HANDOUT NOTES – HAEMATOLOGY

FIBRINOLYSIS – PROF DORA MBANYA

OBJECTIVES:

At the end of this lecture, the student should be able to:

• Describe the components of the fibrinolytic system

• Describe the mechanism by which fibrinolysis occurs

• Describe inhibitors of the system

• Define laboratory assessment

INTRODUCTION

It is the lysis of the clot formed during coagulation both at intra & extra-vascular sites. The process
starts during contact activation and Kallikrein is its main activator, as well as FXIIa.

COMPONENTS OF THE FIBRINOLYTIC SYSTEM:

– Plasminogen: Is an inactive single-chain GP; N = 200ug/ml; activated by plasminogen

activators (PAs)

– Plasminogen activators: Include Intrinsic (Kallikrein, FXIa, FXIIa, HMWK, t-PA

(vascular t-PA & U-PA) and Extrinsic (non-human sources: the best known is
streptokinase).

– Plasmin: a powerful enzyme.

– Inhibitors of fibrinolysis: Include Anti-activators and Antiplasmins

– Fibrin degradation Products (FDPs): are also a component of this system.

MECHANISM

• t-PA is biologically inactive until it binds FIa. The t-PA/FIa link causes the lysis of plasminogen
to form Plasmin. Plasmin acts on t-PA,↑ its action to produce plasmin. Plasmin is rapidly
inactivated by anti-plasmins (α2-antiplasmin).

• Plasmin acts by fragmenting FIa and FI at several sites to produce FDPs. These FDPs include:

• Fibrinopeptides A, B, C; the D and Y fragments; Y fragments produce D & E fragments) and X

fragments. FDPs inhibit haemostasis, interfering with fibrin polymerization. FDPs also inhibit
platelet function.

IINHIBITORS OF FIBRINOLYSIS

PA Inhibitors: Include Fast-acting PAI -1 (by EC) and PAI-2 (by placenta; so acts during pregnancy)

Plasmin Inhibitors: Include α2-antiplasmin (most potent); N~80ug/ml. It forms a 1:1 complex with
plasmin, thus inactivating it. There is also α2-macroglobulin, and Histidine-rich-glycoprotein
EXPLORING FIBRINOLYSIS

• Measure FDPs (N < 10ug/ml)

• Ethanol Gelation Test: detects high molecular weight FDPs (X and Y fragments)

• Radio-immunoassays of specific FDP fragments (X, D-D dimers)

• Plasminogen levels; N~200ug/ml (↓in↑fibrinolysis)

• α2-antiplasmin levels (N~80ug/ml)

• FI assay

• Euglobulin lysis test: screens fibrinolytic activity. N= 2- 4Hrs. If lysis<2hrs (abnormal)

CONCLUSIONS

Fibrinolysis is a complex system, indispensable for proper wound healing.