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February 1, 1987American Journal of Clinical Pathology

Heparin-Protamine Complexes in the Production of Heparin Rebound and Other Complications of Extracorporeal Bypass Procedures

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Key result

Heparin-protamine complexes can become unstable due to enzymatic breakdown of free protamine, leading to heparin rebound and potentially causing acute pulmonary hypertension.

Population

In vitro plasma

Design

Preclinical

Authors

JSJ. N. ShanbergeMarquette UniversityMMMakoto MuratoBeaumont Hospital, Royal OakTQTherese M. Quattrociocchi-LongeBeaumont Hospital, Royal Oak

Discussion

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Implication

May warrant caution with protamine dosing after bypass; animal data leave open clinical relevance to heparin rebound.

Key Points

  • Characterize the equilibrium dynamics of heparin neutralization by protamine and elucidate the mechanisms underlying post-bypass heparin rebound and associated pulmonary toxicity.
  • Assessed in vitro plasma interactions between heparin, protamine, and antithrombin III under mass action equilibrium conditions.
  • Analyzed the effects of free protamine enzymatic degradation, antithrombin III addition, and protamine excess on complex stability and antithrombin activity.
  • Heparin remains neutralized only in the presence of excess protamine; enzymatic clearance of free protamine causes complex dissociation and liberates active heparin.
  • Heparin rebound is provoked by elevated heparin concentrations or increased antithrombin III availability, such as via fresh frozen plasma transfusions.
  • Excessive protamine promotes the formation of large heparin-protamine aggregates that retain antithrombin III activation capacity and may occlude the pulmonary microcirculation.

Structured PICO

P
Population
In vitro plasma
E
Exposure
Protamine neutralization of heparin
O
Outcome
Heparin rebound and antithrombin III activationsurrogate

Heparin rebound after bypass procedures may result from the enzymatic breakdown of excess protamine, releasing active heparin from unstable complexes.

Cite This Study

Shanberge et al. (1987) studied Complications of extracorporeal bypass procedures. Heparin-protamine complexes was evaluated. Heparin-protamine complexes can become unstable due to enzymatic breakdown of free protamine, leading to heparin rebound and potentially causing acute pulmonary hypertension.

synapsesocial.com/papers/6a93c4e417f1bd54554645bahttps://doi.org/10.1093/ajcp/87.2.210
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Protamine Reversal of Heparin Affects Platelet Aggregation and Activated Clotting Time After Cardiopulmonary Bypass1998 · 153 citations
  2. 2Heparin Anticoagulation during Cardiopulmonary Bypass in an Antithrombin-III Deficient Patient: Implications Relative to the Etiology of Heparin Rebound1980 · 48 citations
  3. 3Anticoagulation and Reversal Paradigms: Is Too Much of a Good Thing Bad?2009 · 15 citations
  4. 4HEPARIN‐REBOUND IN THE EARLY POSTOPERATIVE PHASE FOLLOWING CARDIOPULMONARY BYPASS1995 · 22 citations
  5. 5Heparin Neutralization with Methylene Blue, Hexadimethrine, or Vancomycin After Cardiopulmonary Bypass1996 · 50 citations