السلام عليكم
تم سؤالي عن الـ D-Dimer وهذا ايضاح له من احدى محاضراتي في ال hemostasis.
تم سؤالي عن الـ D-Dimer وهذا ايضاح له من احدى محاضراتي في ال hemostasis.
Fibrinolytic System
Now we have ceased and arrest bleeding,; the blood vessel will repair broken endothelium, by the differentiation of the smooth muscle cells in the media the cells in the media layer, then these will move down to replace and repair the broken endothelium. But what about the deposited fibrin together with the platelet plug? This should be digested and removed, and this is done by the fibrinolytic system. The key enzyme of the fibrinolytic system is the plasmin enzyme, which the activated form the plasminogen, which is produced in the kidney.
Plasminogen Plasmin
But what are the activators of plasminogen? The activators are Factor XII and prekallikrein:
XII XIIa prekallikrein
kallikrein
Plasminogen Plasmin
But also not factor XIIa and kallikrein can activate the fibrinolytic system but also Tissue Plasminogen Activator (TPA) that is released by the endothelial cells (do not forget that as plasminogen is activated to plasmin, the fibrinolytic system is activated!) .
XII XIIa prekallikrein
kallikrein
Plasminogen Plasmin
TPA
Also urokinase, an enzyme found in urine can activate the fibrinolytic system
As plasmin is activated it attack insoluble cross-linked fibrin trying to digest it into smaller fragments and products. First it will digest cross-linked fibrin into X fragments, subsequent attack of plasmin on X fragments will yield D and Y fragments, subsequently Y fragments will be digested to D and E fragments by plasmin:-
Plasmin
Fibrin X fragments D + Y Fragments D + D +E
Smaller Fragments
X + Y + D+ E Fragments or Products are called Fibrin Degradation Products (abbreviated as FDP’s), or some are call it Fibrin Split Products (FSP’s). These products will be cleared from our bodies by the liver.
Actually plasmin does not only attack or digest Fibrin but also Fibrinogen, plasmin have the same affinity for fibrin and fibrinogen, the result of fibrinogen digestion is fibrinogen degradation products.
So, how we can differentiate between Fibrin Degradation Products and Fibrinogen Degradation Products??!
Before answering this question, follow me, relax, and please open your mind:- We say before 10 minutes that factor XIIIa crosslink fibrin by a covalent bonds, right ? right, Ok, as factor XIIIa cross-links fibrin, it covalently crosslink covalently 2 D fragments, these fragments are only found in cross-linked insoluble fibrin. When plasmin digest cross-linked fibrin it cannot digest or break these 2 D fragments, these 2 D cross-linked fibrin fragments are called D-Dimer, these D-dimer are resistant to be lysed by plasmin enzyme. So, if we test for the presence of D-Dimer, and the test yields positive result for the presence of D-Dimer, this means that these products are only Fibrin Products and not fibrinogen products. If we have a positive test for D-Dimer (FDP’s will also be positive, which will be considered now as fibrin degradation products and not fibrinogen degradation products as a result of positive D-Dimer test, I hope you understood what I mean by this) this means that we have thrombin which formed fibrin, and also we have factor XIIIa which cross-linked fibrin, and finally we have plasmin which have digested the fibrin, to give FDP’s and D-Dimer. But when D-Dimer test is negative and FDP’s is positive, what does this mean? This means that there is only plasmin, but no thrombin and no factor XIIIa, since D-Dimer test is negative.
In summary D-Dimer is specific for fibrin, and when it is positive, the FDP’s should be positive, and these FDP’s are guaranteed now that they are Fibrin Degradation Products, moreover we guarantee the presence of thrombin and factor XIII. These events (i.e. +ve D-Dimer) do occur with hyperocoaguable states (also called thrombophilic), such as deep vein thrombosis (DVT), pulmonary embolism (PE), DIC, acute myocardial infarction (MI) , and unstable angina.
Thrombin
Fibrinogen soluble fibrin monomers soluble fibrin
XIIIa
Cross-linked Insoluble Fibrin Fibrinogen
Plasmin Plasmin
D-Dimer + FDP’s Only FDP’s
Plasmin also is able to degrade and thus inactivate coagulation factors: V, VIII, IX, and XI. Also, plasmin biodegrades: ACTH, Insulin, and Growth hormones. Moreover plasmin can activate complement system through both the classical and alternative pathway’s.
