Coagulation Flashcards
Heparin pharm and monitoring
Unfractionated = large molecular weight polysaccaride
Low molecular weight = dalteparin, enoxiparin
Fondaparinux = synthetic based on minimal AT binding region
MOA
- binds AT
- > induces conformational change
- > increases inactivation of coagulation factors
- all inactivate factor Xa
- inactivation of thrombin
- > unfractionated is more efficient than LMW
- > fondaparinux is too small
Pharmacology
- water soluble (given parentally)
- short half life (LMW =slower acting, longer half life)
- metabolised by liver and reticuloendothelial
- LMW excreted partially by kidneys/unfractionated is not
- doesn’t cross placenta or breast milk
- Antedote
- > protamine sulfate only for LMWH
Monitoring
- aPPT (can’t be normalised)
- > 4-6 hrs
- > daily once stable
- platelet count
- > for both LMWH and UFH
- > days 0,3,5 then alternating
Warfarin MOA and pharm and monitoring
MOA
- block vitamin K epoxide reductase in liver
- > depletion of reduced form of vitamin K that serves as co-factor for gamma carboxylation of factor II, VII, IX, X
- > non-functional as they cannot bind calcium and phospholipid membranes
- also inhibit gamma carboxylation of protein C and S, which inhibit factor V and VIII
- > brief pro-coagulant period initially (usually benign)
Pharmacology
- effect determined by coagulation factor synthesis and breakdown
- factor II and X are primary effects (half life 3 days)
- > delayed onset of action (1 week)
- factor VII shortest half life (6 hours)
- > prolonged PT
- lipid soluble (given orally)
- highly protein bound (albumin)
- > only unbound is active
- long half life
- metabolised by CYP450 in liver
Antedote
- FFP
- parenteral vitamin K
Monitoring
- PT/INR
- daily until stable then no longer than 4 weeks
- self testing possible when stable long term
Warfarin SE and precautions
SE
- bleeding
- skin necrosis
- > initial inhibition protein C
- > thrombi of subcutaneous vessels
- purple toes
- alopecia
- fever
- rash
- nausea/vomiting/diarrhoea
- vessel calcification (no associated CVA, MI effect)
- liver dysfunction
Precautions
- contraindicated
- > alcoholism
- > active bleeding/bleeding disorder
- > high risk falls
- surgery
- > generally safe with INR <1.5
- > minor procedures = INR <2.5
- > moderate-high risk = stop 4-5 days prior for INR <1.5
- > consider bridging therapy and vit K supplementation
- pregnancy
- > teratogenic
- breast feeding
- > safe
Heparin SE and precautions
SE
- bleeding
- HIT
- > polysaccaride binds to PF4 on platelet surface
- > neo-antigen -> opsonised by antibodies
- > removed by reticuloendothelial system
- > cross reactivity with endothelial cell -> thrombosis
- non-immune thrombocytopaenia (benign)
- skin necrosis (part of HIT)
- skin rash (delayed hypersensitivity reaction)
- hyperkalaemia
- osteoporosis/alopecia with long term use
Cautions
- avoid LMWH in renal disease
- avoid heparins in severe liver disease
- surgery
- > UFH = bleeding risk for 12hrs prior
- > LMWH = bleeding risk for 36hrs prior
Lifestyle advice warfarin
General
- Stay with same brand (bioequivalence no demonstrated)
- Take at same time every day
- Record dose, time and INR in book
- Tell doctor if vomiting, diarrhoea, illness (dose adjust)
- Tell doctor is pink/black urine or faeces
Advise
- tell doctor/pharmacist before starting drug/supplement
- physio’s, chiro’s, podiatrist etc
Diet
- educate on food that contain vitamin K
- > spinach, kale, greens
- goal is to maintain stable intake, not limit intake
- avoid multivitamins and caution over counter supplements
Smoking
- induces CYP450
- > decrease warfarin levels
Cannabis
- can induce CYP450
- > may lower levels
Drinking
- impairs warfarin metabolism
- > increased levels
- 1-2 drinks is generally safe
Medication adherence
- anticoagulation clinic
- education
- apps/dosing algorithm/self monitoring
Warfarin interactions
Increased bleeding
-altered intestinal flora -> reduced vitamin K synthesis
(antimicrobials)
-inhibit CYP2C9 (sulfamethoxazole)
-interrupt vitamin k recycling (paracetamol)
-displace from albumin (eg. amiadarone)
-combination with NSAIDs
Decreased bleeding
- induce CYP2C9 (carbamazepine, phenytoin)
- bypass VKORC1 (supplements)
- bile sequestrants
Clopidogril
MOA
- irreversibly blocks the P2Y12 receptor on platelet surface
- > prevents binding of ADP and activation
SE
- diarrhoea
- rash/urticaria
- bleeding/GI ulcer
Dipyridamole
MOA
- inhibits adenosine deaminase and phosphodiesterase
- > accumulation of adenosine, adenine nucleotides and cAMP
- > inhibits platelet aggregation
SE
- bleeding
- headache (common)
- were concerns of MI
abciximab
MOA
chimeric monoclonal antibody against platelet IIb/IIIa receptor
->prevents cross linking and platelet aggregation
SE
- haemorrhage
- chest pain/back pain
- nausea
direct thrombin inhibitors
Parenteral: bivalirudin
Oral: dabigatran
MOA
-inactivate circulating and clot-bound thrombin
Pharmacology
- hepatic metabolism
- cleared by kidneys
SE
- bleeding
- gastritis/dyspepsia/GI bleeding (swallow capsule whole)
- oesophageal ulcers
- hepatotoxicity
Precautions
- Contraindications
- > high risk for bleeding
- > recent GI haemorrhage
- > prothetic valve
- > severe kidney disease
- > severe liver disease
- Caution
- > cease approx 3 days before surgery
- > dose reduce in elderly
- > safety unknown in pregnancy and breastfeeding
direct Xa inhibitors
Parenteral: none
Oral: rivaroxaban, apixaban, edoxiban
MOA
-inactivate circulating and clot bound factor Xa
Pharmacology
-metabolised by liver and kidneys
SE
- bleeding
- peripheral oedema
- itch
- blisters
- muscle spasm
- hepatotoxicity
Precautions
- renal disease
- > severe = contraindicated
- > mild = dose reduce
- pregnancy and breastfeeding
- > limited data for safety
thrombolytic
alteplase
MOA
-initiates local fibrinolysis by binding to fibrin in thrombus and converting entrapped plasminogen to plasmin
SE
bleeding
small risk, grows over time
