Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII

• The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Muller et al has been cited greater than100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of less than10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology (hsv//eng)

Keyword

MEDICINE

MEDICIN

Coagulation

Publication and Content Type

ref (subject category)

art (subject category)