Help, my patient is bleeding! the veterinary nurse's guide to coagulation: part 1
Anyone else find coagulation the most confusing thing in the world?
I’ll let you in on a secret - I did too for the longest time! There’s so many steps, factors and pathways… but here’s the thing.
It doesn’t really matter how bleeding happens - the most important thing is how you nurse your bleeding patient. And most of those nursing considerations will be the same, regardless of which factors, steps or pathways are affected.
In this post, I’m going to talk you through exactly how haemostasis - the method of stopping haemorrhage - works. We’ll discuss the tests we use to diagnose the various haemostatic diseases, and focus on platelet disorders. In part 2 of this post, we’ll look at coagulopathies and nursing considerations for bleeding patients.
If you want to learn even more about these patients, join me in a few weeks for the haematology nursing workshop on July 18th. We’ll work together to plan care for these patients, calculate and administer transfusions and much more! You’ll also get a free copy of the VIMN haematology guide for signing up!
Haemostasis
Haemostasis is how the body stops bleeding. We can break haemostasis down into three main stages:
Primary haemostasis
Secondary haemostasis
Fibrinolysis
Primary Haemostasis
When blood vessels become injured or damaged, the body immediately activates the haemostatic system.
Initially, the vessel contracts to reduce blood flow to the damaged area. The damage to the inner lining of the vessel (endothelium) then activates primary haemostasis.
Primary haemostasis is all about our platelets. These clump together and stick to the vessel wall to form a platelet plug.
In order for this plug to form, we need two things:
Enough platelets
Those platelets to adhere together properly
Fibrinogen (factor 1) and von Willebrand’s factor are the substances that make those platelets stick together properly. So a patient with von Willebrand’s disease has enough platelets, but they cannot clump together to stop haemorrhage - and that’s why they bleed!
The platelet plug is unstable and very short-lived (a matter of seconds), but provides a framework for a blood clot to form around.
Secondary Haemostasis
Secondary haemostasis is how the body forms this blood clot. It’s a complex, tightly-controlled cascade where different clotting factors are activated. The end result of this cascade is a fibrin-based blood clot.
There are a number of different clotting factors involved in clot formation. They are activated via two pathways - the intrinsic pathway, and the extrinsic pathway.
The intrinsic coagulation pathway is activated by blood being exposed to the damaged endothelium. This causes the activation of factor XII, which in turn activates factor XI, which causes the activation of factors IX and VIII.
The extrinsic pathway is activated by exposure of blood to tissue factor, which is a protein present on the outside of extravascular tissues. So haemorrhage outside of the vessel kicks off the extrinsic pathway. This causes the activation of factor VII.
The intrinsic and extrinsic pathways merge to form the common coagulation pathway. This pathway involves the activation of factors X, V, prothrombin, and XIII, which leads to the conversion of fibrinogen to the fibrin blood clot.
Want an easy way to remember the intrinsic pathway factors? ‘It’s not 12, it’s 11.98’ will help you remember all of the factors and the order they are activated in: factor 12, then 11, then 9, then 8.
Fibrinolysis
The final process in haemostasis is fibrinolysis.
This is how clots are broken down in the body.
As well as being able to form clots, the body needs to regulate clotting and break down clots no longer necessary, in order to restore proper blood flow.
This process occurs due to plasmin, an enzyme responsible for breaking fibrin down. Fibrin degradation products result from this process, which can be measured in the blood to diagnose conditions such as disseminated intravascular coagulation (DIC).
Common haemostatic diseases
There are a lot of different haemostatic diseases we see in practice, including:
Thrombocytopenia
Platelet function disorders (aka thrombocytopathia)
Inherited coagulation factor deficiencies
Acquired coagulopathies
In this post, we’ll be discussing our platelet disorders. Part 2 (the next post) will look at clotting factor disorders!
Thrombocytopenia
Thrombocytopenia is a decrease in circulating platelet levels. It occurs due to four mechanisms:
Decreased platelet production within the bone marrow
This is quite rare but is associated with viral infections, neoplasia, radiation therapy, cytotoxic medications and immune-mediated damage to platelet precursor cells within the bone marrow.
Increased platelet loss or consumption (use)
Loss occurs due to haemorrhage or trauma. This usually results in mild-to-moderate, self-limiting thrombocytopenia which resolves once the haemorrhage has stopped.
DIC is a classic example of platelet consumption. Systemic diseases activate haemostatic mechanisms in the body, causing lots of tiny clots to form. This uses up the body’s platelets and coagulation factors.
Increased platelet destruction
This is the most common cause of thrombocytopenia we see in practice. It is usually caused by the immune system (immune-mediated thrombocytopenia or IMTP). IMTP can be a primary or idiopathic condition or occur secondary to various infections, neoplasia or the administration of some medications.
Sequestration of platelets
Platelet sequestration is a rare cause of thrombocytopenia. It includes hypersplenism (when platelets become sequestered within the spleen). Extreme hypothermia may also cause sequestration of platelets.
It is also important to remember that certain breeds have normal or non-clinical thrombocytopenia – these include greyhounds and cavalier King Charles spaniels.
Cavaliers also have macro-platelets (large platelets) commonly present within the bloodstream, which can be identified easily on blood smear examination.
These can make interpreting an automated platelet count challenging, as the analyser may identify them as other cells, due to their large size. For this reason, it is always best to double-check your automated counts with a blood smear examination and manual estimate, when assessing any patient with a platelet disorder.
