Bleeding and overanticoagulation with unfractionated heparin

The risk of bleeding during therapy with unfractionated heparin (UFH) is increased if activated partial thromboplastin time (APTT) is above the target range. Patient-related risk factors 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.

If clinically significant bleeding occurs while a patient is receiving intravenous UFH, stop the UFH and check APTT urgently. For major or potentially life-threatening bleeding, immediate reversal of the anticoagulant effect may be requiredFrontera, 2016.

Protamine sulfate reverses the effect of UFH, and it can manage bleeding or an UFH overdose. The protamine dose is determined by the dose of UFH given and the time since the UFH was given. If it has been more than 3 hours since the UFH was given, protamine reversal may be unnecessary because the UFH has been metabolised; the half-life of UFH is 60 to 90 minutes.

Clinical data to guide dosage are lacking; if available, follow a local protocol for protamine dosage.

If a local protocol is not available, first calculate the amount of UFH given in the preceding 3 hours. For example, if the UFH infusion rate is 1300 units/hour, then 3900 units of UFH require reversal.

To reverse the anticoagulant effect of UFH, give:

The maximum protamine dose is 50 mg because it can have a weak anticoagulant effect at higher doses.

APTT should normalise rapidly after giving protamine. If bleeding persists and APTT remains elevated, a repeat dose of protamine (0.5 mg per 100 units of UFH) can be given (the half-life of protamine is only 7 minutes). Seek specialist haematologist advice if bleeding is not controlled Frontera, 2016.

Protamine can cause hypotension, flushing, pulmonary oedema and bradycardia. It is a derivative of fish sperm, and can cause anaphylaxis; however, the benefit of protamine in a patient with clinically significant bleeding outweighs the risk of an allergic reaction. The risk of an allergic reaction increases in patients who have developed preformed antibodies, including those patients who:

• have previously received protamine (eg during coronary artery bypass grafting [CABG] surgery)
• use, or have used, protamine insulin
• are allergic to fish
• have had a vasectomy.