Now we have ceased and arrest bleeding,; the blood vessel will repair broken endothelium, by the differentiation of the smooth muscle cells in the media the cells in the media layer, then these will move down to replace and repair the broken endothelium. But what about the deposited fibrin together with the platelet plug? This should be digested and removed, and this is done by the fibrinolytic system. The key enzyme of the fibrinolytic system is the plasmin enzyme, which the activated form the plasminogen, which is produced in the kidney.
Plasminogen Plasmin
But what are the activators of plasminogen? The activators are Factor XII and prekallikrein:
XII XIIa prekallikrein
kallikrein
Plasminogen Plasmin
But also not factor XIIa and kallikrein can activate the fibrinolytic system but also Tissue Plasminogen Activator (TPA) that is released by the endothelial cells (do not forget that as plasminogen is activated to plasmin, the fibrinolytic system is activated!) .
XII XIIa prekallikrein
kallikrein
Plasminogen Plasmin
TPA
Also urokinase, an enzyme found in urine can activate the fibrinolytic system
As plasmin is activated it attack insoluble cross-linked fibrin trying to digest it into smaller fragments and products. First it will digest cross-linked fibrin into X fragments, subsequent attack of plasmin on X fragments will yield D and Y fragments, subsequently Y fragments will be digested to D and E fragments by plasmin:-
Plasmin
Fibrin X fragments D + Y Fragments D + D +E
Smaller Fragments
X + Y + D+ E Fragments or Products are called Fibrin Degradation Products (abbreviated as FDP’s), or some are call it Fibrin Split Products (FSP’s). These products will be cleared from our bodies by the liver.
Actually plasmin does not only attack or digest Fibrin but also Fibrinogen, plasmin have the same affinity for fibrin and fibrinogen, the result of fibrinogen digestion is fibrinogen degradation products.
So, how we can differentiate between Fibrin Degradation Products and Fibrinogen Degradation Products??!
Before answering this question, follow me, relax, and please open your mind:- We say before 10 minutes that factor XIIIa crosslink fibrin by a covalent bonds, right ? right, Ok, as factor XIIIa cross-links fibrin, it covalently crosslink covalently 2 D fragments, these fragments are only found in cross-linked insoluble fibrin. When plasmin digest cross-linked fibrin it cannot digest or break these 2 D fragments, these 2 D cross-linked fibrin fragments are called D-Dimer, these D-dimer are resistant to be lysed by plasmin enzyme. So, if we test for the presence of D-Dimer, and the test yields positive result for the presence of D-Dimer, this means that these products are only Fibrin Products and not fibrinogen products. If we have a positive test for D-Dimer (FDP’s will also be positive, which will be considered now as fibrin degradation products and not fibrinogen degradation products as a result of positive D-Dimer test, I hope you understood what I mean by this) this means that we have thrombin which formed fibrin, and also we have factor XIIIa which cross-linked fibrin, and finally we have plasmin which have digested the fibrin, to give FDP’s and D-Dimer. But when D-Dimer test is negative and FDP’s is positive, what does this mean? This means that there is only plasmin, but no thrombin and no factor XIIIa, since D-Dimer test is negative.
In summary D-Dimer is specific for fibrin, and when it is positive, the FDP’s should be positive, and these FDP’s are guaranteed now that they are Fibrin Degradation Products, moreover we guarantee the presence of thrombin and factor XIII. These events (i.e. +ve D-Dimer) do occur with hyperocoaguable states (also called thrombophilic), such as deep vein thrombosis (DVT), pulmonary embolism (PE), DIC, acute myocardial infarction (MI) , and unstable angina.
Thrombin
Fibrinogen soluble fibrin monomers soluble fibrin
XIIIa
Cross-linked Insoluble Fibrin Fibrinogen
Plasmin Plasmin
D-Dimer + FDP’s Only FDP’s
Plasmin also is able to degrade and thus inactivate coagulation factors: V, VIII, IX, and XI. Also, plasmin biodegrades: ACTH, Insulin, and Growth hormones. Moreover plasmin can activate complement system through both the classical and alternative pathway’s.
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