A greater proportion of blood replacement needs are being met by packed red cell concentrates rather than whole blood in situations of major blood loss. Twelve patients, who required major blood replacement during elective surgery, were studied to determine the changes in coagulation when packed red cells were used to replace major blood loss. In addition, the coagulation abnormalities present at the time an observer noted excessive bleeding were determined. Prior to blood product replacement and after the estimated loss of each 0.3 blood volume, coagulation tests were obtained including prothrombin time (PT), partial thromboplastin time (aPTT), platelet count, thrombin time (TT), fibrinogen levels, and assays of coagulation Factors V, VIII, and IX. Coagulation tests were repeated when clinical hemostasis was judged inadequate by the anesthesiologist and attending surgeon. Significant decreases in platelet count, fibrinogen levels, and Factor V, VIII, and IX levels occurred as increasing blood volumes were replaced. Increases in PT and aPTT above control occurred in nine of the 12 patients prior to replacement of 1 blood volume; none of the nine patients had increased clinical bleeding. In four of seven patients who had blood replacement of greater than 1 blood volume, increased clinical bleeding was noted by the observer. Platelet counts were less than 100,000/mm3 in each of these four patients, and a platelet concentrate obtained by pheresis of a single donor was administered. In two of the four patients platelet counts increased, but clinical bleeding did not resolve.(ABSTRACT TRUNCATED AT 250 WORDS)