The role of fibrinogen degradation products in the pathogenesis of the respiratory distress syndrome.

Abstract

Pulmonary dysfunction in awake rabbits was induced by intravenous infusion of a highly purified human fibrin split product (fragment D). The dose of infused fragment D was chosen to achieve observed plasma concentrations of fibrin split products in hospitalized patients with severe burns or trauma (about 100mug of FSP/ml of blood). Four hours after infusion, the animals displayed a clinical and pathological pattern which closely resembled post-traumatic acute respiratory distress syndrome, including hypoxia, hypocarbia, thrombocytopenia, increased pulmonary capillary permeability to albumin, interstitial edema, hypertrophy of alveolar lining cells, and intra-alveolar hemorrhage. In vivo production of fibrin split products by infusion of thrombin with induction of secondary fibrinolysis produced similar pulmonary changes, although intravascular clots and platelet aggregates also were prominent. Infusion of human fibrinogen and human albumin at identical doses failed to induce pulmonary dysfuction. The results suggest that fibrin split products (fragment D) alone are toxic to the respiratory system and may contribute to the development of acute respiratory distress syndrome in severely traumatized or burned patients.