Protamine reversal of low molecular weight heparin: clinically effective?

Blood Coagul Fibrinolysis. 2011 Oct;22(7):565-70. doi: 10.1097/MBC.0b013e3283494b3c.


Low molecular weight heparins (LMWHs) are frequently used in the prophylaxis or treatment of venous thrombosis, acute coronary syndromes and peri-operative bridging. Major bleeding occurs in 1-4% depending on dose and underlying condition. Protamine is recommended for reversal but only partially reverses the anti-Xa activity and there are very limited data on clinical effectiveness. We retrospectively studied the effect of emergency reversal of LMWH with protamine in actively bleeding patients and patients requiring emergency surgery in our institution. Eighteen patients were identified through haematology referral/pharmacy records of protamine prescriptions between 1998 and 2009. Case notes were checked for the reversal indication, type/dose of LMWH, dose and clinical response to protamine, timing in relation to the last dose of LMWH and anti-Xa levels before and after protamine. All but one patient received enoxaparin. Fourteen were actively bleeding, three required emergency surgery without active bleeding and one had an accidental overdose without bleeding. The three patients requiring surgery had an uneventful procedure. In 12 of 14 patients with active bleeding, protamine could be evaluated. Bleeding stopped in eight. In the four with continuing bleeding, one had an additional coagulopathy. Protamine only partially affected anti-Xa levels. Protamine may be of use in reversing bleeding associated with LMWH but not in all patients. Anti-Xa levels were useful to assess the amount of anticoagulation before protamine administration but unhelpful in assessing its effect. Better reversal agents and methods to monitor LMWH therapy are required.

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / pathology
  • Acute Coronary Syndrome / prevention & control*
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Factor Xa / analysis
  • Female
  • Hemorrhage / blood
  • Hemorrhage / drug therapy*
  • Hemorrhage / prevention & control
  • Heparin Antagonists / administration & dosage
  • Heparin Antagonists / therapeutic use
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Male
  • Protamines / administration & dosage*
  • Protamines / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • United Kingdom
  • Venous Thrombosis / blood
  • Venous Thrombosis / pathology
  • Venous Thrombosis / prevention & control*


  • Anticoagulants
  • Heparin Antagonists
  • Heparin, Low-Molecular-Weight
  • Protamines
  • Factor Xa