Clinical Signs
Patients with thrombocytopenia typically present with evidence of bleeding, and signs associated with haemorrhage. These include:
Petechiation – pinpoint haemorrhage on mucous membranes
Ecchymoses – small skin bruises, classically seen on the ventral abdomen
Scleral haemorrhage
Melena
Epistaxis
Haematuria
Gingival bleeding
Lethargy
Exercise intolerance
Anorexia
Weakness
Collapse
It is important to collect a full history on arrival at the clinic, including:
Travel history
Any previous or current medications
Potential toxin exposure
Vaccination/parasite treatment status
In order to rule in or out any underlying causes. In cases of severe haemorrhage, these patients may present as a medical emergency with significant anaemia and hypovolaemia.
Diagnostics
We perform a LOT of different tests in our haematology patients! It’s really important that we understand what these tell us, and why we do them.
For the thrombocytopenic patient, we’ll perform:
A complete blood count
A blood smear examination and manual platelet estimate
Infectious disease testing (e.g. 4Dx)
+/- Chest X-rays
+/- Abdominal ultrasound (to identify an underlying cause where IMTP is suspected)
In order to investigate haemorrhage, additional coagulation testing may also be performed (such as aPTT and PT). As IMTP is frequently seen in conjunction with IMHA (Evans syndrome), specific IMHA diagnostics like an in-saline agglutination test may also be performed.
Treatment and nursing care
Treatment of IMTP involves suppressing the immune system, in order to stop it attacking the body’s own platelets.
This is achieved through using combination therapy, in order to minimise the doses needed, and therefore the side effects seen, of any one agent.
Common medications include prednisolone +/- mycophenolate, ciclosporin, azathioprine or cyclophosphamide.
Some of these medications are cytotoxic, and so require careful handling and administration, both within the clinic and at home.
Clients should be given appropriate advice when handling these medications, and the patients should be carefully managed in the hospital, including their saliva and eliminations.
Vincristine, as well as being used to manage common cancers, can also be used in low doses to stimulate platelet release from the bone marrow. This should be done so carefully, with medications prepared in full PPE within a secure area. A closed system transfer device should be used for administration, in order to prevent environmental contamination with a cytotoxic drug, and a new, first-stick IV catheter should be placed ahead of vincristine administration.
In patients who present with severe haemorrhage secondary to thrombocytopenia, a blood product transfusion may be required.
The only reliable source of platelets available in the UK is fresh whole blood, collected and transfused within 4 hours. After this time, platelets are considered non-viable, so if whole blood is being lost and platelet replacement is required, a stored blood product is not ideal.
Other supportive treatments include intravenous fluid therapy, antiemetics, and gastroprotectant agents as necessary, based on the individual patient and their clinical signs.
Thrombocytopathia
Thrombocytopathia is platelet dysfunction. These patients have enough platelets, but they don’t work properly.
There are several causes, including:
Inherited defects
The administration of certain medications
Von Willebrand’s Disease
The classic example of thrombocytopathia is von Willebrand’s disease (vWD).
This is the most common inherited haemostatic defect in dogs and is seen most commonly in Dobermans. A number of other breeds can also be affected, including Daschunds, Bernese mountain dogs, Airedale terriers and golden retrievers.
Von Willebrand’s disease is associated with a deficiency of von Willebrand’s factor (vWF). As we discussed earlier, vWF is necessary for platelet adhesion and the formation of a platelet plug. This initially stops haemorrhage, and creates an attachment site for the fibrin blood clot.
If vWF is deficient, haemostasis cannot be effectively initiated and ongoing haemorrhage results.
Clinical Signs
The clinical signs of von Willebrand’s disease are similar to thrombocytopenia; however, petechial haemorrhage is uncommon.
Other signs include prolonged oestral haemorrhage in intact female dogs, cutaneous bleeding, and prolonged haemorrhage after surgery or injury.
Diagnosis
Von Willebrand’s disease is diagnosed by confirming low levels of plasma von Willebrand’s factor. Other diagnostic tests commonly performed include:
Platelet count (which should be normal or demonstrate mild-to-moderate reductions where haemorrhage has recently occurred)
Coagulation times (which should be normal)
Buccal mucosal bleeding time (which should be prolonged)
Treatment
Treatment of vWD is aimed at stopping any active haemorrhage and replacing von Willebrand’s factor.
This is achieved through the administration of fresh frozen plasma or cryoprecipitate, both of which reliably contain wVF.
Desmopressin (yes, anti-diuretic hormone!) has also been shown to stimulate vWF release, and is recommended as a pre-surgical treatment in von Willebrand’s patients undergoing surgery.
So that’s an overview of how haemorrhage stops in our patients, and the common platelet disorders that we see. But remember, don’t get bogged down in all of those factors and pathways - the most important thing is how we nurse our bleeding patients. And that’s exactly what we’ll be talking about in our haematology workshop on July 18th! If you’ve not got your ticket yet, grab it here. And be sure to join me for part 2 of this post, where we’ll focus on coagulation disorders and nursing the bleeding patient!
References
Day, M. and Kohn, B. 2012. BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine. Gloucester: BSAVA.
Merrill, L. 2012. Small Animal Internal Medicine for Veterinary Technicians and Nurses. Iowa: Wiley-Blackwell.
