Review of haemostasis EACTS/ Hannes Meyer symposium 2012 Dr J Jordaan Dept Cardiothoracic surgery and Critical care University of the Free State Bloemfontein

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.

Theories on the coagulation of blood have existed since antiquity 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).

Coagulation 1. Platelets 2. Coagulation factors Blood clot

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

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

1. Platelet agregation

2. Platelet activaton

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

Intrinsic pathway Extrinsic Pathway FXII FXIIa Hageman factor TF- FVIIa F XI F XIa FIX FIXa Ca Ca F VIII Phospholipid FX FXa F V Ca Fibrinogen Pro thrombin Thrombin Fibrin F XIII Firm clot

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

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

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

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

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

Priming: F VIIIa F XIa F Va Activated Platelet

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