Evidence for an active fibrinolytic system in normal human bone marrow

Area of Science:

• Hematology
• Hemostasis and Thrombosis
• Biochemistry

Background:

• The fibrinolytic system regulates blood clot breakdown.
• Understanding fibrinolysis in bone marrow is crucial for its physiological functions.
• Bone marrow's role in hemostasis and potential fibrin deposition requires investigation.

Purpose of the Study:

• To quantitatively analyze components of the fibrinolytic system in normal human bone marrow.
• To compare the balance of fibrinolytic proteases and inhibitors in bone marrow versus plasma.
• To elucidate the functional state and potential role of the fibrinolytic system within bone marrow.

Main Methods:

• Quantitative analysis of fibrinolytic system components using functional and immunological assays.
• Analysis of normal human bone marrow samples obtained from cardiac surgery patients.
• Measurement of tissue-type plasminogen activator (t-PA), plasminogen, PAI-1, PAI-2, alpha2-antiplasmin (alpha2-AP), and related complexes.

Main Results:

• Bone marrow exhibits significant fibrinolytic activity due to high levels of active t-PA.
• Despite inhibitors (PAI-1, PAI-2), t-PA remains active.
• Bone marrow has higher t-PA, PAI-1, PAI-2 and lower u-PA, plasminogen, alpha2-AP compared to plasma.
• Presence of plasmin-alpha2-AP complex indicates active plasmin generation.

Conclusions:

• Normal human bone marrow possesses a potent and active fibrinolytic system.
• The unique balance of proteases and inhibitors favors fibrinolysis in bone marrow.
• The active fibrinolytic system likely clears excess fibrin deposits, maintaining marrow cavity patency and flow.