SCD Acquired bleeding disorders Flashcards
What is prolonged bleeding?
- continues beyond 12 hours
- causes the patient to return to the dental surgery or to A&E department
- results in large haematoma or ecchymosis (bruising) within the soft tissues
- requires transfusion
List some extraoral features of a prolonged bleed
- purpura
- petechiae
What is purpura?
this is a discolouration that occurs in the skin and mucous membranes due to haemorrhage from small blood vessels
What are the main features of purpura ?
- does not blanch
- usually measures 0.3-1cm
What is petechiae?
these are small purpuric lesions which usually measure up to 2mm
Petechiae are usually associated with…
- underlying acquired disorder of platelets
or
- underlying acquired disorder of coagulation
Outline instances where petechiae are commonly seen
children or older people as a result of
* injury
* trauma
* ageing skin
* bacterial infection
What special test is particularly valuable for acquired bleeding disorders (e.g. patients on anticoagulant medication)?
prothrombin time (PT)
What are the main uses of prothrombin time (PT) tests?
determine clotting ability in patients on warfarin or patients with liver damage
What is the reference range of PT ?
12-15 seconds
What is the normal range for INR?
0.8-1.2
What clotting factors does the PT measure?
II, V, VII, X
(2, 5, 7, 10)
as well as fibrinogen
(factor 2 is prothrombin)
PT is used in conjuction with …
APTT
Activated partial thromboplastin clotting time
What drug therapies can result in the development of bleeding disorders?
- antiplatelet drugs
- anticoagulants
- corticosteroids
- chemotherapy
Antiplatelet drugs offer great benefit to patients with …
ischaemic heart disease
What is the main role of antiplatelet drug therapy?
to prevent thrombosis formation in atheroscletotic arteries which often lead to major complications such as ischaemic heart disease, stroke, intermittent claudation in limbs and heart failure
What represents the final common pathway of platelet aggregation?
binding of fibrinogen to gpIIb/IIIa
List the most commonly used antiplatelet drugs
- aspirin
- other NSAIDs
- clopidogrel
- dipyradamole
- fibrinogen receptor inhibitors
What is the duration of action of aspirin? Why is this
8-10 days
Irreversibly binds to COX-1 in platelets
therefore it lasts the lifespan of aforementioned platelets; lifespan is usually 7-10 days
What is the MOA of aspirin?
irreversibly inhibits COX-1 in platelets
preventing production of TXA2
What is the role of TXA2 ?
- potent vasoconstrictor
- platelet aggregant
Following use of aspirin, platelet aggregation can occur by day 4 in 80% of cases. True or false
What is this indicative of ?
True
This shows that aspirin only has an effect on platelet function but not on platelet count
What is the usual oral prescription of aspirin?
75-300mg
Outline indications for use of aspirin
- prevent thrombotic cardiovascular or cerebrovascular disease
- following CABG / coronary bypass surgery
Briefly describe the effect of NSAIDs such as ibuprofen and diclofenac have on platelet aggregation and function
they have a reversible on platelet aggregation and function
Why are NSAIDs such as ibuprofen and diclofenac not used clinically for their antiplatelet action?
this is because their effects last as long as the half life of the drug
What is the MOA of clopidogrel?
inhibition of ADP signalling and thus reduces platelet activation
Metabolised by liver and binds to P2Y1 receptors (ADP platelet receptors) thus reducing platelet activation
What is th MOA of dipyradamole?
inhibition of phosphodiesterase and inactivation of cAMP
What is the clinical use of clopidogrel?
- prevention of athero-thtombotic events in patients who suffer with MI, ischaemic stroke or in PAD
peripheral artery disease
State some instances when clopidogrel can be used in conjunction with aspirin
- unstable angina
- following insertion of coronary artery stent (unlicensed indication)
Upon cessation of clopidogrel, platelet function recovers fully after ____ days.
