Fibrinolytic System Defects

I. Review - Fibrinolysis

Crosslinked fibrin is the end product of the coagulation cascade.
The fibrinolytic system breaks down cross-linked fibers to avoid excessive thrombosis.
Plasmin is the molecule that is directly responsible for degrading fibrin.
Plasminogen activator converts plasminogen to its active form, plasmin.

II. Mechanisms of impaired fibrinolysis

A. Decreased or dysfunctional plasminogen levels

B. Decreased plasminogen activator level

C. Increased levels of fibrinolytic system inhibitors

1. Alpha2-antiplasmin

2. Alpha2-macroglobulin

D. Inhibition of plasminogen activator

Impaired fibrinolysis is often a reactive process and is also often seen in the setting of acute myocardial infarction, gereralized atherosclerosis, diabetes, thrombotic thrombocytopenic purpura, deep venous thrombosis, pulmonary embolus, liver disease, post-operative state, scleroderma, and sepsis.

III. Congenital plasminogen deficiency

A. Very rare but may account for 1% of unexplained venous thrombosis in young individuals.

B. Inheritance - autosomal dominant

C. Two forms - absent fibrinogen and dysfunctional plasminogen. Dysfunctional form is more common.

D. Clinical features are similar to Antithrombin III, Protein C and Protein S deficiencies:

1. Venous thrombosis is common and begins in mid-late teenage years.

2. Arterial thrombotic events are rare.

3. Thrombosis can occur when plasminogen levels drop below 40% of normal biologic activity.

E. Must specifically assay plasminogen activity to make the diagnosis.

F. aPT, aPTT, platelet count, thrombin time, and bleeding time are all normal.

G. Treatment - similar to Antithrombin III, Protein C and Protein S deficiencies:

1. Warfarin for long-term anticoagulation

2. Heparin for acute thrombosis

3. Anti-platelet agents

IV. Plasminogen Activator and Inhibitor Defects

A. Congenital deficiency of plasminogen activator and congenital increase in plasminogen activator inhibitor are rare but are associated with thrombosis.

B. Acquired deficiency of plasminogen activator is seen in:

1. Unstable angina, acute myocardial infarction, post-angioplasty

2. Type II diabetes (gets better with better diabetes control)

3. Inflammatory bowel disease

C. Decreased activity of the plasminogen activator is seen in:

1. Alcohol ingestion

2. Hyperlipidemia - especially with elevated LDL

3. Vascular disorders such as scleroderma and TTP

V. Congenital Dysfibrinogenemia

Go to Antithrombin III Deficiency

Go to Protein C Deficiency

Go to Protein S Deficiency

Go to Activated Protein C Resistance

Go Back to Hypercoagulable States

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