PATHOLOGY - Haemostatic Disorders Flashcards
Describe primary haemostasis
Primary haemostasis is when there is damage to the endothelium, triggering vasoconstriction and platelet plug formation. Where there is damage to the endothelium, these damaged endothelial cells release von willebrands factors which come into contact with and bind to the now exposed subendothelial collagen. Circulating platelets bind to these von willebrands factors, activating the platelets which will release ADP and thromboxane A which attract and activate more platelets which will aggregate to form a platelet plug as well as a scaffolding system allowing for the binding of fibrinogen
Describe secondary haemostasis
Secondary haemostasis is where the extrinsic coagulation cascade is triggered by exposure of subendothelial tissue factor and the intrinsic coagulation cascade is triggered by exposure of subendothelial collagen. Both of these cascades will trigger the final common pathway which converts prothrombin the thrombin through the action of thromboplastin enzymes, and thrombin converts fibrinogen to fibrin which forms a cross-linked fibrin network to form a clot
Which coagulation factors are involved in the extrinsic coagulation cascade?
Factor VII
Factor X
Which coagulation factors are involved in the intrinsic coagulation cascade?
Factor VIII
Factor IX
Factor X
Factor XI
Factor XII
Which coagulation factors are involved in the final common pathway?
Factor I
Factor II
Factor XIII
Which factors are involved in modulating coagulation?
Antithrombin
Tissue factor pathway inhibitor
Protein C - Protein S system
Describe tertiary haemostasis
Tertiary haemostasis is the process of fibrinolysis where the presence of fibrin triggers enzyme t-PA which converts circulating plasminogen into plasmin which breaks down the fibrin clot
Which history questions should you consider when investigating a possible haemostatic disorder case?
Has the patient had any exposure to anticoagulant rodenticides?
Is the patient regularly wormed?
Is there a history of travel outside of the UK?
Has the patient been systemically ill in the run up to the bleeding?
What can be indicated by young animals presenting with spontaneous bleeding?
Congenital haemostatic disorders
List four examples of primary haemostasic disorders
Thrombocytopenia
Thrombocytopathia
Von willebrands disease
Vasculopathies
Which two laboratory tests can you do to investigate primary haemostatic disorders?
Manual and automated platelet count
Buccal mucosal bleeding time (BMBT)
What would be an adequate number of platelets when doing a manual platelet count using a blood smear?
10 to 15 platelets per x100 power view would be an adequate number of platelets
What value would be indicative of thrombocytopenia when using an automated analyser for platelet counts?
Less than 50 x 10^9/litre
At what value would spontaneous bleeding begin when using an automated analyser for platelet counts?
Less than 30 x 10^9/litre
Why is it so important to check the blood smear as well as the automated platelet count value?
It is important to check the smear for platelet clumping which could lead to inaccurate values counted by the automated analyser
What should you be aware of when doing automated platelet counts in cats?
Cat platelets are approximately the size of erythrocytes and thus the platelets are often miscounted by automated analysers
Which dog breed normally has a low platelet count?
Cavalier King Charles Spaniels
This low platelet count is normal for them
What can be tested by doing a buccal mucosal bleeding test (BMBT)?
Platelet function
How do you carry out a buccal mucosal bleeding test (BMBT)?
Using a gadget to make a uniform incision into the buccal mucosa and time how long is takes for the mucosa to stop bleeding. The bleeding should cease within 2 to 4 minutes
What are six key clinical signs of thrombocytopenia?
Petechiation
Ecchymoses
Epistaxis
Gastrointestinal bleeding (i.e. meleana)
Bleeding from gums
Clinical signs associated with haemorrhagic anaemia
Thrombocytopenia is heavily associated with mucosal bleeding
What are four possible causes of thrombocytopenia?
Immune-mediated thrombocytopenia (IMTP)
Primary bone marrow disease
Infectious diseases
Increased platelet consumption
What is the signalement for immune-mediated thrombocytopenia (IMTP)?
Medium sized dogs usually between 4 - 5 years old
Which breed of dog is predisposed to immune-mediated thrombocytopenia (IMTP)?
Cocker Spaniels
What are the typical clinical signs of immune-mediated thrombocytopenia (IMTP)?
Signs of a primary haemostatic disorder
Anaemia
What causes anaemia in immune-mediated thrombocytopenia (IMTP)?
Immune-mediated thrombocytopenia (IMTP) causes spontaneous bleeding throughout the body which can cause anaemia
What is Evan’s syndrome?
Evan’s syndrome is a very rare syndrome where immune-mediated thrombocytopenia (IMTP) presents concurrently with immune-mediated haemolytic anaemia (IMHA)
How do you diagnose immune-mediated thrombocytopenia (IMTP)?