2
What can modified release preparations of clopidogrel be used for?
secondary prevention of
* ischaemic strokes
* transient ischaemic attacks
Clopidogrel has an effect on APTT. What is the consequence of this?
it has an effect on post-operative bleeding
According to UKMI guidelines, what clinical conditions require patients taking antiplatelet medication to be referred to secondary care/specialist service ?
- dual antiplatelet therapy
- liver impairment and/or alcoholism
- renal failure
- thrombocytopenia (reduction of platelet count) / other haemostasis disorder
- patients receiving a course of cytotoxic medication
What are the most common coumarins (anticoagulants)?
warfarin
followed by heparin
Warfarin is a true derivative of courmarin. True or false
True
What is coumarin?
this is a chemical that is naturally found in plants
What is the MOA of warfarin ?
inhibits biosynthesis of vitamin K dependent clotting factors II, VII, IX, X
Whta is the effect of warfarin on PT and APTT?
prolongs PT and APTT
When is the maximal effect of warfarin seen ?
at 36 hours
How is the activity of warfarin expressed clinically?
INR (international normalised ratio) which is the PT ratio
What should the INR of an individual not taking warfarin be?
1.0
How is the effect of warfarin reversed?
administration of vitamin K
Give examples of drugs that can interact with warfarin
- antibiotics- metronidazole, tetracyclin
- antifungals- miconazole, fluconazole, ketoconazole
- analgesics- aspirin and NSAIDs
- antidiabetics- chlropromamide
- antiepileptics- phenytoin
- homeopatic medications e.g. St John Wort
- some foods such as grape fruit juice
What effect can high protein bound drugs have on warfarin?
- displace warfarin (from albumin)
- causes an increase in serum/plasma warfarin thus increasing its effect
- increase in INR
Give examples of highly protein bound drugs that can impact the action of warfarin
- simvastatin
- NSAIDs
Briefly describe the effect of metronidazole and antifungals on warfarin
- they potentiate the effect of warfarin by decreasing its metabolism
- [through competition for specific liver enzyme for metabolism]
What is the effect of broad spectrum anitbiotics on warfarin?
decrease the gut bacterial flora
decrease synthesis of vitamin K?
increase INR; increase the effect of warfarin
What is the effect of leafy foods on warfarin?
they contain vitamin K so they reduce the effect of warfarin
What is the effect of grape fruit on warfarin?
increases the effect due to competition with liver CYP450 enzyme
What is the effect of hyperthyroidism on warfarin?
increase the effect of warfarin
this may be due to a change in rate of metabolism of the clotting factors
Why is discontinuing warfarin a few days prior to dental surgery no longer recommended?
this is because it increases the risk of thrombo-embolic events
What INR is recommended for patients on anticoagulants to safely receive dental treatment?
4.0 or below
What course of action should be taken for a patient with an INR of >4.0 requiring invasive dental treatment ?
- consultation required with patients clinican responsible for anticoagulant regime
- warfarin dose can then be adjusted if needed
When should the INR be taken prior to undertaking dental procedure?
- 24 hour before procedure
- for patients with stable INR, it can be measured within 72 hours of the procedure
Why is it prudent to time procedures to occur in the morning or earlier in the week for patients on anticoagulants?
this is because it allows time to deal with delayed bleeding episodes
What is Heparin?
it is a natural sulphated glycosaminoglycan found in mast cells
What is the MOA of heparin ?
- it is a catalyst for plasma antithrombin III
- antithrombin III regulates coagulation by inactivating coagulation proteases such as thrombin and factor Xa
- also decreases platelet aggregation
they therefore prevent clot formation
Outside of its use as an anticoagulant, state another biological effect of heparin
immunosuppresive effects
How is heparin administered ?
- intravenously
- subcutaneously
What is the half life of heparin?
