The common conception of “heparin rebound” invokes heparin returning to circulation
in the postoperative period after apparently adequate intraoperative reversal with
protamine. This is believed to portend increased postoperative bleeding and provides
the rationale for administering additional empiric doses of protamine in response
to prolonged coagulation tests and/or bleeding. However, the relevant literature of
the last 60+ years provides only a weak level of evidence that “rebounded” heparin
itself is a significant etiology of postoperative bleeding after cardiac surgery with
cardiopulmonary bypass. Notably, many of the most frequently cited heparin rebound
investigators ultimately concluded that although exceedingly low levels of heparin
activity could be detected by anti-Xa assay in some (but not all) patients postoperatively,
there was no correlation with actual bleeding. An understanding of the literature
requires a careful reading of the details because the investigators lacked standardized
definitions for “heparin rebound” and “adequate reversal” while studying the phenomenon
with significantly different experimental methodologies and laboratory tests. This
review was undertaken to provide a modern understanding of the “heparin rebound” phenomenon
to encourage an evidence-based approach to postoperative bleeding. Literature searches
were conducted via PubMed using the following MeSH terms: heparin rebound, heparin
reversal, protamine, platelet factor 4, and polybrene. Relevant English language articles
were reviewed, with subsequent references obtained from the internal citations. Perspective
is provided for both those who use HepCon-guided management and those who do not,
as are practical recommendations for the modern era based on the published data and
conclusions of the various investigators.
Key Words
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Published online: December 23, 2022
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