Prolonged Bleeding

Question 1

what is haemostasis?

Answer 1

prevention of blood loss, process starts as soon as blood vessel is ruptured or damaged

Question 2

what is the mechanism for haemostasis?

Answer 2

1. Vascular spasm
2. Platelet activation, platelet aggregation –> formation of platelet plug
3. Blood coagulation (through intrinsic and extrinsic cascade) leading to final common pathway –> production of fibrin plug
4. blood clot is populated by fibroblasts, monocytes and other WBC that turn blood clot into fibrous scar to produce permanent sealing of the blood vessel

Question 3

what type of drug is Warfarin?

Answer 3

anti-coagulant

Question 4

what does warfarin interfere with? what happens to your production of factors?

Answer 4

vitamin K metabolism (vitamin K is used by the liver to produce factors 2,7,9 and 10.
- reduction to produce factors

Question 5

what are some examples of newer anticoagulants? how do they work?

Answer 5

Apixaban, Rivaroxaban and Edoxaban
- act on specific points in the pathway, mostly preventing activation of factor 10

Question 6

why are new anti-coagulants that act on single point in the mechanism advantageous?

Answer 6

• much less variable in their action (eg: warfarin takes a long time to start acting and if you stop warfarin it takes a long time for it to wear off AND can also be affected by other drugs/foods)
• act in specific point in pathways and their action is very reliable/predictable
• quick onset (take once a day – some need to be taken 2x a day)

Question 7

what is the role of plasmin in blood clotting?

Answer 7

break down fibrin clots in order balance the haemostatic mechanism and control it

Question 8

Scenario: pt taking warfarin requires XLA asks to stop warfarin, what is key management decisions?

Answer 8

• should NOT be stopping warfarin (evidence that if you stop warfarin, the chances of causing harm > than preventing harm
• check INR (depending on whether it’s stable/unstable) if it’s stable we check it within 72hrs of extraction, if its unstable we check it within 24hrs of the extraction
• need INR to be 4 or less for that pt

Question 9

what are examples of anti-platelet drugs?

Answer 9

• Aspirin (Persantin)
• Dipyridamole (Plavix)
• Clopidogrel (Ticlid)

Question 10

how do aspirin and clopidogrel work?

Answer 10

• interfere with platelet metabolic pathways
• used as anti-inflammatories
• aspirin taken as a painkiller in order to interfere with cyclooxygenase and thromboxane pathways involved in inflammation (those pathways are also involved with platelet activation/aggregation

ASPIRIN: binds irreversibly to platelets – all the platelets in body at time will be affected, need to wait for those platelets to die, for effects of Warfarin to wear off !!
- It inactivates platelet COX (cyclooxygenase) required for thromboxane A2 mediated aggregation

CLOPIDOGREL: - binds to the P2Y12 receptor irreversibly and prevents Adenosine Di Phosphate (ADP) mediated aggregation
- takes a long time for the effects of drug to wear off
- waiting for platelets to die off and be replaced with new ones (platelets renewed over about 10 days)

Question 11

which patients might be taking aspirin and clopidogrel?

Answer 11

• pts who have vascular disease, ischaemic heart disease (IHD)
• pts who have thromboembolic disease (DVT)
• pts who have had a stroke
• pts who have peripheral vascular disease
• anyone in whom platelet aggregations are likely to form within vascular system

Question 12

What are the interactions with anti-fungals and warfarin? what are the problems associated with this?

Answer 12

they interfere with warfarin and can get unwanted impact on INR (increase) including miconazole, fluconazole, metronidazole and erythromycin
–> can get bleeding
–> can get spontaneous haemorrhage
–> can get bleeds aound the retina

Question 13

what are some local measures for prolonged bleeding? what drugs should be avoided that might prolong bleeding directly?

Answer 13

• surgicel
• sutures
• tranexamic acid
• pressure
• avoid NSAIDs; COX-2 inhibitors

Question 14

what clotting disorder can lead to prolonged bleeding and how?

Answer 14

haemophilia - Inherited deficiency of clotting factors (VII, X etc)

Question 15

what is the main purpose of antiplatelets and anticoagulants?

Answer 15

prevent clots from forming in places we don’t want them to form

Question 16

for stasis of blood, are anticoagulants or antiplatelets better?

Answer 16

blood stasis triggers activation of coagulation factors (DVT or PE) so anticoagulants are better (warfarin etc)

Question 17

for vessel wall injury is anticoagulants or antiplatelets better?

Answer 17

the damage to the vessel wall will result in platelet activation therefore anti platelets are better (MI, stroke) - aspirin or clopidogrel

Question 18

who might be taking warfarin?

Answer 18

risk of stroke, heart valve disease or AF