Fibrinolysis is the process of breaking down blood clots to maintain blood fluidity, involving primary and secondary types caused by normal bodily functions or medical interventions. The system consists of components including plasminogen, activators, and inhibitors, with key roles in both health and disease, particularly in managing clotting and bleeding disorders. Therapeutically, fibrinolytic drugs are used to dissolve clots in emergencies like heart attacks and strokes, while antifibrinolytics can help control excessive bleeding.

1. FIBRINOLYTIC SYSTEM
DR. JITENDRA KUMAR JAIN
IInd YEAR RESIDENT
JMC ,JHALAWAR

2. Fibrinolysis
 Is a process that prevents blood clots from growing and
becoming problematic.
 the dissolution of intravascular thrombi and extravascular deposi
ts of fibrin by the enzyme fibrinolysin. Fibrinolysis is important f
or keeping the blood liquid and the blood vessels and glandul
ar ducts patent.
 This process has two types: primary fibrinolysis and secondary
fibrinolysis. The primary type is a normal body process, whereas
secondary fibrinolysis is the breakdown of clots due to a
medicine, a medical disorder, or some other cause.
 In fibrinolysis, a fibrin clot, the product of coagulation, is broken
down. It’s main enzyme plasmin cuts the fibrin mesh at various
places, leading to the production of circulating fragments that
are cleared by other proteases or by the kidney and liver.

3. History of Fibrinolysis
 The term was proposed by the French physiologist A.
Dastre in 1893.
 Uncoagulated blood was first discovered in the blood
vessels of persons who died suddenly by the Italian
physician G. Morgagni (1769) and the Scotch anatomist J.
Hunter (1794).
 In 1906 the German researcher P. Morawitz showed that such
blood lacks fibrinogen and fibrin. He attributed the absence of
these proteins in plasma to the action of a specific enzyme.
 The enzymatic nature of fibrinolysis was demonstrated by the S
oviet scientist V. S. Il’in between 1948 and 1955.

4.  The fibrinolysis system consists of four components:
1. profibrinolysin (or plasminogen),
2. fibrinolysin (or plasmin),
3. profibrinolysin activators
4. fibrinolysin inhibitors.
 Profibrinolysin is converted in the body by the action of enzymatic activators
(plasma and tissue activators and urokinase) to fibrinolysin, which under n
ormal physiological conditions is bound by inhibitors—antiplasmins.
 In certain pathological conditions—thromboses
caused by the breakdown of the clotting mechanism, the bond with the anti
plasmins is broken, and fibrinolysin hydrolyzes the fibrin of thrombi.

5.  Normally, the activity of the fibrinolysis enzymatic system in the bo
dy is low. In the presence of stress, during physical exertion, or after t
he injection of adrenaline, it may increase sharply.
The formation of excessive fibrinolysin by the release of large qua
ntities of tissue activator, resulting from changes in the permea
bility of blood vessels or injury to them, produces extreme activation o
f fibrinolysis, which causes bleeding, for example, during obstetrical co
mplications, in cirrhosis of the liver, and during transfusions of i
ncompatible blood.
 Bleeding is arrested by injection of artificial fibrinolysin inhibitors. A d
ecrease in activity ofthe fibrinolysis system is associated with the devel
opment of atherosclerosis and thromboembolic
complications. In such conditions, fibrinolysis is used for th
rombolytic therapy.

6. Plasmin
 Plasmin is produced in an inactive form, plasminogen, in
the liver. Although plasminogen cannot cleave fibrin, it still
has an affinity for it, and is incorporated into the clot when
it is formed.
 Tissue plasminogen activator (t-PA)and urokinase are the
agents that convert plasminogen to the active plasmin, thus
allowing fibrinolysis to occur.
 t-PA is released into the blood very slowly by the
damaged endothelium of the blood vessels, such that, after
several days (when the bleeding has stopped), the clot is
broken down. This occurs because plasminogen became
entrapped within the clot when it formed; as it is slowly
activated, it breaks down the fibrin mesh.

