16. Coagulation Disorders Flashcards
What is the treatment for bleeding disorders?
Recombinant purified coagulation factors
What does APTT test?
Intrinsic pathway
What test examines the extrinsic pathway?
PT
Why is vitamin K necessary for clotting?
Vitamin K dependent proteases in the liver need it to produce gla domains on the ends of clotting factors
What conditions result from a vitamin K deficiency?
Bruising
Haemorrhagic disease of newborn
What causes a vitamin K deficiency?
Antibiotic overdose
Alcoholic liver disease
What is the MOA of Warfarin?
Prevents Gla domain function in coagulation enzymes by inhibiting vitamin K
Complexes needed to clot aren’t produced
What is the MOA of heparin?
Boosts antithrombin function:
binds to antithrombin and alters it to recognise thrombin and factor Xa
Binds AT and thrombin together
Where is heparin sulphate found?
Endothelial cells
What is the composition of unfractionated heparin?
Different length polysaccharides
What is the function of factor XIII and what kind of enzyme is it?
Strengthens clots
Transglutaminase
What is the MOA of dabigatran?
Directly inhibits thrombin
What is the MOA of rivaroxaban?
Inhibits factor Xa
what is the benefit of DOACs over warfarin or heparin?
Antidote is available
What converts plasminogen to plasmin?
Tissue plasminogen activator
What type of cell releases TPA?
Intact endothelial cells
What is d-dimer?
Specific degradation fragment of cross-linked fibrin made when plasmin degrades a thrombus
What is the use of d-dimers in diagnosis?
Normal d-dimers exclude a thrombotic effect
Elevated does not mean there has been a DVT or PE
How is fibrinolysis controlled?
TPA requires fibrin as a cofactor
Plasminogen Activator Inhibitor turns off TPA
Antiplasmin targets plasmin
What is recombinant TPA used for?
Rapidly degrade thrombi eg. ischaemic stroke
Name 3 forms of recombinant TPA
Alteplase
Reteplase (longer half life)
Tenecteplase (more specific to fibrin)
Why is recombinant TPA only safe within 4 hours after an ischaemic stroke?
After that it can cause haemorrhage due to blood vessel damage
Name an anti-fibrinolytic agent
Tranexamic acid
What is the MOA of tranexamic acid?
Synthetic lysine analogue
Slows the covertion of plasminogen to plasmin to reduce bleeding in trauma, surgery and childbirth