- Detect thrombocytopenia on a platelet count - tends to have a very low platelet count of less than 30 x 10^9/litre
- Exclude any other causes of thrombocytopenia
How do you manage and treat patients with immune-mediated thrombocytopenia (IMTP)?
Gentle handling is very important
Blood transfusion if severly anaemic
Immunosuppressive therapy
Low dose vincristine
Omeprazole
What can you administer to immune-mediated thrombocytopenia (IMTP) patients that are refractory to immunosuppressive treatment?
Human intravenous immunoglobulins
Why would you administer low dose vincristine to patients with immune-mediated thrombocytopenia (IMTP)?
Vincristine stimulates platelet release from the bone marrow
Why would you administer omeprazole to patients with immune-mediated thrombocytopenia (IMTP)?
Immune-mediated thrombocytopenia (IMTP) can cause severe gastrointestinal bleeding and since steroids are being administered as immunosuppressive therapy, they can cause gastrointestinal ulceration which can also cause bleeding. Omeprazole protects the GI tract from ulceration
What is the prognosis for patients with immune-mediated thrombocytopenia (IMTP)?
Immune-mediated thrombocytopenia (IMTP) causes spontaneous bleeding which can eventually cause death
What would be a key indicator of thrombocytopenia caused by primary bone marrow disease?
If other cell lines are affected, i.e. there is a pancytopenia or bicytopenia, this can indicate primary bone marrow disease
Which infectious agent can cause thrombocytopenia?
Anaplasmsa
Anaplasma can be carried by ixodes ricinus and dermacentor reticulatus ticks so it is important to consider tick history
List two examples of things that can cause increased platelet consumption and thrombocytopenia
Disseminated intravascular coagulation (DIC)
Severe blood loss
What are four key clinical signs of von willebrands disease?
Remeber von willebrands is congenital
Prolonged bleeding at surgical sites i.e. after neutering
Prolonged bleeding at oestrus
Prolonged bleeding after losing deciduous teeth
Clinical signs associated with haemorrhagic anaemia
How do you diagnose von willebrands disease?
Normal platelet count
Normal coagulation tests
Prolonged buccal mucosal bleeding test (BMBT)
Send a sample to an external lab to test for reduced von willebrands
Which breed of dog is predisposed to von willebrands disease?
Dobermans
How do you treat and manage von willebrands disease?
Desmopressin (DDAVP)
Cryoprecipitate
When is cryoprecipitate particularly good for managing von willebrands disease?
Cryoprecipitate is a portion of plasma rich in von willebrands factors which can be useful to administer prior to surgery in patients with von willebrands disease
List three examples of secondary haemostasic disorders (also known as coagulopathies)
Anticoagulant rodenticide toxicity
Liver failure
Haemophilia
What are four key clinical signs of coagulopathy?
Haematomas
Haemoarthrosis
Bleeding into body cavities i.e. haemoabdomen, haemothorax
Clinical signs associated with haemorrhagic anaemia
Which three laboratory tests can you do to investigate secondary haemostatic disorders/coagulopathies?
Prothrombin time (PT)
Activated partial thromboplastin time (aPTT)
Fibrinogen levels
What is evaluated by a prothrombin time (PT) test?
Extrinsic coagulation cascade
Final common pathway
Coagulation factor VII
What is evaluated by an activated partial thromboplastin time (aPTT)?
Intrinsic coagulation cascade
Final common pathway
Coagulation factors VIII, IX, XI, XII
What is the mechanism of action for anticoagulant rodenticides?
Anticoagulant rodenticides are slowly absorbed by the gastrointestinal tract and mechanically inhibit an enzyme which is crucial for the production of vitamin K1, a necessary component for clotting factors II, VII, IX and X. When the production of these clotting factors in the liver is inhibited, prothrombin cannot be adequately converted to thrombin, and coagulopathy results
What are the clinical signs of anticoagulant rodenticide poisoning?
Clinical signs associated with a coagulopathy
May be anaemic
May be thrombocytopenic
Which laboratory tests should you do to diagnose anticoagulant rodenticide poisoning?
Prolonged prothrombin time (PT)
Prolonged activated partial thromboplastin time (aPTT)
(T/F) Thrombocytopenia caused by blood loss would not have an automated platelet count of less than 50 x 10^9/litre
TRUE.
How to you treat/manage patients with anticoagulant rodenticide poisoning?
Vitamin K1
Goal directed fluid therapy
Whole blood transfusion if severely anaemic
Fresh frozen plasma transfusion to replace coag factors
Which liver diseases can cause coagulopathies?
Severe/chronic cholestasis
End-stage liver disease
How can severe/chronic cholestasis cause a coagulopathy?
