U3 O3 - Haematological and Haemostatic Emergencies Flashcards
What does anaemia arise due to?
Anaemia arises due to -
➢ increased loss of RBCs through haemolysis or haemorrhage OR
➢ decreased production
What is anaemia?
This is a reduction in number of circulating erythrocytes/red blood cells (RBC).
What detrimental effects can anaemia have?
Anaemia leads to tissue hypoxia and organ dysfunction as red blood cells contain haemoglobin which is responsible for transporting oxygen to cells. Hypoxia can lead to cell death and ultimately patient death
Is anaemia a diagnosis?
Anaemia is a clinical sign rather than a diagnosis – the clinical signs of a patient with anaemia
depend on the underlying cause, the acuteness and severity of the condition.
How can you differentiate pale mucous membranes associated with anaemia compared to vasoconstriction?
Pale mucous membranes are usually associated with anaemia although this may be masked by coexisting clinical signs e.g. jaundice in a patient with
haemolytic anaemia. Pallor of mucous membranes due to anaemia needs to be differentiated from pale mucous membrane caused by peripheral vasoconstriction due to e.g. hypovolaemia, or any other reason for a decrease in cardiac output. This can
be challenging in some cases but assessing perfusion parameters and PCV can help to differentiate.
What signs will a patient with severe anaemia display?
A patient with severe anaemia will have very pale mucous membranes, be obtunded, tachycardic, and possibly tachypnoeic – the central pulses may be
bounding- ‘tall and narrow’. N.B The pulse pressure is the difference between the systolic and diastolic pressures
If a pulse is strong what will be the difference between systolic and diastolic blood pressure?
If the pulse is strong, the difference between systolic and diastolic blood pressure will be ~ 30 mmHg
What are weak central pulses usually due to?
If central pulses are weak it is usually due to decreased systolic pressure because of reduced cardiac output and indicates severe hypotension e.g. decompensated hypovolaemic shock or cardiac tamponade but there are other causes
What will the blood pressure show if a patient had bounding pulses?
Because there is a large difference between the systolic and diastolic blood pressure, the pulse feels bounding
Why will a patient with chronic anaemia have a bounding narrow pulse?
A patient with chronic anaemia, may have a bounding, narrow pulse – this is because adaptations help them
to maintain a normal systolic blood pressure but due to the blood vessels being emptier than they should (fewer RBCs), the diastolic pressure is low.
What is the normal PCV for a dog?
The normal PCV for the dog is ~ 45 % (0.45 l/l) - range ~ 37%-55% (0.37l/l – 0.55 l/l)
What is the normal PCV for a cat?
The normal PCV for the cat is ~ 36% (0.36 l/l) – range ~ 26%- 46% (0.26 l/l – 0.46 l/l)
What will the PCV be on an anaemic and dehydrated animal?
A patient that is dehydrated but also anaemic may initially have a PCV within the normal range. Once the fluid deficit has been corrected and the patient is rehydrated, the true PCV will be apparent
What would be considered a normal pulse for a pregnant bitch and why?
In pregnant patients at full term, the PCV will be reduced due to a dilutional anaemia.
The PCV of a pregnant bitch, is often around 30-35%. Therefore a ‘normal’ PCV of 45% in this pregnant patient is likely to indicate significant dehydration
How is a young animals PCV different to that of an adult?
young animals (under 6 months) have a lower PCV. Therefore, other clinical findings are very important because again a PCV of ~ 45% suggests the patient is considerably dehydrated
What is regenerative anaemia?
If there has been increased loss of RBCs, the bone marrow generally responds by increasing the RBC production and release. This is called regenerative anaemia
What two different types of anaemia are generally regenerative?
- both haemorrhagic and haemolytic are generally regenerative
What are the 5 different causes of haemolytic anaemia in dogs?
- Immune mediated haemolytic anaemia (IMHA)
- Haemolysis due to genetic defects of red blood cells
- Haemolysis secondary to zinc intoxication or onion/garlic/chives ingestion
- Infection with Babesia canis or Babesia gibsoni - babesiosis
- Microangiopathic anaemia
- Congenital e.g. pyruvate kinase deficiency
What is the most common cause of immune-mediated haemolytic anaemia?
Immune mediated haemolytic anaemia (IMHA)- this is the commonest cause.
Where does haemolysis occur with immune-mediated haemolytic anaemia?
Haemolysis of RBCs may occur in the intravascular or, more often, the extravascular space
What are the two types of immune-mediated haemolytic anaemia?
a. Primary idiopathic
b. Secondary to:
i. Drugs (beta-lactams e.g. cephalosporins and penicillin’s)
ii. Neoplasia
What breeds are prediposed to haemolytic anaemia due to genetic defects of red blood cells?
Beagles, West Highland White Terriers, Cairn Terriers
What can be the main cause of zinc toxicity in dogs and what can this cause?
Ingestion of some coins, skin preparations, nuts and screws which contain zinc can lead to zinc toxicity. This can cause intravascular haemolytic anaemia and
gastro-intestinal signs. Zinc toxicity is very serious due to the high mortality rate
How does onion/garlic ingestion cause haemolytic anaemia?
Onion/ garlic ingestion causes oxidative injury and denaturation of haemoglobin- this leads to Heinz Body formation and decreased red cell survival.
Heinz bodies appear like small blobs protruding from the RBC surface.
What type of disease is Babesia canis and what can it cause?
This causes haemolytic anaemia
Infection with Babesia canis or Babesia gibsoni - babesiosis. This is a tickborne, protozoal blood parasite which was previously rarely seen in the UK.
However, it has become more prevalent with increased importation and the more relaxed recent pet passport scheme of recent years. It can occasionally be a cause of illness in imported dogs (Solano-Gallego, 2016). Clusters of case have been reported in the UK with dogs imported from Europe. There have also
been some recent outbreaks of babesiosis in the UK in dogs that have not travelled out with the UK (Wright, 2018). Babesiosis, however, is mainly
confined to North America, Asia and Africa.
What is microangiopathic anaemia and what can it be caused by?
Its a type of haemolytic anaemia
Microangiopathic anaemia – mechanical damage to RBCs as they circulate.
This could be associated with haemangiosarcoma, splenic torsion and heartworm disease (Goggs and Hackner, 2018). Broken RBCs (schistocytes)
are often seen on blood smears from affected patients.
What are the 5 different causes of haemolytic anaemia in cats?
- Immune-mediated disease
- Toxicity
- Drug related
- Severe hypophosphataemia
- Incompatible blood transfusions
What can immune mediated haemolytic anaemia be secondary to?
- Immune mediated disease- can be secondary to FeLV; or Mycoplasma haemofelis (aka haemoplasma)- (previously known as Haemobartonella felis).
What toxins can cause haemolytic anaemia in cats?
