Effect of albumin on the inhibition of platelet aggregation by β-lactam antibiotics

Platelet aggregation and bleeding time abnormalities are reported in patients receiving β-lactam antibiotics (βLAs), although clinical bleeding most frequently occurs in chronically ill, malnourished patients. Although most βLAs bind to serum albumin, the relative influence of bound versus unbound βLAs on platelet function is unknown. We examined the effect of βLAs on the aggregation of gel-filtered platelets from normal subjects and on platelet-rich plasma (PRP) from hypoalbuminemic patients. Therapeutic concentrations of five βLAs were added to normal platelets at different albumin concentrations (1.5 to 4.5 g/dL). Inhibition of aggregation by the βLAs was inversely proportional to the albumin concentration, and most antibiotic-treated samples showed more than 50% inhibition at albumin levels below 2.0 g/dL. When PRPs from hypoalbuminemic patients were incubated with cephalothin, aggregation was completely inhibited, in contrast to samples from patients with normal albumin levels, and this decreased platelet aggregation was partially restored (25% to 75%) by increasing the albumin concentration above 4.0 g/dL. Specific binding of [³⁵S]-benzylpenicillin to normal platelets decreased proportionately as the albumin concentration increased in the range of 1.0 to 5.0 g/dL. The inhibitory effects of βLAs on platelets in vitro appear to be influenced by albumin concentration. Plasma albumin concentration may influence bleeding in patients receiving βLAs.