Fibrinolysis

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Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.[1]

In fibrinolysis, a fibrin clot, the product of coagulation, is broken down.[2] Its 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.

Physiology

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

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
(tPA) and urokinase.

α2-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.

Measurement

Plasmin breaks down fibrin into soluble parts 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

deep-vein thrombosis, pulmonary embolism, DIC and efficacy of treatment in acute myocardial infarction. 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.[4]

Testing of overall fibrinolysis can be measured by a

DDAVP or after severe stress.[5]

Role in disease

Few

congenital disorders of the fibrinolytic system have been documented. Nevertheless, excess levels of PAI and α2-antiplasmin have been implicated in metabolic syndrome
and various other disease states.

However, acquired disturbance of fibrinolysis (hyperfibrinolysis), is not uncommon. Many trauma patients have an overwhelming activation of tissue factor and thus massive hyperfibrinolysis.[6] Hyperfibrinolysis may occur in other disease states. 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.

Pharmacology

In a process called

stroke to allow blood flow back to the affected part of the brain; and in the event of pulmonary embolism.[7]

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.[8] This may help to avoid the use of blood products such as fresh frozen plasma with its associated risks of infections or anaphylactic reactions.

Fibrinolytic enzymes

References

  1. ^ Dugdale D. "Fibrinolysis - primary or secondary". MedlinePlus. Retrieved August 7, 2011.
  2. PMID 15842654
    .
  3. OCLC 39465455
    .
  4. PMID 18440953
    .
  5. OCLC 45485184
    .
  6. PMID 17426904
    .
  7. PMID 26308961
    .
  8. PMID 29200009
    .

External links
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