7.  t-PA and urokinase are themselves inhibited
by plasminogen activator inhibitor-1 and plasminogen
activator inhibitor-2 (PAI-1 and PAI-2). In contrast,
plasminogen further stimulates plasmin generation by
producing more active forms of both tissue
plasminogen activator (tPA) and urokinase.
 Alpha 2-antiplasmin and alpha 2-
macroglobulin inactivate plasmin. Plasmin activity is
also reduced by thrombin-activatable fibrinolysis
inhibitor (TAFI), which modifies fibrin to make it
more resistant to the tPA-mediated plasminogen.

9. Plasmin breakdown
 When plasmin breaks down fibrin, a number of soluble
parts are produced. These are called fibrin degradation
products (FDPs).
 FDPs compete with thrombin, and thus slow down clot
formation by preventing the conversion of fibrinogen to
fibrin. This effect can be seen in the thrombin clotting time
(TCT) test, which is prolonged in a person that has active
fibrinolysis.
 FDPs, and a specific FDP, the D-dimer, can be measured
using antibody-antigen technology. This is more specific
than the TCT, and confirms that fibrinolysis has occurred.
It is therefore used to indicate deep-vein
thrombosis, pulmonary embolism, DIC and efficacy of
treatment in acute myocardial infarction.

10.  Alternatively, a more rapid detection of fibrinolytic
activity, especially hyperfibrinolysis, is possible
with thromboelastometry (TEM) in whole blood, even
in patients on heparin. In this assay, increased
fibrinolysis is assessed by comparing the TEM profile
in the absence or presence of the fibrinolysis
inhibitor aprotinin. Clinically, the TEM is useful for
near real-time measurement of activated fibrinolysis
for at-risk patients, such as those experiencing
significant blood loss during surgery

11.  Testing of overall fibrinolysis can be measured by
a euglobulin lysis time (ELT) assay. The ELT measures
fibrinolysis by clotting the euglobulin fraction (primarily
the important fibrinolytic factors fibrinogen, PAI-
1, tPA, alpha 2-antiplasmin, and plasminogen) from plasma
and then observing the time required for clot dissolution.
 A shortened lysis time indicates a hyperfibrinolytic state
and bleeding risk. Such results can be seen in peoples with
liver disease, PAI-1 deficiency or alpha 2-
antiplasmin deficiency. Similar results are also seen after
administration of DDAVP or after severe stress.

12. Role in disease
 Few congenital disorders of the fibrinolytic system have been
documented. Nevertheless, excess levels of PAI and alpha 2-
antiplasmin have been implicated in the metabolic
syndrome and various other disease states.
 However, acquired disturbance of fibrinolysis
(Hyperfibrinolysis), is not uncommon. Many trauma patients
suffer from an overwhelming activation of tissue factor and thus
massive hyperfibrinolysis. Also in other disease states
hyperfibrinolysis may occur. It could lead to massive bleeding if
not diagnosed and treated early enough.
 The fibrinolytic system is closely linked to control
of inflammation, and plays a role in disease states associated
with inflammation. Plasmin, in addition to lysing fibrin clots,
also cleaves the complement system component C3, and fibrin
degradation products have some vascular permeability inducing
effects.

13. Pharmacology
 In a process called thrombolysis (the breakdown of a thrombus),
fibrinolytic drugs are used. They are given following a heart attack to
dissolve the thrombus blocking the coronary artery; experimentally
after a stroke to allow blood flow back to the affected part of the brain;
and in the event of a massive pulmonary embolism.
 Thrombolysis refers to the dissolution of the thrombus due to various
agents while fibrinolysis refers specifically to the agents causing fibrin
breakdown in the clot.
 Antifibrinolytics such as aminocaproic acid (ε-aminocaproic acid)
and tranexamic acid are used as inhibitors of fibrinolysis. Their
application may be beneficial in patients with hyperfibrinolysis
because they arrest bleeding rapidly if the other components of the
haemostatic system are not severely affected. This may help to avoid
the use of blood products such as fresh frozen plasma with its
associated risks of infections or anaphylactic reactions. The
antifibrinolytic drug aprotinin was abandoned after identification of
major side effects, especially on kidney.

14. Fibrinolytic enzymes
 Anistreplase
 Desmoteplase
 Streptokinase
 Nattokinase
 Lumbrokinase
 Papain
 DNase
 Bromelain

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