COAGULATION SYSTEM BREAKDOWN

SYSTEM OVERLOAD
2.4.1 Disseminated Intravascular Coagulation (DIC).
This syndrome is a systemic Thrombo-hemorrhagic disorder.
It occurs in small vessels (micro vascular) or sometimes in large vessels, and can leads to organ failure and death.
It is met with as a mild or severe form in the following conditions:
* Hemolytic
* Gram positive or gram negative sepsis
* Viremia
* Crush injury
* Burns
* Leukemia
* Malignancy with Metastasis
2.4.2 Clinical features
In DIC there is evidence of coagulation activation, fibrinolytic
activation, inhibiter consumption resulting in biochemical
evidence of some end organ damage.

In low grade DIC, there are minimal symptoms and laboratory
evidence while in severe DIC there is life threatening bleeding
disorders.

The simultaneous activation of coagulation and fibrinolytic
systems results in presence of both thrombin, and plasmin in
circulation.

Thrombin alters fibrinogen and fibrin monomers are released.
These cause fibrin clots resulting in microvascular thrombosis.
Platelets are entrapped in Thrombus leading to their depletion in
the blood.
Plasmin in circulation further acts on the degraded products in circulation, resulting in depressed levels of fibrinogen and increased levels of fibrinogen degradation products.
Plasmin also degrades factor V, VIII, IX and XI and
activates complement system all these derangements lead to D
**Fibrinolysis (and Regulation of Thrombosis)

-The fobrinolytic system aims to break down fibrin and dissolve thrombus, allowing healing of the wound. If provides a to limit the thrombotic mechanism.
-The main means for fibrinolysis is the breakdown of fibrin into soluble fragments by the proteolytic enzyme plasmin.
-Plasmin binds fibrin, and splits it at multiple sites, resulting in fibrin split products (FSPs)
The process Steps.
-Plasminogen is the precursor to plasmin. It is converted to plasmin by tissue plasminogen activator (tPA), which is released form endothelial cells near the site of injury.
-Although this reaction is inefficient in the general circulation, in the presence of a fibrin clot it is rapid.
-Thus fibrin is both the target and controler of its own destruction. Urokinase, so named because of its high concentration in the urine, is a plasminogen activator that is not fibrin specific.
-That, it converts plasminogen to plasmin in the circulation and not just on the clot.
-It is also the main activator of fibrinolysis in the extravaseular space.
-Urokinase is formed form the singlechain urokinase plasminogen activator precursor.
-Alpha2 antiplasmin (alpha2-AP) is the main inhihitor of plasmin, but also can bind plasminogen.
-Plasmin is inhibited by alpha2-AP when in the circulation, but its degradation is prevented when bound to the fibrin clot.
-This ensures localized, and not systemic, fibrinolysis.
-Fibrinolysis is kept in check by several inhibitors of plasminogen activation.
-These include plasminogen activator inhibitor type I (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI).**

Lab. Diagnosis
- No test confirm fibriolysis, but the process can be assed by laboratory tests
- One can measure levels of fibrinogen.
- FSPs,
- Plasminogen
- Plasminogen activator and
- Plasimin inhibitors
- The thrombin time (TT) is prolonged in fibrinolysis, and is useful in monitoring the fibrinolytic state during fibrinolytic therapy.
- Bleeding complications from such therapy are more common when the fibrinogen level is less than 100mg/dL and when FSPs are greater the 100U/dL,

Treatment
- Fresh frozen plasma (FFP) can be used to correct fibrinogen levels and reduce coagulopathy in such situations**.

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