- Toxicity e.g. garlic and onion poisoning; lead poisoning which leads to Heinz body formation. Cat haemoglobin is very sensitive to oxidative damage and easily injured- therefore there are several causes of Heinz body anaemia in cats e.g. diabetes mellitus, hyperthyroidism, lymphoma and administration of
propofol for long periods (> 12 hours)
What drugs can cause haemolytic anaemia in cats?
- Drug related e.g. methimazole, paracetamol
What can haemolytic anaemia due to severe hypophosphataemia occur secondary to?
Severe hypophosphataemia (cats < 0.48 mmol/l) – this can occur secondary to other diseases e.g. diabetes mellitus
How long do the clinical signs of IMHA develop over?
Clinical signs are usually acute onset, developing over a period of 2-3 days, and depend on the severity of the anaemia
What are the clinical signs for mildly and severely affected cases of IMHA?
Mildly affected cases may simply appear lethargic and slightly tachypnoeic. Patients with severe anaemia will be weak, obtunded and possibly collapsed.
Increased intravascular haemolysis
Extravascular haemolyis
pulmonary thromboembolism and disseminated intravascular coagulation (DIC) are relatively common sequels to IMHA leading to respiratory distress
Why might a patient with haemolytic anaemia be icteric and/or have haemoglobinuria, what does this indicate?
Break down of RBCs in the circulation leading to an accumulation of haemoglobin and bilirubin in soft tissue and urine.
Consequently, the patient may have icteric/jaundiced mucous membranes; and haemoglobinuria where the urine is stained by haemoglobin pigment so appearing darker in colour than normal ‘port wine urine’.
This indicates intravascular haemolysis
What symptoms may be seen in a patient with increased intravascular haemolysis with haemolytic anaemia?
Increased intravascular haemolysis – break down of RBCs in the circulation leading to an accumulation of haemoglobin and bilirubin in soft tissue and urine.
Consequently, the patient may have icteric/jaundiced mucous membranes; and haemoglobinuria where the urine is stained by haemoglobin pigment so
appearing darker in colour than normal ‘port wine urine’. If the anaemia is severe, the patient is likely to be tachycardic with bounding pulses- cats may
also have a haemic murmur. There may be splenomegaly and hepatomegaly.
The clinical signs and prognosis tend to be poorer for dogs with intravascular haemolysis.
What is extravascular haemolysis and what symptoms is the patients less likely to show with type of haemolytic anaemia?
Extravascular haemolysis – the RBCs are phagocytosed prematurely by macrophages in the spleen, liver and bone marrow so there is less likelihood of jaundice and haemoglobinuria
In cats with Mycoplasma haemofelis what have been the three main presentations reported?
In cats with Mycoplasma (Haemobartonella) haemofelis, three main presentations have been reported (Weingart et al., 2015) -
1. Kittens and some adults develop peracute anaemia with collapse and
hypothermia
2. Kittens and most adults develop acute anaemia and fever, splenic enlargement
and tachypnoea - as well as appearing generally sore all over their bodies.
3. Adult cats developing mild anaemia, mild pyrexia, lethargy and loss of weight.
The condition is often more chronic.
What are the limitations of a PCV/TP when helping to diagnose something like haemolytic anaemia?
There will be abnormal haematological parameters e.g. decreased PCV, RBC count and haemoglobin levels. PCV is quick and easy to check but can be affected by factors such as dehydration- total protein/ total solids (TP/TS) should be checked at the same time to gain as much information as possible e.g. the PCV will be decreased but TP/TS should be normal with IMHA. The patient may have thrombocytopaenia +/-
neutrophilia.
What type of diagnostic test can give you evidence of a strong regenerative response with haemolytic anaemia?
A lot of information can be found from a blood smear so these should be performed routinely in any patient with anaemia (Sharkey, 2015). On a blood smear from a patient with haemolytic anaemia there is often evidence of a strong regenerative response.
What features of a blood smear would indicate a regenerative response in haemolytic anaemia??
Features of a regenerative response are- • large, polychromic red cells • anisocytosis • a high reticulocyte count ** • +/- an increase in the number of nucleated red cells.
Roughly how long does it take to see a regenerative response on a blood smear?
‘Since a regenerative response takes approximately 3 to 5 days to mount, acute
cases may initially appear poorly regenerative
What is a spherocyte?
There may be spherocytes- these are red blood cells which are spherical rather than the usual disc shape.
How are spherocytes formed?
They can be present for several reasons but can be associated with IMHA- produced when macrophages remove part of the red cell wall
What can lack of spherocytes in a dog with haemolytic anaemia suggest?
It is harder to recognise spherocytes in cat blood smears. N.B. Lack of spherocytes in a dog with haemolytic anaemia can be suggestive of zinc toxicity
Why are white cell counts often high with haemolytic anaemia?
White cell counts are also often elevated due to the increased bone marrow activity of a regenerative response.
When might basophilic stippling of erythrocytes be seen in dogs and cats?
Basophilic stippling of erythrocytes may be seen with lead poisoning, but this may also be seen in cats with a marked red blood cell regenerative response.
What are heinz bodies a result of?
Heinz bodies are the result of oxidative damage to haemoglobin in the red cells and appear as refractile, poorly staining structures located beneath the red cell membrane or protruding from it. In cats, Heinz bodies are suggestive of intoxication e.g. paracetamol or onion poisoning.
What type of stain is used to demonstrate reticulocytes?
Staining of the blood smear with new methylene blue, will demonstrate reticulocytes.
How will a reticulocyte appear on a blood smear?
They have a fine trabecular structure within the cells (made up of nuclear material and cellular organelles)
How do reticulocytes in cats appear on a blood smear and what do large numbers of these indicate?
In cats, reticulocytes may appear with punctate dots or clusters and lines of condensed organelles. These start out as the aggregate form (clusters
and lines) and mature to the punctate dots. Therefore, the presence of large numbers of the aggregate form of reticulocyte, in cats, demonstrates active regeneration.
The presence of immature nucleated red blood cells also demonstrates a marked regenerative response. These cells are more basophilic and much larger than the mature erythrocytes.
What is the best means of diagnosing mycoplasma haemofelis?
The best means of diagnosing Mycoplasma haemofelis infection is by polymerase chain reaction (PCR)
How will the organism mycoplasma haemofelis appear on an erythrocyte?
the organism Mycoplasma haemofelis may be found as chains, discs or rods on the surface of erythrocytes. The PCV can decrease rapidly in cats with this
condition
How does an auto agglutination test work and what does it indicate if it is positive for auto agglutination?
With an immune mediated condition, cells destined to be destroyed are first coated with antibodies. Auto-agglutination is caused by cross-linking of the antibodies which are bound to the erythrocyte membranes- strongly suggesting that the haemolysis is
immune-mediated
What is auto agglutination and how does it look on a slide?
Auto-agglutination makes RBCs stick together- macroscopically this looks like small flecks, within the drop of blood on a slide; microscopically the RBCs stick to each other, looking like bunches of grapes.
