Haemostasis and Thrombosis Flashcards
The patient has a bleeding tendency if there is a problem with the following structures/cells/factors:
Endothelial surface
Platelets
Von Willebrand Factor
Coagulation factors
The patient has a clotting tendency if reduced or absent:
Natural anticoagulants
What do platelets release during the first response to injury: blood vessel constriction?
Serotonin (5HT)
Thromboxane A2
When the vessel wall is damaged, what is exposed?
Collagen
How can platelets bind to the exposed collagen of the endothelium?
Directly by GP1a (glycoprotein) receptor
Through von Willebrand factor using GP1b receptor
Which clotting factor is von Willebrand factor a main carrier of?
VIII
How does von Willebrand factor help platelets bind together to form a platelet plug?
vWF binding to GP1b platelet receptor leads to the release of fibrinogen which works together with vWF to add more platelets
What is the purpose of the common pathway in the coagulation cascade?
Formation of fibrin mesh
What is involved in the common pathway cascade?
CF10a activates CF5
CF5a activates thrombin and then breaks down fibrinogen into fibrin
What test is the intrinsic pathway of the coagulation cascade represented by?
aPTT blood test
What is involved in the intrinsic pathway cascade that goes on to activate the common pathway?
CF12a activates CF11 followed by CF9 then CF8
Where does the tissue factor that activates coagulation in the body come from?
Activated endothelium
White cells in the bloodstream during infection or sepsis
What happens during the extrinsic pathway of the coagulation cascade which then leads to the common pathway?
Tissue factor binds to and activates CF7
What do we need for healthy coagulation?
Platelets - normal number & normal function
Von Willebrand Factor
Coagulation factors
Clot stability
What steps to take when meeting a patient with a known bleeding disorder?
- Patient should tell you
- Registered at the local haemophilia centre
- Carry haemorrhagic states card/necklace/bracelet
- Bleeding history should be consistent with clinical severity of disorder
What is vWF for?
Help platelets bind to endothelial surface
Help platelets bind together to form a platelet plug
What are coagulation factors needed for?
Form fibrin mesh
What is haemophilia?
Genetically inherited X-linked condition
Congenital deficiency in factor 8 (Haem. A) and factor 9 (Haem. B)
Unable to stabilise the platelet plug as fibrin strands cannot be formed properly
Why is the vast majority of women with mutation for haemophilia less likely to be affected with symptoms/problems?
Usually, they have the mutation on only one X chromosome and the other one will be unmutated
How do boys get affected by haemophilia?
They inherit their mother’s mutated X chromosome
Y chromosome unable to counter the mutation
Which haemophilia is more common?
Haemophilia A
What is the concentration of coagulation factor (8 or 9) that will determine the diagnosis of haemophilia?
<50%
What is the concentration of the coagulation factor for a patient with severe haemophilia presenting spontaneous bleeding episodes predominantly in the joints of muscles?
<1%
What is the range of the coagulation factor concentration for patients presenting with severe bleeding episodes after surgery and slight bleeding episodes after minor trauma?
5 to 25%
What is the range of the coagulation factor concentration for patients presenting with severe bleeding episodes even after slight trauma?
1 to 5%
What will young patients with haemophilia that don’t get treated develop?
Severe arthritis and arthropathy in their joints
What was given to patients with haemophilia to deal with severe bleeding starting from 1900, 1965, and 1970s?
1900 Whole blood transfusions
1965 Cryoprecipitate (contains clotting factors)
1970s Factor VIII concentrates (derived from cryoprecipitate)
1970s Anti-fibrinolytic therapy (tranexamic acid)
In the 1970s, what was noticed in patients who received transfusions when they were tested for their liver function?
Abnormal liver function tests indicative of Hepatitis C (‘Non-A, Non-B Hepatitis’) which was transmitted through the plasma treatment the patients were receiving
What was first identified in the homosexual male population in 1981?
AIDS
What year was AIDS first identified in patients with haemophilia?
1982
What viruses could be transmitted to patients through plasma products?
Hepatitis C virus
Human immunodeficiency virus (HIV)
Which year did screening for anti-HIV in blood donors start?
1985
Apart from screening for anti-HIV in blood donors, what other precautionary steps were taken in the late 1980s and early 1990s to prevent the spread of viruses through plasma products?
Virus inactivation of factor concentrates
Anti-HCV tests
Screening for anti-HCV in blood donors
Plasma-derived products are no longer given to patients with haemophilia A as clotting factor ___ is now made in the lab. In 1984, the cloning of the clotting factor ___ gene began. In 1987, the clinical trials of recombinant clotting factor ___ replacement began. The treatments were licensed in the early 1990s and by the end of the 1990s they were being given throughout the UK.
VIII
What does Hemlibra aka emicuzimab do?
It is a new drug that does the job of factor VIII but not actually replacing it as it is an antibody that binds factor 9 and factor 10 and activates them leading to the formation of fibrin strands
Is Hemlibra/emicuzimab injected into the vein or into the skin?
Into the skin
How often is Hemlibra/emicuzimab given?
Once every 2 weeks
Occasionally once every 3 weeks
What was given to the first Newcastle patient with Haemophilia B undergoing gene therapy?
