Virchow's triad revisited: abnormal flow.

Virchow rightly recognised that blood flow plays an important role in thrombosis. The roles of blood flow in haemostasis, and in arterial, intra-cardiac, and venous thrombosis are reviewed. In streamline (laminar) flow, shear stresses are maximal at the vessel wall, and affect endothelial cell morphology and function (e.g. secretion of NO, prostacyclin,t-PA and vWF). Platelets are also concentrated at the vessel wall (due to axial concentration of red cells)where they can be activated by high shear stresses and are well-placed to interact with vWF and subendothelium,resulting in platelet adhesion and the initial stages of haemostasis. On the other hand, increasing wall shear forces increase removal of thrombin and fibrin monomer, hence stasis (induced by internal or external pressure) is required to allow fibrin formation and secondary haemostasis. Atherogenesis occurs in areas of arterial flow separation,which promotes platelet, leucocyte, LDL and fibrinogen adhesion and wall infiltration. Rheological variables (e.g. wall shear stress, viscosity, haematocrit,fibrinogen, LDL) have been correlated with the extent of ultrasonic carotid intima-media thickening. Arterial thrombosis usually follows rupture of atherosclerotic plaques and intra-plaque haemorrhage: high intra-stenotic shear stresses may activate platelets,promoting the initial platelet-rich "white-head" of arterial thrombi, while low post-stenotic shear stresses may promote the subsequent, fibrin--and red cell-rich "red tail". Blood viscosity, platelet microemboli, and activated leucocytes may each reduce post-stenotic microcirculatory blood flow, promoting infarction. Such mechanisms may explain the associations of increased levels of blood and plasma viscosity, haematocrit, white cell count, fibrinogen and vWF with risk and outcome of myocardial, cerebral and limb infarction. Areas of recirculating blood flow under low shear stresses predispose to intracardiac thromboembolism(e.g. atrial fibrillation, in which elevated fibrin D-dimer levels are normalised after cardioversion) and venous thromboembolism (fibrin D-dimer levels are associated with most risk factors). There is good evidence that reduction of venous stasis in the legs reduces the risk of venous thromboembolism. There is increasing evidence that regular exercise and avoidance of immobility reduces the risk of both arterial and venous thrombosis and also has systemic antithrombotic and anti-inflammatory effects. So: "Go with the flow!"