How is a slide agglutination test performed and what would indicate auto-agglutination?
A saline dispersion test (also called slide agglutination test) should be performed to determine if there is genuine auto-agglutination of red blood cells or if, instead, rouleaux formation has occurred. Rouleaux is a physiological clumping/stacking of red blood cells- adding saline will cause the RBCs to separate/disperse if rouleaux is present. It is not a sign of immune-mediated disease. If auto-agglutination has
occurred, the RBCs will remain stuck to each other because they are coated with antibody. In this test, a drop of anticoagulated blood, from an EDTA blood tube or capillary tube, is mixed with 3 drops of saline on a microscope slide
What is a Coombs test and what does it help to confirm?
Further confirmation of IMHA, can be done using both the direct and indirect Coombs test. The direct Coombs test demonstrates RBC coating with anti-RBC antibodies; the indirect Coombs test demonstrates the presence of anti- RBC antibodies in serum.
The Coombs test is of debatable value being very specific but not very sensitive. It also needs to be carried out by an external laboratory- due to the critical nature of many of these patients, presumptive treatment is likely to be required before the results come back.
How can radiography help to determine the cause of haemolytic anaemia?
Radiography
Metallic foreign material e.g. coins may be visible on abdominal radiographs in dogs with zinc toxicity
Why should phophate levels be checked in a patient with haemolytic anaemia?
Phosphate levels should be measured, particularly in cats as levels <0.48mmol/L can induce haemolysis. This is a common issue in patients with diabetic ketoacidosis for example. Other causes include decreased intestinal absorption, increased renal losses and transcellular shifts
What biochemical tests should be carried out in a patient with haemolytic anaemia?
organ function tests, particularly for liver and kidney function, and electrolyte levels should be checked as well. Bilirubin may be increased secondary to
the breakdown of the red blood cells (pre-hepatic). Renal parameters may be elevated and azotaemia is common. Assessment of renal function including urine specific gravity is important.
What initial care should be provided to a patient with anaemia?
The patient should be cage rested and stress avoided to minimise additional oxygen requirements. Supplementary oxygen may be administered - however it is important to consider that the problem is not with the respiratory system but an issue with the
binding and delivery of oxygen. Therefore, the hypoxia will really only improve once the haemoglobin level increases. If using supplemental oxygen techniques,
consideration should be given to the potential for an anaemic patient to have a coagulopathy. Placing nasal prongs or catheters may cause significant haemorrhage.
An IV catheter should be placed, on vet direction, to allow vascular access for medications, fluids and possible blood transfusion(s). Care should be taken when placing due to the increased risk of thrombus formation. Intravenous access may be challenging in these patients. Due to the immune system compromise,
that can accompany some of these disease processes, an aseptic technique is absolutely vital and repeated venepuncture should be avoided. It is sometimes more
successful accessing a saphenous vein that has not been used for blood sampling.
Placing a central line (jugular catheter) is an option for some patients but only if certain there is not a concurrent coagulopathy.
How do you treat anaemia?
With IMHA being an immune-mediated condition, immunosuppressive treatment is the main long-term treatment (e.g. prednisolone) – discussed further below.
If the PCV has dropped below 20% and there are clinical signs related to anaemia, blood products may be required- packed red blood cells would be appropriate in this situation (Goggs and Hackner, 2018). However, the veterinary surgeon’s decision to transfuse (termed transfusion trigger) will be based on various factors, including clinical signs, and not just the PCV (Walton and Tappin, 2018). There are risks associated with transfusion which need to be balanced against the benefit to the patient and the effect the anaemia is having on the individual. If a patient’s own RBCs
are being destroyed by antibodies, it is possible that transfused RBCs are even more likely to be destroyed, thus precipitating a serious transfusion reaction.
What monitoring and nursing care should be provided to a patient with anaemia?
Ongoing monitoring should involve assessment of mucous membrane colour, heart rate, pulse quality, capillary refill time (CRT), PCV and patient mentation. It is important to monitor for complications e.g. sepsis/ transfusion reactions as well as meeting the
patient’s basic nursing needs. Nursing care will include addressing patient comfort and ensuring they cannot cause themselves further harm; providing enrichment, if appropriate, as these patients need to be restricted; grooming; TLC and nutritional support
What treatment can help to reduce the effects of IMHA in dogs and what can be the side effects of these?
If a diagnosis of IMHA is confirmed, immunosuppressant treatment will be required e.g. corticosteroids (prednisolone in tapering doses). Other immunosuppressant therapy may be required for dogs that are refractory to treatment e.g. azathioprine or
cyclosporine. These additional drugs generally permit the prednisolone dose to be reduced sooner, thus lessening the side-effects of corticosteroids on the animal. As side-effects, including bone marrow suppression may be seen, patients will need to
be closely monitored during use.
What medication is used to help treat mycoplasma haemofelis? What can be the side effects of these?
In cats, doxycycline or oxytetracycline for 3 weeks may be required if Mycoplasma (Haemobartonella) haemofelis has been diagnosed/suspected. Doxycycline has been reported to cause oesophagitis and dogs/cats should therefore eat after administration
(BSAVA, 2020)
Pradofloxacin is a relatively new fluoroquinolone antibiotic reported to be effective (International Cat Care, 2018). Enrofloxacin may be used for 3 weeks but may not fully clear the parasite as well as increasing the risk of acute renal failure. Treated cats,
may however, remain as carriers.
What thrombo-prophylaxis treatment can be used in dogs with IMHA?
With IMHA, thrombo-prophylaxis using drugs such as clopidogrel or aspirin may be required- affected dogs are prone to developing thromboembolic disease (pulmonary thromboembolism, DIC or portal thrombi) which will worsen the prognosis for recovery
(Goggs and Hackner, 2018) (Day, 2012). It is unclear currently what the best antithrombotic is- recent research has indicated that that unfractionated heparin or rivaroxaban could be useful (Goggs and Hackner, 2018).
The American College of Veterinary Emergency and Critical Care have developed a consensus statement on the rational use of anti-thrombotics in Veterinary Critical Care
How do you treat zinc toxicity?
Zinc toxicity
Immediate emergency treatment is required due to the high risk of death -IVFT (based on perfusion parameters and hydration status); GIT protectants packed red blood cell transfusion if there are clinical signs relating to the anaemia. As soon as the patient’s condition is sufficiently stable, the foreign material should be removed endoscopically or surgically (Goggs and Hackner, 2018).
Removal and/or treatment of underlying causes of oxidative RBC damage is needed
e.g. propofol infusion, hypophosphataemia etc
What sepearte pathways lead to the final common pathway resulting in blood clot formation?
The classic model of coagulation, with the separate extrinsic and intrinsic pathways leading to a final common pathway resulting in blood clot formation (fibrin plug) shows how coagulation takes place in a laboratory setting (in vitro).
