The Role of Platelet Aggregation and Release in Fragment D-induced Pulmonary Dysfunction

Publisher Website
Google Scholar
Abstract
The plasma concentration of fibrinogen degradation product D (fragment D) is markedly increased following major burn or traumatic injury. Purified human fragment D infused into awake, restrained, nontraumatized rabbits (100 .mu.g/ml blood) causes progressive thrombocytopenia, pulmonary dysfunction, vascular leak and interstitial neutrophilia. Rabbits treated with the antihistamine diphenhydramine (Benadryl) prior to fragment D infusion fail to develop these symptoms. Platelet aggregation, platelet ATP secretion and platelet malondialdehyde [MDA] release was studied in rabbits which received fragment D alone or fragment D following diphenhydramine pretreatment. Platelet-rich plasma was prepared from citrated blood drawn from femoral arterial catheters at 0, 2 1/2 and 4 h postinfusion. Platelet aggregation was stimulated with collagen or ADP. MDA, a byproduct of thromboxane synthesis, was measured by colorimetry. Platelet aggregation and function (stimulated with collagen) were enhanced in fragment D platelet-rich plasma, since all response times decreased. Total ATP and MDA release increased. Diphenhydramine pretreatment inhibited fragment D-enhanced aggregation. ATP release and prostaglandin (thromboxane) synthesis. No animal pretreated with diphenhydramine exhibited thrombocytopenia or respiratory dysfunction. Stimulation of platelet aggregation and release may represent 1 mechanism by which fragment D induces pulmonary dysfunction. Diphenhydramine inhibits these responses and may prove therapeutic in posttraumatic pulmonary complications.