Effect of acid and pepsin on blood coagulation and platelet aggregation

In a series of in vitro studies, both the soluble (plasmatic) coagulation system and the cellular (platelet-mediated) aspect of blood coagulation were shown to be extremely sensitive to relatively minor increases in hydrogen ion concentration.All studies became abnormal at pH 6.8.At pH 6.4, assays of the intrinsic and extrinsic coagulation systems, the polymerization of fibrinogen, and assay of the availability of platelet phospholipid (platelet factor 3) were twice prolonged over control values.Platelet aggregation was reduced by more than 50%.At pH 5.4 in vitro, platelet aggregation and plasma coagulation were both virtually abolished.Furthermore, previously formed platelet aggregates disaggregated at a slightly acid pH.Pepsin further enhanced platelet disaggregation.Because gastric acidity is normally two to four orders of magnitude greater than that which abolishes platelet aggregation and plasma clotting in vitro, and pepsin is present in abundance, we call attention to the probable antihemostatic effect of hydrocloric acid and pepsin in the upper gastrointestinal tract.This in vitro study may provide a rationale for meticulous regulation of intragastric pH in an effort to control upper gastrointestinal hemorrhage.Hemostasis in the upper gastrointestinal tract contrasts with that observed in external wounds.Gastroduodenal hemorrhage is often characterized by prolonged oozing and rebleeding lasting hours to days, frequently resulting in massive blood loss.With standardized punctures of the human skin, such as are made during an Ivy bleeding time test, hemorrhage normally stops in 3 to 8 min, rebleeding rarely occurs, and blood loss does not exceed 0.5 ml.' Explanations for the observed poor hemostatic response in the upper gastrointestinal tract of otherwise normal human beings include: continued and increased motility during hemorrhage;2 inaccessibility of bleeding sites to pressure or tamponade effect; the highly vascular nature of gastric and duodenal tissue which, furthermore, fails to demonstrate autoregulation of local blood flo~;~ and the possibility of local antihemostatic chemi-