What is cell based model of haemostasis?
it is proposed that a different process takes place in a living patient that is bleeding (in vivo)- the cell-based model of haemostasis. This model considers the
roles of cells in haemostasis in the living patient
What three overlapping phases occurs with haemostasis?
Research shows that haemostasis occurs on the surface of certain cells and it involves three overlapping phases- initiation, amplification and propagation.
What does the initiation phase of haemostasis involve and what does it activate and lead to the production of?
Following tissue damage, it is proposed that exposure of tissue factor to blood results in the activation of factor VII (and some other factors) – INITIATION. This leads to the production of a small amount of thrombin
What is the amplification phase of haemostasis and what does it activate?
This thrombin production activates platelets which then bind factors V, VIII, and IX on their surface (i.e. cell based) - AMPLIFICATION.
What is the propagation phase of haemostasis and what does it activate?
Once bound to platelets, the activated clotting factors lead to the conversion of large amounts of
prothrombin to thrombin - PROPAGATION.
Describe the three overlapping phases in haemostasis - initiation, amplification and propagation?
Research shows that haemostasis occurs on the surface of certain cells and it involves three overlapping phases- initiation, amplification and propagation.
Following tissue damage, it is proposed that exposure of tissue factor to blood results in the activation of factor VII (and some other factors) – INITIATION (Sucker and Zotz, 2015). This leads to the production of a small amount of thrombin (refer to diagram above). This thrombin production activates platelets which then bind factors V, VIII, and IX on their surface (i.e. cell based) - AMPLIFICATION. Once bound to platelets, the activated clotting factors lead to the conversion of large amounts of prothrombin to thrombin - PROPAGATION.
This sudden production of a large amount of thrombin (‘thrombin burst’) leads to the conversion of a large amount of fibrinogen to fibrin (the clot), as well as further activation of factor XIII. The clot is formed at the site of blood vessel injury.
What are the different stages of haemostasis starting from a healthy intact blood vessel becoming damaged to the formation of a clot?
Healthy, Intact Blood Vessel containing blood (red blood cells, white blood cells, platelets and plasma containing clotting factors (CF)). Tissue factor (TF) in blood vessel smooth muscle and outer coating -
Damage to blood vessel
The first phase, initiation, occurs on cells with tissue factor (TF) and leads to a small amount of thrombin being produced. N.B. Tissue factor (TF) is a protein which is on the surface of many extravascular cells, which make up the walls (not the lining) of the blood vessels e.g. vascular smooth muscle cells and adventitial cells. Normally blood would not contact cells bearing tissue factor. Therefore, if blood does encounter TF, it is because there is damage to the blood vessel meaning haemorrhage is likely to be occurring. Tissue factor is considered to be the primary initiator of blood coagulation in vivo
The second phase, amplification, is when platelets and co-factors are activated.
The third phase, propagation, occurs on the surface of platelets, and results in the production of large amounts of thrombin. This in turn leads to conversion of fibrinogen to fibrin and the formation of a clot at the site of the injury.
What are disorders of primary haemostasis generally associated with?
Disorders of primary haemostasis are generally associated with thrombocytopaenia (decreased platelet number) and, occasionally, thrombocytopathia (platelets not functioning normally).
What are disorders of secondary haemostasis generally associated with?
Disorders of secondary haemostasis are generally associated with clotting disorders such as haemophilia A, liver disease, rodenticide poisoning (relative vitamin K deficiency) and DIC
What clinical signs do disorders associated with primary haemostasis present with?
History, signalment and clinical signs are important when trying to identify an underlying cause. A disorder of primary haemostasis (thrombocytopaenia or
thrombopathia) usually presents with mucosal/ epithelial haemorrhage and/ or petechiation. With primary haemostatic disorders evidence of bleeding is commonly seen on the mucosa or the skin.
What clinical signs do disorders associated with secondary haemostasis present with?
A disorder of secondary haemostasis is usually associated with a larger volume bleed e.g. haematoma and intracavity bleeding (e.g. thorax, abdomen, joints).
What can thrombocytopaenia occur due to ?
Thrombocytopaenia may occur due decreased platelet production or increased platelet use, destruction or removal from the circulation
What platelet count with thrombocytopaenia are clinical signs usually associated with?
Clinical signs associated with thrombocytopaenia are not likely to be apparent until the platelet count is < 40 x 109 /l
How can thrombocytopaenia be caused by a drug reaction?
Thrombocytopaenia may be caused by a drug reaction e.g. cephalosporins; or platelet activity can be affected by certain drugs e.g. aspirin.
Aspirin, in particular, will have a long-lasting effect on platelet function. Once administered, the platelet function remains depressed for the lifespan of the platelet, rather than the half-life of the drug e.g. the time the drug is in the animal’s system.
What is von willebrands disease?
Clotting Defects
Von Willebrand’s disease is caused by an absence of von Willebrand’s factor (vWF). Unlike the other clotting factors which are made in the liver, Von Willebrand’s factor is made within endothelial cells and megakaryocytes- it is an adhesive protein which is required to encourage platelet aggregation and adhesion during primary haemostasis
What breeds is von willebrands most commonly inherited in?
Von Willebrand’s disease is a common inherited disease in Dobermans, Rottweilers and German Shepherd Dogs
What is the most common inherited coagulation deficiency disorder in dogs?
Haemophilia A is the most common inherited coagulation deficiency disorder in dogs
Which clotting factor is decreased in Haemophilia A?
Haemophilia A is the most common inherited coagulation deficiency disorder in dogs.
There is decreased factor VIII which is essential for the intrinsic clotting cascade.
What does rodenticide intoxication create a deficiency in and why is this an issue?
Rodenticide intoxication creates a deficiency in active vitamin K - vitamin K is required by factors II (prothrombin), VII, IX and X (vitamin K dependent clotting factors) for functional clotting activity.
What clotting factors require vitamin K for functional clotting activity?
vitamin K is required by factors II (prothrombin), VII, IX and X (vitamin K dependent clotting factors) for functional clotting activity.
What two compounds is rodenticide divided in to and why was it developed?
Rodenticides are divided into first and second-generation compounds - the latter being developed as resistance to the first-generation products
had developed in the wild rodent population
What do second generation compounds in rodenticide include?
The second-generation rodenticides include compounds such as brodifacoum, bromadiolone and difenacoum.
How long after ingestion are signs of rodenticide intoxication usually apparent and what are the clinical signs related to?
The signs are caused by spontaneous haemorrhage, usually within two to five days of ingestion. As this is a disorder of secondary haemostasis, there may be clinical signs relating to
➢ bleeding into body cavities e.g. the pleural space, the pericardium, abdomen,
joints
➢ pulmonary haemorrhage
➢ GI tract haemorrhage
➢ external bleeding from orifices (nasal cavity, oral cavity), wounds etc.
➢ intracranial or intraspinal cord haemorrhage
What can clinical signs of rodenticide intoxication include?
Clinical signs will include varying degrees of lethargy, weakness and anaemia.
