Thromboelastometry fails to detect autoheparinization after major trauma and hemorrhagic shock

J Trauma Acute Care Surg. 2022 Mar 1;92(3):535-541. doi: 10.1097/TA.0000000000003464.


Background: Heparan sulfate is an integral component of the glycocalyx that provides an anticoagulant layer close to the endothelium. Hypoperfusion, inflammation, and sympathoadrenal activation following major trauma result in glycocalyx shedding and subsequent release of heparan sulfate into the bloodstream. The possible anticoagulant effect of this "autoheparinization" has been suggested as a potential driver of trauma-induced coagulopathy. We investigated whether thromboelastometry can be used to detect trauma-induced autoheparinization.

Methods: This study comprised three parts. First, in a retrospective clinical study of 264 major trauma patients, the clotting time (CT) in the intrinsic activation (INTEM) and intrinsic activation plus heparinase (HEPTEM) assays were evaluated upon emergency room admission. Second, in an in vivo experimental rat model of hemorrhagic-traumatic shock, the release of heparan sulfate was investigated with INTEM and HEPTEM analyses of whole blood. Third, in vitro spiking of whole blood from healthy volunteers was undertaken to assess the effects of clinically relevant quantities of heparan sulfate and heparin on CT in the INTEM and HEPTEM assays.

Results: In the first part, severe injury and hemorrhagic shock was not associated with any increases in INTEM CT versus HEPTEM CT. Part 2 showed that an approximate threefold increase in heparan sulfate resulting from hemorrhagic traumatic shock in rats did not prolong INTEM CT, and no significant differences between INTEM CT and HEPTEM CT were observed. Third, spiking of whole blood with heparan sulfate had no impact on INTEM CT, whereas heparin elicited significant prolongation of INTEM CT.

Conclusion: Despite structural similarity between heparan sulfate and heparin, the amounts of heparan sulfate shed in response to trauma did not exert an anticoagulant effect that was measurable by the intrinsically activated CT in thromboelastometry. The extent to which heparan sulfate contributes to trauma-induced coagulopathy has yet to be elucidated.

Level of evidence: Prognostic and Epidemiologic; Level III.

Publication types

  • Clinical Study

MeSH terms

  • Animals
  • Blood Coagulation Disorders / blood*
  • Blood Coagulation Tests
  • Female
  • Glycocalyx / metabolism*
  • Heparin / metabolism*
  • Heparin / pharmacology
  • Heparitin Sulfate / metabolism*
  • Heparitin Sulfate / pharmacology
  • Humans
  • Male
  • Rats
  • Retrospective Studies
  • Shock, Hemorrhagic / metabolism*
  • Thrombelastography / methods*
  • Wounds and Injuries / metabolism*


  • Heparin
  • Heparitin Sulfate