1. REVIEW OF HAEMOSTASIS Dr J Jordaan Dept Cardiothoracic surgery and Critical care University of the Free State Bloemfontein EACTS/ Hannes Meyer symposium 2012

3. Blood Jean-Baptiste Denis first blood transfusion-3U Sheep blood in 1667. Dr P Physick, Philadelphia first successful blood transfusion in 1795. Dr Karl Landsteiner discovered A B and O blood types in 1900. First blood bank USA, 1937. 14 MU packed cells given in 2001 in USA.

4. Theories on the coagulation of blood have existed since antiquity. Physiologist Johannes Peter Müller in 1858 described fibrin, and isolated chemically by Prosper Sylvain Denis in 1863 Alexander Schmidt suggested that the conversion from fibrinogen to fibrin is the result of an enzyme process, and labeled the hypothetical enzyme "thrombin" and its precursor "prothrombin". Nicolas Maurice Arthus discovered in 1890 that calcium was essential in coagulation. Platelets were identified in 1865, and their function was elucidated by Giulio Bizzozero in 1882. The theory that thrombin is generated by the presence of tissue factor was consolidated by Paul Morawitz in 1905. At this stage, it was known that thrombokinase/thromboplastin (factor III) is released by damaged tissues, reacting with prothrombin (II), which, together with Calcium, forms thrombin, which converts fibrinogen into fibrin (I).

5. Coagulation 1. Platelets 2. Coagulation factors Blood clot

6. FIRST RESPONSE: Initial Vasoconstriction Release of TA2 and Endothelin Reduction in Prostacyclin and Nitric oxide Immediately limits blood loss

7. Endothelium: Endothelium damage Exposure of Collagen Collagen and vWF interaction Platelet activation

8. 1. Platelet agregation

9. 2. Platelet activaton

12. Traditional pathway: Intrinsic and extrinsic pathways Activation of F X Activation of F II Fibrin formation with Fibrin clot In Vitro and In Vivo results findings not supportive

13. FXII FXIIa F XI F XIa FIX FIXa FXFXa Pro thrombinThrombin Fibrinogen Fibrin Firm clot Intrinsic pathway Ca F VIII Phospholipid F V Ca F XIII Extrinsic Pathway TF- FVIIa Hageman factor

14. Left with fibrin strands free floating binding to platelets and red cells

15. Cell based coagulation Initiation Priming Propagation Monroe DM, Arterioscler Thromb Vasc Biology 22:1381-1389, 2006

16. Cell based coagulation Vascular injury Tissue factor exposed by TF bearing cell Endothelium Myoepithelium Adventitia Monocytes Macrophages

17. 1. Initiation: Tissue factor bearing cell Endothelium Adventitial cells Myoepithelium Squamous cells Monocytes Macrophages TF FVIIa FVIIFX FXaF X-F Va Pro thrombin Thrombin F IX FIXa TF FVIIa Enhance platelet activation Accelerate coagulation response

18. Priming: Tissue factor bearing cell TF VIIaXa Va Platelet Thrombin Platelet primed due to collagen exposure through GP 1b reseptor Shape conformation and release of granules F V F Va F XI F XIa vWF/F VIII vWF F VIIIa

19. Priming: Activated Platelet F XIa F VIIIa F Va

20. 3 Propagation: Activated Platelet F XIa F VIIIa F IX F IXa F VIIIa F IXa F X F Xa FVa Pro Thrombin Thrombin burst.