Review of haemostasis

Dr J Jordaan

Dept Cardiothoracic surgery and Critical care

University of the Free State

Bloemfontein

EACTS/ Hannes Meyer symposium 2012

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. 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 factorsBlood 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

FXII FXIIa

F XI F XIa

FIX FIXa

FX FXa

Pro thrombin Thrombin

Fibrinogen

Fibrin

Firm clot

Intrinsic pathway

Ca CaF VIIIPhospholipid

F VCa

F XIII

Extrinsic Pathway

TF- FVIIa

Hageman factor

• 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

EndotheliumAdventitial cellsMyoepitheliumSquamous cellsMonocytesMacrophages

TF

FVIIa

FVII FX

FXa F X-F Va

Pro thrombin

Thrombin

F IX

FIXa

TF

FVIIa

Enhance platelet activationAccelerate coagulation response

Priming:

Tissue factor bearing cell

TF

VIIa Xa

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

Priming:

Activated Platelet

F XIaF VIIIa

F Va

3 Propagation:

Activated Platelet

F XIa

F VIIIa

F IX

F IXa

F IXa

F VIIIa

F IXa

F X

F XaFVa

Pro Thrombin

Thrombin burst.