Additionally, depending on the location of the bleeding, clinical signs can include
bruising, haematomas
dyspnoea due to pleural space disease (see Unit 3 Outcome 2)
coughing, haemoptysis
abdominal distension
joint swelling/ lameness
pericardial effusion- muffled heart sounds (see Unit 3 Outcome 1)
seizures, paresis, paralysis
What is disseminated intravascular coagulation (DIC) and what does it often arise in association with?
Disseminated intravascular coagulation (DIC) is a complicated derangement of the clotting pathways that arises secondary to some other serious problem. It often arises in association with systemic inflammatory response syndrome (SIRS)/ sepsis but can develop secondary to serious conditions e.g. trauma, heatstroke, pancreatitis.
Widespread inflammation results in systemic coagulation- a hypercoagulable state.
This leads to a prothrombotic state and the formation of multiple intravascular clots (microthrombi) that ultimately lead to reduced organ perfusion- being a further complicating factor in organ failure. Due to the prothrombotic state and formation of many intravascular clots, the clotting factors are consumed or ‘used-up’- this then leads to a clotting factor deficiency making the patient hypocoagulable (coagulopathic) with a tendency to bleed. In all cases, there will be clinical signs associated with the
underlying disease process that has caused the systemic inflammation and DIC (e.g. pancreatitis, IMHA, sepsis). DIC may be present but be asymptomatic whereas some patients will have very serious signs with overt/ clinical bleeding
How do you diagnose disseminated intravascular coaglopathy?
The diagnosis of DIC can be challenging especially in the early stages where it is subclinical (Hackner and Rousseau, 2015)- as it is a dynamic condition the signs and findings change frequently. There is also no specific diagnostic test for DIC- patients
with clinical signs attributable to DIC often have thrombocytopaenia and prolonged clotting times (PT, aPTT) (Goggs and Hackner, 2018). Schistocytes may be apparent on a blood smear. One of the first indicators of a patient developing DIC, alongside clinical signs, is platelet consumption - so serial blood smears monitoring platelet numbers in patients at risk should be performed. The prognosis for patients that
develop DIC is poor- early identification is essential to improve survival rates. It is essential in a patient with suspected or confirmed DIC to identify the underlying reason and treat it.
What are other possible acquired disorders of secondary hemostasis (Coagulopathy)?
Other possible causes of acquired disorders of secondary haemostasis (coagulopathy) include liver failure (clotting factors are made in the liver) and dilution coagulopathy e.g. when larger volumes of fluids are given. In a patient with acute blood loss, platelets and clotting factors will be consumed. If the patient also receives intravenous fluid therapy (likely with hypovolaemia), all clotting factors (including von
Willebrand’s factor) and platelets will be diluted. This can result in prolonged bleeding in some patients. Acquired coagulopathy can develop secondary to severe hypothermia. In human medicine the triad of death is reported and is certainly a concern in animal patients also.
What are the clinical signs of acute or chronic haemorrhage?
These vary from patient to patient, the underlying cause, the location and the rate of blood loss. Depending on the underlying cause, blood loss can be acute or chronic.
With acute blood loss, there will be signs of hypovolaemia e.g. pale mucous membranes, tachycardia, prolonged capillary refill time etc. A patient with chronic haemorrhage (e.g. endo/ectoparasites) may not show clinical signs until their iron store is significantly depleted. As young animals have less of an iron store, they may show clinical signs relatively earlier in the disease process.
Patients can develop organ dysfunction (e.g. kidney) secondary to decreased perfusion due to hypovolaemia or microthrombi (hypercoagulable state).
Diagnostic testing
It is important to identify whether the bleeding is localised e.g. gastric ulcer or widespread e.g. coagulopathy
Why might you not see a change in PCV with blood loss and when may you start to see a change?
PCV
Whole blood loss will influence blood composition and the PCV and TP/TS. How exactly it is affected depends on how recent the blood loss was. During active
bleeding, whole blood is being lost (RBC, plasma proteins and plasma). At this stage, the actual PCV will not necessarily alter very much (Jasani, 2015) although the total blood volume will be decreased. Once compensatory mechanisms start to take an
effect, fluid moves from the interstitial space into the bloodstream- meaning the remaining RBC and proteins will be diluted (so the PCV and TP/TS will decrease). In
dogs, the spleen often contracts in response to haemorrhage meaning the PCV may remain in the normal range temporarily- the TP/TS, however, will still be reduced at this stage. This splenic response tends not to occur in cats. If there is ongoing, recurrent bleeding then the PCV will decrease.
How can you determine whether an abdominal or thoracic bleed is active or from previous?
If an abdominal or thoracic bleed is suspected, comparing the PCV of peripheral blood with the
abdominal/thoracic blood can indicate whether there is active, current bleeding or whether it has occurred previously. If there is current haemorrhage, the PCV of
peripheral blood and the thoracic/ abdominal sample will be very similar. If the haemorrhage occurred previously, the peripheral PCV could be higher, the same or less than the sample obtained by abdominocentesis or thoracocentesis. The fluid
obtained from abdominocentesis/ thoracentesis will not clot as the clotting factors will have already been consumed at the time of the haemorrhage. If blood obtained doing ‘centesis does clot, it suggests accidental penetration of an organ/ blood vessel.
Is an abdominal or thoracocentesis appropriate in an animal with a clotting disorder?
Abdominocentesis/ thoracentesis would not be appropriate in a patient with marked thrombocytopaenia or coagulopathy- therefore, before performing, a blood smear should be prepared, and an estimate made of the platelet count. If thrombocytopaenia/coagulopathy is suspected, blood samples should always be taken from peripheral veins and pressure applied for at least 5 minutes post-sampling.
What is usually seen on a haemotological test in a patient that has a coagulopathy?
With haemorrhage, usually the blood smear picture is a regenerative one with polychromasia, macrocytosis and an increased number of reticulocytes.
What clotting disorders are schistocytes usually seen with?
In cases associated with neoplasia, particularly haemangiosarcoma, or disseminated intravascular coagulation (DIC), fragments of red cells may be seen in the circulation these are known as schistocytes
How can thrombocytopaenia and haemorrhage be related?.
As platelets/ thrombocytes are integral to haemostasis, thrombocytopaenia may be the underlying cause of haemorrhage; however, thrombocytopaenia could also arise secondary to platelet consumption during severe haemorrhage
What part of a smear and what setting on the microscope can thrombocytes be analysed?
Several fields (~10) are examined in the monolayer segment of the smear under oil immersion. The monolayer segment lies between the main body of the smear and the feathered edge- it is composed of a single layer of cells.
What platelet count does each one platelet in an oil immersion field roughly equivalent to ?
Each one platelet seen in an oil immersion (x100)
field is roughly equivalent to a platelet count of 15x109platelets/L.
How many platelets should a normal blood smear have per field and what does this equate to?
