12.5 Management of Coagulopathies & Bleeding Disorders Flashcards
Acute vs long-term goals of antiplatelet therapy
Acute: Stop progression of acute thrombus
Long-term: prevent recurrence of CVA, MI etc.
Acetylsalicylic acid is also known as…
Aspirin
“Low-Dose Aspirin” is the typical dosage in Australia; how much is it, and how often is it taken?
- 100mg
- Once daily
Describe the mechanism of aspirin
Inhbits COX-1 enzyme, prevents synthesis of Thromboxane A2, which is otherwise used for autocrine platelet activation, thus inhibiting platelet aggregration.
Clopidogrel mechanism
IRREVERSIBLY binds to ADP receptor
Ticagrelor mechanism
REVERSIBLY binds to ADP receptor
Antiplatelets vs anticoagulants
Antiplatelets: stop primary haemostasis
Anticoagulants: stop secondary haemostasis
Acute vs long-term goals of anticoagulant therapy
Acute:
- Prevent extension of acute thrombus
- Prevent embolisation
Long-Term:
- Preventing AF-association thromboembolism
- Prevent VTE recurrence
Heparin mechanism
- Binds to antithrombin; makes it up to 1000 times more effective (!)
- Increased thrombin breakdown -> decreased fibrin production -> decreased coagulation
Warfarin mechanism
- Prevents recycling of vitamin K
- Depletse Vit-K dependent factors from the coagulation cascade
Which clotting factors are Vitamin-K Dependent
2, 7, 9, 10
Targets of LMW vs unfractionated heparin…
LMW: Predominantly Factor Xa
Unfractionated: both Xa and antithrombin
Direct acting anticoagulant (DOAC) mechanism
Binds to and inhibits factor Xa
Give two examples of Direct acting anticoagulants
- Apixaban
- Rivaroxaban
Common uses of thrombolysis
- Acute ischaemic stroke
- Acute MI
- Acute Limb Ischaemia
- Massive PE
How do tissue Plasminogen Activators (tPAs) cause fibrinolysis?
- catalyse the activation of plasminogen into plasmin
Give some examples of tPAs
- Tenecteplase
- Alteplase
How is gene therapy used in Factor IX replacement therapy?
- Viral vector carries gene to liver
- Cause expression of gene to synthesise protein
Indications for antiplatelets
Arterial thrombotic disease:
- Cardio (such as in coronary PCI)
- Cerebrovascular disease
- Peripheral vascular disease
- Pre-eclampsia prevention
Contraindications for antiplatelets
- Avtice/recent haemorrhage
- Upcoming/recent surgery
- Thrombocytopaenia
Side effects of antiplatelets
- Blood loss
- GI irritation
What are three specific side effects associated with ticagrelor
- Dyspnoea
- Bradycardia
- Gout
Can most procedures be done on aspirin? What about dual platelet therapy?
- MOST (not necessarily all) can be done on aspirin
- Usually, allow one antiplatelet to wash out of system for 5-7 days before surgery if on dual
Which has higher bleeding risk: anticoagulants or antiplatelets?
Anticoagulants
What advice would you give to a patient who you are prescribing anticoagulants to?
- No contact sports :(
- High-risk occupations
- Important to keep doses consistent/don’t miss them
Indications for prophylactic vs therapeutic heparin
Prophylaxis: VTE prevention
Therapeutic: treatment of VTE, acute arterial events, or mechanical valve prophylaxis
Contraindications for heparins
- Active/recent haemorrhage
- Severe thrombocytopaenia
Side effects of heparins
- Heparin-induced thrombocytopaenia syndrome (HIITS)
- Bleeding; liver enzyme elevation
- Long term: alopecia, osteoporosis
Describe Heparin-Induced Thrombocytopaenia Syndrome
- Antibodies formed against platelets
- Leads to antibody destruction, and yet HYPERthrombotic state
Benefits/limitations of LMW heparin
Benefits:
- Subcutaneous (can be used for outpatients)
- Fixed dosage
- No monitoring needed
Limitations:
- Only partially reversible
- Short half life
Benefits/limitations of unfractionated heparin
Benefits:
- Fully reversible
- Independent of renal function
Limitations:
- IV (so only for inpatients)
- Requires frequent monitoring
- Complex dosing algorithm
What are some rare circumstances where a patient requires monitoring for being on LMW heparin
- Obesity
- Pregnancy
- Renal impairment
Indications for therapeutic vs prophylactic DOACs
- Prophylaxis: VTE prevention
- Therapeutic: VTE or AF treatment
Contraindications for DOACs
- Renal impairment
- Recent haemorrhage
- Severe thrombocytopaenia
- Pregnancy
Risks of DOACs
- No reversal agent currently
- Rivaroxaban also has higher risk of menorrhagia than apixaban
Indications for warfarin
- Mechanical heart valve (arterial thrombi prophylaxis)
- Anticoagulation in renal disease
Contraindications for warfarin
- Active/recent haemorrhage
- Severe thrombocytopaenia
- Pregnancy
Side effects of warfarin
- Bleeding
- Long-term: alopecia, hepatic dysfunction
Importance of diet in warfarin prescription
If suddenly changed, vitamin K levels could change, altering drug effectiveness
Why do you start enoxaparin when you start warfarin?
Because, initially warfarin depletes Protein C before is inhibits vitamin K recycling, creating a prothrombotic state. The enoxaparin prevents this from causing acute thrombotic events.
Describe factor replacement therapy in Haemophilia A and Haemophilia B
H. A: Recombinant Factor VIII
H. B: Recombinant Factor IX
Describe factor replacement therapy for von Willebrand’s Disease
- First, give desmopressin, which increases endothelial release of vWF
- If not enough, give purified vWF with Factor VIII
What is the function of Tran Examic Acid (TXA)?
- Opposes the function of tPA; opposes conversion of plasminogen into plasmin
What are some indications for antifibrinolytic therapy?
- GI bleeding
- Menorrhagia
- Gum/dental bleeding
- Epistaxis
Describe novel therapy of Haemophilia A
- Synthetic replacement of Factor VIII by using a bi-specific antibody that binds factors IX and X
