Biomaterials Research - Manfred Maitz

The Blood Clotting Cascade

Manfred Maitz FZ-Rossendorf www.manfred.maitz-online.de

Biomaterials Research - Manfred Maitz

The Clotting Cascade

Thrombin

Fibrin polymers

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

The Clotting Cascade

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

Serine Proteases
RN O C HN :O H RN

Ser

O-

O H

Ser
Tetraedric Transition State

HN
RC Break of the Peptide Bonding

RC

HN H RC RN H2O C :O Release of the H N-terminal peptide RN O

OH

Ser

Ser

Enzyme-acetyltransition-state

Biomaterials Research - Manfred Maitz

The Fibrinolytic System

Clotting Cascade Fibrin degradation products

Fibrinogen

Fibrin-clot

Plasminogen T-PA F XIIa HMWK Kallikrein Urokinase Streptokinase

Plasmin

Biomaterials Research - Manfred Maitz

Effect of Antithrombin III/Heparin

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

Thrombin Time (TT)

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

The Quick (PT)-Test

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

Partial Thromboplastin Time [(a)PTT]

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen

Biomaterials Research - Manfred Maitz

Surface Sensitive Steps

Intrinsic Pathway
Surface Contact Collagen FXII activator F XII F XI F XIIa
Ca2+

Extrinsic Pathway
Tissue/Cell Defect

F VIIa F XIa
Ca2+

Ca2+

F VII

F IX
F VIII

F IXa

F VIIIa Platelet Factor 3

F III (Tissue Thromboplastin) Factor F Xa

F Va Ca2+ FV

Factor F X

Ca2+

Factor F X

Prothrombin I F XIIIa Crosslinked Fibrin Meshwork F XIII Fibrin polymers

Ca2+

Thrombin

Fibrin monomers

Fibrinogen