Therefore, a normal blood smear should have ~ 11-15 platelets per field (x 100) - equating to a platelet
count of 165- 225 x109platelets/L
What does less that 0-3 platelets per oil immersion field equate to?
Consistently (over several fields), less than 0-3
platelets per oil immersion field equates to a very dangerously low platelet count (equivalent to 0-45x109/L)
Patients with < 5 platelets per field should be closely
monitored for evidence of active haemorrhage.
What do very large platelets suggest on a blood smear?
Very large platelets suggest thrombopoiesis e.g. a bone marrow response.
What breed of dogs can have an inherited macrothrombocytopaenia and why?
Certain breeds of dog can have inherited macrothrombocytopaenia due to a mutation.
This is common in Cavalier King Charles Spaniels, Norfolk and Cairn terriers amongst
others
How can a true platelet count be carried out?
A true platelet count may be done, manually, using a haemocytometer, commercial diluting fluid and a microscope. A commercial ammonium oxalate diluent pipette system should be used e.g. ‘Unopette Micro-Collection System for WBC and Platelet Determination’ (BD Diagnostics, 2008). This is filled as directed and lyses the red cells after 10 minutes or so. A Neubauer modified haemocytometer is then filled with the
mixture and left in a humid environment (a small covered dish with a layer of wet filter paper in the bottom) for 5-10 minutes, to allow the platelets to settle to the floor of the haemocytometer. A platelet count is performed by examining the haemocytometer
microscopically. Platelets can be differentiated from white cells by their smaller size and refractile nature. The total number of platelets, in the central major square on each side of the haemocytometer, is counted. This square is divided into 25 smaller
squares, each of which contains 16 further squares.
The average of the two major square counts is then the total platelet count in 109/L.
Normal values for dogs are 200-700x109/L and for cats are 300-800 x109/L
How can an abdominocentesis be carried out and what information can this give you?
Abdominocentesis
If abdominal bleeding is suspected, the abdomen may be examined using ultrasound (POCUS) - anechoic free fluid would be present. A peritoneal tap (abdominocentesis) should be performed to confirm the presence of the blood, unless coagulopathy/thrombocytopaenia is suspected/known. Blood that has been present in the abdomen for some time will not clot due to the clotting factors already having been used. As previously discussed, blood from a haemoabdomen may have the same PCV, lower PCV or higher PCV than the peripheral PCV depending on how
chronic the condition is
What process is checked with a platelet count and what test is evaluated?
Process Checked Screening Test What Test Evaluates
What process is checked with a platelet count and what does this test evaluate?
Primary Haemostasis
Platelet Count
Platelet numbers
What process is checked with a Buccal mucosal bleeding time and what does this test evaluate?
Primary Haemostasis
Buccal Mucosal Bleeding Time (BMBT)
Platelet numbers and function; endothelial function
What process is checked with a Platelet Function Analyser (PFA- 100) ** and what does this test evaluate?
Primary Haemostasis
Platelet Function Analyser (PFA- 100) **
Platelet function
What process is checked with a Platelet Aggregometry and what does this test evaluate?
Primary Haemostasis
Platelet Aggregometry **
Platelet function
What process is checked with a Thromboelastography (TEG) and thromboelastometry (ROTEM) **and what does this test evaluate?
Primary Haemostasis
Thromboelastography (TEG) and thromboelastometry
(ROTEM) **
Platelet numbers and function, coagulation factors, haematocrit
What process is checked with a Fibrinogen and what does this test evaluate?
Secondary Haemostasis
Fibrinogen
Fibrinogen concentration
What process is checked with a Prothrombin time and what does this test evaluate?
Secondary Haemostasis
Prothrombin time
Factors VII:TF, X, V, II and fibrinogen
What process is checked with a Activated partial thromboplastin time (aPTT) and what does this test evaluate?
Secondary Haemostasis
Activated partial thromboplastin time (aPTT)
Factors XII, XI, IX, VIII, X, V, II and fibrinogen
What process is checked with Activated clotting time (ACT) and what does this test evaluate?
Secondary Haemostasis
Activated clotting time (ACT)
Factors XII, XI, IX, VIII, X, V, II and fibrinogen
What process is checked with Thrombin time (TT) and what does this test evaluate?
Secondary Haemostasis
Thrombin time (TT) **
Fibrinogen concentration and quality
What process is checked with D-dimers and what does this test evaluate??
Fibrinolysis
D-dimers
Lysis of cross-linked fibrin
What process is checked with a Tissue plasminogen activator, TEG and ROTEM **and what does this test evaluate?
Fibrinolysis
Tissue plasminogen activator, TEG and ROTEM **
Endogenous fibrinolytic potential
What is the main test used to determine if there is an abnormality of primary hemostasis?
The main test that is used to determine if there is an abnormality of primary haemostasis is the buccal mucosal bleeding time (BMBT).
How is a buccal mucosal bleeding time test carried out?
Buccal mucosal bleeding time (BMBT) - The BMBT uses a commercial device to produce two standardised cuts to the buccal mucosa of the upper lip - 5mm long and
1mm deep. Cats may need sedation for this test. The patient is placed in lateral recumbency, the upper lip reflected, to expose the mucosal surface, and held in place by a gauze tape lightly applied around the maxilla (BSAVA, 2010) (Oakley, 2007). The
BMBT device is then placed on the mucosa and activated. The incisions are then left alone until bleeding stops- the time taken should be recorded. This is assessed by using a swab or filter paper placed near to the incisions (3-4 mm below), but not touching them- bleeding is judged to have stopped when blood stops being taken up by the clean edge of the swab/filter paper. The BMBT is taken as the mean bleeding time of the two incisions and should normally be less than 4 minutes (1.7- 3.3. minutes dogs and 1.0- 2.4 minutes in cats (BSAVA, 2010).
What does buccal mucosal bleeding time evaluate?
The BMBT evaluates primary haemostasis by assessing platelet and vascular aspects of haemostasis
What instances might a buccal mucosal bleeding time be prolonged?
Instances where BMBT may be prolonged include: • thrombocytopaenia • thrombopathia • blood vessel anomalies • von Willebrand’s disease • drug therapy e.g. aspirin
Why should a buccal mucosal bleeding time test not be performed on an animal that is thrombocytopenic?
A BMBT should NOT be performed on patients that are already known to be thrombocytopaenic- thrombocytopaenia should be confirmed on a blood smear, as previously discussed. Thrombocytopaenic animals will have a prolonged BMBT so
confirmation with the test is unnecessary.
What pathways does activated partial thromboplastin time assess?
Activated partial thromboplastin time (aPTT) assesses the function of both the intrinsic and common pathways.
What clotting factors are evaluated by assessing activated partial thromboplastin time?
Factors XII, XI, IX and VIII (intrinsic pathway) are evaluated by assessing aPTT; factor V, factor X, prothrombin (II) and/or fibrinogen (I) (common pathway) are also evaluated by assessing aPTT
Why is activated partial thromboplastin time not very sensitive?
