Biomaterials ResearchBiomaterials Research - Manfred Maitz The Blood Clotting Cascade Manfred Maitz FZ-Rossendorf www.manfred.maitz-online.de.

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Presentation transcript:

Biomaterials ResearchBiomaterials Research - Manfred Maitz The Blood Clotting Cascade Manfred Maitz FZ-Rossendorf

Biomaterials ResearchBiomaterials Research - Manfred Maitz The Clotting Cascade Fibrinogen Fibrin monomers Fibrin polymers Thrombin

Biomaterials ResearchBiomaterials Research - Manfred Maitz Factor F X F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII Intrinsic Pathway Ca 2+ The Clotting Cascade Factor F X F VIIF VIIa F III (Tissue Thromboplastin) Tissue/Cell Defect Extrinsic Pathway Ca 2+ Fibrinogen Fibrin monomers Fibrin polymers Thrombin Prothrombin I Factor F Xa Ca 2+ Platelet Factor 3 Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII

Biomaterials ResearchBiomaterials Research - Manfred Maitz Ser :O H RNRN C O HN RCRC Serine Proteases H2OH2O O RNRN C O-O- HN RCRC Ser H Tetraedric Transition State RNRN C O OH :O H Ser Release of the N-terminal peptide HN H RCRC O RNRN C O Ser Break of the Peptide Bonding Enzyme-acetyl- transition-state

Biomaterials ResearchBiomaterials Research - Manfred Maitz The Fibrinolytic System Fibrin degradation products FibrinogenFibrin-clot PlasminPlasminogen T-PA F XIIa HMWK Kallikrein Urokinase Streptokinase Clotting Cascade

Biomaterials ResearchBiomaterials Research - Manfred Maitz Effect of Antithrombin III/Heparin Fibrinogen Fibrin monomers Prothrombin I Thrombin Factor F XaFactor F X F VIIF VIIa F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII F III (Tissue Thromboplastin) Tissue/Cell Defect Intrinsic Pathway Extrinsic Pathway Platelet Factor 3 Ca 2+ Fibrin polymers Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII Ca 2+

Biomaterials ResearchBiomaterials Research - Manfred Maitz Thrombin Time (TT) Fibrinogen Fibrin monomers Prothrombin I Thrombin Factor F XaFactor F X F VIIF VIIa F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII F III (Tissue Thromboplastin) Tissue/Cell Defect Intrinsic Pathway Extrinsic Pathway Platelet Factor 3 Ca 2+ Fibrin polymers Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII Ca 2+

Biomaterials ResearchBiomaterials Research - Manfred Maitz The Quick (PT)-Test Fibrinogen Fibrin monomers Prothrombin I Thrombin Factor F XaFactor F X F VIIF VIIa F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII F III (Tissue Thromboplastin) Tissue/Cell Defect Intrinsic Pathway Extrinsic Pathway Platelet Factor 3 Ca 2+ Fibrin polymers Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII Ca 2+

Biomaterials ResearchBiomaterials Research - Manfred Maitz Partial Thromboplastin Time [(a)PTT] Fibrinogen Fibrin monomers Prothrombin I Thrombin Factor F XaFactor F X F VIIF VIIa F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII F III (Tissue Thromboplastin) Tissue/Cell Defect Intrinsic Pathway Extrinsic Pathway Platelet Factor 3 Ca 2+ Fibrin polymers Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII Ca 2+

Biomaterials ResearchBiomaterials Research - Manfred Maitz Surface Sensitive Steps Fibrinogen Fibrin monomers Prothrombin I Thrombin Factor F XaFactor F X F VIIF VIIa F IXaF IX F XIaF XI Surface Contact Collagen FXII activator F XIIaF XII F III (Tissue Thromboplastin) Tissue/Cell Defect Intrinsic Pathway Extrinsic Pathway Platelet Factor 3 Ca 2+ Fibrin polymers Crosslinked Fibrin Meshwork F XIIIaF XIII F VF Va F VIIIaF VIII Ca 2+