Role of Blood Components in Mediating Lung Vascular Injury after Pulmonary Vascular Thrombosis

¹ From the Department of Physiology, Albany Medical College of Union University, Albany

Figure 1 indicates the postulated mechanisms of the increased lung vascular permeability after thrombin-induced pulmonary microembolization. Thrombin converts fibrinogen to fibrin, and fibrin is a necessary requirement for the mediation of lung vascular injury because thrombin failed to increase lung vascular permeability in the absence of fibrinogen (induced by Ancrod). Fibrin may act by 2 mechanisms: (1) by inducing the activation of plasmin, and (2) by serving as a source of fibrin degradation products. Plasmin activation is important since inhibiting plasminogen activation with tranexamic acid also prevented the increase in lung vascular permeability. Plasmin may act by activating the complement system to generate chemotactic fragments such as C5a and also by lysing fibrin to generate fibrin degradation products which are also chemotactic.

Granulocyte aggregation is a crucial step in the genesis of lung vascular injury because granulocyte depletion with hydroxyurea prevented the increased pulmonary vascular permeability. The final step is not certain, but may be related to generation of oxygen radicals and proteases from the activated granulocytes. Platelets do not figure into this scheme because platelet depletion failed to prevent the increase in lung vascular permeability after activation of the clotting mechanism with thrombin.