This is not a very sensitive test, as, at least, one factor must be reduced to less than 30% of their normal values before aPTT. A dog with bleeding caused by haemophilia A, (lack of factor VIII) or von Willebrand’s disease, may have a prolonged aPTT but it is possible that it could still be within the normal reference
range. aPTT is more sensitive to heparin and DIC
What deficiencies in clotting factors does the prothrombin time test Identify?
Prothrombin time (PT)- this identifies deficiencies in the extrinsic (factor VII:TF) and common pathways (fibrinogen (I), prothrombin (II), V and X).
What does the prothrombin time test measure? and what is it very sensitive to?
It measures the time for fibrin to be produced after activation of factor VII. As with aPTT, at least one factor must be decreased by more than 30% for PT to be prolonged. Factor VII has the shortest half-life of the clotting factors, so PT maybe increased before aPTT in a patient with a coagulopathy. Vitamin K is required to activate factors II, VII, IX and X which are produced in the liver. Acquired vitamin K deficiency (rodenticide poisoning) is an example of a condition that can prolong PT (due to lack of active factor VII). Because of factor VII’s relatively short half-life, PT may be the only
clotting test to be prolonged in the early stages of vitamin K deficiency, so PT is very sensitive to vitamin K deficiency. In rodenticide toxicity PT will be elevated first - however both aPTT and PT are likely to be prolonged over time.
PT may also be prolonged due to DIC, chronic liver disease or endotoxaemia. The deficiency of factor VII will prolong PT even if there is no change in other clotting tests.
What is a point of care coagulometer?
Point of care coagulometers are now available, from a variety of companies, which can be used in practice to evaluate aPTT and PT (N.B. this link demonstrates the use of one such coagulometer). They are very useful for in-house rapid results, especially when evaluating the intrinsic and common pathways. However, as they are not 100% sensitive and specific, any results that do not fit with clinical findings should be confirmed via conventional laboratory testing . It is very important that the samples are collected and stored, and analysers are used according to the manufacturer instructions. Some require a sample to be placed in sodium citrate; others involve taking a sample from the patient and placing directly in the analyser.
For reliable information about coagulation, the sampling technique needs to be considered – a clean stick is needed, the sample should not be haemolysed and it should be handled carefully once obtained.
What is an activated clotting time test?
Activated clotting time. This is another point of care, in-house test-kit that can be used to measure activated clotting time (ACT) on a non-coagulated whole blood sample. It is a simple rapid test which identifies serious abnormalities in the intrinsic and common pathways. 2ml of blood is placed into a tube, warmed to 37°C, containing a contact activator e.g. diatomaceous earth. After careful mixing, the tube is gently tilted, at 10
second intervals, to determine if a clot has formed. Normal ACT for dogs is 60-110 seconds and for cats is 50-75 seconds.
What is a normal activated clotting time test for a dog and cat?
Normal ACT for dogs is 60-110 seconds and for cats is 50-75 seconds.
What is a d-dimers test sensitive to?
D-dimers – these are fibrin degradation products (FDPs) that are created when a fibrin clot is broken down by plasmin. They are a sensitive test for DIC
What emergency treatment may be required for a patient with hemorrhage?
A patient with serious blood loss will have signs of hypovolaemia/ hypovolaemic shock.
Vascular access should be gained, preferably via the peripheral cephalic vein, in case of an underlying coagulopathy. Blood samples should be obtained at this stage, prior to starting treatment, for PCV, TS and blood smear evaluation initially; additional haematological, biochemical and clotting evaluation may be performed once the patient is more stable. As these patients may already have significant blood loss, care needs to be taken, especially in small patients, not to worsen the anaemia. If the patient is clearly coagulopathic at presentation, it may be sensible to take all the samples required at one time to prevent further venepuncture being required. This will be the decision of the attending veterinary surgeon. If possible, further blood loss should be prevented e.g. pressure on bleeding wound. Additionally, depending on the volume and rate of blood loss, crystalloid fluids or colloids may be required. Rarely, hypertonic saline (HTS) may be used. However, it should be noted that if the patient is bleeding uncontrollably e.g. into a cavity such as the abdomen, the increase in blood pressure and cardiovascular volume from HTS administration is likely to increase the blood loss. If the animal is severely anaemic or the PCV has dropped rapidly, a whole blood transfusion may be required. For animals who are bleeding due to deficiencies in coagulation factors (e.g. secondary to anticoagulant rodenticide intoxication), fresh frozen plasma, frozen plasma or packed RBCs may be administered. (PBBUK, 2020)
If there is no access to processed blood products then a whole blood transfusion may be required. For feline patients in the UK, there is no access to a UK based feline blood bank with blood products meaning the only option for those patients is a whole
blood transfusion.
Oxygen supplementation may be required in some cases
What are the nursing considerations for a patient with haemorrhage?
The patient should be cage rested with minimal handling- deep bedding should be provided to prevent injury, including padding on the front of the kennel if they are likely to rub their face/nose or try to escape. Excessive venepuncture and other invasive
techniques should be avoided to minimise further haemorrhage and effective haemostasis should be performed (pressure should be applied for a full five minutes).
Jugular venepuncture should not be performed in patients with known or suspected abnormalities in primary or secondary haemostasis; and subcutaneous injections should be avoided. The patient should be observed closely for any deterioration/ complications e.g. ongoing/further haemorrhage, neurological signs, dyspnoea etc.
Positioning of patients with suspected abdominal masses for procedures must be performed with extreme care to prevent inducing further haemorrhage -ideally the patient will be allowed to adopt the position they are most comfortable in.
If haemorrhage into the pleural space is suspected to be the cause of dyspnoea, thoracocentesis may be required, depending on the patient’s clotting ability (for
technique see Unit 3 Outcome 2). Pericardiocentesis may be required for the patient with cardiac tamponade due to haemopericardium (also dependent on clotting ability)
What emergency treatment is required for a patient with abdominal haemorrhage?
If abdominal haemorrhage is present, a pressure abdominal wrap may be applied if considered appropriate, in some cases. Additionally, with abdominal haemorrhage, if fresh blood is not available, auto-transfusion is a treatment possible option, the abdominal blood is collected and auto-transfused back into the patient’s circulation. As the clotting factors will already have been used, this will not correct any
clotting deficiencies. It may, however, be enough to stabilise the patient whilst the
underlying problem is corrected, or additional blood products are sourced. Autotransfusion should be performed through a blood giving set with a microfilter to remove any clots
How do you treat rodenticide intoxication?
Rodenticide poisoning
In the case of rodenticide associated haemorrhage, or where rodenticide is suspected of being absorbed, vitamin K treatment will be required. It should be noted that it is no longer recommended to routinely start prophylactic vitamin K treatment as soon as
ingestion of an anticoagulant rodenticide is confirmed (VPIS,2020).
