Fibrinolytic System Flashcards
What is the key enzyme in fibrinolysis?
Plasmin – breaks polymer bonds & releases FDP’s
What are the ways that plasmin is activated?
-results from the cleavage of inactive form (zymogen) - plasminogen by either of two pathways:
-Extrinsic pathway activation: TF3 and fibrin as cofactor
-Urokinase can also convert plasminogen to plasmin and is used as a thrombolytic agent
-Streptokinase is a streptococcal-derived protein used as thrombolytic (clot busting) drug
-Intrinsic pathway activation: involves Factors XIIa, kallikrein, or HMWK
When Glu-Plasminogen is cleaved, what is the new terminal amino acid?
Lysine- Lys-plasminogen is more readily activated
Are plasminogen activators exogenous/endogenous and where are they found?
Endogenous – present in the blood & other tissues
Primary source of activators are in the blood vessel endothelium
what are the primary endogenous plasminogen activators?
Endogenous activators include: Urokinase t-PA Scu-PA Other
What is the primary activator of plasminogen in the genitourinary system?
Urokinase
What induces the release of Tissue Plasminogen Activator (t-PA)?
Thrombin induces the release of t-PA
If a patient shows no increase in t-PA, what are they at an increased risk for?
If patient shows no increase in t-PA activity, at an increased risk for DVT
What are the general characteristics of Plasminogen Activator Inhibitor – 1?
- Synthesized by blood vessel endothelium & released in an inactive state
- An acute phase reactant
- Primary substrate is t-PA = thus regulation of fibrinolysis is dependent on the interaction of t-PA w/ PAI-1
- Excess of this inhibitor associated with thrombotic disease
How does plasmin limit the coagulation process?
Limits coag process by cleaving & rendering inactive FV & FVIII, XII & GPIb (vWF receptor)
What action does plasmin take and what are the byproducts?
-degrades both fibrin clots & native fibrinogen
Fragment X
-X = Y & D fragments
-Y = D & E fragments
-D = D only
-D-Dimer = cleaved cross-linked fibrin
-Products have inhibitory effects on coag system
What is the primary plasmin inhibitor and what is its overall effect?
- alpha 2-antiplasmin inhibitor
- Overall effect – plasmin activity is limited to area of fibrin deposition
What are the indication for fresh frozen plasma use?
-Significant coagulopathy
-A significant coagulopathy results when the PT > 3 sec., INR >1.5 sec. And the patient has
An active bleed
Anticipated invasive procedure
Massive RBC transfusion (dilutional coagulopathy)
Congenital def. of F2, 5, 10, 11, 12, or 13 w/ bleeding/invasive proc & conc’s are not available
Emergent reversal of warfarin effect (Vit. K reversal takes 6-8 hours
Plasmaphoresis for TTP
What is cryoprecipitate?
Cryoprecipitate:
Is prepared by taking FFP and thawing it slowly between 1-6oC. The white
precipitate that forms at the bottom of the bag is the cryoprecipitate…so it
is the cold, insoluble portion of plasma.
The cryo, can then be separated from the plasma and refrozen. Each unit of
FFP will yield ~15-20 mL of cryo.
The left over plasma (non-cryo portion) can also be refrozen and labeled as
Cryo-Reduced Plasma. This can be used to treat TTP patients as an alternative to FFP.
It is important to refreeze both components within 1 hr. of prep.
What does cryoprecipitate contain?
150-250 mg/dL of fibrinogen (half-life: 4-6 days)
80-150 units of FVIII (half-life: 12 hrs)
and some F 13: 50-75 U (half-life: 4-12 days)
also contains some F 8:C (procoagulant portion of factor 8)
vWF: 100-150 U (half-life: 24 hours)
and fibronectin (but there is no clinical indications for fibronectin replacement at this time)