An adenovirus factor that has resulted in them being able to produce their own factor IX
How to manage a patient with haemophilia during surgery?
- Close liaison with haemophilia centre
- DDAVP infusion for mild haemophiliacs
- Factor VIII/IX replacement for moderate/severe haemophiliacs
- Atraumatic technique
- Secure local haemostasis
- Oral tranexamic acid or tranexamic acid mouthwash (antifibrinolytic)
How common is von Willebrand’s disease?
Very common, affecting up to 1% of our population
What does ‘variable phenotype’ mean when describing the von Willebrand disease?
Quite a few mutations that can cause this disease - some can cause a lot of problems and others very little
How to recognise/when to suspect someone with von Willebrand disease?
Bruising since childhood
Evidence of mucosal bleeding such as nosebleeds, menorrhagia, GI bleeding
Bleeding post-surgery and post-trauma
What are the three different types of von Willebrand disease?
Type I - mild deficiency in VWD (very common; typically asymptomatic until post-surgery)
Type II - qualitative not quantitative problem (normal VWF level but maybe can’t bind platelets very well or can’t find endothelium very well)
Type III - severe deficiency in VWD (very rare; can behave like a haemophilia patient since VWF is a factor VIII carrier and they might have bleeding into joints and into muscles as well as mucosal bleeding)
How to manage a patient with vWD during surgery?
- Close liaison with haemophilia centre
- DDAVP infusion for type I vWD
- vWF replacement
- Atraumatic technique
- Secure local haemostasis
- Oral tranexamic acid or tranexamic acid mouthwash
If coming across a patient with low platelet count during surgery consultation, what needs to be done?
Find out the cause
If surgery is not urgent, delay it until the cause is determined so it can be reversed
In general, dental surgery is safe if the platelet count is above 50 x10^9/L
What are the possible causes of low platelet count?
Functional defect
Antiplatelet drugs such as aspirin or clopidogrel
How to manage a patient with a platelet problem during surgery?
- Close liaison with haemophilia centre
- May need platelet transfusion or DDAVP
- Atraumatic technique
- Secure local haemostasis
- Oral tranexamic acid or tranexamic acid mouthwash
What chemical component was found in fermented clover that the cattle were eating causing them to die of haemorrhage following surgery, that was then used to make warfarin?
Coumarin
What is the normal range of INR in someone not on warfarin?
<1.5
What is the normal range of INR for patients receiving warfarin?
2 to 3
What is the main action of warfarin?
Inhibit thrombin
At what range of INR would be associated with an exponentially increased risk of major bleeding?
> 4.5
What are the options of managing patients taking warfarin during dental surgery?
Don’t alter warfarin and just carry on with surgery
Check that the patient is not over-anticoagulated by measuring INR is not over 4.5
Omit warfarin until INR is below 2 or 1.5 then only proceed with surgery
The risk of significant bleeding with a stable INR between the range of __ to __ is very _____ and the risk of thrombosis may be ________ in patients in whom oral anticoagulants are temporarily discontinued.
2 to 4, small, increased
Should oral anticoagulants be discontinued in the majority of patients requiring outpatient dental surgery including dental extraction (provided that they’re stable with an INR 2 to 4)?
No
For patients stable anticoagulated on warfarin (INR ___ to ____) and who are prescribed a single dose of antibiotics as prophylaxis against _________, there is no necessity to alter their anticoagulant regimen.
2 to 4, endocarditis
How can the risk of bleeding be minimised post-dental surgery?
Use of oxidised cellulose (Surgicel) or collagen sponges and sutures
5% tranexamic acid mouthwashes used 4x per day for 2 days
What is the recommended time range to check the INR of a patient with a bleeding disorder prior to dental surgery?
Within 72 hours
What should not be prescribed to patients taking warfarin as analgesia following dental surgery?
Non-selective NSAIDs
COX-2 inhibitors
An example of DOAC is dabigatran. It is a ___-______ which works by reversibly inhibiting ________. Its peak plasma levels is in ___ hours. It has a half-life of __ to __ hours if the renal function of the patient is normal. It is excreted ___________.
Pro-drug, thrombin, 6, 12 to 14, renally
An example of DOAC is the Xa inhibitors. Examples of Xa inhibitors include ________, ________ and edoxaban. They can bind directly to Xa (activated factor 10) and reach peak plasma levels at ___ to ___ hours. Rivaroxaban is ____ excreted. Apixaban is mainly _______ cleared but some _____ (30%). The half-life of rivaroxaban is ___ hours and apixaban is ___ hours.
Apixaban, rivaroxaban, 2 to 4, renally, hepatically, renal, 8, 12.
Is pre-operative testing required for patients taking DOACs?
No
How to manage a patient taking DOACs when multiple extractions and surgical procedures are needed?
When practical, limit extractions to 3 to 4 teeth. Assess bleeding after first tooth.
How to manage patients on short courses of anticoagulant requiring dental surgery?
Delay any elective treatment until patient is recovered
What should be done if a patient taking DOACs presents with a post-operative haemorrhage?
Contact the haematology department for advice
Which haemophilia is also known as Christmas disease?
Haem. B (Factor IX deficiency)
