0.0 coagulation & bleeding disorders

fibrinolytic system

removes fibrin from the vascular system preventing clots from occluding the vessel

the central part of fibrinolysis

is the activation of plasminogen → plasmin

plasminogen circulates the body as an inactive protein

activated by urokinase/UPA into plasmin

plasmin causes the breakdown of the fibrin clot into smaller products

to be excreted by the body

UPA + tissue plasminogen activator  (TPA) activate the transition of

plasminogen → plasmin

UPA circulates in the body in it inactive form n requires its receptor UPAR to activate

TPA circulates in the body in its inactive form n requires its receptor to activate

serpin

AKA pi 1/2/3

serpins block the activation of UPA/TPA into their active form

thus halting the excessive break down of clots preventing mass bleeding

fibrinolytic drugs can either

antifibrinolytic agents

thrombus blasters

antifibrinolytic agents

inhibit the destruction of thrombi

thrombus blasters

activate the destruction of thrombi (clots)

urokinase can be given as a bolus dose

for people with thromboembolic strokes or very bad heart attacks

urokinase AKA

clot breakers

clot blasters

thrombi blasters

streptokinase is also a thrombi blaster

however the serine protease tissue proactivators, TPA is more commonly used

antifibrinolytic agents like tranexamic acid 

are used to prevent excessive bleeding post surgery + to treat excessive bleeding disorders

von Willebrand disease cause

reduced production/ abnormality of Von Willebrand’s factor which promotes normal platelet function and stabilises factor 8 

von Willebrand disease treatment

desmopressin

tranexamic acid

blood products

desmopressin

a synthetic version of vasopressin which stimulates the body to released stored VWF and factor 8 into bloodstream

desmopressin has a versatile administration route

IV

nasal spray

Haemophilia A cause

deficiency in factor 8

Haemophilia A treatment

desmopressin

tranexamic acid

emicizumab

factor 8

emicizumab

a monoclonal antibody that bridges activated factor 9 and factor 19 to restore function of the missing activated factor 8

factor 8

can also be infected to replace the missing clotting factor in the body

Haemophilia B cause

deficiency of factor 9

Haemophilia B treatment

factor 9

gene therapy Hemgenix

Haemophilia C cause

deficiency of factor 11

Haemophilia C treatment

fresh frozen plasma

tranexamic acid

factor 11 concentrate

factor 5 Leiden cause

variation in factor 5 gene that renders it resistant to metabolic inactivation (clots stay)

factor 5 Leiden treatment

anticoagulant