Histone induced platelet aggregation is inhibited by normal albumin

Thromb Res. 2013 Jul;132(1):69-76. doi: 10.1016/j.thromres.2013.04.018. Epub 2013 May 11.


Introduction: Histones are small, nuclear proteins that serve to package DNA. Recent reports suggest that extracellular histones, including histone H4, may contribute to the pathogenesis of sepsis; they promote platelet aggregation and thrombosis when released into the circulation during inflammation or cell death. The mechanisms by which the body minimizes the deleterious effects of circulating histones are unclear. Because histones can bind to plasma proteins, including albumin, we hypothesized that normal albumin can prevent histones from activating platelets.

Materials and methods: Platelets and platelet-free plasma were obtained from healthy, adult subjects. The dose-dependent effects of histone H4 on platelet aggregation were studied by optical aggregometry. The effects of native and albumin-depleted plasma (prepared by affinity chromatography) on histone-induced platelet aggregation were also assessed. The effects of normal and surface-neutralized albumin (through modification of carboxyl groups) on histone-induced platelet activation and aggregation were evaluated using flow cytometry and aggregometry.

Results: Histone H4 induced platelet aggregation in a dose-dependent manner. This histone-induced platelet aggregation was inhibited by both plasma and human serum albumin in a dose-dependent fashion. Furthermore, depletion of albumin from plasma reduced its ability to inhibit aggregation. Finally, surface neutralization of albumin decreased its ability to inhibit histone-induced activation and aggregation.

Discussion: These data suggest that normal albumin serves a role in preventing histone-induced platelet aggregation in a charge-dependent manner.

Keywords: Aggregation; Albumin; Histone; Platelet; Sepsis; Thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Blood Platelets / cytology*
  • Blood Platelets / metabolism
  • Histones / metabolism*
  • Humans
  • Platelet Aggregation*
  • Platelet Function Tests
  • Serum Albumin / metabolism*


  • Histones
  • Serum Albumin