Fibrinolysis

 

 

ACTIVATORS OF FIBRINOLYSIS
tPA : tissue Plasminogen Activator uPA : urokinase type Plasminogen Activator

The major activator of vascular fibrinolysis, which activates plasminogen on the the fibrin surface. The Zymutest tPA: Ag assay measures homogenously tPA as well as its complexes with
PAI-1 or other inhibitors.

The Zymuphen tPA Activity is based on tPA’s  ability  to transfer plasminogen into plasmin.

uPA is involved in vascular fibrinolysis, but also in extra vascular fibrinolysis, cell migration and tissue remodeling. Kallicrein, Factor Seven Activating Protease (FASEP), cathepsins and plasmin activate the single chain uPA (ScuPA) to two chain uPA (Tcu-PA), the active form, especially when it is bound to its cell receptor uPAR.

Zymutest uPA:Ag measures homogeneously the total uPA protein, whether the presentation is (ScuPA, TcuPA, HMW-uPA, LMW-uPA), free or complexed with its inhibitors.

  • Zymutest tPA:Ag (#RK011A),
  • Zymuphen tPA Activity (#521296)
  • Zymutest uPA:Ag (#RK013A)
Plasminogen Fibrinogen
Plasminogen is the inactive precursor of plasmin, a potent serine protease involved in the dissolution of fibrin blood clots. Both hereditary and aquired forms of plasminogen deficiency have been described. These are usually associated with either a thrombotic or a hypherfibrinolytic condition. Plasminogen binding to fibrin clot is modulated by Histidin Rich Glyco-Protein (HRGP) and alpha2 Anti-plasmin.  Biophen Plasminogen LRT is the new, liquid reagent based,  chromogenic assays from Hyphen BioMed  Fibrinogen, when clotted to fibrin, triggers and regulates fibrinolysis functions. Fibrin binds alpha2-AP, tPA, plasminogen (in a regulated manner) and is a substrate for TAFI and plasmin. Fibrinogen can be measured using functionnal clotting assays, such as Clauss Method (Fibriphen),  Elisa assays (Zymutest Fibrinogen) or latex immunoassays (Liaphen Fibrinogen).
  • Biophen Plasminogen LRT (#221511)
  • Fibriphen (CK571)
  • Zymutest Fibrinogen (#RK024A)
  • Liaphen Fibrinogen (#120102)
INHIBITORS OF FIBRINOLYSIS
TAFI: Thrombin Activatable Fibrinolysis Inhibitor PAI-1 Plasminogen Activator Inhibitor-I
The zymogen form of Thrombin Activatable Fibrinolysis Inhibitor also known as activatable TAFI, procarboxypeptidase U, of procarboxypeptidase B, is described as a plasma glycoprotein synthesized in the liver. It can be catalysed into its active form, TAFIa, carboxypeptidase U or B) by thrombin-thrombomodulin complex.

TAFI can potentially inhibit fibrinolysis by removing carboxyterminal lysine residues from partially degraded fibrin, decreasing plasminogen binding onto the fibrin, decreasing plasminogen binding onto the fibrin surface, which thereby results in a decreasing fibrinolytic activity.

Zymutest Activatable TAFI is specific for the intact zymogen from whilst Zymutest (Total) TAFI measures all the TAFI molecular forms, including non-activated and inactivated ones.

 The major inhibitor of tPA and uPA, intravascularly and extravascularly. PAI-1 forms rapidly inactive tPA-PAI-1 and uPA-PAI-1 complexes in presence of tPA or uPA. Most of the blood PAI-1 (>90% in pathology) is in the latent form in platelets.

Zymutest PAI-1:Ag measures all the PAI-1 forms, irrelevantly of their presentation.

Zymutest PAI-1 Activity measures active PAI-1, through its binding to tPA

  • Zymutest PAI-1 : Ag (#RK012A)
  • Zymutest PAI-1 Activity (#RK019A)
Alpha2-Anti-Plasmin
The major fast acting plasmin inhibitor in plasma which deficiency induces hyperfibrinolysis and bleeding risk. Alpha2 Anti-Plasmin is measured with a functional assay, through its rapid plasmin inactivation. Biophen α2-antiplasmin LRT is th new, liquid reagent based, chromogenic assay from Hyphen BioMed
  • Zymutest Activatable TAFI (#RK037A)
  • Zymutest (Total) TAFI:Ag (#RK008A)
  •  Biophen α2-antiplasmin LRT (#220502)

 

MARKERS OF FIBRINOLYSIS
Ddimeren uPA-PAI-1 complexes
The circulating enzyme, plasmin, cleaves the fibrin gel in a number of places. The resultant fragments. “high molecular weight polymers”, are digested several times more by plasmin to lead to intermediate forms and then to smaller polymers (fibrin degradation products or FDP’s). The crosslink between two D fragments remains intact however, and these are exposed on the surface when the fibrin fragments are sufficiently digested.

Typical Ddimer fragment contains two D domains and one E domain of the original fibrinogen molecule and is present in blood clot forms and degraded by fibrinolysis. Zymutest Ddimer is an Elisa assay with high specifity and no interference from fibrinogen.

uPA-PAI-1 complexes can be generated in blood circulation when increased levels of uPA and PAI-1 are present, but these complexes are usually formed extravascularly. Can be marker of some cancer types (especially breast tumors), as a prognosis of disease evolution, when measured in tumor extracts or exsudates.
  • Zymutest uPA-PAI-1 (#RK018A)
tPA-PAI-1 Complexes
tPA-PAI-1complexes are generated in blood circulation when fibrinolysis is stimulated and increased levels of tPA and PAI-1 are present.

Elevated concentrations of tPA-PAI-1 complexes reflect the involvement of fibrinolytic mechanisms in circulation.

  • Zymutest Ddimer (#RK023A)
  •  Zymutest tPA-PAI-1 (#RK017A)