something surgical but they need volume. They have got to be able to perfuse the brain, the heart and the tissues and if you do not let that happen they can arrest or do something silly,” John advises.
When do you give a blood transfusion?
“There’s always this debate [on] when to transfuse. It’s really based on clinical science.” John’s decision to deliver a blood transfusion is based mainly on the patient’s context. Usually it is at a PCV of about 15% but there is no magic number.
John says he sees a lot of cases coming in with profound anaemia where veterinarians are hesitating to transfuse because a blood source is difficult to obtain. “It is very important [to transfuse] if you have an animal that is tachypnoeic, tachycardic, weak and has syncope. All those signs are saying it has profound anaemia and you need do something about it, we give a blood transfusion. We won’t work on these animals until they are transfused. The owners are told we must transfuse so we can work safely with [their] animal.”
Factors you should consider:
- Breed differences:
The normal haematocrit of brachycephalic breeds is 50-60% compared to a Shih Tzu which is 35-40%. If a brachycephalic breed’s PCV drops to 30 they will be in trouble, they will also show signs a lot earlier. In many cases John transfuses these dogs at a PCV of 20-25%.
- Acute patients:
“A general rule of thumb for rapid acute haemorrhage or haemolysis is these animals are going to show profound signs at around PCV 20%, effectively half [the normal PCV].” They are not going to cope with this sudden drop. Hence they need a transfusion earlier.
- Chronically anaemic patients:
These patients can cope at PCV 10-15% however “they are the difficult ones because the difference between 10% and death is only about 4%” (PCV 6-7% is the minimum for adequate oxygen carrying capacity). “These patients will be walking around white but may not be tachypnoeic or tachycardic. You tend to transfuse quickly because one or two points lower and they can die. These animals are often not producing red cells and usually have a bone marrow production issue.” When multiple blood transfusions are required John tries to spread them out because blood resources are limited.
- Early transfusion:
“It’s important to be proactive. Transfusing earlier is a lot safer for everyone.” In cases where there is going to be a predictable drop in red blood cells, such as in immune-mediated haemolytic anaemia cases, John says he will transfuse them to give himself a safety margin of 3-5 days for the drugs to work. (He will often transfuse them at 20% to achieve a PCV of approximately 30%).
Practical blood transfusion advice
In dogs, the first blood transfusion does not require cross matching but it is required for the second one. Cross matching test kits are available and reliable but they are very expensive (approximately $50-100 AUD for each test). Hence, John does a quick in house cross match test instead.
“Everyone gets stressed about major and minor cross-matches, you just need to think about what you are doing. What counts is you are going to be giving red blood cells (RBCs) from another dog and you want to know if there are antibodies [in the recipient’s plasma] that will clot the blood. That is what a major cross match is. It is essentially cells from a donor dog and serum from the recipient.”
To do this:
- Wash the donor cells two to three times in saline by mixing the blood with 0.9% saline, spinning it and removing the plasma. (This will take about 15-20 minutes).
- Add this to the recipient serum on a slide and check for clumping (incompatibility) under the microscope. It is really clear when you get a major incompatibility. (Compare with a saline control).
The minor cross match is the reverse; mixing donor serum with recipient RBCs. It tests for delayed red cell loss. It is still valuable, so worth doing, but less important for preventing transfusion reactions.
For cats, John advises; “I still type them and only type them. I won’t cross-match my cats. There’s only one additional antigen that’s been proven out there, the mic antigen, and it is very rare.” It may become more of a risk factor in chronically anaemic cats that receive many transfusions.
The major issue for most vets will be access to blood. Many clinics rely on donors. There are some companies starting which will give better access to canine blood supplies. However, donor cats are always going to be needed.
Diagnostic investigation should only happen when you are in a position to do so. “Never forget that at the end of the day it is nice to get an answer but you still need a live animal.”
“One of the key things for anaemia cases is to have that basic list of causes in mind.” John highlights there are species differences to consider. In cats, infectious disease, for example Mycoplasma haemophilis, is very common. In dogs, there have been reports of Babesia in the Northern Territory, particularly in bulldog breeds, but otherwise infectious diseases are very rare in this species in Australia. Therefore, immune mediated disease and neoplasia are higher priorities.
The initial approach is the same for both species: Identify causes such as rodenticide toxicity or other toxins, check for signs of trauma, look for swelling or any signs suggestive of haemorrhage, and consider other differentials including congenital diseases (e.g. Von Willebrand’s) or in cats; enzyme deficiencies (e.g. pyruvate kinase deficiency in Somalis and Abyssinians).
When collecting blood, John recommends collecting the whole sample in one draw with a 23G needle, usually from the jugular vein. If the animal is not coping well or if a coagulopathy is suspected, blood can be collected from the tarsal or saphenous veins with a butterfly catheter. However, blood flow can be a problem. The cephalic veins should be left for catheters.
Diagnostic testing starts with the PCV/TPP. It is a very quick method of quantifying the anaemia. A blood smear can be performed at the same time to check the cell types present and detect any atypical cells. Look for nucleated red blood cells, polychromasia and in breeds susceptible to leukaemia (e.g. Rottweiler); neoplastic cells.
Note: Make blood smears from fresh blood not from an EDTA tube as EDTA removes some organisms from the surface of cells.
John does not do manual platelet counts because he’s comfortable estimating it. However, for those who are not so comfortable estimating you can do manual counts. The old rule of thumb is the platelet count = the number of platelets on a high power field (1000x) x 20 by 109 (It is more accurate if you obtain an average from several platelet counts). Essentially if you are not seeing platelets it’s likely to be thrombocytopenic.
