Bleeding and overanticoagulation with low molecular weight heparin
The patient-related risk factors for bleeding during low molecular weight heparin (LMWH) therapy include recent surgery or trauma, advanced age and female sex; see also patient-associated factors for increased bleeding risk in Patient-associated factors that increase bleeding risk with anticoagulant therapy. Impaired kidney function is a more important risk for bleeding with LMWH than with unfractionated heparin (UFH), because LMWH is excreted via the kidneys.
If clinically significant bleeding occurs while a patient is receiving LMWH, stop the LMWH and check the anti-Xa level urgently to assess the extent of residual anticoagulant activity. For major or potentially life-threatening bleeding, immediate reversal of the anticoagulant effect may be required.
Protamine sulfate reverses 60 to 75% of the anticoagulant effect of LMWH and it can manage bleeding or LMWH overdose. The protamine dose needed will decrease with the time since LMWH was given.
If it has been less than 8 hours since the last dose of LMWH, use:
protamine intravenously, at a maximum rate of 5 mg/minute: protamine sulfate protamine protamine
1 mg per 100 units dalteparin (maximum 50 mg)
1 mg per 1 mg enoxaparin (maximum 50 mg).
If it has been 8 to 12 hours since the last dose of LMWH, use:
protamine intravenously, at a maximum rate of 5 mg/minute: protamine sulfate protamine protamine
0.5 mg per 100 units dalteparin (maximum 50 mg)
0.5 mg per 1 mg enoxaparin (maximum 50 mg).
The maximum protamine dose is 50 mg because it can have a weak anticoagulant effect at higher doses. Protamine does not completely reverse the anticoagulant effect of LMWH, so if bleeding is not controlled, seek specialist haematologist advice.
If it has been more than 12 hours since the last dose of LMWH (depending on the LMWH dose and the patient’s kidney function), protamine reversal may be unnecessary because the LMWH has been metabolised. Check the anti-Xa level and seek specialist haematologist advice. For adverse effects of protamine, see Bleeding and overanticoagulation with unfractionated heparin.