1-2 hours
The dose of heparin is adjusted in accordance with …
APTT
The effects on clotting are lost within ____ of stopping heparin
6 hours
Give examples of low molecular weight heparin
- certoparin
- dalteparin
- enoxaprin
- riviparin
- tinzaparin
LMWH interacts mostly with …
factor Xa
(activated factor 10)
What is the half-life of LMWH ?
2-4 hours
(longer than heparin)
What are the indications of use of LMWH?
- long term out-patient prophylaxis for pregnancy
- patients intolerant to warfarin
- prophylaxis for patients with lupus anticoagulant factor
What is the main caveat with using LMWH?
they do not affect standard blood results so their use poses a difficulty with assessing bleeding tendency prior to invasive dental treatment
Why are patients receiving heparin able to be scheduled to receive simple dental extractions the day after its administration?
this ie because it hase a shorter half life than warfarin
Give examples of local haemostatic measures
- local anaesthetic
- minimise trauma
- haemostatic agents e.g. surgicel, gelatine sponge
- suture
- POI
- tranexamic mouthwash- not in DPF
What is a possible indication for ginger and what is its effect on INR?
Nausea
increase INR (increased bleeding risk- blood is clotting too slowly)
What is a possible indication for St Johns Wort and what is its effect on INR?
Depression
decreases INR (lower risk of bleeding)
What is the effect of ginger, ginseng and gingko on INR?
increased INR- increased risk of bleeding
What is the effect of ginger, gingseng and ginko on platelets?
inhibit platelet adhesion and aggregation
(increased risk of bleeding)
What is a possible indication for the use of ginseng?
increase energy levels
What is the possible indication for use of garlic as herbal medication?
decrease cholesterol
What is the possible indication for use of gingko as herbal medication ?
increase cerebral flow therefore improving memory and decreasing dementia
What are the indications for use of heparin ?
- atrial fibrillation
- prophylaxis and treatement of peripheral arterial emboli
- prevention of clotting
- prevention of clotting during heart surgery
- acute thrombo-embolic episdoes
- prevention of DVT and pulmonary emboli following surgery
- IV renal hameodialysis to prevent thrombosis in pumps
- prophylactic prevention of thrombosis after MI
How do coroticosteroids gain their anti-inflammatory effect?
- suppression of phospholipase A2
- therefore the inhibit the main products of inflammation
Why would a patient on corticosteroids experience prolonged bleeding?
- decreases plalete function as a result of inhibition of TXA2
- effects of corticosteroids on vessel wall; interferance with initial haemostatic interactions between vessel wall, platelets and clotting factors
- immunosuppresion leading to increased risk of infection and therefore fibrinolysis [!!]
What does chemotherapy refer to?
generally refers to targetting neoplastic cells
Chemotherapy also damages cells that divide rapidly under normal circumstances. True or false
True
How might chemotherapy cause prolonged bleeding?
target rapidly dividing cells in bone marrow
This results in myelo-suppresion and a reduction in platelet count
Give an example of a cancer that is sensitive to chemotherapy. State why
Hodgkins lymphoma
this is because a large proportion of the targeted cells are undergoing cell division at any time
Aside from cancer, give other conditions where chemotherapy is appropriate?
- autoimmune disorders such as rheumatoid arthritis or multiple sclerosis
When should dental procedures be scheduled for patients on chemotherapy? Explain your reasoning
- One cycle of chemotherapy lasts for approx 6 weeks with a 6-week rest in between cycles
- life span of platelets is 7-10 days
- lifespan of leucocytes is 4 weeks
- dental procedures should be scheduled around week 4 to allow optimal healing and haemostasis before next cycle
Give indications for corticosteroid use
- addisons disease- adrenal insufficiency
- suppression of allergic reactions e.g. asthma, dermatitis
- suppression of inflammatory conditions e.g. arthritis, IBD, crohns dsease, UC, termoral arteritis
- suppression of SLE, sarcoidosis
- post transplant immunosuppresant
- grafts versus host disease to prevent transplant rejection
- chemotherapy