John also checks the plasma for signs of icterus.
You may also be looking for immune-mediated disease, so you will need to check for auto-agglutination. John recommends mixing one drop of blood with one drop of saline on a slide, spreading it and looking for clumping.
John has in house haematology machines at his clinic for more comprehensive results which he will also use but they take longer (5-10minutes) and often do not cope well with severely anaemic blood. Sending the sample to an external laboratory is another option but there is obviously a time delay.
Regenerative vs Non-regenerative:
The next step is to define the anaemia as regenerative or non-regenerative. John advises to remember that regeneration can take 3-5days after an acute haemorrhage or haemolysis so do not panic and proceed down the non-regenerative approach too quickly. If there are persistent non-regenerative signs after completing sequential reticulocyte counts then you will need to question what is happening to the bone marrow, particularly if other cell lines are absent. In regenerative anaemias reticulocytes will appear 2-3 days after the onset of anaemia.
Haemorrhage vs. Haemolysis:
If it’s regenerative then you need to further categorise the disease as haemolysis or haemorrhage. To differentiate, it is important to check for signs of haemolysis such as hyperbilirubinaemia and icterus.
Haemorrhage can usually be detected as swelling, or if it is in the chest, as tachypnoea, which triggers you to radiograph the animal. Gastrointestinal haemorrhage is more difficult to detect. Melena can be seen 1-2 days later. John finds faecal occult blood tests unreliable because they are strongly influenced by the animal’s diet. Clinical signs include nausea, inappetance and vomiting. If there are no other anaemic causes John will give gastric protectants (antacids and sucralfate) during the investigation. Blood tests and imaging, most likely ultrasound, are used to further localise the cause.
Note: Haemorrhage and haemolysis can occur simultaneously which can be confusing. Often one process is more dominant and you can focus on identifying its cause. The presence of both processes may be suggestive of neoplasia.
John only collects bone marrow aspirates when there is a pancytopenia. In these cases he suspects neoplasia (myelophthisis). He rarely investigates bone marrow in immune mediated thrombocytopenia and haemolytic anaemia cases because there is very little reward. Multiple myelomas are rare but there will often be high globulin levels and other flags which will increase your suspicion of this disease.
Coagulopathies are a very common cause of haemorrhage. The first clinical signs noticed are usually petechiations, ecchymoses or bruising. Firstly check the primary haemostasis by measuring the platelet count with a blood smear and/or CBC. If there are no platelets in the smear or on the feathered edge then you have a severe thrombocytopenia. In these cases you will need to consider primary and secondary immune mediated disease and thrombocytopenia.
For secondary coagulopathies like rodenticide toxicities the history will give clues but John will quickly use an ACT tube and if it’s prolonged then check PT and APTT. ACT tubes will give you a rough idea on whether you have a coagulopathy or not. “If you’ve been mixing for 5minutes and it has not clotted it will probably have a coagulopathy.” They are inexpensive and quick which is great for emergency situations. Remember, a serum tube which has not clotted after 10 minutes can also indicate a coagulopathy.
PT and APTT are beneficial in determining if it is an extrinsic, intrinsic or common pathway problem and hence narrow down the differentials but they are more expensive tests.
If you have a normal platelet count, PT and APTT always remember to consider platelet function defects. Von Willebrand’s disease is very common in Dobermans, Golden Retrievers and Basset hounds. This can be tested by performing a buccal mucosal bleeding time test. You can use a simTM plate or just make a little nick with a size 11 scalpel blade on the mucosa. Do not touch your incision because you need to give it a chance to clot. Wick it underneath with a piece of gauze or paper and soak up the blood. If normal, it will clot after 3-5 minutes. This is the third step and should not be done until the other tests have been completed because you do not want to put a hole in the mucosa if you have low platelets or a known coagulopathy.
If they are all normal then also consider vasculitis but there will generally be a lot of other flags to make you consider this differential.
The anaemic patient requires thorough monitoring, supportive care and diagnostic investigation. “They are animals to respect.” John’s key action points to remember when confronted with a pale patient are:
- Look at your animal and assess how they are coping
- Decide your diagnostic approach- the first set of samples you take are the key
- Do not hesitate to give a blood transfusion
- Work with your animal and do not push them too hard and too fast.
We would like to thank John for sharing his expertise in working with the anaemic patient with us.
Dr John Angles BVSc, BSc(Vet), MVS, PhD, MANZCVSc, DACVIM (Small Animal Medicine), DECVIM-CA
Small animal medicine specialist
John graduated in 1988 with honours from the University of Sydney and worked for 5 years in small animal practice in Canberra, before completing a small animal medicine residency at the University of California at Davis. He then spent 4 years as lecturer in Small Animal Medicine at the University College Dublin prior to joining the Animal Referral Hospital in 1993.
John has advanced training in veterinary immunology and genetics, and extensive experience working with dog and cat breed clubs in Europe and the USA. He was awarded a PhD in Comparative Pathology in 2005 by the University of California at Davis, investigating causes for autoimmunity in dogs. John has published extensively in both veterinary and medical literature. His current research is directed at molecular causes for diseases in dogs and cats, with specific emphasis on mitochondrial DNA defects, haematologic diseases and breed-associated autoimmunity.
John is a Diplomate of both the American and European Colleges of Veterinary Internal Medicine (ACVIM and ECVIM). He receives referrals in all aspects of canine and feline medicine.