Drugs affecting haemostasis Flashcards
what is virchow’s triad?
endothelial injury, change in pattern of blood flow and hypercoagulability
why are these drugs needed?
bleeding patients e.g. clotting disorders, surgical bleeding
patients prone to clotting e.g. cats with heart disease (saddle thrombus)
what is primary haemostasis?
affects blood vessels and platelets. causes petechiae. vascular response = vasoconstriction and exposure of collagen platelet response = degranulation. adherence to exposed collagen, activated platelets produce chemotactic granules to attract further platelets and also trigger the clotting cascade
what is secondary haemostasis?
the coagulation cascade. clinical sign if problem - cavitary bleeds e.g. rodenticide poisoning.
activation of thrombin which converts fibrinogen to fibrin (cross-links platelet plug to strengthen it)
describe the clotting cascade
intrinsic and extrinsic pathways. both end by activating factor 10. this converts prothrombin to thrombin which then cleaves fibrinogen to fibrin. this is cross linked by factor 13 to form stable thrombus
why is vitamin K important in haemostasis?
(= fat soluble vitamin so needs solubilisation in bile salts for absorption)
aids production of many clotting factors - 2,7, 9, 10.
used to treat rodenticide poisoning and poor coagulation due to lack of absorption of vit K.
how does vit K produce clotting factors?
active form involved in carboxylation of glutamyl residues to activate clotting factors
vit K is activated by epoxide reductase reaction. rodenticides prevent this from happening
give examples of vitamin K antagonist rodenticides (coumarins)
explain how they work
1st gen = warfarin - less potent
2nd gen = brodifacoum - more potent
work by blocking activation of vit K by preventing the epoxide reductase reaction
cats/ dogs may eat rodent killed my these and show clinical signs
how is rodenticide poisoning treated?
phytomenadione - vit K1. SC then orally with fatty meal. don’t give IV (anaphylaxis) or IM (bleeding)
50mg tablets
how are haemostatic drugs used topically?
assist in the control of persistent capillary bleeding,
ideally provide good haemostasis, minimal tissue reactivity, and be easy to sterilise and handle
only work if no haemostatic/ fibrinolytic defects
e.g. in surgery
give some examples of topical haemostatic drugs/ products
adrenaline/ NA - cause vasoconstriction
misc e.g. silver nitrate - precipitate proteins, seal off blood vessel
haemostatic sponges - act as a scaffold e.g. oxidised cellulose
thrombogenic coils - fibres which induce fibrosis
systemic - blood and blood products
not useful to replace platelets, very useful for clotting factors - vary in amount depending on formulation
how is ddAVP used?
synthetic analogue of ADH, injectable/ nasal spray/ tablets. used to increase levels of vWF (clotting)
how is protamine used?
inactivates heparin
list 2 features of a good anticoagulant
preservative effect and maintains function of individual components of blood
contained in blood collection bags
describe the use of anticoagulants in diagnostic samples
sodium oxalate - yellow - glucose
sodium citrate - purple - clotting times
EDTA - pink - haematology
heparin - orange - urgent biochem
what patients have increased risk of clotting?
cats with heart disease at risk of saddle thrombi
D/C with heartworm, immune-mediated haemolytic anaemia, disseminated intravascular coagulation
name 2 types of drugs that reduce clotting and give examples
antiplatelet drugs - aspirin
anticoagulants - heparin (warfarin)
describe the use of aspirin as an antiplatelet
tablet. NSAID causes irreversible inhibition of platelet COX. therefore reduced production of eicosanoids needed for clotting
no GI signs at doses used for this effect
describe the use of clopidogrel as an antiplatelet
tablet prodrug (slow onset of action), prevents platelet aggregation. reduces saddle thrombus risk in cats with heart disease
describe the use of heparin as an anticoagulant
reversibly binds to antithrombin 3, increased inhibition of thrombin
IV/ SC
SE = haemorrhage
controversial use
what is tertiary haemostasis?
fibrinolysis. tendency to clot if problem with this. liver produces plasminogen which is cleaved to plasmin. breaks up the clot
name 2 fibrinolytic agents
streptokinase and tissue plasminogen activator
how is streptokinase used?
converts plasminogen to plasmin.
topical/ parenteral use (care - sytemic fibrinolysis)
not licensed
how is tissue plasminogen activator used?
selectively acts on plasminogen in fibrin clots. less likely to induce systemic fibrinolysis.
not licensed
