Fibrinolysis

Fibrinolysis

fibrin clot is degraded after bleeding has stopped

Fibrinolysis is the breakdown of ___ starting after formation of __ __ __

fibrin

hemostatic fibrin plug

Fibrinolysis may start a __ __ after formation of the clot

few hours

Fibrinolysis is a delicate balance between

activators and inhibitors

Too much fibrinolysis

bleeding continues due to premature clot lysis

Inadequate fibrinolysis

clot extension, dangerous thrombosis

1st step of fibrinolysis

site of injury slowly releases tissue plasminogen activator (t-PA)

Step 2 of fibrinolysis

t-PA enters the fibrin clot and converts plasminogen to plasmin

___ is the main player in fibrinolysis

Plasmin

Step 3 of fibrinolysis

Plasmin cleaves fibrin to fibrin degradation products

Step 4 and 5 of fibrinolysis

Macrophages clear the fibrin after degradation products

Plasmin also digests fibrinogen, FV, FVIII, prothrombin and FXII

Plasmin cleaves fibrinogen to form

E and D fragments

Plasmin cleaves fibrin to form

E and D=D fragments

D=D dimers are specific to plasmin cleavage of

fibrin

Presence of D-dimers indicates occurrence of ___ and ongoing ___

thrombosis

fibrinolysis

Normally D-dimer concentration is less than ___, but fibrinolysis can give D-dimer concentrations greater than

2 ng/mL

200 ng/mL

Measuring D-dimers is used in the diagnosis of

disseminated intravascular coagulation (DIC)

DIC is the

widespread activation of clotting cascade

In DIC,

blood clots form in small vessels throughout the body

DIC is also used to diagnose (2)

deep vein thrombosis

pulmonary embolism

6 tests used to measure fibrinolysis

Fibrinogen assay

D-dimer assay

Thromboelastography

Plasminogen activity assay

Euglobulin lysis time

Fibrin split product assay

Thromboelastography (TEG) should be used in conjunction with

PT, PTT, and platelet count

TEG can assess

platelet function

clot strength

fibrinolysis

TEG can detect __ __ when other tests do not

severe fibrinolysis

TEG detects combined __ __, __ __ or __ __ and ___, but not specific

low platelet

low fibrinogen

low platelet and fibrinogen

TEG is

relatively fast

TEG is poor at

factor level and fibrinogen estimation

Inhibitors of fibrinolysis

Plasminogen activator inhibitor 1 (PAI-1)

a2-antiplasmin (A2AP)

Thrombin-activatable fibrinolsis inhibitor (TAFI)

PAI-1 and A2AP are

serine protease inhibitors (serpins)

PAI-1 is stored in ___ but produced by

platelets

produced by many types of cells

PAI-1 binds up

circulating fPA

PAI-1 inhibits ____ activation to ____ by inactivating ___

plasminogen

to plasmin

fPA

A2AP is made by the

liver

A2AP binds directly to

plasmin to inactivate the plasmin

TAFI is not a

serpin

RAFI prevents

plasminogen from binding to fibrin to slow plasmin generation

Ischemic stroke is when

blood clot blocks artery

___ is adminstered to a patient intravenously

t-PA

What intimal cell synthesizes and stores vWF?

endothelial cell

What subendothelial structural protein triggers coagulation through activation of factor VII?

Tissue factor

What coagulation plasma protein should be assayed when platelets fail to aggregate properly?

Fibrinogen

What role does vitamin K play for the prothrombin group factors?

carboxylates the factors to allow calcium binding

What is the source of fibrinopeptides A and B?

thrombin proteolysis of fibrinogen

What serine protease forms a complex with factor VIIIa and what is the substrate of this complex?

Factor IXa and factor X

What protein secreted by endothelial cells activates fibrinolysis?

TPA

What two reglatory proteins form a complex that digests activated factors V and VIII?

APC and protein S

Coagulation factor VIII circulates bound to

vWF

Most coagulation factors are synthesized in the

liver

what condition causes the most pronounced elevation in the result of the quantitative D-dimer assay?

DIC

What component of the fibrinolytic process binds and neutralizes free plasmin?

a2-antiplasmin