Cholestasis reduces enterohepatic circulation of bile acids and subsequently reduces the absorption of vitamin K1 in the intestine, which is essential for the production of coagulation factors
How can end-stage liver disease cause a coagulopathy?
End-stage liver disease reduces the production of coagulation factors
What laboratory tests should you do to diagnose a coagulopathy secondary to liver disease?
Prolonged prothrombin time (PT)
Prolonged activated partial thromboplastin time (aPTT)
Biochemistry to assess for increased liver enzymes, hyperbilirubinaemia and assess for decreased proteins
Why do you get decreased urea and creatinine levels in patients with liver disease?
The liver synthesises urea and creatinine
What should you do before any intervention in patients with liver disease?
Before any intervention (such as surgery) in patients with liver disease, you should do a PT and aPTT to see if they have a coagulopathy as this will prolong their clotting time following the procedure and you may need to alter your treatment plan
How do you treat and manage coagulopathy secondary to liver disease?
Manage/treat the underlying liver disease
Vitamin K1
Whole blood transfusion if severely anaemic
Fresh frozen plasma transfusion to replace coag factors
What are the two classifications of haemophilia?
Haemophilia A
Haemophilia B
Which coagulation factor is affected by haemophilia A?
Coagulation factor VIII
Which coagulation factor is affected by haemophilia B?
Coagulation factor IX
Which dog breed is predisposed to haemophilia?
Remember haemophilia is congenital
German Shepherds
How do you diagnose haemophilia A and B?
Prolonged activated partial thromboplastin (aPTT)
Normal prothrombin time (PT)
What is haegman factor deficiency?
Haegman factor deficiency is a condition seen in cats where there is a deficiency in coagulation factor XII deficiency which caused a prolonged aPTT however there is no bleeding associated with this condition
Which three laboratory tests can be done to investigate tertiary haemostatic disorders?
D-dimers
Fibrin degredation products
Thrombo-elastography (TEG)
Has to be done in an external lab
What is thrombo-elastography (TEG)?
Thrombo-elastography (TEG) measures whole blood capability to make and sustain clot formation
Give an example of a tertiary haemostatic disorder
Hyperfibrinolysis
Which dog breed is predisposed to hyperfibrinolysis?
Greyhounds
What should you administer to greyhounds prior to surgery and why?
Administer tranexamic acid to greyhounds prophylactically as tranexamic acid is a fibrinolysis inhibitor and will reduce the risk fo excessive bleeding during surgery
List four examples of more complex or ‘mixed’ haemostatic disorders
Disseminated intravascular coagulation (DIC)
Angiostrongylus vasorum infection
Sepsis
Trauma associated coagulopathy
What is disseminated intravascular coagulation (DIC)?
Disseminated intravascular coagulation (DIC) is an aquired syndrome characterised by the dysfunction of the normal regulatory mechanisms of the coagulation and fibrinolysis resulting in an unregulated production of thrombin resulting in the formation of intravascular thrombi and the eventual depletion of platelets and coagulation factors leading to haemorrhage
What causes disseminated intravascular coagulation (DIC)?
Disseminated intravascular coagulation (DIC) is caused by widespread endothelial cell damage and the release of thromboplastins which convert prothrombin to thrombin
What are the three main causes of disseminated intravascular coagulation (DIC)?
Neoplasia
Systemic inflammation
Sepsis
How do you diagnose disseminated intravascular coagulation (DIC)?
Prolonged prothrombin time (PT)
Prolonged activated partial thromboplastin time (aPTT)
Platelet count to detect thrombocytopenia
Decreased fibrinogen
Increased D-dimers
Increased fibrin degredation products
How do you treat and manage disseminated intravascular coagulation (DIC)?
Treat the underlying cause
Supportive care of organs prone to thrombi, ischaemia and haemorrhage
Whole blood transfusion
Fresh frozen plasma transfusion
What is the prognosis for disseminated intravascular coagulation (DIC)?
Very poor prognosis
What are the clinical signs of angiostrongylus vasorum infection?
Haemostatic signs
Cardiorespiratory signs
Sometimes neurological signs
How do you diagnose angiostronglylus vasorum infection?
Faecal Baermann’s test for L1 larvae
Prolonged prothrombin test (PT)
Prolonged activated partial thromboplastin time test (aPTT)
Thrombocytopenia
Low fibrinogen levels
Be aware there may not be haemostatic changes
How do you treat and manage angiostrongylus vasorum infections?
Antiparasitic drugs
Supportive care for haemorrhage (transfusion)
Tranexamic acid
Which antiparasitic drugs can you use to treat angiostrongylus vasorum?
Moxidectin
Imadicloprid
What is tranexamic acid?
Tranexamic acid is a fibrinolysis inhibitor
