Platelet and neutrophil sequestration after fragment D-induced respiratory distress

The serum concentration of fibrinogen split product D (fragment D; Fg D) is often elevated after trauma and sepsis. Purified human Fg D infused into awake rabbits causes progressive thrombocytopenia and complement depletion, pulmonary dysfunction, increased vascular permeability to albumin, and neutrophil congestion. This study demonstrates the sites of organ sequestration of platelets and neutrophils after Fg D-induced respiratory distress. Washed, 51Cr-labeled rabbit platelets were infused into control (n = 10) and Fg D-infused rabbits (n = 10) Washed, 51Cr-labeled rabbit neutrophils were infused into two additional rabbit groups (control, n = 10; Fg D, n = 10). Four animals from each group were sacrificed at 2 h and six animals at 4 h postinfusion. Four biopsies from the lung, kidney, liver, heart, and spleen of each rabbit were counted for isotope uptake. Data for like groups were analyzed by the Student's t-test. At 2 h platelets that disappear from the circulation begin to sequester in the lung, liver, kidney, and heart of Fg D-infused rabbits (p less than 0.001). Neutrophils are not yet trapped in organ vasculature. However, 4 h postinfusion after thrombocytopenia and complement depletion, platelets are trapped in all organs studied (P less than 0.001) Neutrophils have significantly increased in lung and liver (P less than 0.001). Platelets activated by Fg D in this model sequester before neutrophils, suggesting that the platelet membrane effects of Fg D may initiate organ failure after shock and sepsis.