Recommendations are like other intoxications - including gastric decontamination, supportive therapy as needed and checking a baseline clotting profile (PT and APTT). The clotting profile is then checked every 24hrs for abnormalities – PT will become elevated first at which point Vitamin K therapy can begin if necessary
The actual treatment regime depends on the type of rodenticide ingested and the results of blood tests to assess clotting function (see Unit 5, outcome 3). However, it will take at least 12 hours for new clotting factors to be produced by the patient, therefore a plasma transfusion may be required initially to provide an emergency supply of these. If the patient is anaemic, then packed RBCs may be administered as well; or a whole blood transfusion may be performed. The half-life of clotting factors is short so a second plasma transfusion may be required.
Lower doses of vitamin K1 and a shorter course of treatment will be needed for patients with known first-generation rodenticide toxicity (BSAVA, 2020). Vitamin K1 is administered initially by subcutaneous injection (there is a risk of anaphylaxis with intravenous injection). The subcutaneous injection sites should be alternated and the patient’s activity restricted during this period to prevent the chance of bleeding
(BSAVA, 2020).
Modern, second generation rodenticides, such as brodifacoum, have prolonged halflives, remaining active in the body for a relatively long period- thus a longer course of vitamin K1 therapy may be needed – up to 3-4 weeks in most cases).Whilst parenteral
vitamin K1 is used for the initial treatment, oral vitamin K can be administered for the remainder of the treatment. A final prothrombin time (PT) should be assessed 2-3 days after the last planned treatment. If the PT is prolonged, another 2 weeks of vitamin K1 therapy is indicated. Following this PT should again be
performed 2-3 days after the last vitamin K1 treatment
What monitoring is required for patients with ongoing haemorrhage?
Ongoing nursing care for patients with blood loss
Once blood loss has been stopped and volume replacers administered as required, ongoing assessment of the patient’s vital signs should be instigated. This should focus on perfusion parameters- MM colour, CRT, heart rate, pulse quality and patient
mentation. In addition, blood pressure and PCV should be monitored closely to identify any ongoing blood loss as quickly as possible. Clinical examination should
include monitoring of the patient for development of DIC- in particular the patient should be monitored for signs of ecchymoses, petechiation, prolonged haemorrhage from venepuncture and/or haematuria. Bruising may develop especially on the ventral
abdomen in some patients - clipping small patches of hair to be able to visualise that can be helpful. Clear nursing orders are required e.g. if the patient is
thrombocytopaenic, it is therefore prone to spontaneous haemorrhage.
Additional tests, such as aPTT and PT, may also be required to assess response to treatment, where clotting deficiencies are suspected.
What is responsible for non-regenerative anaemia?
Non-regenerative anaemia
This is when there is a reduced or failure of erythropoiesis in the bone marrow.
What are the possible causes for non-regenerative anaemia?
Possible aetiologies
Non-regenerative anaemia could be associated with any of the following
➢ Bone marrow suppression or dysfunction associated with drug therapy e.g. chemotherapy, oestrogen, sulpha drugs, chloramphenicol and phenylbutazone
➢ Chronic organ failure (e.g. kidney disease- the kidneys are responsible for producing erythropoietin, a hormone which stimulates red cell production
(erythropoiesis) and release from the bone marrow)
➢ Infection e.g. FeLV, FIV and Ehrlichia canis are possible causes.
➢ Myelodysplasia or aplasia of the bone marrow
➢ Neoplasia of the bone marrow or metastatic infiltration of the bone marrow by neoplastic cells - myelophthisis
➢ Lead poisoning
➢ Malabsorption or nutritional deficiencies e.g. iron or vitamin B12 may be a cause of non-regenerative anaemia.
➢ Chronic disease- anaemia of chronic disease is a very common cause of nonregenerative anaemia e.g. chronic inflammation, neoplasia, endocrinopathy
etc.
How can haematological testing help with the diagnosis of non-regenerative anaemia?
Haematology
Typically, there is no or minimal evidence of regeneration. The anaemia will usually be normocytic and normochromic. If it is associated with iron loss, then it may be microcytic and hypochromic. Reticulocytes will not be present with non-regenerative
anaemia. However, with acute blood loss (haemorrhage / haemolyis), it can take 2-4
days for there to be a bone marrow response and evidence of regeneration. It is increasingly recognised that marrow-directed immunemediated disease exists, sometimes in conjunction with peripheral IMHA.
In these cases, there may be no evidence of regeneration.
Immunosuppressive therapy is often needed for weeks to months before the animal’s bone marrow becomes regenerative once again.
The following card is information on non-regenerative anaemia
Anaemia associated with chronic renal failure tends to be relatively mild - whereas it will be severe in leukaemia induced aplastic anaemia. A concurrent leucopaenia and thrombocytopaenia (pancytopaenia) may be seen with some bone marrow conditions.
Identification of the underlying cause of the non-regenerative anaemia is required- e.g. underlying kidney disease or endocrinopathy. Bone marrow biopsy may be indicated although this is not likely to be an emergency investigation.
The prognosis for non-regenerative anaemia is often poorer due to the, often, serious nature of the underlying cause e.g. neoplastic infiltration of the bone marrow.
The clinical findings will depend on the degree of the anaemia and how rapidly it has developed. Often non-regenerative anaemia develops slowly as RBCs have a relatively long lifespan (Fry, 2011). Clinical findings may be more related to the underlying condition e.g. polyuria/polydipsia with hyperadrenocorticism.
What emergency and nursing care is required for a patient with non-regenerative anaemia?
Like patients with regenerative anaemia, the focus is on supporting the cardiovascular system and maintaining an effective circulation of oxygenated blood. There is unlikely to be volume depletion (i.e. it is normovolaemic) but a packed red blood cell transfusion may be required to increase oxygen carrying capacity. A patient with chronic anaemia will have had time to adjust to the anaemia, and so the urgency for transfusion is usually less than with acute blood loss. Having chronically adjusted to the low haematocrit, the patient may be extremely anaemic on presentation e.g. PCV <15%.
What different types of blood products can be transfused?
Whole blood, packed red blood cells, plasma, and different subgroups of plasma may be administered to patients for different reasons.
Why must whole blood transfusions ideally be from in house donors?
Because of the necessary short time- scale from
collection to administration to ensure the viability of platelets and some clotting factors (PBBUK, 2020) whole blood transfusions must be from in-house donors.
Feline patients will need a fresh whole blood transfusion from a local donor in most
scenarios. However, it is now possible to import feline blood into the UK for use in
veterinary clinics.
What does canine fresh whole blood contain? How is it stored and what time frame should it be administered?
Canine Fresh Whole Blood (FWB) contains
red blood cells, platelets, leucocytes and all
plasma proteins including the labile and nonlabile clotting factors. Not refrigerated and
administered within 4-8 hours
What are the indications to use fresh whole blood?
Whole blood loss, platelet deficiency, no
access to blood components e.g. packed
RBCs
