Lecture - Module 4 Flashcards
the physiological process that removes insoluble fibrin deposits by enzymatic digestion of the stabilized fibrin polymers.
FIBRINOLYSIS
Clots are dissolved by
plasmin
Plasmin digests fibrin and fibrinogen by __________ to produce progressively smaller fragments.
hydrolysis
________ circulates in the plasma until an injury occurs
inactive plasminogen
Plasminogen activation to plasmin is a result of the activity of a number of proteolytic enzymes which are referred to as
Plasminogen Activators
Actions of plasmin
Digest fibrin, fibrinogen, II, V, VIII, XII, results in hypocoagulability- hemorrhagic diasthesis
Plasmin is made up of
Plasminogen and tPA
These are called dead end degradation Products
fragment D and E
Endogenous plasminogen activators
TPA
UPA
XIa, XIIa, Kallikrein
Exogenous plasminogen activators
Streptokinase
APSAC (acyl-plasminogen streptokinase activator complex)
PLASMINOGEN INHIBITORS
Alpha 2- antiplasmin
Alpha 2- macroglobulin
Thrombomodulin
PAI 1 and PAI 2
Increased Activator will cause
Increased risk of thrombosis
Increased Inhibitor will cause
Increased risk of bleeding
Main converter of Plasminogen to plasmin
Tissue Plasminogen Activator
It is secreted by Endothelial cells
Tissue Plasminogen Activator
It is bound with thrombus and PAI-1
Tissue Plasminogen Activator
It is secreted by , Kidneys, UT epithelial cells, Monocytes and Macrophages
Urokinase Plasminogen Activator
Circulates in plasma
Urokinase Plasminogen Activator
Principal inhibitor of plasminogen activation (in tPA and uPA)
Plasminogen Activator Inhibitor 1
Produced by ECs, Megakaryocytes, smooth muscle cells, Fibroblasts, Monocytes, Adipocytes, Hepatocytes
Plasminogen Activator Inhibitor 1
_______ has high concentration than tPA
Plasminogen Activator Inhibitor 1
deficiency in Plasminogen Activator Inhibitor 1 will cause
Chronic Mild Bleeding
It also functions as Acute Phase Reactant
Plasminogen Activator Inhibitor 1
Primary inhibitor of Free Plasmin
Synthesized in the liver
α2-Antiplasmin
Inhibits plasmin and prekallikrein
a2-Macroglobulin
Also synthesized in the liver
Functions as anti-fibrinolytic enzyme
TAFI Thrombin Activatable Fibrinolysis Inhibitor
Inhibits the binding of TPA and plasminogen to fibrin
TAFI Thrombin Activatable Fibrinolysis Inhibitor
Also plays a role in inflammation and wound healing
Thrombin Activatable Fibrinolysis Inhibitor
stable fibrin clot – Will lead to formation of
D-Dimers
digestion of these factors will prevent clot formation
factors II, V, VIII and XII
Protein C and S are inhibitors of
factor V and VIII
Inhibitor of thrombin
Antithrombin III
Amplifies the activity of antithrombin III
Heparin
Inactivate/inhibitors kallikrein (activated form of PK)
C1 inhibitor
Inhibits thrombin, Xa, XIa
Alpha-1-antitrypsin
Suppresses fibrinolysis by removing fibrin C-terminal lysine binding sites
TAFI
Allow to clot in a test tube @ 37 C
Place in water bath to 48 hours
Form a clot
Whole Blood Clot Lysis Time
NV and AV in Whole Blood Clot Lysis Time
NV: clot is intact in 24 hours
AV: clot is lysed before 24 hours
More sensitive, Same as whole blood clot lysis time but blood is diluted
Dilute Whole Blood Clot Lysis Time
NV Dilute Whole Blood Clot Lysis Time
Lysis of clot after 6-10 hours
Plasma is treated with an acid to precipitate certain clotting factors
Euglobulin Lysis Time
Euglobin fraction will be allowed to clot at
37degC and incubated
Normal Value in euglobulin Lysis Time
Lysis in about 300 mins or longer - normal.
Lysis in 120 mins – increased lytic activity.
Lysis in 60 mins or less – strong lysis.
Based on agglutination
Uses monoclonal antibodies specific for FDPS
Quantitative assay of fibrin/fibrinogen degradation products
Types of agglutination in Quantitative assay of fibrin/fibrinogen degradation products
Hemagglutination
Staphylococcal
Latex agglutination
Superior test; Same principle as FPD TEST but more sensitive
D-dimer test
Uses monoclonal antibodies specific for D-Dimers
D-dimer test
